Textbook of Addiction Treatment International Perspectives
Textbook of Addiction Treatment International Perspectives
Textbook of Addiction Treatment International Perspectives
Editors
Textbook of
Addiction
Treatment:
International
Perspectives
1 3Reference
Textbook of Addiction Treatment:
International Perspectives
Nady el-Guebaly • Giuseppe Carrà
Marc Galanter
Editors
Textbook of Addiction
Treatment: International
Perspectives
Giuseppe Carrà
UCL Division of Psychiatry
Faculty of Brain Sciences
University College London
London, UK
Substance use and abuse is widespread around the world. There are clear cultural
differences between countries and sometimes even within the same country regarding
the use and abuse of substances. Various cultural and social factors play an important
role in defining and treating patterns of substance abuse. Reasons for substance use
and abuse vary from genetic, social, and psychological. Depending upon the degree
of abuse and recognition of the patterns of abuse, help may be sought from a number
of sources. Cultures and societies dictate how resources are allocated and how people
are encouraged to use certain pathways into care. Identifying the unmet needs and
mental health gap in the field of substance use and abuse is the first crucial step.
This reference text – a significant output from the International Society of Addic-
tion Medicine – meets the aims of the Society. These aims are eminently laudable as
they recognize the role of physicians in treating and managing addictions. The key
challenges remaining include policy differences across countries and how these must
be addressed. Furthermore, training of all health professionals in recognizing physical
and psychiatric problems associated with substance abuse is a must. Depending upon
human and financial resources, perhaps a tiered approach may be indicated. Physi-
cians in partnership with others have a significant role to play in a public mental
health agenda. Substance abuse – varying from tobacco to drugs, prescribed or
otherwise – is a major challenge in the field of public mental health. The editors
have done a sterling job in bringing together over 250 authors from a rich global
background to have shared their expertise and experiences. This volume provides an
excellent introduction at an international level to epidemiology, biological, social,
and psychological interventions and recognition of medical consequences and
comorbidities. The editors deserve our congratulations on a job well done.
Dinesh Bhugra
F.R.C.P., F.R.C.P.E., F.R.C.Psych., F.F.P.H., M.Phil., Ph.D.
Professor of Mental Health & Cultural Diversity
Institute of Psychiatry, King’s College London
Health Service & Population Research Department
London, UK
President, World Psychiatric Association
v
vi Foreword
The past decade has witnessed disturbing growth in the prevalence and diversity of
substance use problems throughout the world. First considered a “US problem” and
later a problem “of the Western world,” substance abuse and addiction are now
clearly world-wide problems producing dramatically greater loss of life, morbidity,
and costs than virtually any other health condition.
Perhaps because addictions have been so prevalent and serious in the USA for
the past 40 years, over 80 % of published clinical research on addiction to alcohol
and other drugs of abuse has been done by the USA and other English-speaking
investigators. But this body of work has at best only partially informed our
understanding of how to prevent and treat addiction. This is because so many
factors that contribute to susceptibility to initial substance use; transition from
voluntary use to uncontrolled addiction; and to treatment entry, adherence,
and effectiveness are determined as much by environmental, family, and
interpersonal forces as they are by genetics and metabolism. These factors
vary substantially across countries and cultures. Thus, world understanding
about how to prevent, intervene early, and treat addiction will require far more
diverse study.
In this context, the ISAM Textbook of Addiction Treatment, with its broad and
diverse contributions representing 265 scientists and 30 countries, is a timely and
welcome addition to worldwide understanding on how to intervene and treat
addictions. In particular, the Textbook introduces a wide range of new perspectives
on the development of substance use disorders and a number of previously
unreported interventions to reduce the prevalence, severity, and associated harms
from substance abuse and addiction.
To be sure this Textbook will not resolve decades-long controversies in
optimal prevention, intervention, and treatment responses, there is still too little
information and too many preexisting views to yet achieve consensus. But this
Textbook signals something that has frankly been lacking in US-dominated
research and treatment of addiction: a willingness to incorporate, evaluate, and
include effective new approaches, methods, and tools. It is clear that no country,
profession, or theory can claim adequate success in preventing or treating addic-
tion to justify the all-too-common political, financial, and even scientific resis-
tance to new methods.
If there is a need to reduce diversity, it is in our methods of diagnosing
substance use disorders, in articulating common goals of treatment, and in
adopting common measures and methods for evaluating treatment access, adher-
ence, and effectiveness. These kinds of consensus standards should help this still-
developing field of public and clinical health to identify and agree upon effective
Foreword vii
new interventions. This is an obvious and needed role for the International
Society of Addiction Medicine and should be a natural outgrowth of continued
international collaboration and sharing of results through venues such as this
Textbook.
A. Thomas McLellan
CEO, Treatment Research Institute
Philadelphia, PA, USA
Former Deputy Director
Office of National Drug Control Policy
USA
The initiative to write a textbook addressing the global aspects of addiction, whether
prevalence, types, and methods of abuse or different management approaches, is
unique and welcome. The chapters are comprehensive to deal with all psychoso-
cial–biological aspects of addiction. Psychoactive substance use poses a significant
threat to the health, social, and economic fabric of families, communities, and
nations. The extent of worldwide psychoactive substance use is estimated at 2 billion
alcohol users, 1.3 billion smokers, and 185 million drug users.
In an initial estimate of factors responsible for the global burden of disease,
tobacco, alcohol, and illicit drugs contributed together 12.4 % of all deaths world-
wide in the year 2000. Looking at the percentage of total years of life lost due to
these substances, it has been estimated that they account for 8.9 %.
The level of economic development in countries also plays an important role.
The burden from psychoactive substance use is higher in developed countries than
especially in high-mortality developing countries. The sex ratio for the attributable
deaths of psychoactive substance use varies from 80 % male for tobacco and illicit
drug use to 90 % for alcohol. With regard to DALYs, it is between 77 % and 85 %
for all substances. The largest proportion of DALYs is on males in developed
countries, where psychoactive substance use accounts for 33.4 % of all DALYs
(WHO Website).
WHO seeks to promote the concept of health for all through its strategy of
reducing the incidence and prevalence of psychoactive substance use and providing
the best available evidence on the management of substance-related problems.
The achievement of this goal is designed to lead to reductions in the demand for
psychoactive substances and to reduce the health and social problems associated
with such use.
viii Foreword
References
ix
x Preface: What Does an International Perspective Bring?
Not all such approaches have been evaluated to the same extent, with the major
effort directed at the investigation of Motivational Interviewing, Cognitive Behav-
ioral Therapy, and Contingency Management.
Challenges in the international dissemination of these approaches include the
significant effort required for the transfer of knowledge and skills as well as the
need to balance the evidence-based principles and methods of the approach with the
adaptation needed to incorporate new cultural contexts and values in a translated
language. Like in the biological approaches, innovative techniques continue to be
created and are at various stages of investigation.
Social therapies and their accessibility
Faced with the difficulties in abating, if not ending, the disease of addiction,
a diverse group of socially grounded therapies have sprung worldwide. Approaches
have included peer-led movements with no formal affiliation such as the 12-step
programs which are spanning most of the globe. Other peer-led programs have
evolved as institutions regulated by governments such as therapeutic communities.
These approaches are not identical worldwide but have nevertheless many similar-
ities. A major advantage of these approaches has been their cost-effectiveness
rendering them accessible to a range of economic capabilities.
The second advantage has been their adaptability to social institutions as diverse
as the workplace, the justice system, or the residential treatment programs. These
approaches have gained widespread acceptance particularly in developing
countries.
The diverse elements of a systems approach
A community treatment system requires a comprehensive network of different
approaches, services, and participants. A public health perspective stresses connec-
tions among services. These services share concepts of different indications and
rules for patient pathways through treatment phases following a stepped care
model.
The network, in addition to formal therapeutic regimes, includes low-threshold
approaches through outreach activities and harm reduction interventions. The
resources and priorities will of course differ between developing and developed
countries. A comprehensive network remains a work in progress with continuous
adaptations. An overall drug policy document should reflect political support to
provide adequate and sustainable resources.
A system must include continuous monitoring and evaluation. The education
and training of staff must be informed by the results of the evaluation. Stakeholders
are to be involved in the priority setting as well as ethical and legal considerations.
What constitutes a behavioral addiction?
Over the last 30 years, an increasing range of behaviors have been recognized as
susceptible to develop from excessive engagement to a habitual or compulsive
pattern. In addition to the investigation of common biological and psychological
underpinnings, an international perspective highlights the difference between the
required quasiuniversal use of a medium like the Internet and the susceptibility to
develop an Internet addiction along sociocultural differences. The same applies to
the meeting of basic needs such as food, sex, or exercise and their evolution into
xii Preface: What Does an International Perspective Bring?
Concerning the recognition of a specialty status, there is no “one size fits all”
model. This journey must adapt to local educational and licensing requirements that
govern the national practices of medicine.
Beyond training, the recruitment of an adequate workforce must take into
consideration the provision of attractive career paths countering stigma as well as
adequate remuneration and working conditions.
In conclusion, as no country has so far been able to eradicate the misuse of
substances or control excessive behaviors, pooling the international experience is
warranted. A global scanning of the options allows us to forecast potentially
promising approaches. Considering the world experience, we are also reminded
of the dictum “Absence of evidence may not necessarily mean evidence of
absence.” It may just be that the evidence has yet not been unearthed and our
current investigations are still not sensitive enough.
N. el-Guebaly
G. Carrà
M. Galanter
Acknowledgments
xv
Contents
Volume 1
Section I Basic Sciences and Clinical Foundations ............. 1
Andreas Heinz and Nady el-Guebaly
1 Basic Sciences and Clinical Foundations: An Introduction . . . . . 3
Andreas Heinz and Nady el-Guebaly
2 Neurobiology of Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Miriam Sebold, Maria Garbusow, Christian A. M€uller,
Katrin Charlet, and Andreas Heinz
xvii
xviii Contents
Volume 2
Section IV Behavioural Approaches . . . . . . . . . . . . . . . . . . . . . . . . 773
Richard A. Rawson and Marc Galanter
46 Behavioural Approaches: An Introduction . . . . . . . . . . . . . . . . . 775
Richard A. Rawson and Marc Galanter
47 Motivational Interviewing and Behaviour Change in
Addiction Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 779
Gillian Tober
48 Cognitive Behavioural Therapies for Substance Use Problems ... 793
Nicole K. Lee
49 Psychodynamic Psychotherapy for the Treatment of
Substance Use Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 811
Edward J. Khantzian
Contents xxi
Volume 3
Section VII Behavioural Addictions and Management
Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1405
Nady el-Guebaly and Hermano Tavares
89 Behavioural Addictions and Management Applications:
An Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1407
Nady el-Guebaly and Hermano Tavares
90 Biological Underpinning of Behavioural Addictions and
Management Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1411
Yvonne H. C. Yau, Robert F. Leeman, and Marc N. Potenza
91 The Psychological Underpinnings of Addictive Behaviours . . . . 1443
Tanya E. Mudry, Jonathan N. Stea, and David C. Hodgins
92 Clinical Management of Gambling Disorder . . . . . . . . . . . . . . . . 1475
Enrique Echeburúa
93 The National Problem Gambling Clinic . . . . . . . . . . . . . . . . . . . . 1491
Henrietta Bowden-Jones and Neil Smith
94 Internet Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1499
Sophia Achab, Olivier Simon, Stéphanie M€uller, Gabriel Thorens,
Giovanni Martinotti, Daniele Zullino, and Yasser Khazaal
95 Internet Gaming Addiction: The Case of Massively
Multiplayer Online Role-Playing Games . . . . . . . . . . . . . . . . . . . 1515
Jo€el Billieux, Jory Deleuze, Mark D. Griffiths, and Daria J. Kuss
96 Compulsive Buying Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1527
Tatiana Zambrano Filomensky and Hermano Tavares
97 Sexual Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1543
Meyen Hertzsprung and Stephen Amadala
98 The Association Between Binge Eating, Obesity and
Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1557
Stephanie C. Yarnell, Susan Murray, Nicole M. Avena, and
Mark S. Gold
Contents xxv
109 Sexual Function and Alcohol and Other Drug Use . . . . . . . . . . . 1789
Richard Hallinan
Volume 4
Section IX Psychiatric Comorbidities and Complications of
Alcohol and Other Drugs . . . . . . . . . . . . . . . . . . . . . . . . 1919
Kathleen Brady and Giuseppe Carrà
115 Psychiatric Comorbidities and Complications of Alcohol and
Other Drugs: An Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 1921
Kathleen T. Brady and Giuseppe Carrà
116 Substance-Induced Mental Disorders . . . . . . . . . . . . . . . . . . . . . . 1925
Alex Baldacchino, V. Arvapalli, Anthony Oshun, and
Serenella Tolomeo
117 Co-Occurring Mood and Substance Use Disorders . . . . . . . . . . . 1937
Edward V. Nunes, Deborah S. Hasin, and Roger D. Weiss
118 Bipolar Disorders and Co-Occurring Addictions . . . . . . . . . . . . 1959
Carlos Roncero, Lara Grau-lópez, Constanza Daigre, and
Miguel Casas
119 Comorbid Anxiety and Alcohol or Substance Use Disorders:
An Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1971
Francesco Bartoli, Daniele Carretta, Massimo Clerici, and
Giuseppe Carrà
120 The Comorbidity of Post-Traumatic-Stress Disorder (PTSD)
and Substance Use Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1985
Kathleen T. Brady, Jenna L. McCauley, and Sudie E. Back
121 A Drug Treatment Program for Young Israeli-Military
Veterans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2005
Hagit Bonny-Noach and Haim Mell
122 Psychotic Disorders and Substance Use Disorders . . . . . . . . . . . 2013
Daniele Carretta, Massimo Clerici, Francesco Bartoli, and
Giuseppe Carrà
Contents xxvii
136 Risk and Protective Factors for Substance Use and Abuse . . . . . 2279
Judith S. Brook, Kerstin Pahl, David W. Brook, and
Neo K. Morojele
xxxi
xxxii Contributors
David Best Turning Point Alcohol and Drug Centre, Fitzroy, VIC, Australia
Monash University, Melbourne, Australia
Warren K. Bickel Virginia Tech Carilion Research Institute, Roanoke, VA, USA
Jo€el Billieux Laboratory for Experimental Psychopathology, Psychological
Sciences Research Institute, Catholic University of Louvain, Louvain-La-Neuve,
Belgium
Roger Bloor Keele University Medical School, Keele, UK
Julio Bobes Department of Medicine - Psychiatry, University of Oviedo, Centro
de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Oviedo, Spain
Teresa Bobes-Bascarán CIBERSAM, University of Valencia, Valencia,
Comunidad Valenciana, Spain
Hagit Bonny-Noach Education & Prevention Division, Israel Anti-Drug
Authority, Ariel University & Beit Berl Academic College, Israel
Jeffrey J. Borckardt Department of Psychiatry and Behavioral Sciences,
Medical University of South Carolina, Charleston, SC, USA
Kristopher J. Bough Division of Basic Neuroscience and Behavioral
Research, National Institute on Drug Abuse, National Institutes of Health,
Bethesda, MD, USA
Henrietta Bowden-Jones National Problem Gambling Clinic and Division of
Brain Science, Imperial, London, UK
Kathleen T. Brady Department of Psychiatry and Behavioral Sciences,
Clinical Neuroscience Division, Medical University of South Carolina,
Charleston, SC, USA
Jørgen G. Bramness Norwegian Centre for Addiction Research, University of
Oslo, Oslo, Norway
Marı́a Dolores Braquehais Integral Care Program for Sick Doctors, Galatea
Clinic, Galatea Foundation, Catalan Medical Association, Barcelona, Spain
Department of Psychiatry, Hospital Universitari Vall d’Hebron, CIBERSAM,
Universitat Autònoma de Barcelona, Barcelona, Spain
Integral Care Program for Sick Health Professionals, Galatea Clinic, Galatea
Foundation, Catalan Medical Association, Barcelona, Spain
Barbara Broers Unit for Dependencies, Division for Primary Care, Department
for Community Medicine, Primary Care and Emergencies, Geneva University
Hospitals, Geneva, Switzerland
David W. Brook New York University School of Medicine, New York, USA
xxxiv Contributors
Judith S. Brook New York University School of Medicine, New York, USA
Eugeni Bruguera Integral Care Program for Sick Doctors, Galatea Clinic,
Galatea Foundation, Catalan Medical Association, Barcelona, Spain
Department of Psychiatry, Hospital Universitari Vall d’Hebron, CIBERSAM,
Universitat Autònoma de Barcelona, Barcelona, Spain
Gregor Burkhart European Monitoring Centre for Drugs and Drug Addiction
(EMCDDA), Lisbon, Portugal
Anja Busse United Nations Office of Drugs and Crime, Vienna, Austria
Guang Chen Drug Health Service, Royal Prince Alfred Hospital, Camperdown,
NSW, Australia
Discipline of Addiction Medicine, University of Sydney, Sydney, Australia
Paul Griffiths European Monitoring Centre for Drugs and Drug Addiction,
Lisbon, Portugal
Marc N. Potenza Department of Psychiatry, Yale University, New Haven, CT, USA
Department of Neurobiology, Yale University, New Haven, CT, USA
Yale Child Study Center, Yale University, New Haven, CT, USA
J€
urgen Rehm Centre for Addiction and Mental Health (CAMH), Toronto, ON,
Canada
Dalla Lana School of Public Health (DLSPH), University of Toronto, Toronto, ON,
Canada
Institute of Medical Science, University of Toronto, Toronto, ON, Canada
Department of Psychiatry, University of Toronto, Toronto, ON, Canada
Institute for Clinical Psychology and Psychotherapy, Technische Universit€at
Dresden, Dresden, Saxony, Germany
Abstract
We here introduce the section “Basic Scienes and Clinical Foundations”. In this
section we will adress the social, cultural, and regional as well as the neurobi-
ological and genetic aspects of addiction. The foundational section of this
international textbook on addiction treatment aims to provide an apt prologue
to the topic. This section includes chapters on neurobiology, a thorough review
of the neurotoxic and neuroadaptive consequences of chronic drug intake with a
focus on alcohol. A chapter on genetics presents the heritability of addiction and
its genetic and epigenetic components; another chapter presents the international
epidemiological aspects of addiction with a focus on the findings of the Global
Burden of Disease study. Another focus is on sociocultural dimensions, thus two
chapters present roles of socio-environmental factors in diagnosis and treatment
and their impact on the patient-clinician interpersonal dynamics as well as
interaction with the family, intimate social networks, community at large, and
policy makers. Moreover, we show cultural factors, i.e., the shared beliefs,
norms, and patterns of behaviors. The social patterning of psychoactive drug
use differs as to whether it is medicinal, regular, intermittent, or addictive.
Finally, two other chapters focus on the prevention applications of the
A. Heinz (*)
Department of Psychiatry and Psychotherapy Charité, Universitätsmedizin Berlin Charité Campus
Mitte Charitéplatz 1, Berlin, Germany
e-mail: [email protected]; [email protected]
N. el-Guebaly
Division of Addiction, Department of Psychiatry, University of Calgary, Alberta Gambling
Research Institute, Calgary, AB, Canada
e-mail: [email protected]
Drug use and dependence is one of the leading causes of disability and suffering
particularly in adolescence and younger adults (Gore et al. 2011). Addictive
disorders also contribute to a substantial percentage of interpersonal violence,
partly due to the direct effect of drugs of abuse such as alcohol (Heinz
et al. 2011) and partly due to social consequences of illicit drug abuse (Macleod
et al. 2004; Nutt et al. 2007; Toumbourou et al. 2007). In this section, we will
discuss the social, cultural, and regional as well as the neurobiological and genetic
aspects of addiction. The appreciation of this term has evolved. In 1976, Griffith
Edwards suggested to focus on key aspects of drug dependence, namely, tolerance
to drug effects developing with its chronic (ab)use and withdrawal symptoms
appearing when chronic drug use is suddenly intermittent (Edwards and Gross
1976). He suggested replacing the term “addiction,” as more likely to stigmatize
patients because it points to strong drug urges and the allegedly impaired ability to
control such desires. Edwards instead proposed to focus on the “somatic” aspects of
the addictive disorders, most notably tolerance and withdrawal. However, tolerance
also develops to nonaddictive drugs such as b-blockers, which are used as
antihypertensive medication, and withdrawal symptoms emerging as a sign of
impaired cerebral homoeostasis can appear when b-blocker consumption is sud-
denly stopped (Karachalios et al. 2005). Therefore, current textbooks of addictive
disorders often tend to emphasize the craving for the drug of abuse and the impaired
ability to control the consumption of this drug in spite of its adverse effects as
key aspects of addictive disorders (American Psychiatric Association and DSM-5
Task Force 2013).
Craving, loss of control, and consumption despite negative consequences have
often been labeled as the “psychological” symptoms of an addictive disorder, while
tolerance development and withdrawal symptoms have been called “somatic” signs of
the disease; however, in our view, this distinction between psychological and somatic
symptoms of addictive disorders should no longer be supported, as both withdrawal
symptoms and craving for the drug of abuse have cerebral correlates. Tolerance
development is associated with neuroadaptations within affected neurotransmitter
systems, and withdrawal symptoms result from an imbalance between central
excitatory and inhibitory neurotransmitters, causing an overshoot of autonomic
nervous system responses (Hughes 2009). Craving in turn might be attributable to
dysfunctions of motivational systems including dopaminergic neurotransmission in
the ventral striatum (Heinz 2002; Everitt et al. 2008). Furthermore, current theories of
addictive behavior emphasize a gradual shift from goal-directed, reward-seeking
behavior towards automatic drug intake, a concept that has previously been
promoted by Tiffany and Carter (1998) with respect to nicotine dependence and
that has currently gained a lot of behavioral as well as neurobiological support
1 Basic Sciences and Clinical Foundations: An Introduction 5
The second part by the same authors discusses the important regional and cultural
aspects of prevention. Societal values influence student and adolescent behaviors as
well as parenting practices. Again, an international perspective is presented as to
recent developments and trends in preventative measures. Examples of the previ-
ously described strategies in different regions of the world and their relative
acceptance are described along with resulting lessons about successful transfer
and adaptation of the experience between continents and countries.
In conclusion, we hope this foundational section provides an informative basic
science review of current knowledge. Due to the different scientific backgrounds
involved, several “Glossaries of Terms” are included. The first section of this
textbook aims to reflect the commonalties and differences of broad global and
international perspectives as salient determinants of management strategies.
References
American Psychiatric Association, DSM-5 Task Force (2013) Diagnostic and statistical manual of
mental disorders: DSM-5. American Psychiatric Association, Arlington
Barr CS, Newman TK, Becker ML, Champoux M, Lesch KP, Suomi SJ, Higley JD (2003) Sero-
tonin transporter gene variation is associated with alcohol sensitivity in Rhesus Macaques
exposed to early-life stress. Alcohol Clin Exp Res 27(5):812–817
Chen G, Cuzon Carlson VC, Wang J, Beck A, Heinz A, Ron D, Buck KJ (2011) Striatal
involvement in human alcoholism and alcohol consumption, and withdrawal in animal models.
Alcohol Clin Exp Res 35(10):1739–1748
Edwards G, Gross MM (1976) Alcohol dependence: provisional description of a clinical
syndrome. Br Med J 1(6017):1058–1061
el-Guebaly N, Cathcart J, Currie S, Brown D, Gloster S (2002) Public health and therapeutic aspects
of smoking bans in mental health and addiction settings. Psychiatr Serv 53(12):1617–1622
Everitt BJ, Robbins TW (2005) Neural systems of reinforcement for drug addiction: from actions
to habits to compulsion. Nat Neurosci 8(11):1481–1489
Everitt BJ, Belin D, Economidou D, Pelloux Y, Dalley JW, Robbins TW (2008) Neural mecha-
nisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction.
Philos Trans R Soc B Biol Sci 363(1507):3125–3135
Fahlke C, Lorenz JG, Long J, Champoux M, Suomi SJ, Higley JD (2000) Rearing experiences and
stress-induced plasma cortisol as early risk factors for excessive alcohol consumption in
nonhuman primates. Alcohol Clin Exp Res 24(5):644–650
Goldstein RZ, Volkow ND (2011) Dysfunction of the prefrontal cortex in addiction: neuroimaging
findings and clinical implications. Nat Rev Neurosci 12(11):652–669
Gore FM, Bloem PJ, Patton GC, Ferguson J, Joseph V, Coffey C, Sawyer SM, Mathers CD
(2011) Global burden of disease in young people aged 10–24 years: a systematic analysis.
Lancet 377(9783):2093–2102
Heinz A (2002) Dopaminergic dysfunction in alcoholism and schizophrenia–psychopathological
and behavioral correlates. Eur Psychiatry 17(1):9–16
Heinz AJ, Beck A, Meyer-Lindenberg A, Sterzer P, Heinz A (2011) Cognitive and neurobiological
mechanisms of alcohol-related aggression. Nat Rev Neurosci 12(7):400–413
Higley JD, Hasert MF, Suomi SJ, Linnoila M (1991) Nonhuman primate model of alcohol abuse:
effects of early experience, personality, and stress on alcohol consumption. Proc Natl Acad Sci
88(16):7261–7265
Hinckers AS, Laucht M, Schmidt MH, Mann KF, Schumann G, Schuckit MA, Heinz A (2006)
Low level of response to alcohol as associated with serotonin transporter genotype and high
alcohol intake in adolescents. Biol Psychiatry 60(3):282–287
8 A. Heinz and N. el-Guebaly
Contents
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
2.2 Neurobiological Factors for the Development and Maintenance of
Alcohol Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
2.2.1 Dispositional Factors for the Development of Alcohol Dependence . . . . . . . . . . . . 12
2.2.2 Effects of Acute Alcohol Consumption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
2.2.3 Addiction and the Reward System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2.2.4 Consequences of Chronic Alcohol Consumption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
2.2.5 Pharmaco-fMRI: New Insights of Pharmacological Treatment . . . . . . . . . . . . . . . . . . 27
2.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
Glossary of Terms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
Abstract
Chronic drug intake (including alcohol) has profound neurotoxic and
neuroadaptive consequences on neurotransmitter systems and brain circuitries
that are strongly involved in learning and memory. Neuroadaptive alterations
within these systems can contribute to addiction development and maintenance.
Current brain-imaging studies identified neural correlates of behavioral
processes that play a key role in addiction, such as cue-induced craving or automatic
action tendencies. Such neurobiological findings reflect neuroadaptations to
chronic drug intake, to further environmental as well as genetic factors and serve as
dispositional factors for the maintenance of addictive behavior patterns. In this
chapter, we describe neurobiological theories of addiction development and main-
tenance with a focus on motivational alterations and their neurobiological correlates
as revealed by current neuroimaging studies in alcohol dependence. We discuss
findings that assess alterations in reward anticipation and processing and their
respective effects on learning mechanisms that are known to be implied in alcohol
dependence. A better understanding of neural processes directly associated with the
development and maintenance of addiction can help to improve prevention pro-
grams as well as therapeutic and specifically pharmacological interventions in the
treatment of addicted patients.
Abbreviations
5-HTT Serotonin transporter
ACC Anterior cingulate cortex
ADH Alcohol dehydrogenase
ALDH Aldehyde dehydrogenase
CNS Central nervous system
CS Conditioned stimulus
dlPFC Dorsolateral prefrontal cortex
DRD2 D2 receptors
EEG Electroencephalogram
fMRI Functional magnetic resonance imaging
GABA Gamma-aminobutyric acid
GHB Acid Gamma-hydroxybutyric acid
HPA Hypothalamic-pituitary-adrenal
ICD-10 International classification of diseases 10th revision
MID task Monetary incentive delay task
mPFC Medial prefrontal cortex
MRI Magnetic resonance imaging
ms Milliseconds
NAcc Nucleus accumbens
NMDA N-methyl-D-aspartate
OFC Orbitofrontal cortex
PET Positron emission tomography
PFC Prefrontal cortex
SSRIs Selective serotonergic reuptake inhibitors
US Unconditioned stimulus
VTA Ventral tegmental area
WHO World Health Organization
2 Neurobiology of Addiction 11
2.1 Introduction
Several risk factors for the development of alcohol dependence have been reported
in the literature including the influence of genes and environment (Ehlers and Gizer
2013; Zimmermann et al. 2007). We will focus on key mechanisms identified in
animal experiments and human studies.
amount of alcohol consumption and thus the risk of developing alcohol dependence
(Birley et al. 2009; Frank et al. 2011; Hurley and Edenberg 2012). When alcohol is
metabolized, acetaldehyde is produced as the first intermediate product by ADH
(Spanagel 2009). Acetaldehyde is assumed to be responsible for some short- and
middle-term consequences of excessive alcohol intake such as the feeling of
“hangovers” due to its own harmful effects to the body. Primarily in East Asian
population, protective ADH variations occur resulting in rapid accumulation of
acetaldehyde, which triggers an unpleased “flush” reaction including erythema
(redness of the skin) of parts or, in some cases, the entire body and therefore
often results in less alcohol consumption (Hurley and Edenberg 2012). Thus,
variations in the ADH genes influence alcohol sensitivity, i.e., the acute effects of
alcohol consumption (Birley et al. 2009; Chen et al. 2009; Hurley and Edenberg
2012; Whitfield 1994). Altogether, these studies suggest that less negative and
aversive effects of acute alcohol consumption are associated with more intake
and a higher risk to develop alcohol dependence (Heinz et al. 2001; Schuckit and
Smith 1996).
in the ventral tegmental area (VTA) (Whitaker et al. 2013). The VTA is the center
of origin of striatal dopaminergic projections and is thus significantly involved in
reward-based learning as well as in the development of dependent behavior. In
these socially isolated rats, Whitaker et al. (2013) observed an increased learning
rate for drug-associated stimuli, which was more resistant to extinction, suggesting
that NMDA receptor plasticity is one mechanism though which the vulnerability of
drug dependence is adjusted during a critical period in adolescence (Whitaker
et al. 2013).
studies show that adolescence is a period with a decreased sensitivity to the sedative
effects of acute alcohol consumption, with adolescents showing substantially less
acute alcohol sensitivity (Silveri and Spear 1998). Monti et al. (2005) observed that
adolescent as well as alcohol-preferring rats show low sedative effects of alcohol,
comparable to humans at risk for developing an alcohol dependence (Schuckit and
Smith 1996). Critically, this may entice adolescents to binge drink, although, they
are more vulnerable than adults to neurotoxicity induced by ethanol (Crews
et al. 2000; Monti et al. 2005). Crews et al. (2000) described binge drinking-
induced brain damages in adolescent rats in frontal and temporal cortical regions,
while adult rats showed no binge drinking-induced alterations in these areas. In line
with this, De Bellis et al. (2005) observed in a human study using magnetic
resonance imaging (MRI) a smaller PFC in subjects with an adolescent-onset-
alcohol use disorder. Here, a smaller PFC correlated with a higher number of drinks
per drinking episode and a higher number of drinks per maximum drinking episode
(De Bellis et al. 2005).
Fig. 2.2 (a) Burst of dopaminergic firing in occurrence of an unpredicted reward (R) at reward
onset (positive prediction error). (b) After pavlovian conditioning: burst of dopaminergic firing not
at reward but at conditioned stimulus (CS) onset. (c) No reward: Dip of dopaminergic firing at
expected reward onset (negative prediction error) (Adapted from Schultz (1998))
because the pharmacological effect of the drug itself causes a persistent dopaminergic
release in the striatum (Wise and Rompre 1989). Furthermore, in animals (Paulson
and Robinson 1995), repeated administration of drugs fosters augmented dopamine
release. This phenomenon – commonly termed as sensitization – was also confirmed
to some degree in humans (Boileau et al. 2006). Thus, repeated administration of
addictive drugs might cause a hypersensitive dopaminergic system. Moreover, it
has been suggested that in addiction, dopamine is released by formerly neutral cues
that have predicted drug intake previously (Heinz 2002). Several animal studies
demonstrated that in addiction drug-associated stimuli activate dopamine release in
the medial prefrontal cortex and the ventral striatum (Bassareo et al. 2007; Dayas
et al. 2007; Di Chiara 2002; Shalev et al. 2002). These findings have been extended to
2 Neurobiology of Addiction 19
endpoint of a series of transitions: from initial drug intake that causes hedonic
feelings (liking) to a stage when substance use becomes habitual (wanting) and
ultimately to a loss of control that is characterized by compulsive drug seeking and
intake. Habitual drug consumption is assumed to be disentangled from anticipatory
drug effects. Evidence for this comes from animal studies: rats that have learned
a specific response in order to self-administer drugs continue to perform this
response even when drug delivery is suppressed (Katner et al. 1999; Katner and
Weiss 1999). Thus in addiction, action selection may no longer be guided by
outcome expectancy, but rather be driven by external sensory information that
elicits pavlovian-conditioned responses. The standard test of habitual action selec-
tion is the demonstration that sensory-specific devaluation or revaluation of rewards
has no immediate effect on choice behavior. In the devaluation design the value of
a specific reward is decreased, for instance, by associating it with sickness, whereas
in the revaluation design, the value of the reward is increased, for instance, by
determining to experience the reward in a state of deprivation. Crucially, neither
devaluation nor revaluation of a stimulus alters choice behavior on that stimulus,
when action selection is habitual. This has been supported by studies demonstrating
that unlimited access to alcohol fosters ethanol consumption in rats, which is
insensitive to quinine, which has a bitter taste and is thus not rewarding
(Hopf et al. 2010; Wolffgramm and Heyne 1995). Crucially, it has been demon-
strated that responding for ethanol becomes insensitive to devaluation at a stage
when responding for food reward is still sensitive to devaluation, indicating that the
shift from goal to stimulus-directed consumption is more rapid for alcohol than for
natural rewards (Dickinson et al. 2002).
On the neural level “wanting” might be mediated by the ventral striatum and the
state of habitual intake by the dorsal striatum. Thus the development of an addiction
might be mediated by a transformation from goal-directed to stimulus-driven, auto-
matic behavior, which is assumed to be accompanied by a shift of ventral to dorsal
striatal activity. Animal studies seem to confirm this contention: once substance use
becomes habitual, drug-associated stimuli foster release of dopamine in the dorsal
striatum (Balleine et al. 2007; Corbit et al. 2012; Ito et al. 2002; Wong et al. 2006).
However the translation of observations in animals excessively trained to perform
lever presses for food or drugs, which finally habitize, to human behavior, which can
be consciously reflected and verbalized, is controversial. Existing studies in humans
have demonstrated that smoking cessation in nicotine-dependent subjects increases
motivation for tobacco smoke (Madden and Bickel 1999; Perkins et al. 1996),
indicating goal-directed responses in nicotine dependence. However, as these tests
were not conducted in extinction, the effect of deprivation might have been mediated
by the experience of an increased reward value in the deprivation state rather than the
altered reward value of the expectancy (Stephens et al. 2010).
Also compulsions and obsessions as in obsessive compulsive disorder (OCD) do
hardly resemble habitual intake (Schoofs and Heinz 2013). Therefore, the role of
habitual vs. goal-directed drug intake in humans in addiction remains to be
explored.
22 M. Sebold et al.
2.2.4.1 Cue-Reactivity
Physiological and subjectively experienced cue-reactivity has been suggested to play
an important role in addiction maintenance and relapse. More precisely, in addiction
it is assumed that drug-associated stimuli signal upcoming reward and thus prompt
drug-seeking behavior (Robinson and Berridge 1993). This evidence has been
generated from a number of studies using fMRI in order to investigate neural
correlates of cue-reactivity. These studies have shown that substance-dependent
subjects display increased activation of several core regions of the mesolimbic
pathway, when confronted with drug-associated stimuli. This finding has been
reported in various substance dependencies, including heroin (Yang et al. 2009;
Zijlstra et al. 2009), cocaine (Volkow et al. 2006), alcohol (Beck et al. 2012; Gr€usser
et al. 2004; Schacht et al. 2013; Tapert et al. 2004b; Wrase et al. 2007), cannabis
(Filbey et al. 2009), and nicotine dependence (B€uhler et al. 2010; David et al. 2005).
Although these studies suggest substantial overlap between neural structures impli-
cated in cue-reactivity, the identified brain structures considerably vary between
studies, depending on the experimental design of the study (duration of stimulus
presentation, block design vs. event-related design), cue-modality (visual, olfactory,
gustatory), and state of the subjects (detoxified patients or actively drinking, treat-
ment seeking vs. no treatment seeking patients) (Heinz et al. 2010; Yalachkov
et al. 2012). Brain regions which have reliably been identified in different
cue-reactivity fMRI studies include the anterior cingulate cortex (ACC), the medial
prefrontal cortex (mPFC), the ventral and dorsal striatum and the orbitofrontal cortex
(OFC), the dorsolateral prefrontal cortex (dlPFC), and the amygdala (Charlet
et al. 2013, see Table 2.1). Several neuroimaging studies also reported correlations
between cue-induced hyperactivity in the mesolimbic circuit and self-reports of
craving in substance-dependent patients, suggesting that cue-related neural activation
of reward-associated brain regions may be associated with the motivation to consume
drugs and therefore with prospective relapse. In alcohol dependence, a positive
correlation between craving and cue-induced neural activity was found in the
subcallosal gyrus (Tapert et al. 2004a), the ventral striatum, the orbitofrontal cortex,
and the anterior cingulate cortex (Myrick et al. 2004). As the assessment of craving is
limited by the fact that it relies on individuals’ ability to accurately rate and report
their own desire for the substance, some studies add more objective relapse indica-
tors, such as days of abstinence in a given observation period following brain imaging
assessment. Here, cue-induced activity in the ventral putamen/striatum (Braus
et al. 2001) and the medial prefrontal cortex (Gr€usser et al. 2004) predicted relapse
in detoxified alcohol-dependent patients within a follow-up period of 3 months.
A recent study by Beck et al. (2012) observed that functional connectivity patterns
differ between prospective relapsers and abstainers from alcohol: while subsequent
relapsers displayed increased neural activation in the medial prefrontal cortex during
the presentation of alcohol-associated versus neutral stimuli, subsequent abstainers
activated midbrain regions, such as the ventral tegmental area including the
subthalamic nucleus and showed increased functional connectivity between the
2 Neurobiology of Addiction 23
Table 2.1 Core regions activated by alcohol-related stimuli in imaging studies using
cue-reactivity paradigms
Study design of cue
Brain structure Function Study reactivity paradigm
Anterior Performance monitoring and Tapert Alcohol-related
cingulate error detection, encoding of et al. (2003) vs. nonalcohol pictures
cortex (ACC) motivational salient stimuli Gr€usser Alcohol-related vs. neutral
et al. (2004) pictures
Heinz Alcohol-related vs. neutral
et al. (2004) pictures
Myrick Priming dose of alcohol;
et al. (2004), alcohol-related
Myrick vs. nonalcohol-related
et al. (2008) pictures
Tapert Alcohol-related vs. neutral
et al. (2004a) words
Vollstädt-Klein Alcohol-related vs. neutral
et al. (2011) pictures
Medial Memory and decision making Gr€usser Alcohol-related vs. neutral
prefrontal et al. (2004) pictures
cortex (mPFC) Myrick Priming dose of alcohol;
et al. (2008) alcohol-related
vs. nonalcohol-related
pictures
Beck Alcohol-related vs. neutral
et al. (2012) pictures
Orbitofrontal Evaluation of reward Wrase Alcohol-related vs. abstract
cortex (OFC) et al. (2002) neutral pictures
Myrick Priming dose of alcohol,
et al. (2004) alcohol-related
vs. nonalcohol-related
pictures
Dorsolateral Executive behavioral control George Priming dose of alcohol,
prefrontal et al. (2001) alcohol-related
cortex (dlPFC) vs. nonalcohol-related
pictures
Amygdala Specification of emotional Schneider Olfactory cues associated
salience et al. (2001) with ethanol vs. neutral
odor
Dorsal Consolidation of stimulus- Modell and Multiple sips of alcohol-
striatum reaction patterns and habit Mountz (1995) related vs. multiple sips of
formation water
Gr€usser Alcohol-related vs. neutral
et al. (2004) pictures
Vollstädt-Klein Alcohol-related (complex
et al. (2010b) scenes) vs. neutral pictures
(continued)
24 M. Sebold et al.
midbrain, amygdala, and the orbitofrontal cortex. This observation may suggest that
(preserved) integrity of a circuit that is implicated in the processing of aversive
aspects and the danger of alcohol intake may represent a resilience factor against
relapse (Beck et al. 2012).
response in spite of the generally reduced neurotransmission. This is in line with the
finding that the degree of striatal downregulation of DRD2 in alcohol dependence is
associated with the extent of drug-cue-induced activation in the medial prefrontal
cortex and the anterior cingulate and with the severity of alcohol craving (Heinz
et al. 2004). It has been suggested that the bias towards high dopaminergic
stimulatory drugs can bias choices against weaker primary and secondary rein-
forcers such as food, money, or social interactions. A current study of Kienast
et al. (2013), who combined PET and fMRI, further suggests a failure of dopamine-
modulated emotion processing of aversive stimuli in alcohol-dependent patients.
Here, no association was found between dopamine synthesis in the amygdala and
functional activation in the amygdala and ACC elicited by aversive emotional
stimuli in recently detoxified alcohol-dependent patients, while such correlations
were observed in healthy volunteers (Kienast et al. 2008). Furthermore, the patients
displayed impaired functional connectivity between the amygdala and the ACC
while viewing the aversive cues, which may contribute to increased trait anxiety
due to malfunctional corticolimbic neuromodulation. Negative mood states, such as
high anxiety, can lead to an increased relapse risk especially in late abstinence
(Kienast et al. 2013).
Dopaminergic dysfunction may primarily interfere with learning of new condi-
tional stimuli and contexts that predict nondrug reward. Indeed a study demon-
strated impairments in learning from nondrug-related rewards in alcohol
dependence (Park et al. 2010), which correlated with craving for (well-learned
non-explicit) alcohol intake. The shift of natural reward processing to preferential
drug-related reward processing has been metaphorically described as a “hijacking
of the reward system,” which was substantiated by several studies using a Monetary
Incentive Delay task (MID, Knutson et al. 2001). For example, it was shown that
alcohol-dependent subjects compared to healthy controls displayed a decrease in
ventral striatum activity during expectation of monetary gains but an increased
activation in the same region when confronted with drug cues (Beck et al. 2009;
Wrase et al. 2007). Activity in the ventral striatum elicited by drug cues was
correlated with self-reports of craving (Wrase et al. 2007). These findings are in
line with other studies suggesting an essential role for the ventral striatum in relapse
prediction. For instance, the degree of ventral striatal activity elicited by drug-
associated stimuli presentation was associated with time until relapse (Braus
et al. 2001) and the amount of prospectively consumed alcohol (Gr€usser
et al. 2004), suggesting that the ventral striatum plays a role not only in the
acquisition but also in the maintenance of alcohol dependence. In accordance
with the assumption of a hijacked reward system, it has been suggested that strong
neural responses to rewarding, nondrug-related stimuli might serve as a potential
protective brain mechanisms against relapse. Indeed, it was demonstrated that
increased ventral striatal responses to affectively positive connoted pictures were
related to more subsequent abstinent days and less prospective alcohol intake
(Heinz et al. 2007). Furthermore, Charlet et al. (2013) observed heightened neural
responses to emotionally negative facial stimuli in the ACC, which also predicted
better treatment outcome (days of abstinence and days of binge drinking) in
26 M. Sebold et al.
Albeit treatment of drug-associated harm with drug substitution has been proven to
be a very successful option in opiate addiction (Mattick et al. 2009), in alcohol
addiction, treatment with substitutive psychoactive compounds (such as
g- Hydroxybutyric Acid, GHB) is prohibited in many countries, due to limited
responder rates in GHB therapy (Maremmani et al. 2011). Instead, in many
European countries, drugs potentially counteracting alcohol-associated neuro-
adaptations such as naltrexone or acamprosate are temporarily applied for relapse
prevention. Even though Cochrane Reviews have demonstrated significant effec-
tiveness of both pharmacological treatments (Relative Risk reduction of naltrexone
(0.83) and acamprosate (0.86) compared to no medication) (Rösner et al. 2010a, b),
the exact mechanisms by which acamprosate and naltrexone decrease alcohol
ingestion and relapse rates in alcohol-dependent patients are yet to be explored.
The application of neuroimaging techniques in pharmacologically treated alcohol-
dependent patients is useful in predicting which medication helps to prevent
relapse. For example, elevated levels of m-opioid receptors have been observed in
the ventral striatum of some detoxified alcohol-dependent patients (Heinz
et al. 2005a) and are targeted by naltrexone, which blocks m-opioid receptors.
A combination of fMRI and pharmacological treatment (Pharmaco-fMRI)
allows to investigate how and where a specific pharmacological drug acts in the
central nervous system. For example, a study conducted by Myrick et al. (2008)
28 M. Sebold et al.
2.3 Conclusion
Acknowledgment This work was supported by the German Research Foundation (Deutsche
Forschungsgemeinschaft, DFG, FOR 1617: grants HE2597/14-1 and ZI1119/3-1).
Glossary of Terms
References
Abi-Dargham A, Krystal JH, Anjilvel S et al (1998) Alterations of benzodiazepine receptors in
type II alcoholic subjects measured with SPECT and [123I]iomazenil. Am J Psychiatry
155:1550–1555
Acquas E, Carboni E, Leone P, Chiara GD (1989) SCH 23390 blocks drug-conditioned place-
preference and place-aversion: anhedonia (lack of reward) or apathy (lack of motivation) after
dopamine-receptor blockade? Psychopharmacology 99:151–155
Addolorato G, Leggio L, Ferrulli A et al (2007) Effectiveness and safety of baclofen for mainte-
nance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised,
double-blind controlled study. Lancet 370:1915–1922
Agartz I, Brag S, Franck J et al (2003) MR volumetry during acute alcohol withdrawal and
abstinence: a descriptive study. Alcohol Alcohol 38:71–78
Ameisen O (2005) Complete and prolonged suppression of symptoms and consequences of
alcohol-dependence using high-dose baclofen: a self-case report of a physician. Alcohol
Alcohol 40:147–150
Balleine BW, Delgado MR, Hikosaka O (2007) The role of the dorsal striatum in reward and
decision-making. J Neurosci 27:8161–8165
Bassareo V, De Luca MA, Di Chiara G (2007) Differential impact of pavlovian drug conditioned
stimuli on in vivo dopamine transmission in the rat accumbens shell and core and in the
prefrontal cortex. Psychopharmacology 191:689–703
Beck A, Schlagenhauf F, W€ ustenberg T et al (2009) Ventral striatal activation during reward
anticipation correlates with impulsivity in alcoholics. Biol Psychiatry 66:734–742
2 Neurobiology of Addiction 31
Beck A, Wustenberg T, Genauck A et al (2012) Effect of brain structure, brain function, and brain
connectivity on relapse in alcohol-dependent patients. Arch Gen Psychiatry 69:842–852
Bendszus M, Weijers HG, Wiesbeck G et al (2001) Sequential MR imaging and proton
MR spectroscopy in patients who underwent recent detoxification for chronic alcoholism:
correlation with clinical and neuropsychological data. AJNR Am J Neuroradiol
22:1926–1932
Berridge KC (2009) Wanting and liking: observations from the neuroscience and psychology
laboratory. Inquiry 52:378
Birley AJ, James MR, Dickson PA et al (2009) ADH single nucleotide polymorphism associations
with alcohol metabolism in vivo. Hum Mol Genet 18:1533–1542
Boileau I, Dagher A, Leyton M et al (2006) Modeling sensitization to stimulants in humans: an
[11C]raclopride/positron emission tomography study in healthy men. Arch Gen Psychiatry
63:1386–1395
Boileau I, Dagher A, Leyton M et al (2007) Conditioned dopamine release in humans: a positron
emission tomography [11C]raclopride study with amphetamine. J Neurosci Off J Soc Neurosci
27:3998–4003
Boothby LA, Doering PL (2005) Acamprosate for the treatment of alcohol dependence. Clin Ther
27:695–714
Braus DF, Wrase J, Grusser S et al (2001) Alcohol-associated stimuli activate the ventral striatum
in abstinent alcoholics. J Neural Transm 108:887–894
B€uhler M, Vollstädt-Klein S, Kobiella A et al (2010) Nicotine dependence is characterized by
disordered reward processing in a network driving motivation. Biol Psychiatry 67:745–752
Bushman BJ, Cooper HM (1990) Effects of alcohol on human aggression: an integrative research
review. Psychol Bull 107:341–354
Carlen PL, Wortzman G, Holgate RC, Wilkinson DA, Rankin JC (1978) Reversible cerebral
atrophy in recently abstinent chronic alcoholics measured by computed tomography scans.
Science 200:1076–1078
Carlson RH, Lydic R (1976) The effects of ethanol upon threshold and response rate for self-
stimulation. Psychopharmacology 50:61–64
Carter BL, Tiffany ST (1999) Meta-analysis of cue-reactivity in addiction research. Addiction
94:327–340
Charlet K, Beck A, Heinz A (2013) The dopamine system in mediating alcohol effects in humans.
Curr Top Behav Neurosci 13:461–488
Chen YC, Peng GS, Wang MF, Tsao TP, Yin SJ (2009) Polymorphism of ethanol-metabolism
genes and alcoholism: correlation of allelic variations with the pharmacokinetic and pharma-
codynamic consequences. Chem Biol Interact 178:2–7
Childress AR, Ehrman RN, Wang Z et al (2008) Prelude to passion: limbic activation by “unseen”
drug and sexual cues. PLoS ONE 3:e1506
Cohen C, Perrault G, Sanger DJ (1997) Evidence for the involvement of dopamine receptors in
ethanol-induced hyperactivity in mice. Neuropharmacology 36:1099–1108
Corbit LH, Janak PH (2007) Ethanol-associated cues produce general pavlovian-instrumental
transfer. Alcohol Clin Exp Res 31:766–774
Corbit LH, Nie H, Janak PH (2012) Habitual alcohol seeking: time course and the contribution of
subregions of the dorsal striatum. Biol Psychiatry 72:389–395
Courtyn J, Goethals P, Van der Eycken J, Dams R (2001) Synthesis of C-11-labelled acamprosate
for PET studies. J Labelled Comp Radiopharm 44:643–651
Crews FT, Braun CJ, Hoplight B, Switzer RC 3rd, Knapp DJ (2000) Binge ethanol consumption
causes differential brain damage in young adolescent rats compared with adult rats. Alcohol
Clin Exp Res 24:1712–1723
Crews F, He J, Hodge C (2007) Adolescent cortical development: a critical period of vulnerability
for addiction. Pharm Biochem Behav 86:189–199
D’Esposito M, Detre JA, Alsop DC, Shin RK, Atlas S, Grossman M (1995) The neural basis of the
central executive system of working memory. Nature 378:279–281
32 M. Sebold et al.
Gilman JM, Ramchandani VA, Davis MB, Bjork JM, Hommer DW (2008) Why we like to drink:
a functional magnetic resonance imaging study of the rewarding and anxiolytic effects of
alcohol. J Neurosci Off J Soc Neurosci 28:4583–4591
Glasner SV, Overmier JB, Balleine BW (2005) The role of Pavlovian cues in alcohol seeking in
dependent and nondependent rats. J Stud Alcohol 66:53–61
Glue P, Nutt D (1990) Overexcitement and disinhibition. Dynamic neurotransmitter interactions in
alcohol withdrawal. Br J Psychiatry 157:491–499
Goldstein A (2001) Addiction: from biology to drug policy. Oxford University Press, Oxford
Gr€
usser SM, Wrase J, Klein S et al (2004) Cue-induced activation of the striatum and medial
prefrontal cortex is associated with subsequent relapse in abstinent alcoholics. Psychopharma-
cology 175:296–302
Hanchar HJ, Dodson PD, Olsen RW, Otis TS, Wallner M (2005) Alcohol-induced motor impair-
ment caused by increased extrasynaptic GABA(A) receptor activity. Nat Neurosci 8:339–345
Heinz A (2002) Dopaminergic dysfunction in alcoholism and schizophrenia–psychopathological
and behavioral correlates. Eur Psychiatry J Assoc Eur Psychiatrists 17:9–16
Heinz A, Dufeu P, Kuhn S et al (1996) Psychopathological and behavioral correlates of dopami-
nergic sensitivity in alcohol-dependent patients. Arch Gen Psychiatry 53:1123–1128
Heinz A, Higley JD, Gorey JG et al (1998a) In vivo association between alcohol intoxication,
aggression, and serotonin transporter availability in nonhuman primates. Am J Psychiatry
155:1023–1028
Heinz A, Ragan P, Jones DW et al (1998b) Reduced central serotonin transporters in alcoholism.
Am J Psychiatry 155:1544–1549
Heinz A, Jones DW, Mazzanti C et al (2000) A relationship between serotonin transporter
genotype and in vivo protein expression and alcohol neurotoxicity. Biol Psychiatry
47:643–649
Heinz A, Mann K, Weinberger DR, Goldman D (2001) Serotonergic dysfunction, negative mood
states, and response to alcohol. Alcohol Clin Exp Res 25:487–495
Heinz A, Löber S, Georgi A et al (2003) Reward craving and withdrawal relief craving: assessment
of different motivational pathways to alcohol intake. Alcohol Alcohol 38:35–39
Heinz A, Siessmeier T, Wrase J et al (2004) Correlation between dopamine D(2) receptors in the
ventral striatum and central processing of alcohol cues and craving. Am J Psychiatry
161:1783–1789
Heinz A, Reimold M, Wrase J et al (2005a) Correlation of stable elevations in striatal mu-opioid
receptor availability in detoxified alcoholic patients with alcohol craving: a positron emission
tomography study using carbon 11-labeled carfentanil. Arch Gen Psychiatry 62:57–64
Heinz A, Siessmeier T, Wrase J et al (2005b) Correlation of alcohol craving with striatal dopamine
synthesis capacity and D2/3 receptor availability: a combined [18F]DOPA and [18F]DMFP
PET study in detoxified alcoholic patients. Am J Psychiatry 162:1515–1520
Heinz A, Wrase J, Kahnt T et al (2007) Brain activation elicited by affectively positive stimuli is
associated with a lower risk of relapse in detoxified alcoholic subjects. Alcohol Clin Exp Res
31:1138–1147
Heinz A, Beck A, Grusser SM, Grace AA, Wrase J (2009) Identifying the neural circuitry of
alcohol craving and relapse vulnerability. Addict Biol 14:108–118
Heinz A, Beck A, Mir J, Gr€ usser SM, Grace AA, Wrase J (2010) Alcohol craving and relapse
prediction. Imaging studies. In: Koob GF, Kuhn C (eds) Advances in the Neuroscience of
Addiction. Taylor & Francis Group
Heinz AJ, Beck A, Meyer-Lindenberg A, Sterzer P, Heinz A (2011) Cognitive and neurobiological
mechanisms of alcohol-related aggression. Nat Rev Neurosci 12:400–413
Heinz A, Batra A, Scherbaum N, Gouzoulis-Mayfrank E (2012) Neurobiologie der Abhängigkeit:
Grundlagen und Konsequenzen f€ ur Diagnose und Therapie von Suchterkrankungen,
vol 1. Kohlhammer, Stuttgart
Hendler RA, Ramchandani VA, Gilman J, Hommer DW (2013) Stimulant and sedative effects of
alcohol. Curr Top Behav Neurosci 13:489–509
34 M. Sebold et al.
Herrmann MJ, Weijers HG, Wiesbeck GA, Böning J, Fallgatter AJ (2001) Alcohol cue-reactivity
in heavy and light social drinkers as revealed by event-related potentials. Alcohol Alcohol
36:588–593
Hinckers AS, Laucht M, Schmidt MH et al (2006) Low level of response to alcohol as associated
with serotonin transporter genotype and high alcohol intake in adolescents. Biol Psychiatry
60:282–287
Holdstock L, King AC, de Wit H (2000) Subjective and objective responses to ethanol in
moderate/heavy and light social drinkers. Alcohol Clin Exp Res 24:789–794
Hopf FW, Chang S-J, Sparta DR, Bowers MS, Bonci A (2010) Motivation for alcohol becomes
resistant to quinine adulteration after 3 to 4 months of intermittent alcohol self-administration.
Alcohol Clin Exp Res 34:1565–1573
Hurley TD, Edenberg HJ (2012) Genes encoding enzymes involved in ethanol metabolism.
Alcohol Res Curr Rev 34:339–344
Ihssen N, Cox WM, Wiggett A, Fadardi JS, Linden DE (2011) Differentiating heavy from light
drinkers by neural responses to visual alcohol cues and other motivational stimuli. Cereb
Cortex 21:1408–1415
Ikemoto S (2007) Dopamine reward circuitry: two projection systems from the ventral midbrain to
the nucleus accumbens-olfactory tubercle complex. Brain Res Rev 56:27–78
Ito R, Dalley JW, Robbins TW, Everitt BJ (2002) Dopamine release in the dorsal striatum during
cocaine-seeking behavior under the control of a drug-associated cue. J Neurosci 22:6247–6253
Katner SN, Weiss F (1999) Ethanol-associated olfactory stimuli reinstate ethanol-seeking behav-
ior after extinction and modify extracellular dopamine levels in the nucleus accumbens.
Alcohol Clin Exp Res 23:1751–1760
Katner SN, Magalong JG, Weiss F (1999) Reinstatement of alcohol-seeking behavior by drug-
associated discriminative stimuli after prolonged extinction in the rat. Neuropsychophar-
macology 20:471–479
Kiefer F, Mann K (2005) New achievements and pharmacotherapeutic approaches in the treatment
of alcohol dependence. Eur J Pharmacol 526:163–171
Kienast T, Hariri AR, Schlagenhauf F et al (2008) Dopamine in amygdala gates limbic processing
of aversive stimuli in humans. Nat Neurosci 11:1381–1382
Kienast T, Schlagenhauf F, Rapp MA et al (2013) Dopamine-modulated aversive emotion
processing fails in alcohol-dependent patients. Pharmacopsychiatry 2(4):130–136
Knutson B, Wolkowitz OM, Cole SW et al (1998) Selective alteration of personality and social
behavior by serotonergic intervention. Am J Psychiatry 155:373–379
Knutson B, Adams CM, Fong GW, Hommer D (2001) Anticipation of increasing monetary reward
selectively recruits nucleus accumbens. J Neurosci 21:RC159
Koob GF, Le Moal M (1997) Drug abuse: hedonic homeostatic dysregulation. Science 278:52–58
Kril JJ, Halliday GM, Svoboda MD, Cartwright H (1997) The cerebral cortex is damaged in
chronic alcoholics. Neuroscience 79:983–998
Krystal JH, Staley J, Mason G et al (2006) Gamma-aminobutyric acid type A receptors and
alcoholism: intoxication, dependence, vulnerability, and treatment. Arch Gen Psychiatry
63:957–968
Langosch JM, Spiegelhalder K, Jahnke K et al (2012) The impact of acamprosate on cue reactivity
in alcohol dependent individuals: a functional magnetic resonance imaging study. J Clin
Psychopharmacol 32:661–665
Le Merrer J, Becker JA, Befort K, Kieffer BL (2009) Reward processing by the opioid system in
the brain. Physiol Rev 89:1379–1412
Lee E, Namkoong K, Lee CH, An SK, Lee BO (2006) Differences of photographs inducing
craving between alcoholics and non-alcoholics. Yonsei Med J 47:491–497
LeMarquand D, Pihl RO, Benkelfat C (1994) Serotonin and alcohol intake, abuse, and depen-
dence: clinical evidence. Biol Psychiatry 36:326–337
Lesch KP, Bengel D, Heils A et al (1996) Association of anxiety-related traits with
a polymorphism in the serotonin transporter gene regulatory region. Science 274:1527–1531
2 Neurobiology of Addiction 35
Lindenmeyer J (2001) Lieber schlau als blau. Psychologie, VerlagsUnion, Verlagsgruppe Beltz,
Weinheim
Madden GJ, Bickel WK (1999) Abstinence and price effects on demand for cigarettes:
a behavioral-economic analysis. Addiction 94:577–588
Mann K, Willeit W, Praschak-Rieder N et al (2011) S15 • esbra/isbra joint. symposium: imaging in
alcohol research. The role of functional neuroimaging in the choice of treatment for alcoholics.
Alcohol Alcohol 46(suppl 1):i14, S15.1
Maremmani AG, Pani PP, Rovai L, Pacini M, Dell’Osso L, Maremmani I (2011) Long-term
gamma-hydroxybutyric acid (GHB) and disulfiram combination therapy in GHB treatment-
resistant chronic alcoholics. Int J Environ Res Public Health 8:2816–2827
Martin CS, Earleywine M, Musty RE, Perrine MW, Swift RM (1993) Development and validation
of the biphasic alcohol effects scale. Alcohol Clin Exp Res 17:140–146
Matthes HW, Maldonado R, Simonin F et al (1996) Loss of morphine-induced analgesia, reward
effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene. Nature
383:819–823
Mattick RP, Breen C, Kimber J, Davoli M (2009) Methadone maintenance therapy versus no
opioid replacement therapy for opioid dependence. Cochrane Database Syst Rev 3:CD002209
Meyer-Lindenberg A, Tost H (2012) Neural mechanisms of social risk for psychiatric disorders.
Nat Neurosci 15:663–668
Modell JG, Mountz JM (1995) Focal cerebral blood flow change during craving for alcohol
measured by SPECT. J Neuropsychiatr Clin Neurosci 7:15–22
Monti PM, Miranda R Jr, Nixon K et al (2005) Adolescence: booze, brains, and behavior. Alcohol
Clin Exp Res 29:207–220
Moselhy HF, Georgiou G, Kahn A (2001) Frontal lobe changes in alcoholism: a review of the
literature. Alcohol Alcohol 36:357–368
Mucha RF, Geier A, Stuhlinger M, Mundle G (2000) Psychopharmacology 151:428–432
Myrick H, Anton RF, Li X et al (2004) Differential brain activity in alcoholics and social drinkers
to alcohol cues: relationship to craving. Neuropsychopharmacology 29:393–402
Myrick H, Anton RF, Li X, Henderson S, Randall PK, Voronin K (2008) Effect of naltrexone and
ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent
people. Arch Gen Psychiatry 65:466–475
Nader MA, Morgan D, Gage HD et al (2006) PET imaging of dopamine D2 receptors during
chronic cocaine self-administration in monkeys. Nat Neurosci 9:1050–1056
Nagoshi CT, Wilson JR (1989) Long-term repeatability of human alcohol metabolism, sensitivity
and acute tolerance. J Stud Alcohol 50:162–169
Newlin DB, Thomson JB (1990) Alcohol challenge with sons of alcoholics: a critical review and
analysis. Psychol Bull 108:383–402
Oscar-Berman M, Marinkovic K (2007) Alcohol: effects on neurobehavioral functions and the
brain. Neuropsychol Rev 17:239–257
Papaleo F, Kieffer BL, Tabarin A, Contarino A (2007) Decreased motivation to eat in mu-opioid
receptor-deficient mice. Eur J Neurosci 25:3398–3405
Park SQ, Kahnt T, Beck A et al (2010) Prefrontal cortex fails to learn from reward prediction errors
in alcohol dependence. J Neurosci 30:7749–7753
Paulson PE, Robinson TE (1995) Amphetamine-induced time-dependent sensitization of dopa-
mine neurotransmission in the dorsal and ventral striatum: a microdialysis study in behaving
rats. Synapse 19:56–65
Paulus MP, Tapert SF, Pulido C, Schuckit MA (2006) Alcohol attenuates load-related activation
during a working memory task: relation to level of response to alcohol. Alcohol Clin Exp Res
30:1363–1371
Paulus MP, Schuckit MA, Tapert SF et al (2012) High versus low level of response to alcohol:
evidence of differential reactivity to emotional stimuli. Biol Psychiatry 72:848–855
Perkins KA, Grobe JE, Weiss D, Fonte C, Caggiula A (1996) Nicotine preference in smokers as
a function of smoking abstinence. Pharmacol Biochem Behav 55:257–263
36 M. Sebold et al.
Peterson JB, Rothfleisch J, Zelazo PD, Pihl RO (1990) Acute alcohol intoxication and cognitive
functioning. J Stud Alcohol 51:114–122
Petit G, Kornreich C, Noel X, Verbanck P, Campanella S (2012) Alcohol-related context modu-
lates performance of social drinkers in a visual Go/No-Go task: a preliminary assessment of
event-related potentials. PLoS ONE 7:e37466
Pfefferbaum A, Desmond JE, Galloway C, Menon V, Glover GH, Sullivan EV (2001) Reorgani-
zation of frontal systems used by alcoholics for spatial working memory: an fMRI study.
Neuroimage 14:7–20
Pruessner JC, Champagne F, Meaney MJ, Dagher A (2004) Dopamine release in response to
a psychological stress in humans and its relationship to early life maternal care: a positron
emission tomography study using [11C]raclopride. J Neurosci Off J Soc Neurosci
24:2825–2831
Quirk GJ, Mueller D (2008) Neural mechanisms of extinction learning and retrieval. Neuropsy-
chopharmacology 33:56–72
Rando K, Hong KI, Bhagwagar Z et al (2011) Association of frontal and posterior cortical
gray matter volume with time to alcohol relapse: a prospective study. Am J Psychiatry
168(2):183–192
Ray LA, MacKillop J, Leventhal A, Hutchison KE (2009) Catching the alcohol buzz: an exam-
ination of the latent factor structure of subjective intoxication. Alcohol Clin Exp Res
33:2154–2161
Robbins TW, Cador M, Taylor JR, Everitt BJ (1989) Limbic-striatal interactions in reward-related
processes. Neurosci Biobehav Rev 13:155–162
Robinson T, Berridge K (1993) The neural basis of drug craving: an incentive-sensitization theory
of addiction. Brain Res Rev 18:247–291
Robinson TE, Berridge KC (2008) The incentive sensitization theory of addiction: some current
issues. Phil Trans R Soc B Biol Sci 363:3137–3146
Rösner S, Hackl-Herrwerth A, Leucht S, Lehert P, Vecchi S, Soyka M (2010a) Acamprosate for
alcohol dependence. Cochrane Database Syst Rev 9:CD004332
Rösner S, Hackl-Herrwerth A, Leucht S, Vecchi S, Srisurapanont M, Soyka M (2010b) Opioid
antagonists for alcohol dependence. Cochrane Database Syst Rev 12:CD001867
Schacht JP, Anton RF, Voronin KE et al (2013) Interacting effects of naltrexone and OPRM1 and
DAT1 variation on the neural response to alcohol cues. Neuropsychopharmacology
38:414–422
Schneider F, Habel U, Wagner M et al (2001) Subcortical correlates of craving in recently
abstinent alcoholic patients. Am J Psychiatry 158:1075–1083
Schoofs N, Heinz A (2013) Pathologisches Spielen. Der Nervenarzt 1–6
Schroth G, Naegele T, Klose U, Mann K, Petersen D (1988) Reversible brain shrinkage in
abstinent alcoholics, measured by MRI. Neuroradiology 30:385–389
Schuckit MA (2000) Genetics of the risk for alcoholism. Am J Addict Am Acad Psychiatr Alcohol
Addict 9:103–112
Schuckit MA, Smith TL (1996) An 8-year follow-up of 450 sons of alcoholic and control subjects.
Arch Gen Psychiatry 53:202–210
Schuckit MA, Smith TL (2000) The relationships of a family history of alcohol dependence, a low
level of response to alcohol and six domains of life functioning to the development of alcohol
use disorders. J Stud Alcohol 61:827–835
Schuckit MA, Smith TL (2006) An evaluation of the level of response to alcohol, externalizing
symptoms, and depressive symptoms as predictors of alcoholism. J Stud Alcohol 67:215–227
Schuckit MA, Smith TL, Danko GP et al (2009a) An evaluation of the full level of response to
alcohol model of heavy drinking and problems in COGA offspring. J Stud Alcohol Drugs
70:436–445
Schuckit MA, Smith TL, Trim R, Fukukura T, Allen R (2009b) The overlap in predicting alcohol
outcome for two measures of the level of response to alcohol. Alcohol Clin Exp Res
33:563–569
2 Neurobiology of Addiction 37
Wolffgramm J, Heyne A (1995) From controlled drug intake to loss of control: the irreversible
development of drug addiction in the rat. Behav Brain Res 70:77–94
Wong DF, Kuwabara H, Schretlen DJ et al (2006) Increased occupancy of dopamine
receptors in human striatum during cue-elicited cocaine craving. Neuropsychopharmacology
31:2716–2727
World Health Organization (2011a) Global status report on alcohol and health. World Health
Organization, Geneva
World Health Organization (2011b) Report on the global tobacco epidemic 2011: warning about
the dangers of tobacco. World Health Organization, Geneva
World Health Organization (2012) WHO global report: mortality attributable to tobacco. World
Health Organization, Geneva
Wrase J, Grusser SM, Klein S et al (2002) Development of alcohol-associated cues and
cue-induced brain activation in alcoholics. Eur Psychiatry J Assoc Eur Psychiatr 17:287–291
Wrase J, Schlagenhauf F, Kienast T et al (2007) Dysfunction of reward processing correlates with
alcohol craving in detoxified alcoholics. Neuroimage 35:787–794
Yalachkov Y, Kaiser J, Naumer MJ (2012) Functional neuroimaging studies in addiction: multi-
sensory drug stimuli and neural cue reactivity. Neurosci Biobehav Rev 36:825–835
Yang Z, Xie J, Shao Y-C et al (2009) Dynamic neural responses to cue-reactivity paradigms in
heroin-dependent users: an fMRI study. Hum Brain Mapp 30:766–775
Yeomans MR, Wright P (1991) Lower pleasantness of palatable foods in nalmefene-treated human
volunteers. Appetite 16:249–259
Zhou X, Nonnemaker J, Sherrill B, Gilsenan AW, Coste F, West R (2009) Attempts to quit
smoking and relapse: factors associated with success or failure from the ATTEMPT cohort
study. Addict Behav 34:365–373
Zijlstra F, Veltman DJ, Booij J, van den Brink W, Franken IHA (2009) Neurobiological substrates
of cue-elicited craving and anhedonia in recently abstinent opioid-dependent males. Drug
Alcohol Depend 99:183–192
Zimmermann US, Blomeyer D, Laucht M, Mann KF (2007) How gene-stress-behavior interac-
tions can promote adolescent alcohol use: the roles of predrinking allostatic load and childhood
behavior disorders. Pharmacol Biochem Behav 86:246–262
Zorko M, Marusic A, Cebasek-Travnik Z, Bucik V (2004) The frontal lobe hypothesis: impairment
of executive cognitive functions in chronic alcohol in-patients. Psychiatr Danub 16:21–28
The Genetics of Addiction: A Global
Problem with Global Opportunities 3
Joni L. Rutter
Contents
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
3.2 Genetics of Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
3.2.1 Is Addiction Heritable? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
3.2.2 The Phenotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
3.2.3 Genetics and Epigenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
3.2.4 Gene Environment Interactions and Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
3.2.5 Neurobiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
3.2.6 From Treatment to Pharmacogenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
3.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Glossary of Terms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Abstract
Drug addiction is a chronic, relapsing brain disease characterized by compulsive
drug seeking, craving, loss of self-control, and impaired decision making
(National Institute on Drug Abuse NIDA – Drugs, brains, and behavior: the
science of addiction. National Institutes of Health, U.S. Department of Health
and Human Services, Washington, DC, 2010). Drug addiction persists in spite of
many harmful physical and social consequences and cuts across geography,
class, ethnicity, occupation, age, gender, and history. The science of genetics
offers one approach to understanding individual differences in a complex disease
like addiction. Genes provide a scaffold for normal development, for learning,
and for pathophysiology. But genes do not act in isolation of other processes and
genes alone do not cause addiction. Genes act within the environments of the
cell, of the body, and of the world beyond the individual. Indeed, new
J.L. Rutter
Division of Basic Neuroscience and Behavioral Research, National Institute on Drug Abuse,
Bethesda, MD, USA
e-mail: [email protected]
3.1 Introduction
The United Nations Office on Drugs and Crime (UNODC) serves as a warehouse
for statistics about drug abuse. It reports that illicit drug users are found in every
country, and drug abuse is among the top 20 risk factors associated with adverse
health outcomes. On a global scale, the abuse of drugs is staggering: In 2012, out of
a worldwide population estimated to be about 4.5 billion people aged 15–64 years,
as many as 300 million used illicit drugs at least once in the past 12 months,
38 million were problem drug users, and 16 million were injection drug users, a
primary vector for transmission of HIV and other infections (World Drug
Report 2012).
To control the use of drugs, societies around the world employ a variety of
approaches, from prohibition to criminalization, from “zero tolerance” to legal-
ization. Marijuana is a good illustration of changing attitudes and differing
approaches across the globe. As of this writing, the status within the United
States, for example, is that 22 states and the District of Columbia allow the use
of marijuana for medical purposes, while two states have recently (2012) legal-
ized personal use. Coincidently, the 2012 Monitoring the Future Survey showed
that regular marijuana use is on the rise in 8th, 10th, and 12th graders, with 6.5 %
of 12 graders reporting daily/nearly daily use (Johnston et al. 2013). The survey
also reports an increasing perception that marijuana is not harmful. Whether these
laws and attitudes will promote addiction to marijuana or increase other negative
consequences of abuse remains to be seen, but there is reason for concern. We know,
for example, that the risk of addiction nearly doubles for those who start using in
their teenage years, and it increases as well among daily users. Furthermore, the
legalization of marijuana for recreational uses might spur competition among
growers who could produce varying potencies across marijuana strains, leading to
the possibility of higher addiction rates, as well as increased incidence of
psychotic symptoms that are likely to appear in genetically vulnerable initiators
(Tosato et al. 2013). There is an experiment of sorts in progress in the United States,
and the full consequences of these approaches are unknown.
Alcohol and tobacco are the most widely used drugs globally and together
account for high rates of mortality and morbidity. Alcohol dependence causes
about 2.5 million deaths/year by exacerbating a variety of diseases in addition
to alcoholism, including epilepsy, heart disease, cirrhosis, and cancer. The largest
3 The Genetics of Addiction: A Global Problem with Global Opportunities 41
killer, however, is smoking tobacco with nicotine as the major constituent respon-
sible for addiction among smokers (Rehm et al. 2006; Mokdad et al. 2004;
Henningfield et al. 1985), accounting for about 6 million deaths/year largely by
causing cancer, heart disease, stroke, and respiratory disease. In the United States,
approximately 435,000 deaths are attributed to tobacco, 85,000 deaths to alcohol,
and about 17,000 due to illicit drug use, totaling about 537,000 US deaths per year
due to addiction (Mokdad et al. 2004). The economic burden of drug abuse
approaches 2 % of gross domestic product in some countries (World Drug
Report 2012).
For some historical perspective on the number of deaths associated with
drug abuse, consider that 20 million people died in the 4 years of World War I,
some five million deaths per year. Similarly, World War II was fought over
the course of 6 years, with a death toll of about 60 million, some 10 million per year.
Tobacco, alcohol, and illicit drug use together contribute to an annual death toll of
about 8.75 million, a figure that has been relatively constant over the last decade.
With no end in sight, the global problem of addiction is clear. Given time, drug use
and addiction will yoke the young, drain the health of the user, distort global
economics, and penetrate political landscapes. Building the armament of biological
knowledge is a critical piece in helping those affected.
parents becomes addicted. Heritability studies agree that the proportion of pheno-
typic variance (i.e., addiction) attributable to genetic factors is in the range of
40–60 %, which leaves a similar proportion attributable to environmental factors.
It bears repeating that complex phenotypes like addiction are the result of complex
interactions among genes and environments. Understanding the role of environmen-
tal influences on addiction can help home in on the genes that may be missed by
genetic studies that ignore those factors (Hamza et al. 2011). Leveraging cultural
patterns with appropriate study designs could be powerful for uncovering genetic risk
and furthering our ability to educate, inform, prevent, and treat addiction. In the
sections that follow, five key areas of addiction genetics are highlighted: phenotype;
genetics and epigenetics; gene by environment interactions and prevention; neuro-
biology; and treatment and pharmacogenomics. Addressing these areas is critical for
building the scientific foundation to tackle the global problems of addiction.
At the molecular level, genetic approaches examine the structure and function of
DNA and how genetic variation affects the expression of the genetic information.
The hope of understanding the molecular basis of drug addiction and other complex
phenotypes is driven, in part, by the remarkable progress that has been made in the
field of genetics during the past decade. The year 2013 marks the tenth anniversary
of the sequencing of the human genome. As a result, we know that humans share
approximately 99.6 % of the three billion nucleotides of DNA sequence.
Our genetic individuality lies in the remaining 0.4 % (approximately 12 million)
nucleotides that comprise genetic differences largely represented by single-
nucleotide polymorphisms (SNPs), copy number variations, as well as small inser-
tions and deletions that are scattered across the genome. SNPs are the most
well-studied variations and are generally benign with unknown consequence, but
some may account for trait differences that alone, or in combination, contribute to
disease (Barreiro et al. 2008). Approximately six million SNPs are quite common
with allele frequencies greater than 10 % in the population. Others are of moderate
frequency (1–10 %), and many are rare (<1 %).
Table 3.1 Alcohol, cigarette, and drug use macrophenotypes across the HapMap countries. Ranges were determined for all countries (bottom row) and then
44
assigned a colored quartile (low, medium-low, medium-high, and high). HapMap countries represent four populations that have genotype and haplotype data
in the public domain available for download: Ibadan, Nigeria (YRI); US residents of northern and Western European ancestry (CEU); Tokyo, Japan (JPT); and
Han Chinese individuals from Beijing, China (CHB). Countries in the Northern Europe and Western Europe regions are separated for purposes of illustrating
the macrophenotypes
Percentage of
Number of Drug use
Purchase Alcohol Alcohol Purchase All deaths
cigarettes death
HapMap country age for consumption death rates age for attributed
per adult rates per
alcohol L/capita/year per 100,000 smoking to Smoking in
per year 100, 000
the year 2000
Fig. 3.1 Linkage disequilibrium (LD) plots for the CHRNA5/A3/B4 region on chromosome 15.
The orientation of the CHRNA5, CHRNA3, and CHRNB4 genes is shown as the expanded section
underneath the full chromosome 15 map (top). The vertical blue line represents the rs6969968 SNP
and intersects the LD plots from the following populations: Southwestern US residents with African
ancestry (ASW; top), US residents with European ancestry (CEU; middle), and Ibadan, Nigeria
(YRI; bottom). The green line within the blue circles indicates the region of LD. Note the high LD in
the CEU population (long green line), the very low LD in the ASW population (short green line),
and the lack of LD in the YRI population (no green line). The LD plots were generated using the
HapMap Data Phase III/release #2, February 09 on NCBI B36 assembly, dbSNP b126:chr15:
76,640,000 to 76,730,000 (http://hapmap.ncbi.nlm.nih.gov/cgi-perl/gbrowse/hapmap3r2_B36/)
Progress in the field of genetics during the past 20 years has come through
conceptual insights and technological breakthroughs that have produced powerful
approaches for rapid and robust screening of millions of known SNPs. Two key
discoveries revolutionized the field. The first was the recognition that the genome
had specific regions with higher recombination rates, the so-called recombination
46 J.L. Rutter
hot spots. The second was the finding that the genome is organized into block-like
structures or haplotypes that can be “tagged” by SNPs.
Recombination hot spots exploit how the process of inheritance relies on the
basic molecular structure of DNA, rather than on the sequence variation in it. This
has great implications on the nonrandom patterns of DNA sequence variation along
chromosomes, which, in turn, can be used to reveal useful DNA sequence variation
that contributes to disease (Hey 2004). Linkage disequilibrium (LD) describes the
nonrandom association of alleles at adjacent locations on the chromosome, or loci.
The farther apart two loci are, the more likely they are to recombine. Genomes with
low LD are older, where there has been a longer period of time for recombination
events to occur (haplotypes are shorter and made up of fewer SNPs), such as seen in
the African populations. On the other hand, populations with higher LD are the
newer populations such as the European Americans and isolated populations such
as the Ashkenazi Jews (Shifman et al. 2003).
The second discovery was that these LD block structures acted as fingerprints for
geneticists who could use them to identify correlated SNPs across the genome
(Altshuler et al. 2008; Trifanova et al. 2012). In other words, one or a few SNPs
could represent an entire haplotype (because of the high rate of LD), which meant
that rather than screening the entire SNP collection across the genome, only
a subset of proxy SNPs – or TagSNPs – needs to be screened without loss of
information. From this concept, the NIH International HapMap Project was
launched to describe the common patterns of 3.5 million SNPs across populations
(The International HapMap Consortium 2005, 2007). The HapMap Project has been
an invaluable tool for SNP genotyping platform improvements and for helping to
discern the importance of genetic association loci for complex diseases. Subse-
quently, the 1000 Genomes Project was launched with the goal of characterizing
95 % of genetic variation accessible by high-throughput sequencing technologies
and that have 1 % or greater allele frequency in each of five major population
groups, including Europe, East Asia, South Asia, West Africa, and the Americas
(The 1000 Genomes Project Consortium 2010, 2012). Together, these represent the
most extensive collections of human genomic diversity to date and provide
a necessary piece to the puzzle for understanding how genetic diversity impacts
disease. The HapMap and 1000 Genomes data were intended to be a resource used
for identifying and cataloging genetic similarities and differences in humans,
and therefore, these datasets do not have phenotypic information. However, as
illustrated in Table 3.1, they may be useful for initial macrophenotypic assessment,
to then apply to standard case control studies for the purposes of associated
genotypes to phenotypes.
The structure of LD in distinct genomic sites, such as those we know or
suspect to be associated with addiction, is of interest. The LD structure defines
the boundary of a given region. The more population structures one can access
(e.g., through HapMap), the better and narrower those boundaries are defined
(Fig. 3.1). A narrow region is central to this approach because once an initial
SNP has been associated with a disease phenotype, it represents much more of
the genetic variation than just that SNP alone. The importance of the sequence
3 The Genetics of Addiction: A Global Problem with Global Opportunities 47
contained within these regions then becomes the analytic quest, and finding the
genetic variation within that LD block that has functional significance is the next
step in understanding the inherited component of addiction susceptibility. Replica-
tion is imperative; candidate SNPs that have been evaluated repeatedly across
ethnicities and in a variety of association study settings will help to isolate those
variants more likely to show functional effects (Saccone et al. 2008).
Genome-wide association (GWA) studies have been the cost-effective
approach of choice for discovering important genetic regions in complex diseases.
The GWA approach is built on the notion that common alleles predispose to
common disease. Current GWA genotyping platforms include common SNPs
derived from haplotype information to allow for genotyping the most SNP content
across ethnicities. However, the genomic coverage for the GWA genotyping plat-
forms was not selected for specific hypotheses; thus, it is important to understand
the coverage a genotyping array provides (Saccone et al. 2009b) and to replicate
and verify any and all findings. Most GWA studies to date – about 75 % of
them – have been performed in populations of European descent. Of those that
examine non-European populations, the numbers of individuals represented within
them are predominantly from European descent (Rosenberg et al. 2010). As
non-European populations become accessible for GWA analysis on a variety of
traits, it will be possible to test the generalizability of the GWA findings from
European populations to others. Cross-population contrast mapping (Saccone
et al. 2008; Helgason et al. 2007; Liu et al. 2012) compares genotype frequencies
at the associated SNP and the correlated SNPs within the haplotype to define the
genetic architecture for both populations at that locus (Rotimi and Jorde 2010;
Saccone et al. 2008; Zaitlen and Eskin 2010). This approach relies on the assump-
tion that biological mechanisms underlying a given disease are shared across
populations, despite the differences in allele frequencies.
A good example of this approach comes from nicotine dependence studies.
In 2007, a group of scientists from both the public and private sectors
embarked on a small GWA study (n 2,000) for nicotine dependence that
compared nicotine-dependent individuals (“cases”) with exposed (must have
smoked at least 100 cigarettes during lifetime), but not addicted, controls (Bierut
et al.). The cases and controls were of European American descent and their
genotypes were compared across 2.2 million SNPs. From the final analyses
(Bierut et al. 2007; Saccone et al. 2007), several SNPs were identified in the
nicotinic subunit receptor genes that had not been well studied previously. These
genes are in a cluster on chromosome 15, CHRNA5 (alpha 5), CHRNA3 (alpha 3),
and CHRNB4 (beta 4), referred to here as the CHRNA5/B4/A3 cluster. Previous
work using pharmacological methods had identified CHRNA4 and CHRNB2 as the
main culprits involved in smoking dependence, which have been the primary
targets for smoking cessation medications. The GWA study data, however, has
broadened the scope to other nicotinic subunit receptors in the larger nicotinic
subunit receptor family. The SNP that was most interesting was rs16969968
because it represented a change from a conserved aspartic acid at position 398 to
an asparagine (D398N) within the CHRNA5 receptor subunit (Bierut et al. 2008).
48 J.L. Rutter
At the nucleotide level, the A allele of the SNP is the risk allele, and the G allele is
the ancestral, or common, allele (Fig. 3.1). The fact that this SNP was in the part of
the gene that encoded the protein and that it was conserved across species added
impetus to studies seeking to replicate the finding and examine the functional
consequences of the SNP.
As one of the most replicated findings in complex disease genetics, however, it
remained unclear if it would withstand cross-population analyses. This region
has high linkage disequilibrium in European ancestry populations, making it
difficult to differentiate correlation from causation. It turns out that the frequency
of rs16969968 varies widely across 39 different populations (Cann et al. 2002).
Ultimately, a meta-analysis for nicotine dependence in tens of thousands of samples
of European ancestry confirmed the CHRNA5/B4/A3 cluster association
(Thorgeirsson et al. 2010; Tobacco and Genetics Consortium 2010; Liu
et al. 2010). In populations of European and Middle Eastern origin, the frequency
of the A allele was around 40 %, whereas it was uncommon or absent in East Asian,
Native American, and African and African American populations (Fig. 3.1 and
Bierut et al. 2008; Saccone et al. 2009). Although the rs16969968 risk variant is
a strong association, it only explains a small amount of variance (Berrettini and
Doyle 2012). Others have used GWA meta-analysis as a way to identify other
loci involved in smoking dependence in European ancestry populations
(Thorgeirsson et al. 2010) and in African American populations (David
et al. 2012) and have found additional variants of interest, although not as strong.
Genome sequencing methods are needed to look for potential rare variations
with large effects that are missed by the GWA platforms that have been employed
to date.
Because the genetic architecture of the CHRNA5/B4/A3 cluster varies across
populations, comparing associations across diverse populations with differing
genetic architectures can help refine the region of association and point to variants
more likely to have functional relevance (Rotimi and Jorde 2010; Saccone
et al. 2008; Zaitlen and Eskin 2010). Multiple genome-wide and targeted associa-
tion studies now have revealed significant associations between nicotine depen-
dence and variants in the CHRNA5/A3/B4 cluster in subjects of European origin
and Asian (Li et al. 2010) and African American ancestry (n ¼ 32,587), which
extends the involvement of this specific gene cluster across all three populations,
narrowing the region of association (Chen et al. 2012b). Of the variants tested, only
rs16969968 was associated with smoking in these three populations and was
a marker of a larger “high risk” haplotype. The consistently observed association
of rs16969968 with heavy smoking across multiple populations, combined with its
known biological significance, suggests that rs16969968 is most likely a functional
variant that alters risk for heavy smoking. Implications of this work will be explored
in subsequent sections.
The molecular intersection where the environment meets the genes happens
at the epigenome and is worth mentioning here. Epigenomics is the study of
functional, and sometimes heritable, changes in the regulation of gene activity
and expression that are not dependent on gene sequence (Chadwick 2012).
3 The Genetics of Addiction: A Global Problem with Global Opportunities 49
Although each cell type in the human body effectively contains the same genetic
information, epigenetic regulatory mechanisms enable pluripotent stem cells to
give rise to the diversity of differentiated cell types (e.g., skin cells, liver cells, or
neurons).
Genome function and cellular phenotypes are influenced by DNA methylation,
along with histone modifications, which account for associated proteins that acti-
vate or repress the genome function in a context-dependent manner (Bernstein
et al. 2010). Chromatin is the combination of DNA wrapped around histone pro-
teins (called nucleosomes) and associated with DNA-binding factors, accessory
complexes, and noncoding RNAs. Chromatin structure allows the tightly packed
DNA to fit into the nuclei, yet it retains the ability to react dynamically to the
specific gene expression needs of the cell. In states of activity, DNA is loosely
packaged so that specific genes are readily accessed by the transcription machinery
and “turned on.” In states of inactivity, DNA is wrapped around the histones and
“turned off” by structural proteins that ensure the chromatin-containing genes are
tightly packed and inaccessible to the transcriptional machinery. This “winding”
and “unwinding” of chromatin occurs through chemical modifications such as
methylation and acetylation on the histone proteins or to the DNA itself (e.g.,
DNA methylation or hydroxymethylation) that take their cues from elsewhere,
whether that be from the cellular, social, or even historical environment. There
have been several human studies indicating that ancestral environments can dictate
the physiology and behavior of descendants (Kaati et al. 2002).
A 2004 seminal report demonstrated the concept that parenting and early
environmental exposures (e.g., exposures to the gamete, fetus, or offspring) or
experiences influence risk for later life pathologies, and these can be unequivocally
linked to epigenetic changes (Weaver et al. 2004; Johnstone and Baylin 2010). In
rats, maternal behaviors such as licking and grooming can epigenetically “pro-
gram” stress responses in the pups that are stably maintained in adulthood. The
research demonstrated that offspring of mothers displaying high levels of maternal
care showed different DNA methylation patterns in the brain’s stress pathways and
exhibited fewer anxiety-like behaviors compared to offspring of mothers displaying
low-level maternal care, resulting in pups with higher anxiety-like behaviors.
Interestingly, the researchers went on to demonstrate that the effects were reversed
in cross-fostering experiments (Weaver et al. 2004).
Similarly, exposure to drugs of abuse also may have epigenetic influences that
affect the offspring (Kendler et al. 2012). In a recent study, male rat offspring, but
not female rats, sired by cocaine-exposed males were slower to acquire cocaine
self-administration and maintained lower rates of responding for cocaine than in
offspring sired by unexposed males. The investigators went on to show that the
effects were likely due to increased acetylated histone H3 with brain-derived
neurotrophic factor promoter regions in the sperm of sires that self-administered
cocaine (Vassoler et al. 2013). Taken together, these examples indicate the perva-
sive influence of environmental factors that regulate epigenetic mechanisms and
that these influences may not only affect cellular events, but they may affect cellular
events that take place in our children and grandchildren.
50 J.L. Rutter
Not unlike the HapMap and the 1000 Genomes Projects that came before it, the
NIH Roadmap Epigenomics Program and the International Human Epigenome
Consortium (IHEC) are developing atlases of the epigenomic landscape of
a variety of cell types (Chadwick 2012). Scientists have been collecting data to
generate maps of the epigenomic landscape of a variety of tissue types, but there has
been little done to date looking at individual differences and their effects on
epigenomic programming. With the epigenomic maps at hand, it will be possible
to understand influences of drugs of abuse, stress, and diet on epigenetics and then
to consider how environmental context and culture can affect the epigenome as
well. While genetic variation is more tractable to screen, epigenetic variation may
lead to more effective treatment approaches since the mechanisms may be more
malleable than our DNA.
3.2.5 Neurobiology
One of the problems of drug abuse is its ability to “hijack” the brain’s
reward system. Drug users will go to great lengths to seek a high. The discovery
of gene variants that confer vulnerability to addiction promises to improve our
52 J.L. Rutter
highlights the importance of studying the genetics of substance use and schizophre-
nia as distinct and as comorbid disorders. Additional studies have demonstrated
novel associations between other gene variants in the CHRNA5/B4/A3 cluster
with various smoking-related phenotypes, such as nicotine dependence symptoms,
nicotine tolerance, smoking initiation, and comorbid conditions (e.g., regular drink-
ing and depression), with these vulnerabilities being heightened in early-onset
smokers. Once a gene variant is discovered and validated, a systematic analysis of
the functional role that a gene variant plays can be undertaken.
54 J.L. Rutter
Elucidating the genetic and neurobiological basis of addiction, from gene expres-
sion to the neural networks that mediate drug seeking and drug taking, eventually
will enable scientists to translate knowledge into new treatments directed at specific
targets in the brain or to treatment approaches that can be individualized for each
patient (i.e., pharmacogenomics). Drawing a precise molecular portrait of addiction
is challenging, but every new finding provides an unprecedented opportunity to
identify and investigate new potential pharmacological targets or explore and
exploit their clinical utility. For example, recent research has solved the crystal
structure of the four opioid receptors (Wu et al. 2012; Thompson et al. 2012;
Granier et al. 2012; Manglik et al. 2012). Although the opiate receptor has been
studied for decades, the availability of its structure now provides a molecular
framework for structure-based discovery of new medications with targeted phar-
macological properties (Thompson et al. 2012). Understanding how these potent
ligands work in the context of their effects on receptors with known genetic
variation (e.g., the A118G variant mentioned previously) will enable medicinal
chemists to design medications to maximize their therapeutic efficacy while min-
imizing their adverse side effects and abuse liability.
Genetic variation is the key to explaining individual differences in the way that
drugs are distributed and metabolized. Pharmacogenetics/pharmacogenomics is the
study of how genetic variation among individuals affects their capacity to metab-
olize drugs (pharmacokinetics) and the drugs’ effects on the individuals
(pharmacodynamics) (Rutter 2006; Belle and Singh 2008). There is significant
variability in response to drugs of abuse, and pharmacogenetics provides relevant
crossover concepts that tailor a person’s genetic makeup to a drug treatment that
provides the best “match.”
Investment in genetics is bearing fruit for the development of treatment options
for substance dependence. The A118G mu-opioid receptor polymorphism has been
shown to be associated with therapeutic response to naltrexone treatment for
alcohol dependence (Chamorro et al. 2012). This pharmacogenetic finding has
important implications for targeted treatment of alcoholism in individuals with
the 118G variant (Chamorro et al. 2012; Kranzler and Edenberg 2010). Recent
meta-analysis on the A118G SNP of OPRM1 shows that naltrexone-treated patients
carrying the G allele have lower relapse rates when compared to those homozygous
for the A allele (Chamorro et al. 2012). The frequency of the G allele differs across
populations; in Caucasians, it ranges from 15 % to 25 %, and in Asians, it is 60 %.
The potential impact of genetic screening prior to treatment in these ethnicities
warrants consideration. Clinicians and patients may benefit from knowing that
people homozygous for the A allele are not likely to respond to naltrexone.
A similar case can be made for pharmacogenetics of smoking. Nearly half of the
people who smoke want to stop; however, most attempts fail, whereby only about
10 % of individuals achieve abstinence for 6 months or more (Ramoni et al. 2009).
And, nicotine dependence contributes to the failure rate, with more highly
dependent smokers having greater difficulty quitting – and staying abstinent
3 The Genetics of Addiction: A Global Problem with Global Opportunities 55
(John et al. 2004; Xian et al. 2005). There is growing evidence that interactions
between smoker characteristics, medications, and quit success may help personal-
ize the handful of medications that can be prescribed to a given smoker.
Cytochrome P450 (CYP) 2A6 is largely responsible for metabolizing nicotine to
cotinine, and CYP2A6 genotypes contribute to variable metabolism rates that are
seen across ethnicities (Nakajima et al. 2006) and even gender (Lee et al. 2012;
Mwenifumbo and Tyndale 2007). Genetic variation in the CYP2A6 gene can
increase or decrease the pharmacokinetics of the enzyme activity through altering
the protein’s expression level or its structure and function. Further studies show that
the rate of nicotine metabolism predicts which smokers will be more successful at
quitting with bupropion (Patterson et al. 2008) or nicotine replacement therapy
(Malaiyandi et al. 2006; Schnoll et al. 2009). In the highly dependent smokers,
a combination therapy is most beneficial (Loh et al. 2012).
In addition to the pharmacokinetic gene variations, pharmacodynamic gene
differences are also important. The nicotinic subunit receptor B2 has been impli-
cated in smoking cessation (Conti et al. 2008), as have the CHRNA5/B4/A3
cluster variants – although less robustly associated with cessation outcomes
than with measures of smoking quantity. However, those that do show an
association have shown that the same genetic risk variants that contribute to
smoking quantity and nicotine dependence also predict smoking cessation
(Chen et al. 2012). Carriers of the high-risk CHRNA5/A3/B4 haplotype were
three times more likely to respond to smoking cessation medications, making this
haplotype of interest for personalized cessation therapies. A series of randomized
clinical trials grouped by smoking cessation therapy (NRT, varenicline,
bupropion, and placebo) examined the association of CHRNA5/B4/A3 cluster
variants with abstinence at the end of treatment and at 6 months after the quit date.
In this study, treatment-seeking smokers with the CHRNA5/A3/B4-risk alleles
(compared to those without) were less likely to achieve abstinence at 6 months if
prescribed placebo, but more likely to achieve 6-month abstinence with treatment
(Bergen et al. 2013).
Clinical trials assessing the joint effects of both the pharmacokinetic gene
variations (CYP2A6) and the pharmacodynamics gene variations (CHRNA5 and
others) are needed. Early investigations into the feasibility, cost-effectiveness, and
impact of using genetics to tailor treatments in a real-world clinical setting have
been promising (McClure et al. 2013). Larger studies are needed to understand the
generalizability of this type of personalized intervention for smoking cessation.
3.3 Conclusion
yielded exciting findings already and promises to unlock the ages-old gene-
environment conundrum.
A major challenge awaiting resolution is the translation of basic science discov-
eries into novel prevention strategies and effective treatment approaches.
As discussed above, discoveries in genomics and neuroscience have opened up
new vistas for exploration. New medications built upon scaffolds designed com-
putationally to fit ever more precisely specified crystalline structures of brain
receptors herald an era of designer treatments for addiction. And treatment
approaches that capitalize on genomic information about an individual’s metabolic
profile signal a pharmacogenetic approach to guide medical and treatment
decisions.
NIDA has made understanding the interaction among genes, environment, and
development a cornerstone of its agenda. The G E D interaction is thorny, and
research is beginning to tease apart the separate and combined effects of these
factors, but there is still challenging work to be completed. Emerging areas,
including systems biology, epigenetics, computational approaches, and the role of
social context or culture in drug addiction will be important research priorities for
funding agencies across the globe. Future gene-based analyses combined with
environmental interventions have great potential to combat addiction and save
lives. The opportunities offered by global approaches can strengthen these needed
research programs and hasten that goal.
Glossary of Terms
References
Altshuler D, Daly MJ, Lander ES (2008) Science 322(5903):881–888
Barreiro LB, Laval G, Quach H, Patin E, Quintana-Murci L (2008) Natural selection has driven
population differentiation in modern humans. Nat Genet 40:340–345
Belle DJ, Singh H (2008) Genetic factors in drug metabolism. Am Fam Physician 77(11):1553–1560
Bergen AW, Javitz HS, Krasnow R, Nishita D, Michel M, Conti DV, Liu J, Lee W, Edlund CK,
Hall S, Kwok PY, Benowitz NL, Baker TB, Tyndale RF, Lerman C, Swan GE (2013) Nicotinic
acetylcholine receptor variation and response to smoking cessation therapies. Pharmacogenet
Genomics 23(2):94–103
Bernstein BE, Stamatoyannopoulos JA, Costello JF, Ren B, Milosavljevic A, Meissner A,
Kellis M, Marra MA, Beaudet AL, Ecker JR, Farnham PJ, Hirst M, Lander ES, Mikkelsen
TS, Thomson JA (2010) The NIH roadmap epigenomics mapping consortium. Nat Biotechnol
28(10):1045–1048
Berrettini WH, Doyle GA (2012) The CHRNA5/A3/B4 gene cluster in nicotine addiction. Mol
Psychiatry 17:856–866
Bierut LJ, Madden PAF, Breslau N, Johnson EO, Hatsukami D, Pomerleau OF, Swan GE, Rutter J,
Bertelsen S, Fox L, Fugman D, Goate AM, Hinrichs AL, Konvicka K, Martin N,
Montgomery G, Saccone NL, Saccone SF, Wang JC, Chase GA, Rice JP, Ballinger DG
(2007) Novel genes identified in a high density genome wide association study for nicotine
dependence. Hum Mol Genet 16:24–35
Bierut LJ, Stitzel JA, Wang JC, Hinrichs AL, Grucza RA, Xuei X, Saccone NL, Saccone SF,
Bertelsen S, Fox L, Horton WH, Breslau N, Budde J, Cloninger CR, Dick DM, Foroud T,
Hatsukami D, Hesselbrock V, Johnson EO, Kramer J, Kuperman S, Madden PAF, Mayo K,
Nurnberger J, Pomerleau O, Porjesz B, Reyes O, Schuckit M, Swan G, Tischfield JA, Edenberg
HJ, Rice JP, Goete AM (2008) Variants in nicotinic receptors and risk for nicotine dependence.
Am J Psychiatry 165:1163–1171
Buckley PF, Miller BJ, Lehrer DS, Castle DJ (2009) Psychiatric comorbidities and schizophrenia.
Schizophr Bull 35:383–402
Cann HM, de Toma C, Cazes L, Legrand MF, Morel V, Piouffre L, Bodmer J, Bodmer WF,
Bonne-Tamir B, Cambon-Thomsen A, Chen Z, Chu J, Carcassi C, Contu L, Du R, Excoffier L,
Ferrara GB, Friedlaender JS, Groot H, Gurwitz D, Jenkins T, Herrera RJ, Huang X, Kidd J,
Kidd KK, Langaney A, Lin AA, Mehdi SQ, Parham P, Piazza A, Pistillo MP, Qian Y, Shu Q,
58 J.L. Rutter
Xu J, Zhu S, Weber JL, Greely HT, Feldman MW, Thomas G, Dausset J, Cavalli-Sforza LL
(2002) A human genome diversity cell line panel. Science 296:261–262
CASA: The National Center on Addiction and Substance Abuse at Columbia University
(2011) Adolescent substance use: America’s #1 public health problem. http://www.
casacolumbia.org/upload/2011/20110629adolescentsubstanceuse.pdf. Accessed Feb 2012
Chadwick LH (2012) The NIH roadmap epigenomics program data resource. Epigenomics
4(3):317–324
Chambers RA, Krystal JH, Self DW (2001) A neurobiological basis for substance abuse comor-
bidity in schizophrenia. Biol Psychiatry 50(2):71–83
Chamorro AJ, Marcos M, Mirón-Canelo JA, Pastor I, González-Sarmiento R, Laso FJ (2012) Asso-
ciation of m-opioid receptor (OPRM1) gene polymorphism with response to naltrexone in
alcohol dependence: a systematic review and meta-analysis. Addict Biol 17(3):505–512
Changeux J (2010) Nicotine addiction and nicotinic receptors: lessons from genetically modified
mice. Nat Rev Neurosci 11:389–401
Chen L, Johnson EO, Breslau N, Hatsukami D, Saccone NL, Grucza RA, Wang JC, Hinrichs AL,
Fox L, Goate AM, Rice JP, Bierut LJ (2009) Interplay of genetic risk factors and parent
monitoring in risk for nicotine dependence. Addiction 104(10):1731–1740
Chen L, Baker T, Piper M, Breslau N, Cannon D, Doheny K, Gogarten S, Johnson E, Saccone N,
Wang J, Weiss R, Goate A, Bierut L (2012a) Interplay of genetic risk factors (CHRNA5-
CHRNA3-CHRNB4) and cessation treatments in smoking cessation success. Am J Psychiatry
169:735–742
Chen L, Saccone N, Culverhouse R, Bracci P, Chen C, Dueker N, Han Y, Huang H, Jin G,
Kohno T, Ma J, Przybeck T, Sanders A, Smith J, Sung Y, Wenzlaff A, Wu C, Yoon D, Chen Y,
Cheng Y, Cho Y, David S, Duan J, Eaton C, Furber H, Goate A, Gu D, Hansen H, Hartz S,
Hu Z, Kim Y, Kittner S, Levinson D, Mosley T, Payne Y, Rao D, Rice J, Rice T, Schwantes
An T, Shete S, Shi J, Spitz M, Sun Y, Tsai F, Wang J, Wrensch M, Xian H, Gejman P, He J,
Hunt S, Kardia S, Li M, Lin D, Mitchell B, Park T, Schwartz A, Shen H, Wjencke J, Wu J,
Yokota J, Amos C, Bierut L (2012b) Smoking and genetic risk variation across populations of
European, Asian, and African American ancestry—a meta-analysis of chromosome 15q25.
Genet Epidemiol 36:340–351
Conti W, Lee DV, Li D, Liu J, Van Den Berg D, Thomas PD, Bergen AW, Swan GE, Tyndale RF,
Benowitz NL, Lerman C (2008) Nicotinic acetylcholine receptor beta2 subunit gene impli-
cated in a systems-based candidate gene study of smoking cessation. Hum Mol Genet
17:2834–2848
David S, Hamidovic A, Chen G, Bergen A, Wessel J, Kasberger J, Brown W, Petruzella S,
Thancker E, Kim Y, Nalls M, Tranah G, Sung Y, Ambrosone C, Arnett D, Bandera E,
Becker D, Becker L, Berndt S, Bernstein L, Biot W, Broeckel U, Buxbaum S, Caporaso N,
Casey G, Chanock S, Deming S, Diver W, Eaton C, Evans D, Evans M, Fornage M,
Franceschini N, Harris T, Henderson B, Hernadez D, Hitsman B, Hu J, Hunt S, Ingles S,
John E, Kittles R, Kolb S, Kolonel L, Marchand L, Liu Y, Lohman K, McKnight B, Millikan R,
Murphy A, Neslund-Dudas C, Nyante S, Press M, Pasaty B, Rao D, Redline S, Rodriques-Gil J,
Rybicki B, Signorello L, Singleton A, Smoller J, Snively B, Spring B, Stanford J, Strom S,
Swan G, Taylor K, Thun M, Wilson A, Witte J, Yamamura Y, Yanek L, Yu K, Zheng W,
Zieglere R, Zondereman A, Jorgenson E, Halmlan C, Furberg H (2012) Genome-wide meta-
analyses of smoking behaviors in African Americans. Transl Psychiatry 2:e119
Dick DM (2011) Gene-environment interaction in psychological traits and disorders. Annu Rev
Clin Psychol 7:383–409
Duncan L, Keller M (2011) A critical review of the first 10 years of candidate gene-by environ-
ment interaction research in psychiatry. Am J Psychiatry 168:1041–1049
Fowler CD, Kenny PJ (2012) Habenular signaling in nicotine reinforcement. Neuropsychophar-
macology 37(1):306–307
Fowler CD, Lu Q, Johnson PM, Marks MJ, Kenny PJ (2011) Habenular a5 nicotinic receptor
subunit signalling controls nicotine intake. Nature 471(7340):597–601
3 The Genetics of Addiction: A Global Problem with Global Opportunities 59
Giovino GA, Mirza SA, Samet JM, Gupta PC, Jarvis MJ, Bhala N, Peto R, Zatonski W, Hsia J,
Morton J, Palipudi KM, Asma S, GATS Collaborative Group (2012) Tobacco use in 3 billion
individuals from 16 countries: an analysis of nationally representative cross-sectional house-
hold surveys. The Lancet 380(9842):668–679
Granier S, Manglik A, Kruse AC, Kobilka TS, Thian FS, Weis WI, Kobilka BK (2012) Structure
of the d-opioid receptor bound to naltrindole. Nature 485:400–404
Hamza TH, Chen H, Hill-Burns EM, Rhodes SL, Montimurro J, Kay DM, Tenesa A, Kusel VI,
Sheehan P, Eaaswarkhanth M, Yearout D, Samii A, Roberts JW, Agarwal P, Bordelon Y,
Park Y, Wang L, Gao J, Vance JM, Kendler KS, Bacanu SA, Scott WK, Ritz B, Nutt J, Factor
SA, Zabetian CP, Payami H (2011) Genome-wide gene-environment study identifies glutamate
receptor gene GRIN2A as a Parkinson’s disease modifier gene via interaction with coffee.
PLoS Genet 7(8):e1002237
Hartz S, Short S, Saccone N, Culverhouse R, Chen L, Schwantes T, Coon H, Han Y, Stephens S,
Sun J, Chen X, Ducci F, Duckeer N, Franceschini N, Frank J, Guobjartsson D, Nadia N,
Hansel N, Chenhui J, Keskitado-Vuokko K, Zhen L, Leo-Pekka L, Michel M, Rawall R,
Rosenberge A, Scheet P, Shaffer J, Teumer A, Thompson J, Vink J, Vogelzangs N,
Wenzlaff A, Wheeler W, Xiao X, Yang B, Aggen S, Balmforth A, Baumeiser S, Beauty T,
Bennett S, Bergen A, Boyd H, Broms U, Campbell H, Chatterjee N, Chen J, Chen Y, Cichon S,
Couper D, Cucca F, Dick D, Foroud T, Furberg H, Giegling I, Gu F, Hall A, Hallfors J, Han S,
Hartmann A, Hayward C, Heikkia K, Hewitt J, Hottenga J, Jensen M, Jousilahti P,
Kaakinen M, Kittner S, Kontec B, Korhomen T, Landi M, Laatkanin T, Leppert M,
Levvy S, Mathias R, McNeil D, Medland S, Montgomery G, Muley T, Murray T, Nauck M,
North K, Pergadia M, Polasek O, Ramos EM, Ripatti S, Risch A, Rucqinski I, Rudan I,
Salmonaa V, Schlessinger D, Styrkarrkarsdottir U, Tereracciano A, Uda M, Willensen G,
Wu X, Abecasis G, Barnes K, Bickeboller H, Boerwinkle E, Noomsma D, Caporaso N, Duan J,
Edenberg H, Franks C, Gejman P, Gelernter J, Grabe H, Hops H, Jarvelin M, Viikari J,
Kahonen M, Kendler K, Lehtimaki T, Levinson D, Marazita M, Marchini J, Melbye M,
Mitchell B, Murray J, Nothen M, Penninx B, Raitakari O, Rietschel M, Rujescu D,
Samani N, Sanders A, Schwartz A, Shete S, Shi J, Spitz M, Stefansson K, Swan G,
Thorgeirsson T, Volzke H, Wei Q, Wichmann H, Amos C, Breslau N, Cannon S,
Ehringer M, Grucza R, Hatsukami D, Heath A, Johnson O, Kaprio J, Madden P, Martin N,
Stevens V, Stitzel J, Weiss R, Kraft P, Bierut L (2012) Increased genetic vulnerability to
smoking at CHRNA5 in early-onset smokers. Arch Gen Psychiatry 69:854–861
Helgason A, Pálsson S, Thorleifsson G, Grant SF, Emilsson V, Gunnarsdottir S, Adeyemo A, Chen Y,
Chen G, Reynisdottir I, Benediktsson R, Hinney A, Hansen T, Andersen G, Borch-Johnsen K,
Jorgensen T, Schäfer H, Faruque M, Doumatey A, Zhou J, Wilensky RL, Reilly MP, Rader DJ,
Bagger Y, Christiansen C, Sigurdsson G, Hebebrand J, Pedersen O, Thorsteinsdottir U, Gulcher
JR, Kong A, Rotimi C, Stefánsson K (2007) Refining the impact of TCF7L2 gene variants on type
2 diabetes and adaptive evolution. Nat Genet 39(2):218–225
Henningfield JE, Miyasato K, Jasinski DR (1985) Abuse liability and pharmacodynamic charac-
teristics of intravenous and inhaled nicotine. J Pharmacol Exp Ther 234:1–12
Hey J (2004) What’s so hot about recombination hotspots? PLoS Biol 2:e190
Homish GG, Leonard KE (2005) Spousal influence on smoking behaviors in a US community
sample of newly married couples. Soc Sci Med 61(12):2557–2567
Huang P, Chen C, Magule S, Blendy J, Liu-Chen L (2012) A common single nucleotide
polymorphism A118G of the u opioid receptor alters its N-glycosylation and protein stability.
Biochem J 441:379–386
John U, Meyer C, Rumpf HJ, Hapke U (2004) Smoking, nicotine dependence and psychiatric
comorbidity – a population-based study including smoking cessation after three years. Drug
Alcohol Depend 76:287–295
Johnson EO, Chen LS, Breslau N, Hatsukami D, Robbins T, Saccone NL, Grucza RA, Bierut LJ
(2010) Peer smoking and the nicotinic receptor genes: an examination of genetic and environ-
mental risks for nicotine dependence. Addiction 105(11):2014–2022
60 J.L. Rutter
Johnston LD, O’Malley PM, Bachman JG, Schulenberg JE (2013) Monitoring the future national
results on adolescent drug use: overview of key findings, 2012. Institute for Social Research.
The University of Michigan, Ann Arbor, 83pp
Johnstone S, Baylin S (2010) Stress and the epigenetic landscape: a link to the pathobiology of
human diseases? Nat Rev Genet 11:806–812
Kaati G, Bygren LO, Edvinsson S (2002) Cardiovascular and diabetes mortality determined by
nutrition during parents’ and grandparents’ slow growth period. Eur J Hum Genet 10:682–688
Kahn RS, Certain L, Whitaker RC (2002) A reexamination of smoking before, during, and after
pregnancy. Am J Public Health 92(11):1801–1808
Kasanetz F, Deroche-Gamonet V, Berson N, Balado E, Lafourcade M, Manzoni O, Piazza PV
(2010) Transition to addiction is associated with a persistent impairment in synaptic plasticity.
Science 328(5986):1709
Kendler K, Ohlssom H, Sundquist K, Sundquist J (2012) Within-family environmental transmis-
sion of drug abuse. Arch Gen Psychiatry 70:E1–E8
Kranzler HR, Edenberg HJ (2010) Pharmacogenetics of alcohol and alcohol dependence treat-
ment. Curr Pharm Des 16:2141–2148
Lee W, Bergen AW, Swan GE, Li D, Liu J, Thomas P, Tyndale RF, Benowitz NL, Lerman C,
Conti DV (2012) Gender-stratified gene and gene-treatment interactions in smoking cessation.
Pharmacogenomics J 12(6):521–532
Leshner AI (1997) Addiction is a brain disease, and it matters. Science 278(5335):45–47
Li MD, Yoon D, Lee J-Y, Han B-G, Niu T, Payne TJ, Ma JZ, Park T (2010) Associations of
variants in CHRNA5/A3/B4 gene cluster with smoking behaviors in Korean population. PLoS
ONE 5(8):e12183
Liu JZ, Tozzi F, Waterworth DM, Pillai SG, Muglia P, Middleton L, Berrettini W, Knouff CW,
Yuan X, Waeber G, Vollenweider P, Preisig M, Wareham NJ, Zhao JH, Loos RJ, Barroso I,
Khaw KT, Grundy S, Barter P, Mahley R, Kesaniemi A, McPherson R, Vincent JB, Strauss J,
Kennedy JL, Farmer A, McGuffin P, Day R, Matthews K, Bakke P, Gulsvik A, Lucae S,
Ising M, Brueckl T, Horstmann S, Wichmann HE, Rawal R, Dahmen N, Lamina C, Polasek O,
Zgaga L, Huffman J, Campbell S, Kooner J, Chambers JC, Burnett MS, Devaney JM, Pichard
AD, Kent KM, Satler L, Lindsay JM, Waksman R, Epstein S, Wilson JF, Wild SH,
Campbell H, Vitart V, Reilly MP, Li M, Qu L, Wilensky R, Matthai W, Hakonarson HH,
Rader DJ, Franke A, Wittig M, Schäfer A, Uda M, Terracciano A, Xiao X, Busonero F,
Scheet P, Schlessinger D, St Clair D, Rujescu D, Abecasis GR, Grabe HJ, Teumer A, Völzke H,
Petersmann A, John U, Rudan I, Hayward C, Wright AF, Kolcic I, Wright BJ, Thompson JR,
Balmforth AJ, Hall AS, Samani NJ, Anderson CA, Ahmad T, Mathew CG, Parkes M,
Satsangi J, Caulfield M, Munroe PB, Farrall M, Dominiczak A, Worthington J, Thomson W,
Eyre S, Barton A, Consortium Wellcome Trust Case Control, Mooser V, Francks C, Marchini
J (2010) Meta-analysis and imputation refines the association of 15q25 with smoking quantity.
Nat Genet 42(5):436–440
Liu C, Ng M, Rybin D, Adeyemo A, Bielinski S, Boerwinkle E, Borecki L, Cade B, Chen Y,
Djousse L, Fornage M, Goodard M, Grant S, Guo X, Harris T, Kabagamble E, Kizer J, Liu Y,
Lunetta K, Mukamal K, Nettleton J, Pankow J, Pate S, Ramos E, Rasmussen-Torvik L, Rich S,
Rotimi C, Sarpong D, Shriner D, Sims M, Zmuda J, Redline S, Kao W, Siscovick D, Florez J,
Rotter J, Dupuis J, Wilson J, Bowden DW, Meigs J (2012) Transferability and fine-mapping of
glucose and insulin quantitative trait loci across populations: CARe, the Candidate Gene
Association Resource. Diabetologia 55:2970–2984
Loh WY, Piper ME, Schlam TR, Fiore MC, Smith SS, Jorenby DE, Cook JW, Bolt DM, Baker TB
(2012) Should all smokers use combination smoking cessation pharmacotherapy? Using novel
analytic methods to detect differential treatment effects over 8 weeks of pharmacotherapy.
Nicotine Tob Res 14(2):131–141
Malaiyandi V, Lerman C, Benowitz NL, Jepson C, Patterson F, Tyndale RF (2006) Impact of
CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of
nicotine replacement therapy. Mol Psychiatry 11(4):400–409
3 The Genetics of Addiction: A Global Problem with Global Opportunities 61
Contents
4.1 Global Burden of Disease Associated with Substance Use Disorders . . . . . . . . . . . . . . . . . . . 66
4.1.1 Methodology of Global Burden of Disease Estimations . . . . . . . . . . . . . . . . . . . . . . . . . . 68
4.1.2 Regional Differences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
4.2 Transition into Substance Use Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
4.2.1 Initiation of Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
4.2.2 Transition into Risky Patterns of Use and Substance Use Disorders . . . . . . . . . . . . 73
4.2.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
J. Rehm (*)
Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
Dalla Lana School of Public Health (DLSPH), University of Toronto, Toronto, ON, Canada
Institute of Medical Science, University of Toronto, Toronto, ON, Canada
Department of Psychiatry, University of Toronto, Toronto, ON, Canada
Institute for Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden,
Saxony, Germany
e-mail: [email protected]
C. Probst
Institute for Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden,
Saxony, Germany
e-mail: [email protected]
K. Shield
Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
Institute of Medical Science, University of Toronto, Toronto, ON, Canada
e-mail: [email protected]
Abstract
This chapter provides and overview of the epidemiological aspects of substance
use disorders. Starting with a methodological introduction into the estimation of
global burden of disease for substance use disorders, this chapter subsequently
reports regional differences in prevalence of substance use disorders and the
resulting attributable burden. The chapter closes with a review of the factors
that impact the incidence and course of substance use disorders.
Substance use disorders have been shown to account for about 1 % of the
global burden of disease in 2010, as measured in disability-adjusted life years.
The underlying methodology for this estimate was restricted to dependence and
excluded abuse as defined in DSM-IV or harmful use as defined in ICD-10, so
the most recent global burden of disease estimates for 2010 underestimate real
burden, especially for alcohol use disorders.
The burden of disease attributable to different substance use disorders varies
strongly across countries. High-income countries experience greater burden
from alcohol as well as from most illegal drugs. However, burden increased in
the past 20 years, especially in the developing world. North African and Middle
Eastern countries experience the lowest burden of alcohol use disorders, prob-
ably due to religious reasons.
A large number of factors influence the course of substance use from initia-
tion to the development of a substance use disorder. The overall picture suggests
that extra-individual, social factors as the cultural background or peer behavior
predominantly influence use initiation and transition to hazardous patterns of
use, whereas intraindividual factors as personality features and genes become
more prominent in the development and possible chronification of substance use
disorders.
Table 4.1 Burden of disease associated with substance use disorders and with substance consumption as a risk factor (GBD 2010 study)
DALYs* in 1,000s DALYs* per 100,000 persons
* *
1990 95 % CI* 2010 95 % CI Delta 1990 95 % CI* 2010 95 % CI* Delta*
Disease categories
Alcohol UD* 13,138 (9,544–17,484) 17,656 (12,923–23,243) 34.4 % 248 (180–330) 256 (188–337) 3.4 %
Drug UD* 13,152 (9,727–17,252) 20,016 (15,293–25,453) 52.2 % 248 (183–325) 291 (222–369) 17.1 %
Opioid UD* 5,284 (3,802–6,859) 9,165 (7,031–11,466) 73.4 % 100 (72–129) 133 (102–166) 33.5 %
Cocaine UD* 863 (531–1,321) 1,111 (650–1,740) 28.7 % 16 (10–25) 16 (9–25) 0.9 %
Amphetamine UD* 1,912 (1,079–2,957) 2,619 (1,480–4,125) 37.0 % 36 (20–56) 38 (21–60) 5.4 %
Cannabis UD* 1,694 (1,118–2,415) 2,059 (1,345–2,972) 21.5 % 32 (21–46) 30 (20–43) 6.4 %
Other drug UD* 3,401 (2,349–4,958) 5,062 (3,573–7,052) 48.8 % 64 (44–94) 73 (52–102) 14.5 %
Tobacco UD* Not examined in GBD study 2010
Risk factor
Alcohol 73,715 (66,090–82,089) 97,237 (87,087–107,658) 31.9 % 1,390 (1,247–1,548) 1,411 (1,264–1,563) 1.5 %
Burden of Disease: The Epidemiological Aspects of Addiction
Drug use 15,171 (11,714–19,369) 23,810 (18,780–29,246) 56.9 % 286 (221–365) 346 (273–424) 20.8 %
Tobacco 151,766 (136,367–169,522) 156,838 (136,543–173,057) 3.3 % 2,863 (2,572–3,198) 2,276 (1,982–2,512) 20.5 %
All DALYs 2,497,280 2,482,260 0.6 % 47,105 36,027 23.5 %
*
DALYs disability adjusted life years, CI confidence interval, UD use disorders, Delta percentage change between 1990 and 2010
67
68 J. Rehm et al.
(Degenhardt and Hall 2012). With respect to alcohol use disorders, prevalence was
based exclusively on a systematic review of high-quality general population surveys
which measured alcohol dependence using standardized measures such as the
Composite International Diagnostic Interview (CIDI; first version by Robins
et al. (1988); several versions currently in use, most importantly the CIDI of the
World Mental Health Survey (http://www.hcp.med.harvard.edu/wmhcidi/instruments.
php), the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) (Wing
et al. 1990) or the AUDADIS (Grant et al. 1995)). Studies in several countries under
the aegis of the WHO have revealed that for alcohol dependence as well as for illegal
drug dependence standardized instruments yield similar diagnoses and, subsequently,
prevalence rates; for harmful use or abuse, these similarities were much less
€ un et al. 1997; Pull et al. 1997); however, even when standardized
pronounced (Ust€
instruments are used, prevalence can differ. For example, consider the above-
mentioned CIDI for the World Mental Health Surveys. In the first years, dependence
items were only asked if the respondent had at least one abuse symptom, thereby
leading to a huge underestimation of dependence prevalence (Grant et al. 2007).
Similarly, small changes in wording seem to be responsible for substantive changes
in Dutch prevalence figures of the past decade (see Rehm et al. 2012 for comparisons).
Globally, the years of life lost due to both disability and premature mortality
(measured in DALYs) due to alcohol use disorders and drug use disorders varied
greatly by geography in 2010. See Figures 4.1 and 4.2 for the age-standardized
DALYs per 100,000 people caused by alcohol use disorders and drug use disorders
by country in 2010, respectively.
In 2010 the burden of alcohol use disorders was highest in Eastern Europe and in
Central Asia, with 1,046 and 435 DALYs per 100,000 people being caused by
alcohol use disorders in Eastern Europe and Central Asia, respectively. The lowest
burden of alcohol use disorders was experienced in North Africa and Middle East,
with 68 DALYs per 100,000 people caused by alcohol use disorders in 2010;
religion (Islam is the main religion in most countries of this region) was the main
factor that influenced the magnitude of the burden of alcohol use disorders in the
North Africa and Middle East region. The country that experienced the greatest
burden of alcohol use disorders in 2010 was Belarus, with 1,272 DALYs per
100,000 people caused by alcohol use disorders. For comparison, the global burden
of alcohol use disorders in 2010 was 256 DALYs per 100,000 people.
In 2010 the burden of drug use disorders was highest in North America (high
income), Australasia, and Eastern Europe, with 676, 573, and 465 DALYs per
100,000 people caused by drug use disorders in 2010 in North America (high
income), Australasia, and Eastern Europe, respectively. The largest burden of
drug use disorders was observed in Equatorial Guinea and the United Arab Emir-
ates, with 1,001 DALYs and 843 DALYs per 100,000 people, respectively, caused by
drug use disorders in 2010. With respect to the burden of specific drug use disorders,
70
<71.4 239.2–290.9
71.4–93.8 290.9–339
93.8–118.6 339–389.8
118.6–184.4 389.8–525.6
184.4–239.2 >525.6
SLB FSM
Caribbean LCA TTO TLS SYC Persian Gulf SGP Balkan Peninsula FJI TON
Fig. 4.1 Alcohol use disorders DALYs per 100,000 people, age-standardized, both sexes, 2010
J. Rehm et al.
4
<189.1 303.2–330.7
189.1–231.3 330.7–374
231.3–251.8 374–428.2
251.8–275.5 428.2–528.7
275.5–303.2 >528.7
Burden of Disease: The Epidemiological Aspects of Addiction
SLB FSM
Caribbean LCA TTO TLS SYC Persian Gulf SGP Balkan Peninsula FJI TON
Fig. 4.2 Drug use disorders DALYs per 100,000 people, age-standardized, both sexes, 2010
71
72 J. Rehm et al.
opioid use disorders and cocaine use disorders were highest in North America (high
income) (292 DALYs and 77 DALYs per 100,000 people for opioid and cocaine use
disorders, respectively). The burden of amphetamine use disorders was highest in South
East Asia (68 DALYs per 100,000 people), for cannabis use disorders it was highest in
Australasia (93 DALYs per 100,000 people), and for other drug use disorders it was
highest in Southern Sub-Saharan Africa (194 DALYS per 100,000 people). For
comparison, the global burden of drug use disorders in 2010 was 291 DALYs per
100,000 people; opioid use disorders were responsible for 133 DALYs per 100,000
people, cocaine use disorders were responsible for 16 DALYs per 100,000 people,
amphetamine use disorders were responsible for 38 DALYs per 100,000 people,
cannabis use disorders were responsible for 30 DALYs per 100,000 people, and other
drug use disorders were responsible for 73 DALYs per 100,000 people.
The burden of alcohol use disorders was much greater in developed countries than
in developing countries, with 453 and 211 DALYs per 100,000 people caused by
alcohol use disorders in 2010 in developed and in developing countries, respectively.
As with the burden caused by alcohol use disorders in 2010, the burden caused by drug
use disorders in 2010 was much greater in developed countries than in developing
countries, with 545 DALYs per 100,000 people and 253 DALYs per 100,000 people
caused by drug use disorders in 2010 in developed and in developing countries,
respectively. For opioid use disorders (222 DALYs lost in developed countries per
100,000 people and 113 DALYs lost in developing countries per 100,000 people),
cocaine use disorders (34 DALYs lost in developed countries per 100,000 people and
12 DALYs lost in developing countries per 100,000 people), cannabis use disorders
(50 DALYs lost in developed countries per 100,000 people and 25 DALYs lost in
developing countries per 100,000 people), and other drug use disorders (114 DALYs
lost in developed countries per 100,000 people and 64 DALYs lost in developing
countries per 100,000 people), the burden was much greater in developed countries
compared to developing countries; however, with respect to amphetamine use disor-
ders, the burden was greater in developing countries (39 DALYs per 100,000 people)
compared to developed countries (34 DALYs per 100,000 people).
The initiation of substance use depends largely on social and environmental factors,
such as cultural context, advertising, or peer influence. Worldwide per capita
4 Burden of Disease: The Epidemiological Aspects of Addiction 73
While most users maintain a non-risky pattern of use, some individuals will develop
hazardous patterns of substance use (Swendsen and Le Moal 2011). In particular, early
onset of substance use has been shown to increase the risk of later hazardous substance
use across substances (Pitkanen et al. 2005; Adam et al. 2011). With respect to alcohol,
recent research indicates that early drunkenness is especially associated with later
hazardous patterns of alcohol consumption (Kuntsche et al. 2013). A review identi-
fying the characteristics of people with hazardous alcohol consumption patterns in
Europe (Kuntsche et al. 2004) observed that hazardous drinking patterns were more
prevalent in males, adolescents, and young adults. Furthermore, the review identified
other social and environmental factors, such as the predominant drinking culture, peer
influences (see also Borsari and Carey 2001), parental monitoring (see also Danielsson
et al. 2011), and concurrent use of other substances. Finally, the motivation for alcohol
consumption seems to evolve from social motives and curiosity, predominantly as
controlled use, to hazardous consumption patterns motivated by enhancement and
coping (Kuntsche et al. 2005).
The factors which influence the transition from hazardous use patterns to substance
use disorders are less evident. Impulsivity-related personality traits, such as sensation-
seeking or the desire to be uninhibited, influence the transition from controlled use to
hazardous use and from hazardous use to the development of substance use disorders
(Kotov et al. 2010; Stautz and Cooper 2013). Intraindividual vulnerabilities, such as
genetic factors (Le Moal and Koob 2007; Kendler et al. 2007) and comorbid
74 J. Rehm et al.
4.2.3 Conclusion
The onset of substance use is largely influenced by cultural factors and often begins
at a young age. It may be assumed that hazardous use precedes the transition to
substance use disorders, but scientific evidence is limited in this regard. The majority
of studies do not investigate the respective transitions separately, and longitudinal
study designs risk missing the phase of hazardous use due to long study intervals.
Furthermore, a large number of risk factors seem to exist for transitions to hazardous
use and to substance use disorders. Environmental and social factors appear to be
more important in the transition to hazardous consumption, whereas genetic risk
factors and individual vulnerabilities appear to be more important for the transition
from hazardous consumption to substance use disorders (Kendler and Prescott 2006;
Tsuang et al. 1998; Vink et al. 2005; Fowler et al. 2007). Social factors play a role in
Genetic factors/vulnerability
Environment/social context
Fig. 4.3 Heuristic model of risk factors for initiation of substance use and transition to substance
use disorders
4 Burden of Disease: The Epidemiological Aspects of Addiction 75
Appendix
References
Adam A, Faouzi M, Gaume J et al (2011) Age of first alcohol intoxication: association with risky
drinking and other substance use at the age of 20. Swiss Med Wkly 141:w13226
American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders,
primary care, 4th edn. American Psychiatric Association, Washington, DC
Borsari B, Carey KB (2001) Peer influences on college drinking: a review of the research. J Subst
Abuse 13:391–424
Danielsson AK, Romelsjo A, Tengstrom A (2011) Heavy episodic drinking in early adolescence:
gender-specific risk and protective factors. Subst Use Misuse 46:633–643
Degenhardt L, Hall W (2012) Extent of illicit drug use and dependence, and their contribution to
the global burden of disease. Lancet 379:55–70
Degenhardt L, Chiu WT, Sampson N et al (2008) Toward a global view of alcohol, tobacco,
cannabis, and cocaine use: findings from the who world mental health surveys. PLoS Med
5:1053–1067
Fowler T, Lifford K, Shelton K et al (2007) Exploring the relationship between genetic and
environmental influences on initiation and progression of substance use. Addiction
102:413–422
Galea S, Nandi A, Vlahov D (2004) The social epidemiology of substance use. Epidemiol Rev
26:36–52
Grant BF, Harford TC, Dawson DA et al (1995) The Alcohol Use Disorder and Associated
Disabilities Interview Schedule (AUDADIS): reliability of alcohol and drug modules in
a general population sample. Drug Alcohol Depend 39:37–44
Grant BF, Compton WM, Crowley TJ et al (2007) Errors in assessing DSM-IV substance use
disorders. Arch Gen Psychiatry 64:379–380
Grant BF, Goldstein RB, Chou SP et al (2009) Sociodemographic and psychopathologic predictors
of first incidence of DSM-IV substance use, mood and anxiety disorders: results from the Wave
2 National Epidemiologic Survey on Alcohol and Related Conditions. Mol Psychiatry
14:1051–1066
Gururaj G, Pratima M, Girish N et al (2011) Alcohol related harm: implications for public health
and policy in India. National Institute of Mental Health and Neurosciences, Bangalore
Hanewinkel R, Isensee B, Sargent JD et al (2011) Cigarette advertising and teen smoking
initiation. Pediatrics 127:E271–E278
Hasin DS, Stinson FS, Grant BF (2007) Prevalence, correlates, disability and comorbidity
of DSM-IV alcohol abuse and dependence in the United States: results from the National
Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry 64:830–842
Kendler KS, Prescott CA (2006) Genes, environment, and psychopathology: understanding the
causes of psychiatric and substance use disorders. Press, G, New York
Kendler KS, Myers J, Prescott CA (2007) Specificity of genetic and environmental risk factors for
symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence. Arch Gen Psy-
chiatry 64:1313–1320
€ un B (2008) The WHO world mental health surveys. Global perspectives of mental
Kessler RC, Ust€
health surveys, 1st edn. Cambridge University Press, New York
Khan SS, Secades-Villa R, Okuda M et al (2013) Gender differences in cannabis use disorders:
results from the national epidemiologic survey of alcohol and related conditions. Drug Alcohol
Depend 130:101–108
Khantzian EJ (1985) The self-medication hypothesis of addictive disorders: focus on heroin and
cocaine dependence. Am J Psychiatry 142:1259–1264
Kotov R, Gamez W, Schmidt F et al (2010) Linking “big” personality traits to anxiety, depressive,
and substance use disorders: a meta-analysis. Psychol Bull 136:768–821
Kuntsche E, Mueller S (2012) Why do young people start drinking? Motives for first-time
alcohol consumption and links to risky drinking in early adolescence. Eur Addict Res
18:34–39
4 Burden of Disease: The Epidemiological Aspects of Addiction 77
Kuntsche E, Rehm J, Gmel G (2004) Characteristics of binge drinkers in Europe. Soc Sci Med
59:113–127
Kuntsche E, Knibbe R, Gmel G et al (2005) Why do young people drink? A review of drinking
motives. Clin Psychol Rev 25:841–861
Kuntsche E, Rossow E, Simons-Morton B et al (2013) Not early drinking but early drunkenness is
a risk factor for problem behaviors among adolescents from 38 European and North American
countries. Alcohol Clin Exp Res 37:308–314
Lembke A (2012) Time to abandon the self-medication hypothesis in patients with psychiatric
disorders. Am J Drug Alcohol Abuse 38:524–529
Le Moal M, Koob GPF (2007) Drug addiction: pathways to the disease and pathophysiological
perspectives. Eur Neuropsychopharmacol 17:377–393
Lin EY, Caswell S, You RQ et al (2012) Engagement with alcohol marketing and early brand
allegiance in relation to early years of drinking. Addict Res Theory 20:329–338
Lipperman-Kreda S, Grube JW, Friend KB (2012) Local tobacco policy and tobacco outlet
density: associations with youth smoking. J Adolesc Health 50:547–552
Logrip ML, Zorilla EP, Koob GPF (2012) Stress modulation of drug self-administration: impli-
cations for addiction comorbidity with post-traumatic stress disorder. Neuropharmacology
62:552–564
Merikangas KR, McClair VL (2012) Epidemiology of substance use disorders. Hum Genet
131:779–789
Murray CJL (1996) Rethinking DALYs. In: Murray CJL, Lopez A (eds) The global burden of
disease: a comprehensive assessment of mortality and disability from diseases, injuries, and
risk factors in 1990 and projected to 2020. Harvard School of Public Health, Boston, pp 1–98
Murray CJL, Vos T, Lozano R et al (2012) Disability-adjusted life years (DALYs) for 291 diseases
and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease
Study 2010. Lancet 380:2197–2223
National Statistics Office (2005) Tobacco and alcohol consumption behaviors among Thai people
in year 2004. The National Statistics Office, Bangkok
Neufeld M, Rehm J (2013) Alcohol consumption and mortality in Russia since 2000: are there any
changes following the alcohol policy changes starting in 2006. Alcohol Alcohol 48:222–230
Olds RS, Thombs DL, Tomasek JR (2005) Relations between normative beliefs and initiation
intentions toward cigarette, alcohol and marijuana. J Adolesc Health 37:75
Pitkanen T, Lyyra AL, Pulkkinen L (2005) Age of onset of drinking and the use of alcohol in
adulthood: a follow-up study from age 8–42 for females and males. Addiction 100:652–661
Popova S, Giesbrecht N, Bekmuradov D et al (2009) Hours and days of sale and density of alcohol
outlets: impacts on alcohol consumption and damage: a systematic review. Alcohol Alcohol
44:500–516
Pull CB, Saunders JB, Mavreas V et al (1997) Concordance between ICD-10 alcohol and drug use
disorder criteria and diagnoses as measured by the AUDADIS-ADR, CIDI and SCAN: results
of a cross-national study. Drug Alcohol Depend 47:207–216
Rehm J, Room R, Monteiro M et al (2004) Alcohol use. In: Ezzati M, Lopez AD, Rodgers A,
Murray CJL (eds) Comparative quantification of health risks: global and regional burden of
disease attributable to selected major risk factors. World Health Organization, Geneva,
pp 959–1109
Rehm J, Room R, Van den Brink W et al (2005) Alcohol use disorders in EU countries and
Norway: an overview of the epidemiology. Eur Neuropsychopharmacol 15:377–388
Rehm J, Mathers C, Popova S et al (2009) Global burden of disease and injury and economic cost
attributable to alcohol use and alcohol use disorders. Lancet 373:2223–2233
Rehm J, Shield KD, Rehm MX et al (2012) Alcohol consumption, alcohol dependence, and
attributable burden of disease in Europe: potential gains from effective interventions for
alcohol dependence. Centre for Addiction and Mental Health, Toronto
Robins LN (1993) The sixth Thomas James Okey Memorial Lecture. Vietnam veterans’ rapid
recovery from heroin addiction: a fluke or normal expectation? Addiction 88:1041–1054
78 J. Rehm et al.
Robins LN, Slobodyan S (2003) Post-Vietnam heroin use and injection by returning US veterans:
clues to preventing injection today. Addiction 98:1053–1060
Robins LN, Wing J, Wittchen HU et al (1988) The composite international diagnostic interview.
An epidemiologic instrument suitable for use in conjunction with different diagnostic systems
and in different cultures. Arch Gen Psychiatry 45:1069–1077
Samokhvalov AV, Popova S, Room R et al (2010) Disability associated with alcohol abuse and
dependence. Alcohol Clin Exp Res 34:1871–1878
Shield K, Rehm M, Patra J et al (2011) Global and country specific adult per capita consumption of
alcohol, 2008. Sucht 57:99–117
Shield K, Rylett M, Gmel G et al (2013) Global alcohol exposure estimates by country, territory
and region for 2005: a contribution to the comparative risk assessment for the 2010 Global
Burden of Disease Study. Addiction 108:912–922
Smith LA, Foxcroft DR (2009) The effect of alcohol advertising, marketing and portrayal on
drinking behaviour in young people: systematic review of prospective cohort studies. BMC
Public Health 9:51
Stautz K, Cooper A (2013) Impulsivity-related personality traits and adolescent alcohol use:
a meta-analytic review. Clin Psychol Rev 33:574–592
Swendsen J, Le Moal M (2011) Individual vulnerability to addiction. Ann N Y Acad Sci
1216:73–85
Swendsen J, Conway KP, Degenhardt L et al (2010) Mental disorders as risk factors for substance
use, abuse and dependence: results from the 10-year follow-up of the National Comorbidity
Survey. Addiction 105:1117–1128
Tsuang MT, Lyons MJ, Meyer JM et al (1998) Co-occurrence of abuse of different drugs in men:
the role of drug-specific and shared vulnerabilities. Arch Gen Psychiatry 55:967–972
United Nations Office on Drugs and Crime (2012) World drug report. United Nations Office on
Drugs and Crime, Vienna
€ un BT, Compton W, Mager D et al (1997) WHO study on the reliability and validity of the
Ust€
alcohol and drug use disorder instruments. Overview of methods and results. Drug Alcohol
Depend 47:161–169
Vink JM, Willemsen G, Boomsma DI (2005) Heritability of smoking initiation and nicotine
dependence. Behav Genet 35:397–406
Vos T, Flaxman AD, Naghavi M et al (2012) Years lived with disability (YLDs) for 1160 sequelae
of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease
Study 2010. Lancet 380:2163–2196
Wing JK, Babor T, Brugha T et al (1990) SCAN. Schedules for clinical assessment in neuropsy-
chiatry. Arch Gen Psychiatry 47:589–593
Wittchen HU, Jacobi F, Rehm J et al (2011) The size and burden of mental disorders and other
disorders of the brain in Europe 2010. European Neuropsychopharmacology 21:655–679
World Health Organization (1957) WHO expert committee on addiction-producing drugs, seventh
report. World Health Organization, Geneva
World Health Organization (1992) ICD-10 classifications of mental and behavioural disorder:
clinical descriptions and diagnostic guidelines. World Health Organization, Geneva
World Health Organization (2011) Global status report on alcohol and health. World Health
Organization, Geneva
Changing Patterns of Drug Use in Georgia:
A Case Vignette 5
Irma Kirtadze and David Otiashvili
Contents
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
5.2 Georgia’s Management Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
5.2.1 Treatment Response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
5.2.2 Policy Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
5.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
Abstract
In Georgia rapid economic, political, and social changes since gaining indepen-
dence from the Soviet Union in 1991 and relaxation of state control have been
accompanied by the scale of the illicit drug market. Drug use has become
a serious public health and social issue. Heroine and buprenorphine injection
epidemics of late 1990s–early 2000s were followed by the widespread abuse of
home-produced injection preparations. Switching to new drugs in many
instances was associated with increased risk of blood-borne infections and
additional harms, such as serious neurological and psychiatric complications.
Restrictive drug policy and limiting access to particular drugs were seen as
solutions to country’s drug problem. In addition, the system of addiction treat-
ment was largely unprepared to provide adequate response to the changing drug
use trends and often failed to meet the needs of the patients. Health-care pro-
viders might often need to engage in policy dialogue and advocate for relevant
systemic reforms in order to ensure that policies, program planning, and resource
allocations are meaningful, adequate, and responsive to the ever-changing needs
of people affected by substance use and dependence.
5.1 Introduction
In 2011–2012 desomorphine (krokodil) and homemade ATS (vint and jeff) were
leading drugs for injection in the country with significant portion of injectors using
both preparations. Data from the database of Georgian Harm Reduction Network
(largest provider of low-threshold services to people who inject drugs in Georgia)
show that in 2012, the last month prevalence of injection use of krokodil was 42 %
and the prevalence of stimulants injection was 37.5 % in a sample of 1,092
participants (40 females) of needle/syringe programs. For comparison, last month
prevalence of heroin, opium, and buprenorphine injection were 31 %, 10 %, and
9 %, respectively (Georgian Harm Reduction Network 2012).
To provide a full picture of the ever-changing drugs scene, it is important to
discuss the abuse of other products and over-the-counter medications that were
popular for shorter periods of time and/or were characteristic to particular geo-
graphic areas of the country. In 2003 Georgia experienced an explosive abuse of
a preparation produced from poppy seeds that are normally used as an ingredient for
different food (confectionery manufacturing). In 2005–2008 injection use of anti-
depressant tianeptin (Coaxil ®) was widely reported from different regions, in
particular West Georgia (Javakhishvili and Sturua 2009). Finally, in 2010–2011
widespread oral consumption of anticonvulsant pregabalin (Lyrica ®) was observed
throughout the country.
Common features of Georgian drug scene can be described as follows: major
drugs are used exclusively intravenously (no sniffing, smoking, or inhaling); daily
doses of Georgian injectors are comparatively low; in most of the cases opioids are
combined with benzodiazepines and other sedatives (including antihistamines with
sedative effect); unstructured polydrug use is common. In the Georgian setting,
benzodiazepines and other sedatives are added to opioids in order to increase the
potency and duration of effect of a small dose of narcotic. In addition to the
concurrent use of sedatives, the use of homemade stimulants is common. Even if
polydrug use is a well-known phenomenon in the region and is confirmed by other
authors (Booth et al. 2008; Kruse et al. 2009), Georgian studies indicate a scenario
of even more chaotic drug use. Among other factors, the reasons for unsystematic
polydrug use (mixing together opioids with other sedatives and with
pseudoephedrine-based stimulants at the same time) might be the fluctuating
availability of particular substances, the high price of all illegal drugs on the
Georgian black market compared to local income levels, and the users’ attempts
to combine different drugs in order to increase the euphoric effects, potency, and
duration of effect of the preparation.
Development in substance use patterns obviously depends on a complex set of
contributing factors and socioeconomic context in the country. Not surprisingly, in
many cases drug use trends in Georgia were shaped by policy response, legal
environment, and law enforcement practice implemented at particular periods of
time. It has been argued that the relatively long-lasting effect of buprenorphine
injection (compared to heroin or opium) and less obvious external signs of intox-
ication contributed to its popularity in the Georgian drug-using setting (Otiashvili
et al. 2010). Since the mid-2000s, there has been a dramatic increase in police
activity aimed at random street searches and (urine) testing of people for drugs,
82 I. Kirtadze and D. Otiashvili
which, in the event of a drug being found or a drug-positive urine toxicology result,
leads to harsh penalties (Otiashvili et al. 2008). Thus, buprenorphine might have
attracted drug users because of its moderate clinically visible signs after its intake.
Furthermore, for several years the police did not check suspects for the presence of
buprenorphine in their urine, but rather concentrated on the traditional opium and
heroin. This lack of detectability could in fact have added to the “attractiveness” of
buprenorphine and other drugs for local drug users. Similarly, a pattern of increased
homemade stimulant and homemade opioid injection followed the reduced avail-
ability of heroin and other “traditional” opioids. This was partially preconditioned
by the fact that police traditionally targeted heroin and opioid markets and users
switched to alternatives, which did not necessarily require involvement with illegal
drug market. Again, for initial period of time, neither vint and jeff nor krokodil was
properly detected through urine toxicology testing. Importantly, these alternatives
were remarkably cheaper, $5–7 per single dose of vint, jeff, or krokodil, compared
to $50–100 per single dose of heroine or buprenorphine.
Abuse of poppy seeds, tianeptin and pregabalin provide an additional proof of
the concept described above. In all those instances, the major reason for
experimenting with new preparations was drug users’ attempt to self-medicate
and substitute their traditional drug of abuse. Importantly, neither tianeptin nor
pregabalin was identifiable through rapid urine testing, and the single dose of either
preparation costs less than $10. As a policy response, all these medications,
including poppy seeds, were rescheduled and put under the strictest control regime,
which ultimately dramatically limited access to these preparations. Not surpris-
ingly, drug users just went on with exploring new options.
Switching to new drugs in many instances was associated with increased risk of
blood-borne infections (high frequency of injection, group character of use, sharing
of paraphernalia, and risky sexual behavior) and additional harms, such as serious
neurological and psychiatric complications (due to toxicity and/or insolubility of
chemical ingredients used for processing the preparations) (Sikk et al. 2007).
Krokodil, which received its name due to association with “crocodile eating your
flesh,” is probably one of the most toxic preparations injected in Georgia. Apart
from quickly progressing severe neurological impairments, its use causes skin
irritation and soft tissue damage. Reports provided by harm reduction and drug
treatment facilities suggest that due to the fluctuating potency of the preparation,
depending on the process of its refinement, krokodil injectors are at increased risk
for overdoses. It is indicative that harm reduction programs in Georgia report an
increased demand for naloxone.
In a country with an HIV epidemic driven by injecting drug use (56 % cumu-
lative HIV cases attributed to IDU route (Chikovani et al. 2011b)), risks associated
with the use of particular substances are of special interest. Common unsafe
injection behavior among Georgian IDUs known to be sharing a cooker and
dividing solution using one syringe (Chikovani et al. 2011a). In-depth analysis of
drug preparation and drug division processes helps provide a meaningful explana-
tion for these particular types of risk behavior. Buprenorphine (Subutex ®) injection
in Georgian setting occurs as a rule in a group of three to four people. They dissolve
5 Changing Patterns of Drug Use in Georgia: A Case Vignette 83
one 8 mg tablet in water and then, using a large-volume syringe, divide the solution
by front or back loading into smaller individual syringes (Otiashvili et al. 2010).
Home preparation of both amphetamine-type stimulants (vint and jeff) and opioids
(krokodil) involves using common cooker to process ingredients through often-
complicated chemical refinement and using large-volume syringe to divide the final
product into smaller syringes for injection (front and back loading). In both cases
drug preparation is a group activity with often-predetermined division of roles and
contributions (money, ingredients, space for production). Injecting stimulants from
preloaded (by someone else) syringes was also reported.
Limiting access to particular drugs, massive searches, and arrests of drug users were
seen as solutions to Georgia’s drug problem. Immediate results of this approach
were obvious; streets became free of people under the influence and signs of drug-
related activities diminished. Thousands of drug users also ended up in prisons.
These actions have had multiple, radiating, unintended consequences. For example,
these actions resulted in drug users switching to more available, cheap, and largely
harmful and toxic home-produced preparations and exercising more life-risky
patterns of use. No evidence of reduced prevalence of drug use is available. As of
2010, there are an estimated 40,000 regular injection drug users in Georgia. Thus,
the problem has not been reduced. In fact, the rate of the problem in drug use is
approximately 2.5 times higher than the average European estimates (Sirbiladze
2010). Within a 4-year period, the prison population has increased fourfold (from
6,000 to 24,000), and Georgia in 2011 rated sixth in the world by per capita number
of prisoners (International Centre for Prison Studies 2011). This high incarceration
rate has placed economic and social burden on the families of incarcerated drug
users (e.g., separating mothers and fathers from children, leaving families without
economic means of support both during the incarceration and after release when
drug users with incarceration histories face extreme difficulties in obtaining a job).
Heavy emphasis on law enforcement measures has resulted in a disproportionate
allocation of resources to programs aiming to provide health and social care to
people with substance use-related problems. Countrywide, only about 6 % of those
who are in need receive any kind of drug dependence treatment (2,520 out of 40,000
in 2011) (Javakhishvili et al. 2012).
Hopefully, as of the start of 2013, major policy reform was discussed; Drug Policy
Coordination Council has been established and drug-related legislative initiatives
have been reviewed in the Parliament. Importantly, this process has been inclusive
and transparent enough and has engaged all major stakeholders: policy-makers,
service providers, field experts, and representatives of affected groups. It is hoped
5 Changing Patterns of Drug Use in Georgia: A Case Vignette 85
that newly elected government officials will be committed to recalibrate current drug
policy regime and will build a system in which tolerance and care for those in
need, effectiveness of interventions, and evidence-driven decision-making will be
prioritized.
5.3 Conclusion
References
Booth RE, Lehman WE, Kwiatkowski CF, Brewster JT, Sinitsyna L, Dvoryak S (2008) Stimulant
injectors in Ukraine: the next wave of the epidemic? AIDS Behav 12(4):652–661 [Research
Support, N.I.H., Extramural]
Chikovani I, Bozicevic I, Goguadze K, Rukhadze N, Gotsadze G (2011a) Unsafe injection and
sexual risk behavior among injecting drug users in Georgia. J Urban Health 88(4):736–748
Chikovani I, Goguadze K, Ranade S, Wertlieb M, Rukhadze N, Gotsadze G (2011b) Prevalence of
HIV among injection drug users in Georgia. J Int AIDS Soc 14:9 [Research Support,
Non-U.S. Gov’t]
Dershem L, Tabatadze M, Kamkamidze G, Aldridge S, Gjibuti M (2012) Youth behavioral
surveillance survey: HIV/AIDS knowledge, attitudes, and practices among school pupils and
university students in Tbilisi, Georgia. Research Triangle Institute and Save the Children,
Tbilisi
Elovich R, Drucker E (2008) On drug treatment and social control: Russian narcology’s great leap
backwards. Harm Reduction J 5:23 [Comment, Editorial]
Georgian Harm Reduction Network (2012) Background characteristics of the clients of needle
exchange programs. HIV prevention program database. Retrieved from 4 Sept 2012
International Centre for Prison Studies (2011) World prison brief. http://www.prisonstudies.org/
info/worldbrief/wpb_stats.php?area¼all&category¼wb_poprate. Retrieved 27 Jul 2011
Javakhishvili J, Sturua L (2009) Drug situation in Georgia – 2008. Southern Caucasus Anti-Drug
Programme, Tbilisi
Javakhishvili J, Kariauli D, Lejava G, Stvilia K, Todadze K, Tsintsadze M (2006) Drug situation in
Georgia – 2005. Southern Caucasus Anti-Drug Programme, Tbilisi
Javakhishvili DJ, Balanchivadze N, Kirtadze I, Sturua L, Otiashvili D, Zabransky T (2012)
Overview of the drug situation in Georgia, 2012. Global Initiative on Psychiatry/Alternative
Georgia, Tbilisi
86 I. Kirtadze and D. Otiashvili
Kirtadze I, Otiashvili D, O’Grady KE, Zule WA, Krupitskii EM, Wechsberg WM et al (2013)
Twice stigmatized: health service provider’s perspectives on drug-using women in the
Republic of Georgia. J Psychoactive Drugs 45(1):1–9
Kruse G, Barbour R, Heimer R, Shaboltas A, Toussova O, Hoffman I et al (2009) Drug choice,
spatial distribution, HIV risk, and HIV prevalence among injection drug users in St. Petersburg,
Russia. Harm Reduct J 6(1):22
Latypov AB (2011) The Soviet doctor and the treatment of drug addiction: “a difficult and most
ungracious task”. Harm Reduct J 8:32
Otiashvili D, Sárosi P, Somogyi G (2008) Drug control in Georgia: drug testing and the reduction
of drug use? The Beckley Foundation Drug Policy Program, Briefing paper fifteen
Otiashvili D, Zabransky T, Kirtadze I, Piralishvili G, Chavchanidze M, Miovsky M (2010) Why do
the clients of Georgian needle exchange programmes inject buprenorphine? Eur Addict Res
16(1):1–8
Sikk K, Taba P, Haldre S, Bergquist J, Nyholm D, Zjablov G et al (2007) Irreversible motor
impairment in young addicts–ephedrone, manganism or both? Acta Neurol Scand
115(6):385–389 [Case Reports, Research Support, Non-U.S. Gov’t]
Sirbiladze T (2010) Estimating the prevalence of injection drug use in Georgia: concensus report.
Bemoni Public Union, Tbilisi
Sturua L, Avaliani N, Giuashvili N, Shishniashvili M, Gvinianidze K, Topuridze M et al (2010)
Noncommunicable disease risk factors survey. National Center for Disease Control, Tbilisi
Social Aspects of Addiction and
Environmental Strategies 6
Joseph Westermeyer
Contents
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
6.2 The Social Context . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
6.2.1 The Addicted Person in Social Context . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
6.2.2 Using Interpersonal Psychodynamics in Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
6.2.3 Impersonal, Formal, and Personal-Informal Relationships . . . . . . . . . . . . . . . . . . . . . . 91
6.2.4 Recapturing Social Integrity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
6.3 The Addicted Person’s Family . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
6.3.1 Recovery Within the Family . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
6.4 The Intimate Social Network in Addiction and Recovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
6.4.1 Intimate Social Networks (ISNs) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
6.4.2 The ISN in Addiction and Recovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
6.4.3 Artifactual ISNs in Recovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
6.5 The Community and Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
6.5.1 State Government and Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
6.5.2 The Sociocultural Milieu and Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
6.6 Addiction from International Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
6.6.1 International Participation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
6.6.2 Technology and Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
6.6.3 Addiction as a Transmissible Condition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
6.7 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
This article reflects the opinions of the author only and not those of the Minneapolis VE Health
Care Center or the University of Minnesota.
J. Westermeyer
Staff Psychiatrist, Minneapolis VA Health Care Center, University of Minnesota, Minneapolis,
MN, USA
e-mail: [email protected]
Abstract
Social-environmental factors serve two functions in addiction care, i.e.,
(Bean, Zinberg (eds) (1981) Dynamic approaches to the understanding and
treatment of alcoholism. New York, The Free Press) for diagnosis, assessing the
social-environmental nature and severity of the addiction and (Berne
(1964) Games people play – the basic handbook of transactional analysis. New
York, Ballantine Books) for treatment, identifying social-environmental obstacles
and resources to recovery. In clinical settings, addicted persons may try to maintain
addiction by eliciting rescuing or enabling behavior from clinicians and other
parental figures; the antidote consists of adult-adult transactions aimed at recovery.
Depending on the clinical context and phase of recovery, clinicians can choose
a variety of roles vis-à-vis the addicted patient, i.e., impersonal or mechanistic I-it
for early detoxification, formal I-You for diagnosis and treatment planning, and
personal I-thou during later recovery. Ultimately, the recovering addict must
achieve trust within himself/herself and regain the trust of others, through acquiring
personal and social integrity. Two available social entities consist of mutual-help
groups (e.g., Alcoholics Anonymous, Narcotics Anonymous) and the family. These
two resources can gird the addicts in re-creating a supportive, functional intimate
social network (ISN) – a core foundation for happy and healthy living. Clinicians’
understanding of the ISN structures and functions provide a potent means for
coaching addicts in recovery. In addition to clinicians, families, and mutual-help
groups, communities, governments, and society at large can design environments
that facilitate relapse or favor recovery. Social-environmental obstacles include
a high prevalence of addiction and local profiteer-enablers who prey upon addicts.
Social-environmental resources include clear norms regarding substance use, avail-
ability of timely treatment, and implementing prevention strategies. Coordinated
international action can bolster local social-environmental initiatives.
6.1 Introduction
The actions of addicted persons in relation to others can be described using the social
roles of “parent,” “adult,” and “child,” as shown in Fig. 6.1. These parent-adult-child
terms correlate loosely with the psychoanalytic terms “superego,” “ego,” and “id.”
Addicted people sometimes assume the “child” role in relation to parental
figures, such as clinicians and judges. This interpersonal strategy aims at eliciting
addiction-perpetuating succor from the other person’s “parent.” As applied to
addiction, a rescuing or enabling interaction may ensue (Berne 1964).
Rescuing entails the “parental-helper” saving the “childish-addict” from the
consequences of his or her behavior. For example, a judge may let the addicted
criminal off without punishment, or a clinician may repeatedly treat the addict’s
damaged health without attending to the addictive disorder that is causing the
illnesses. Enabling implies that the parental figure provides resources that permit
the addicted person to have the time and/or resources to continue an addiction-
focused lifestyle. For example, a family member or friend may provide the addicted
person with money, shelter, food, or transportation to purchase psychoactive sub-
stances and avoid social responsibilities. Both rescuing and enabling are depicted
by the child-parent relationship depicted as “1” in Fig. 6.1 (Berne 1961).
Recovery requires the addicted person to act in “adult-to-adult” relationships;
see relationship “2” in Fig. 6.1. This transition from child-parent to adult-adult
transactions may not be easily accomplished. Clinicians can assist recovering
patients and their rescuers-enablers with this often-difficult change as follows:
• Instruction regarding interpersonal roles, choices, and dynamics
• Feedback regarding “childlike” behaviors of the addicted person’s part (e.g.,
missing or coming late to appointments, requesting prescriptions for addictive
medications, requesting treatment while undermining its beneficial effects by
continued addiction)
• Clinician’s opting out of parental behaviors that promulgate addiction (e.g., pre-
scribing addictive substances, providing written excuses for irresponsible or illegal
behavior, undertaking or persisting in treatments rendered ineffective by addiction).
6 Social Aspects of Addiction and Environmental Strategies 91
Using the paradigm described in Fig. 6.1, recreation with others tends to occur
on a “child-to-child” transactional level. As recovery proceeds, the ability to
recreate without recourse to alcohol-drug use poses an obstacle for many recover-
ing persons. If their former recreation did not depend on substance use, they may
simply return to their former pastimes, hobbies, or avocations. However, if their
former recreation occurred in a context of substance use, they need to seek new
opportunities free of substance use. Mutual-help associations and recovering groups
realize this dilemma and often create recreational activities for times that favor
excessive use (e.g., New Year celebrations). Clinicians should aid in this crucial
aspect of recovery, since the absence of play and social “time out” from daily
responsibilities can undermine an otherwise well-founded recovery.
In certain respects, clinicians can behave appropriately toward recovering
patients in the “parent” role. Examples include making and conveying diagnoses,
providing counsel, or prescribing medications for detoxification, craving, mainte-
nance, or comorbid disorders. Although aimed at being therapeutic, this approach
may engender childlike responses from the recovering patient (e.g., resentment,
sociopathic “acting out” of negative attitudes toward the clinician or the treatment
process, return to addiction). Several alternatives can aid in reducing these
“parental” impediments as follows:
• Working with co-therapists who can assume a more egalitarian approach to the
patient
• Assuming more the role of a “coach-trainee” than a “doctor-patient”
• Providing choices between alternative therapies, so that the patient is engaged as
a codirector of treatment
• Educating the patient to the pros and cons of alternative approaches and allowing
some time interval for the patient to consider the alternatives, seek other
information, or obtain counsel from others before making a decision or
requesting the patient to make a commitment
Addicted persons, as well as their clinicians and other members of their social
networks, can behave on several operational levels vis-à-vis the other. For purposes
here, these three types of interpersonal relationships are used synonymously with
I-focused typologies that have evolved over the last several decades (Farber 1956):
• Impersonal ¼ I-it relationship
• Formal ¼ I-you relationship
• Personal ¼ I-thou relationship
The “I” in an I-it relationship relates to the other person in a mechanistic, largely
I-centered fashion. For example, an addicted person seeking drugs from a clinician
has an unshared goal with the clinician (i.e., obtaining addictive medications) as
opposed to a shared goal (i.e., health seeking). Such patients may experience
problems in changing their attitude toward clinicians from “naı̈ve target” to
“trusted helper.” We as clinicians may act in I-it roles with unconscious patients
92 J. Westermeyer
By the time they seek treatment, many addicted people can no longer rely on them-
selves. Clinicians hear statements like “I can no longer trust myself” or “I lie so much
that I don’t even know what is the truth anymore” or “I can’t make even the simplest
promise or commitment.” Re-acquiring integrity starts with the self. To regain
6 Social Aspects of Addiction and Environmental Strategies 93
integrity, addicts need to work at becoming “one” again. That is, they must have one
truth, one set of values. Such constancy is difficult even for nonaddicted persons, since
the variety of roles played by any one person varies so greatly. Each of us possesses
slightly different personas in our relationships with parents, offspring, spouse, super-
visors, co-workers, friends, old buddies from childhood, and clients. These personas
if extremely diverse can pull the recovering person away from an evolving core
“one-ness,” or integrity, toward duplicity and relapse (Sutker et al. 1980).
Over time many people with addictive disorders lose the trust of other people.
Stated differently, addicts tend to lose their trustworthiness. Without mutual trust,
people are unwilling to live with addicted persons, own material goods in common
with them, or exchange mutual obligations. In the absence of such commitments,
the addicted person is apt to become increasingly isolated. For a time, wealth may
compensate for mutual obligations, posing a greater risk for the wealthy who can
hire to people to provide social support. Unfortunately, using wealth to compensate
for social isolation can delay recovery efforts. To establish trust, the recovering
persons must be honest, truthful, reliable, and morally upright.
Regaining the trust of others presents one of the greatest long-term challenges to
the recovering addict. Depending on the duration and depth of past failures, it may
take many months to years before former relatives, friends, and others can again
trust the recovering addict. With some regular opportunities to regain trust, the
recovering person may experience some moderate trust building within a year.
Deep trust may take longer. Clinicians can support and guide the recovering person
in this quest. Many recovering people expect others to impart trust after one
episode, or within a week or two of abstinence. Such disappointments can reignite
addiction if the patient is not prepared for it. Once prepared for the long haul,
however, most recovering people can launch into the quest of regaining integrity
(Westermeyer and Walzer 1975).
Perhaps one of the advantages of becoming again an integrated, trustworthy
person is the paucity of people in the networks of many people early in recovery.
Since they have lost so many supporters, they can start anew rebuilding on a small
number of relationships. Starting simply with only a few relationships eases the task
of achieving integrity.
The Addicted Family. In most societies, more than half of addicted persons grew up
in a family with an addicted parent. Some addicts even have two parents with an
addictive disorder. Or neither parent may be addicted, but siblings, grandparents,
uncles, aunts, or cousins may be addicted (Galanter 1993).
Coming from an addicted family can produce a myriad of hurdles. Addiction
tends to start earlier in such circumstances. Childhood may have been fraught with
stress and conflict, if the parent or parents had not recovered earlier. Role models
for later adulthood, marriage, and parenting may be absent or flawed (ElGuebaly
et al. 1990; Westermeyer et al. 2001).
94 J. Westermeyer
By the same token, having an addicted family background can also impart
certain advantages. Relatives may recognize the signs of addiction early on, due
to their familiarity with it. Especially if familiar with recovery, they may support
the addicted relative in recovery-oriented endeavors. Those seeking out recovery-
oriented mutual-help groups may come from addiction-afflicted families
(Westermeyer et al. 2001). In some countries, mutual-help groups for the adult
children of addicts have formed.
For addicted adolescents and young adults, family therapy can be a highly effective
intervention. The same is true of couple’s therapy in which one partner is addicted.
A key to either alternative lies in seeking a therapist familiar with addiction,
recovery, and the treatment of addicted families and couples (Coviello et al. 2004).
If both members of a couple are addicted at the same time, concurrent recoveries
occur only rarely. Since recoveries tend to be unique in certain respects and occur
unevenly over time, partners seldom recover in the same fashion along the same
time frame. This discrepancy wears on the relationship, so that maintaining the
blighted relationship while trying to recover becomes nigh unmanageable. A more
viable alternative may lie in recovering separately and then deciding whether the
two recovered-evolved personas can create a new sobriety-based life together
(O’Farrell and Cowles 1989).
Recovered persons, when single, often meet and court other recovered persons.
This common, often vexing-yet-rewarding experience can serve as strong ground-
work for a successful partnership. Each member shares concepts, jargon terms, and
perhaps common recreations and social affiliations with the other. Plus they under-
stand deeply the torments of loss and loneliness, and they share the long, hard trek
from addiction through recovery to wellness.
hundred to a few thousand people). Among adults, the relationships are reciprocal, so
that members contribute to or help one another as well as the corporate group in some
fashion (e.g., exchanging goods or services, providing interpersonal help or support,
meeting common goals). Membership in any one group within the ISN often requires
getting along with several people. In this fashion, a person may transcend conflict with
any one or a few members of the group in order to retain access to valued members of
the group and keep the group intact. Such networks tend to persist over time. Any one
person in the proband’s network knows about 80 % of the people in the total network
(i.e., connectedness ¼ 80 %).
People who seek outpatient mental health services tend to have at least ten, but
less than 20 people in their ISN (Westermeyer and Neider 1988); see Fig. 6.3. The
network members often fall into two or three groups plus an additional number of
one-to-one relationships; see Table 3. These one-to-one relationships may include
a recent friend, lover, or someone who provides service or care (e.g., a therapist,
clergy, bar tender, barber, or hairdresser). The one-to-one relationships may be
more recent as well as vulnerable to change or dissolution over time. At times they
report ISN members as being pets, deceased friends or relatives, or close friends
from years or decades earlier. Connectedness is around 60 %. These people are
typically discomforted, even miserable, but they are functional in one or more
capacities, such as working, parenting, or going to school. Among adults, their
96 J. Westermeyer
Actively employed addicts living with family can have social networks that
resemble normal networks with one exception: as many as half of the network is
comprised of other addicted people (Favazza and Thompson 1984). In order to
pursue recovery, they must abandon and then replace the addicted people with
whom they are affiliated. This precipitates loss, engenders grieving, and can both
help and hinder the adjustment to sobriety.
Most people presenting for addiction treatment have the “discomforted” net-
work, with 10–19 people, 2–3 groups, and one or more individual relationships
(with minimal connectedness to the rest of the network). In achieving
a comfortable, balanced life and recovery, they usually rebuild their network
backup to 20–30 people and four to five groups over a period of years – a much
longer period than that needed by people who must rebuild their ISNs after
relocating for work or education.
Relatively few addicted people seeking treatment have “disabled” networks with
fewer than ten people and a single nonreciprocal group focused on their care. Those
who are in this group may be mentally ill (e.g., Korsakoff dementia, alcoholic
dementia, chronically psychotic). A thorough neuropsychiatric evaluation should
take place early in treatment; neuropsychological, neurological, and medical
assessment may also be needed. So-called skid row alcoholics living on the
periphery of society may also fall into this category.
Assessment that incorporates members of the patient’s ISN can serve several
purposes: elaboration of a complete assessment, communication to the patient
regarding the consequences of his/her behavior on those who care about him/her,
and enlisting ISN members in intervention and recovery (Speck and Attneave
1973). Ongoing treatment that involves ISN members committed to the patient’s
6 Social Aspects of Addiction and Environmental Strategies 97
Most people in a community have a normal social network and do not want
additional network members. Since such relations require reciprocity, regular
contact, and long-term emotional commitment, there is a self-limiting component
to ISN size. It cannot grow beyond finite limits. Moreover, the network tends to
accrete in groups rather than solely via individuals (although individual contacts
can grow to subsequent group affiliations). Such affiliations also grow over time,
almost like a courtship, in a series of small-but-reciprocal events, as trust and
friendship develops. Thus, acquiring new individuals and groups poses a major
challenge during recovery.
During the early period of recovery, a number of created or artifactual groups are
available to the recovering person. These groups can include one or a few mutual-
help groups (e.g., Alcoholics Anonymous) and perhaps a treatment team or case
manager (Willenbring 1995). Certain community organizations open to all can
provide a nidus for later affiliations (e.g., church committees, neighborhood polit-
ical committees, hobbies or pastimes). Each culture and community contains its
own entrees to such groups. Even in remote rural communities of a few hundred
people, recovering people can rebuild a functional social network (Westermeyer
1982).
Recovering people can also be on the lookout for people whose social networks
have been depleted and are expanding. People migrating to a new community
typically rebuild their social network within several months. Those starting a new
job, school, or training program may be open to new affiliations. A limiting factor
for the recovering addict is the need for sober members in at least some of his or her
social network and the absence of addicted people in the remainder of the network.
Some communities are more addiction friendly, some are more recovery friendly,
and many possess elements of both. Perhaps the most important pro-addiction
environmental factor is a high prevalence of people using substances excessively
98 J. Westermeyer
(Hughes et al. 1974). Widespread excessive use reduces social inhibitions against
use. Having a large number of substance merchants also contributes to widespread
use, as it increases access and – if market forces are at work – reduces the cost.
Absence of restrictions against sale to youth or intoxicated persons, or unlimited
hours of sale, fosters widespread use (Smart and Murray 1983).
Widespread intoxication in a neighborhood or illicit sales can, in time, under-
mine a neighborhood (Fagan 1989). Several avenues promote this outcome. Wide-
spread intoxication leads to property crime (to purchase psychoactive substances)
and interpersonal crime (due to increasing discord and disinhibition). Drug sellers
become the role models for youth, due to their relative wealth and apparent power.
Faced with these daily realities, working families involved in raising their families
move elsewhere. Property values drop and licit retail stores move elsewhere. In
many such settings, security falls as police abandon the neighborhood or cannot be
deployed in adequate numbers due to the falling tax base. Corruption of elected
officials and other governmental workers often emerges (Westermeyer 1982).
The current prevalence of addictive disorders can reach crude prevalence rates
(i.e., total population rate) as high as 10–12 %. Examples include Southeast Asian
and South Asian communities that raise opium poppy (Westermeyer 1981) and
American native reservations with high alcohol and drug rates (Kinzie et al. 1992).
Since most addiction in these communities occurs in those aged 18 years or older
and adults comprise about half of the community, the adult prevalence rates are
twice as high, in the range of 20–25 %. Since men in these settings have rates two or
three times that of women, current adult male rates run around 26–38 % and adult
female rates run around 10–26 %. Two additional factors argue for lifetime risks of
addiction that exceed these crude prevalence rates: some of the younger adults will
develop addiction during their adult years in the future, but have not done so yet
(Bean and Zinberg 1981), and some of the addicted adults in the population have
already died at an early age from substance-related causes, so that addicted people
are underrepresented (Berne 1964). Although no firm lifetime rates are available for
these high-rate communities, extrapolations from current prevalence rates, risk factors
favoring future addiction in some adults, and early removal of addicts from the
population through premature death suggest that even higher lifetime rates, perhaps
15–30 % in women and 30–50 % in men, can exist. Burdens in such communities
include child neglect and abuse, malnutrition, marital disruption, violence, infectious
disease, poverty, crime, and premature death (Westermeyer 1999). Although some
community leaders in such settings focus public attention and action on addiction,
many others deny its existence and accuse clinicians or epidemiologists of exagger-
ating or lying about the extent of addiction in the community (Foulks 1989).
Addiction services within a community must be integrated to be successful. For
example, failure to engage newly released prisoners in treatment produced a high
drug-related mortality rate during the first 2 weeks post release (Farrell and
Marsden 2008). Mortality is also high during the first month following discharge
from opioid maintenance treatment (Cornish et al. 2010). Availability of chronic
pain services may comprise a safety net for patients transitioning from one phase of
addiction treatment to another (Barry et al. 2012).
6 Social Aspects of Addiction and Environmental Strategies 99
Actions by governmental bodies can greatly influence the rate and course of
addiction in a society. Governmental efforts can be most effective and efficient
when rates are low and decreasing. Conversely, governmental efforts are most apt
to go awry when rates are high and increasing. Under such circumstances, the
government striving to reduce the addiction rates is at odds with the large number of
the populace who value heavy, excessive, widespread use. The latter group includes
not only the heavy consumers, but also many others who profit from heavy,
widespread use. Profiteers include basic producers (e.g., farmers, biochemists),
manufacturers (distilleries, pharmaceutical companies, illicit gangs), transporters,
wholesalers, retailers, bankers, advertisers (if the substance is legal), private
security forces (if the substance is illegal), and government workers, altogether
comprising a virtual army of citizens and public workers dependent on or corrupted
by the industry (Suwanwela and Poshyachinda 1986).
Despite the myriad of obstacles, many governments have reduced widespread
addiction over the last three centuries (Lowinger 1977). There is evidence from
Mexican glyphs that Aztec laws limited alcohol use even earlier (Anawalt and
Berdan 1992). Successful means of limiting or eliminating certain addictions have
included the following:
• Taxes on import and/or sale of certain psychoactive substances (e.g., beverage
alcohol, tobacco)
• Licensure to import, produce, or sell certain psychoactive substances in specific
amounts
• Restriction of certain substances to medically supervised prescription use (e.g.,
opioids, sedatives, stimulants, cocaine)
• Constraints on density of retail outlets for certain licit psychoactive substances,
as well as hours and days of sale
• Punitive laws against behaviors that undermine governmental authority with
regard to psychoactive substances (e.g., bootlegging, illicit production), risky
behaviors during use (e.g., driving, boating, flying, hunting), and actions that
may engender addiction (e.g., sale to minors or intoxicated persons)
• Providing treatment for addicted victims of alcohol-drug epidemics while punishing
those who illegally produce or distribute these substances or commit illegal acts
while influenced by these substances (the so-called carrot and stick approach)
Governmental actions can also foster addiction and/or the consequences of
addiction in numerous, often unintended ways, as follows:
• Placing tax revenues on psychoactive substances into the general revenues of the
state, so that governmental officials seek to increase substance use as a means of
increasing revenues (rather than targeting these funds to reduce addiction and
address its consequences)
• Providing governmental funds for housing or unemployment incomes to
addicted persons with no supervision or expectation for recovery while
overlooking opportunities for community reinforcement of sober behaviors
(Azrin 1976)
100 J. Westermeyer
ceremonial. The main event is the use of the substance, its subjective effects, and
the peer group experience. If the substance is illicit, it may occur in a surreptitious
fashion (which may add to the excitement of the event and the subjective effects of
the substance). Depending on the culture or the individual group, the coaching
mostly occurs from early adolescence to early adulthood. It may occur when the
person has left home (for school, work, or military service) or during individuali-
zation from the family to adulthood. Initially the peer group sets the occasion and
perhaps also the amount of use. However, with time, individuals decide their own
frequency or amount of use. With age, marriage, parenting, and work responsibil-
ities, many people fall into a pattern of nonuse (if the substance is illicit) or mild-
to-moderate use (if the substance is legal and culturally acceptable). Others choose
heavy or excessive use, paving the way to addiction as a lifestyle (Westermeyer
1999).
Both patterns of instruction can occur in a given family, community, or culture.
For example, alcohol use may be carefully taught within the extended family, while
tobacco smoking may be learned from peers. This scenario would favor addiction to
tobacco but nonproblematic use of alcohol. Supervised substance training may
prevail in traditional societies with specifically traditional substances, such as
alcohol, tobacco and hallucinogens (in the Americas), caffeine (in teas and coffee),
and khat. Society-wide education in the use of certain other substances takes place
infrequently for other substances, such as coca leaf or cocaine, betel-areca, opium
and its derivatives, or industry-produced substances (sedatives, amphetamines,
anesthetics, anticholinergics).
The use of substances can impede enculturation into adulthood by alleviating the
anxiety or insecurity that accompanies acquisition of maturity. Maturity-related
tasks consist of social performance (e.g., speaking or performing before a group),
comfort with sexuality (e.g., conversing with the opposite sex, expressing affection,
courting), and various interpersonal skills and problem solving (e.g., conversation,
coping with confrontation, settling differences). If an individual can engage in these
activities only under the influence of psychoactive substances, two problems ensue:
maturation is delayed, with detrimental effects on self-confidence and self-esteem
(Bean and Zinberg 1981), and the substance is needed to perform the task, setting
the stage for eventual addiction, as a higher dose and more frequent use is required
to alleviate social fears or performance anxiety (Berne 1964).
Psychoactive substance use may accompany certain types of work. For centu-
ries, coca leaf, betel-areca, tobacco, and alcohol use have attended long hours of
heavy or repetitive work (e.g., factories, road building). For tasks requiring height-
ened awareness or bursts of energy (e.g., hunting, warfare, athletics), some societies
have employed stimulant use (caffeine, cola nut, khat, kratom). Traditional healers,
spiritual leaders, or members of spiritual or healing associations (such as Zar-like
healing cults across Asia) may use substances to facilitate trance. Depending on the
culture and current practice, these substances have encompassed opiates, halluci-
nogens, tobacco, and other drugs. Rather than use drugs of any kind, some groups
have employed fasting, sleeplessness, social isolation, silence, or repetitive music
or dance as a means of achieving trance, communication with spirits, or healing.
102 J. Westermeyer
Many workers around the world relax at the end of the work day with a variety of
substances, including alcohol, caffeine, khat, tobacco, opiates, and cannabis.
Epidemics of addiction have occurred around the world over the last five
centuries, beginning with epidemic alcohol use in Europe, epidemics of opium
smoking across Asia and parts of Europe, and tobacco almost everywhere. Factors
supporting these early epidemics comprised the following:
• Appearance of new substance forms, which were not subject to traditional
customs (e.g., gin and rum in European countries where beer, ale, or wine had
been traditional)
• Appearance of new modes of administration not subject to traditional mores
(e.g., smoking opium replaced medicinal oral ingestion of opium)
• New substances (e.g., tobacco, cocaine) over which no traditions or rituals had
governed use
• Profiteers who endeavored to increase use and thereby increase their profits
• Diverse, conflicting, or ambivalent beliefs and attitudes toward use, so that any
given society could not act in a coherent fashion vis-à-vis the substance
• Delay in the appearance of epidemic consequences, so that addiction spread
widely before the extent of the problem could be appreciated
As addiction spreads to epidemic proportions, it tends to do so in a hidden
fashion during its early stages (Westermeyer 1982). This unique phenomenon is
due to the consequences of addiction epidemics showing up in numerous sectors,
including health, family life, productivity, child raising, property crime, interper-
sonal crime, economic burdens, and various other manifestations. Moreover, the
spread occurs over years or even decades and centuries, unlike infectious disease
epidemics that can devastate a population within weeks, months, or a few years.
The low incidence of any one addiction-related index allows profiteers and
other supporters to pass the occasional problem off as being unrepresentative, or
“the small price” necessary in providing this new benefit or recreation or life
enhancement to the population at large.
Beginning five centuries ago, the largest addiction epidemics involved international
trade. Substances were produced legally in one region (e.g., gin and rum in the
Caribbean, opium in India, tobacco and cocaine in the Americas) and transported,
often illegally, to countries in another region. Relatively safe and inexpensive
international transport facilitated the trade. Large investments in production, trans-
port, and security were secured from banks and profiteers – and sometimes even
governments (Westermeyer 1987).
The scenario described above has continued in recent decades. However, several
international organizations have united many countries against addiction.
Government-supported organizations include the United Nations and its Narcotic
6 Social Aspects of Addiction and Environmental Strategies 103
Control Board, the World Health Organization, and numerous other groups
concerned with pharmaceutical production, crime, and drug trafficking. Several
professional groups have formed international associations to oppose addiction,
including physicians, pharmacists, police, and various nonprofit nongovernmental
groups (NGOs).
Many health conditions pose international threats (e.g., HIV, influenza), while
others appear more related to local conditions (e.g., heart disease, diabetes, schizo-
phrenia). Although local factors can impede or accelerate addiction, nonetheless
addiction can resemble the transmissible disorders. An evolving addiction epidemic
in one country threatens its immediate neighbors, and sometimes other countries at
a greater distance. For these reasons, international collaboration in studying
successes as well as failures in reducing addiction stands to benefit all.
6.7 Discussion
References
Anawalt PR, Berdan FF (1992) The Codex Mendoza. Sci Am 266(6):70–79
Azrin NH (1976) Improvements in the community-reinforcement approach to alcoholism. Behav
Res Ther 14:339–348
Barry DT, Savant JD, Beitel M, Cutter C, Moore BA, Schottenfeld RS et al (2012) Use of
conventional, complementary, and alternative treatments for pain among individuals seeking
primary care treatment with buprenorphine-naloxone. J Addict Med 6(4):274–279
Bean MH, Zinberg NE (eds) (1981) Dynamic approaches to the understanding and treatment of
alcoholism. The Free Press, New York
Bennett LA, Ames GM (1985) In: Bennett LA, Ames GM (eds) The American experience with
alcohol: contrasting cultural perspectives. Plunum, New York, p 315
Berne E (1961) Transactional analysis in psychotherapy. Grove, New York
Berne E (1964) Games people play – the basic handbook of transactional analysis. Ballantine
Books, New York
Bride BE, Abraham AJ, Roman PM (2010) Diffusion of contingency management and attitudes
regarding its effectiveness and acceptability. Subst Abus 31:127–135
Castaneda R, Lifshutz H, Galanter M, Franco H (1994) Empirical assessment of the self-
medication hypothesis among dually diagnosed inpatients. Psychiatry 35(3):180–184
Cornish R, Macleod J, Strang J, Vickerman P, Hickman M (2010) Risk of death during and after
opiate substitution treatment in primary care: prospective observational study in UK general
practice research database. BMJ 341:c5475
Coviello DM, Alterman AI, Cacciola JS, Rutherford MJ, Zanis DA (2004) The role of family
history in addiction severity and treatment response. J Subst Abuse Treat 26(1):303–313
Dumont M (1967) Tavern culture: the sustenance of homeless men. Am J Orthopsychiatry
37:938–945
ElGuebaly NA, Walker JR, Ross CA, Currie RF (1990) Adult children of problem drinkers in an
urban community. Brit J Psychiatry 156:249–255
Fagan J (1989) The social organization of drug use and drug dealing among urban gangs.
Criminology 27(4):633–669
Farber LH (1956) Martin Buber and psychiatry. Psychiatry 19(2):109–120
Farrell M, Marsden J (2008) Acute risk of drug-related death among newly released prisoners in
England and Wales. Addiction 103(2):251–255
6 Social Aspects of Addiction and Environmental Strategies 105
Favazza A, Thompson JJ (1984) Social networks of alcoholics: some early findings. Alcohol Clin
Exp Res 8:9–15
Foulks EF (1989) Misalliances in the Barrow Alcohol Study. Am Indian Alsk Native Ment Health
Res 2(3):7–17
Galanter M (1993) Network therapy for alcohol and drug abuse. Basic Books, New York
Hughes PH, Parker R, Senay EC (1974) Addicts, police, and the neighborhood social system. Am
J Orthopsychiatry 44(1):129–141
Kinzie JD, Leung PK, Boehnlein J, Matsungaga D, Johnson R, Manson S et al (1992) Psychiatric
epidemiology of an Indian village: a 19-year replication study. J Nerv Ment Dis 180(1):33–39
Lowinger P (1977) The solution to narcotic addiction in the People’s Republic of China. Am
J Drug Alcohol Abuse 4:165–178
O’Farrell TJ, Cowles KS (1989) Marital and family therapy. In: Hester R, Miller WR (eds)
Handbook of alcoholism treatment approaches. Pergamon Press, New York, pp 183–205
Pattison EM (1977) Clinical social systems interventions. Psychiatry Digest 38:25–33
Schwartz S, Gatto NM, Campbell UB (2011) What would have been is not what would be. In:
Schrout PE, Keyes KM, Ornstein K (eds) Causality and psychopathology. Oxford University
Press, Oxford, pp 25–46
Smart RG, Murray GF (1983) Drug abuse and affluence in five countries: a study of economics and
health conditions, 1960–1975. Drug Alcohol Depend 11:297–307
Speck RV, Attneave CL (1973) Family networks. Pantheon, New York
Sutker PB, Archer RP, Allain AN (1980) Psychopathology of drug abusers: sex and ethnic
considerations. Int J Addict 15:605–613
Suwanwela C, Poshyachinda V (1986) Drug abuse in Asia. UN Bull Narc 38(1, 2):41–53
Ticho EA, Wnnicott DW (1974) Martin Buber and the theory of personal relationships. Psychiatry
37(3):240–253
Westermeyer J (1981) Opium availability and prevalence of addiction in Asia. Brit J Addict
76:85–90
Westermeyer J (1982) Poppies, pipes and people: opium and its use in Laos. University California
Press, Berkeley
Westermeyer J (1987) Cultural patterns of drug and alcohol use: an analysis of host and agent in
the cultural environment. UN Bull Narc 39(2):11–27
Westermeyer J (1999) The role of cultural and social factors in the cause of addictive disorders.
Psychiatr Clin N Am 22(2):253–273
Westermeyer J, Neider J (1988) Social network and psychopathology among substance abusers.
Am J Psychiatry 145(10):1265–1269
Westermeyer J, Walzer V (1975) Sociopathy and drug use in a young psychiatric population. Dis
Nerv Syst 36(12):673–677
Westermeyer J, Myott S, Aarts R, Thuras P (2001) Self-help strategies among substance abusers.
Am J Addict 10(3):249–257
Willenbring ML (1995) Case management applications in substance use disorders. J Case Manag
3:150–157
Cultural Aspects and Responses
to Addiction 7
Robin Room
Contents
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
7.2 Cultural Expectations About and Definitions of Psychoactive Substances and
Their Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
7.3 Norms Concerning Use and Related Behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
7.4 Cultural Factors in Responses to Substance Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
7.5 Intercultural Influences and Diffusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Abstract
The use of psychoactive substances and our interpretations of the effects of the
substances are affected by culture, defined broadly to include social worlds and
subcultures as well as tribal, societal, and linguistic groupings. Prototypical
patternings of use include medicinal use, customary regular use, and festival
and other intermittent uses (where the psychoactivity is most attended to).
A fourth pattern, addictive or dependent use, was a conceptualization arising
after the Enlightenment. Cultural norms may both encourage and discourage use
and heavy use and may make the use more or less problematic. Cultural factors
also shape responses to substance use, including the social handling of problem-
atic situations and persons. Thus, there are characteristic differences between
cultures in the institutional and professional location of the handling of sub-
stance use problems. In the modern world, there is substantial diffusion of
practices and understandings between cultures, and in multicultural societies,
R. Room
Centre for Alcohol Policy Research, Turning Point, Fitzroy, VIC, Australia
Melbourne School of Population and Global Health, University of Melbourne, Carlton, VIC,
Australia
Centre for Social Research on Alcohol and Drugs, Stockholm University, Stockholm, Sweden
e-mail: [email protected]
7.1 Introduction
1
See “Buying and accepting drinks” thread on http://forums.plentyoffish.com/
datingPosts8464582.aspx (accessed 16 June, 2013).
7 Cultural Aspects and Responses to Addiction 109
Conceptualizing repeated heavy use in terms of addiction means that the categori-
zation becomes an explanation – an explanation of why the pattern of use continues,
despite problems resulting from the use for the individual and often for others. The
concept thus focuses not on the pattern of use in itself, but rather on an apparent
inability to control or refrain from use despite adverse consequences.
The addiction concept became established for alcohol in general understandings
of European societies in the period after the Enlightenment. Particularly as tem-
perance movements sprang up in response to the waves of very heavy alcohol
consumption that accompanied the Industrial Revolution, the addiction idea came
into common use as an explanation of why backsliding was common among
temperance members who had pledged to give up drinking (Levine 1978; Room
2003). In the late nineteenth century, the concept was extended by doctors to cover
other psychoactive substances, and more recently popular and professional dis-
course has commonly applied it also to other behaviors (Marks 1990; Saı̈et 2011),
though not without dispute (Jaffe 1990). Though the concept has diffused into many
cultures, there are substantial differences in cultural understandings of what it
characterizes and implies (Room 2006).
are inverted immediately afterward to prove the liquor is gone” (Williams 1998).
Among young adult Italians, as also elsewhere in Europe, drinking games, enforced
as a group ritual, serve the function of “becoming drunk quickly so as to amplify the
effects of drinking: less shyness and disinhibition” (Beccaria and Guidoni 2002).
Cultural expectations may thus facilitate heavy drinking and even enforce it, so that
in some circumstances addiction or dependence might better be described as
located at collective levels rather than in the individual’s mind or body (Room
1973). This idea is carried by the French term alcoolisation, used concerning
a society such as France when alcohol consumption was at its highest there in the
1950s (Jellinek 1954).
No man is an island, and no cultural group in the modern world is completely on its
own. A particular solution to a set of problems worked out in the cultural conditions
of one society may travel far. Thus there is much about the ideas and organization
of Alcoholics Anonymous that reflects cultural understandings and practices in
a particular society, the United States (Mäkelä et al. 1996; Room 1993). But AA has
diffused widely across the world, into cultures with considerable differences from
US society. Even so, it is clear that the patterns of diffusion of AA show some
regularities in terms of which societies it has flourished in, and these regularities tell
us something both about core characteristics of AA and about patterns of culture
(Mäkelä 1991). And to some extent, AA practices have been adapted to the local
culture (Eisenbach-Stangl and Rosenqvist 1998). Furthermore, even where AA was
seen as culturally alien in some way, the news of its existence stimulated adapta-
tions seen as more culturally congenial – and often the outcome has been AA and
the adaptation coexisting side by side (Room 1998).
We have already mentioned above the tendency of cultural groups in multicul-
tural societies to define themselves in distinction from each other, with drinking or
drug use practices fairly often used as markers of the distinctions. On the other
hand, it is clear that there is also some assimilation: Immigrant groups take on
practices from the receiving society, often forming a new cultural bricolage (Room
2005). Influences and diffusion are also common between societies and cultures.
Such influences are carried by four major forces: mass media, producers and other
economic actors, intergovernmental bodies and agreements, and the professions.
News reports, television and film entertainment, and now also Internet channels
convey information and images between cultural groups, perhaps particularly
between youth cultures in different societies. In an increasingly globalized world
with diminishing trade barriers, global corporations and other economic actors
(and their equivalents for illicit drug markets) actively and tirelessly try out
promotion methods and materials which have worked elsewhere in new cultural
settings. Dissemination and influence also flow through the international drug and
tobacco treaties and the agencies which implement them, as well as increasingly
through other agencies such as international nongovernmental organizations in a
7 Cultural Aspects and Responses to Addiction 113
References
Anonymous (1662) The book of common prayer ... according to the use of the Church
of England.... John Baskerville, Cambridge. http://justus.anglican.org/resources/bcp/1662/
Baskerville.pdf
Babor T, Caulkins J, Edwards G, Fischer B, Foxcroft D, Humphreys K, Obot I, Rehm J, Reuter P,
Room R, Rossow I, Strang J (2010) Drug policy and the public good. Oxford University Press,
Oxford
Baumohl J, Room R (1987) Inebriety, doctors and the state: alcoholism treatment institutions
before 1940. In: Galanter M (ed) Recent developments in alcoholism, vol 5. Plenum,
New York, pp 135–174
Beccaria F, Guidoni OV (2002) Young people in a wet culture: functions and patterns of drinking.
Contemp Drug Probl 29:305–334
Bruun K (1971a) Finland – the non-medical case. In: Kiloh LG, Bell DS (eds) 29th international
congress on alcoholism and drug dependence. Sydney, Australia, February, 1970.
Butterworths, Chatswood, pp 545–559
Bruun K (1971b) Implications of legislation relating to alcoholism and drug dependence: govern-
ment policies. In: Kiloh LG, Bell DS (eds) 29th international congress on alcoholism and drug
dependence. Sydney, Australia, February, 1970. Butterworths, Chatswood, pp 173–181
Bunce R (1979) Social and political sources of drug effects: the case of bad trips on psychedelics.
J Drug Issues 9(2):213–233
Cavan S (1966) Liquor license: an ethnography of bar behaviour. Aldine, Chicago
Eisenbach-Stangl I, Rosenqvist P (eds) (1998) Diversity in unity: studies of Alcoholics
Anonymous in eight societies. NAD publication no. 33. Nordic Council for Alcohol & Drug
Research, Helsinki
Greenfield T, Room R (1997) Situational norms for drinking and drunkenness: trends in the
U.S. adult population, 1979–1990. Addiction 92:33–47
Hemström O € (2002) Informal alcohol control in six EU countries. Contemp Drug Probl
29:577–604
Hradilova Selin K, Holmila M, Knibbe R (2009) Informal social control of drinking in intimate
relationships – a comparative analysis. Contemp Drug Probl 36:31–59
Jaffe J (1990) Trivializing dependence. Br J Addict 85:1425–1427
Jellinek EM (1954) International experience with the problem of alcoholism. Prepared for the joint
meeting of expert committee on mental health and on alcohol, Geneva, 27 September–2 October
1954. World Health Organization, Geneva, WHO/MENT/58 & WHO/APD/ALC/12, 2 June
Kerr N (1888) Inebriety, or narcomania: its etiology, pathology, treatment and jurisprudence,
3rd edn. J. Selwin Tait and Sons, New York
114 R. Room
Klingemann H, Hunt G (eds) (1998) Drug treatment systems in an international perspective: drugs,
demons and delinquents. Sage, Thousand Oaks
Klingemann H, Takala J-P, Hunt G (eds) (1992) Cure, care or control: alcoholism treatment in
fourteen countries. State University of New York Press, Albany
Levine HG (1978) The discovery of addiction: changing concepts of habitual drunkenness in
American history. J Stud Alcohol 39:143–174
MacAndrew C, Edgerton R (1969) Drunken comportment: a social explanation. Aldine, Chicago
Mäkelä K (1991) Social and cultural preconditions of Alcoholics Anonymous (AA) and factors
associated with the strength of AA. Br J Addict 86(11):1405–1413
Mäkelä K, Arminen I, Bloomfield K, Eisenbach-Stangl I, Helmersson Bergmark K, Kurube N,
Mariolini N, Ólafsdóttir H, Peterson JH, Phillips M, Rehm J, Room R, Rosenqvist P,
Rosovsky H, Stenius K, Świa˛tkiewicz G, Woronowicz B, Zieliński A (1996) Alcoholics
Anonymous as a mutual-help movement: a study in eight societies. University of Wisconsin
Press, Madison/London
Marks I (1990) Behavioural (non-chemical) addictions. Br J Addict 85:1389–1394
Rittel HWJ, Webber MW (1973) Dilemmas in a general theory of planning. Policy Sci 4:155–169
Robicsek F (1978) The smoking gods: tobacco in Maya art, history and religion. University of
Oklahoma Press, Norman
Room R (1973) Social psychology of drug dependence. In: the epidemiology of drug dependence:
report on a conference: London 25-29 September, 1972. Regional Office for Europe, World
Health Organization, Copenhagen, pp 69–75
Room R (1993) Alcoholics Anonymous as a social movement. In: McCrady BS, Miller WR (eds)
Research on Alcoholics Anonymous: opportunities and alternatives. Rutgers Center of Alcohol
Studies, New Brunswick, pp 167–187
Room R (1998) Mutual help movements for alcohol problems in an international perspective.
Addict Res 6:131–145
Room R (2001) Intoxication and bad behaviour: understanding cultural differences in the link. Soc
Sci Med 53:189–198
Room R (2003) The cultural framing of addiction. Janus Head 6:221–234
Room R (2005) Multicultural contexts and alcohol and drug use as symbolic behaviour. Addict
Res Theory 13:321–331
Room R (2006) Taking account of cultural and societal influences on substance use diagnoses and
criteria. Addiction 101(Suppl 1):31–39
Saı̈et M (2011) Les Addictions [The addictions]. Que-sais-je? series no. 3911. Presses
Universitaires de France, Paris
Shibutani T (1955) Reference groups as perspectives. Am J Sociol 60:562–569
Træen B, Hovland A (1998) Games people play: sex, alcohol and condom use among urban
Norwegians. Contemp Drug Probl 25:3–48
Unruh DR (1980) The nature of social worlds. Pac Sociol Rev 23(3):271–296
Wasson RG (1984) Distilled alcohol dissemination. Drinking Drug Pract Surv 19:6
Williams DM (1998) Alcohol indulgence in a Mongolian community of China. Bull Concern
Asian Sch 30:13–22
Zinberg N (1986) Drug, set, and setting: the basis for controlled intoxicant use. Yale University
Press, New Haven
Prevention Strategies and Basics
8
Gregor Burkhart and Roland Simon
Contents
8.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
8.1.1 Neuroscience and Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
8.1.2 Logic Frame . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
8.1.3 Assessing the Effectiveness of Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
8.2 Prevention Strategies: Definitions and Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
8.2.1 Mass Media Campaigns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
8.2.2 Environmental Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
8.2.3 Universal Prevention: Intervening with Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
8.2.4 Selective Prevention: Intervening with (Vulnerable) Groups . . . . . . . . . . . . . . . . . . . 127
8.2.5 Family-Based Prevention: Universal and Selective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
8.2.6 Indicated Prevention: Intervening with (Vulnerable) Individuals . . . . . . . . . . . . . . . 132
8.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
Abstract
Prevention has the potential to be effective in changing substance use and related
behaviors such as delinquency, violence, and sexual behavior. Interventions that
achieve this do not solely inform people about the dangers of drugs but also
focus on the key determinants of successful socialization, now confirmed by
neuropsychological research: social norms and control, executive and social
skills, as well as impulse control. Thus, universal prevention addresses the
population at large and targets the development of skills and values, norm
perception, and interaction with peers and social life; selective prevention
addresses the vulnerable groups where substance use is often concentrated and
focuses on improving their opportunities in difficult living and social conditions;
and indicated prevention addresses vulnerable individuals and helps them to deal
and cope with the individual personality traits that make them more vulnerable
to escalating drug use. While these prevention types predominantly use persua-
sion, prevention can complementarily and effectively change human behavior
by modifying its social, physical, and economic context. Environmental preven-
tion uses these means to subtly alter social cues and norms and their perception.
Effective examples range from intervening at society level through market
regulations of alcohol and tobacco, changing the physical environment of
party settings, to more rule setting and monitoring within families. The challenge
for drug prevention lies therefore in helping people to adjust their behavior,
capacities, and well-being in fields of multiple influences – such as social norms,
interaction with peers, living conditions, and their own personality traits – in
order to reduce risk behaviors related to substances.
8.1 Introduction
prevention professionals still see substance use as the main risk factor for
substance use disorders and addiction and therefore conclude either that substance
use must be prevented altogether or that it must be detected early and discouraged.
While early use is a necessary step, other variables may be of crucial importance in
the transition from use to substance use disorder. In fact, the same variables that
predict initial acute drug effects and early use may significantly contribute to
continued use, escalation, and dependence (De Wit and Phillips 2012). Traditional
prevention work focuses exclusively on substance use and is based on a stage model
where the use of legal substances precedes and anticipates the use of illicit drugs.
More recent research has introduced an alternative view, the common liability
model, which suggests that early-manifesting personality traits such as
neurobehavioral (i.e., cognitive, affective, and behavioral) disinhibition predict
both early initiation of substance use and rapid escalation into problem use. Other
problem behaviors can also have this effect, especially if both parents have
a substance use disorder (SUD). Longitudinal, prospective studies with Finnish
twins found that the liability to initiate tobacco smoking predicts illicit drug use and
suggested that shared genetic and environmental influences may be related to the
use of tobacco and illicit drugs (Huizink et al. 2010). Early externalizing behavior
also suggests significant and shared underlying genetic and environmental influ-
ences that may lead to later substance use (Korhonen et al. 2012).
Other personality traits, such as high levels of pleasure seeking and low levels of
shyness and avoidance, have shown in prospective studies to increase the risk of
progressing from smoking to several measures of cannabis use (Creemers
et al. 2009). A longitudinal study (Malmberg et al. 2012) showed that hopelessness
and sensation seeking were predictive for using alcohol and tobacco. The latter was
also correlated with marijuana use.
In a recent paper, Sloboda et al. (2012) provide an exhaustive revision of the risk
factor models relevant for prevention, which include many developmental factors
in early childhood that interact with environmental factors in family and school in
later childhood and adolescence.
Instead of targeting drug users generally, these findings point to a need for more
sophisticated prevention interventions that specifically target individual vulnera-
bility traits that are not a priori substance use related. This is the premise for
indicated prevention.
Each part in Sect. 2 refers to the available evidence and describes trends and
examples. As the majority of prevention activities focus in practice on substance
use and problem behavior in general, they do not differentiate between alcohol,
tobacco, and illicit drugs.
While there has been a long-standing tradition in the field of prevention of welcoming
any type of preventive measures – taking the good will for good results – evidence is
now playing a crucial role in prevention work. However, the very nature of the
intervention and target behavior makes research even more challenging than in the
fields of treatment or harm reduction. Most prevention strategies address their target
group at a very young age. This implies that there will be a long period of time
between intervention and assessment of the outcome, which is a challenge to
methodology (many influences will have to be taken into account), sample size
(which inevitably shrinks over time), and research funding and organization. In all
fields of research such long-term follow-ups are extremely rare. Prevention also tends
to be generic, while outcome behaviors with respect to drug use and drug-related
problems are specific. This again makes it more difficult for research to prove
a logical link between intervention and envisaged outcomes. The conclusion drawn
from this long list of difficulties and problems is not to discredit prevention inter-
ventions because they are difficult to evaluate but instead that existing findings should
be critically evaluated to try to further improve the available evidence.
A worrisome case study for this is the evaluation of the National Youth
Anti-Drug Media Campaign (1998–2004) in the USA (Hornik et al. 2008). It
found – besides zero effects overall – that greater exposure to the campaign was
associated with increasing intention to use cannabis (and even actual use) in some
subgroups that previously had little interest in the drug. The analysis found evi-
dence that these effects were due to an increase in the perceived popularity and
prevalence of marijuana use through the campaign. Also, in the evaluation of
Scotland’s Know the Score cocaine campaign, Binnie et al. (2006) found that
11 % of those exposed to it claimed that they were more likely to use cocaine
after the campaign compared to before. There is another reason for being cautious
with warning campaigns that, for example, describe the negative outcomes of first
using marijuana. If non-using adolescents realize that the harms of marijuana use
are not as grave as they had been led to expect, their intention to use it might
intensify considerably (Skenderian et al. 2008).
It is an important ethical concern that mass media campaigns may have iatro-
genic effects – by increasing normative beliefs, resulting in higher intentions to use.
This is even more problematic in this case, as the target population has typically not
requested this (potentially harmful) kind of social intervention, and the organization
funding and/or running the campaign has taken the initiative.
Against this background, the lack of adequate evaluations of media campaigns is
even less acceptable – in Europe, only the Netherlands and Scotland/the UK have
assessed effects of these campaigns on behavior or intentions, while the large
majority of reported campaigns have not been evaluated at all. A few evaluations
in Europe (Bulgaria, Denmark, France, Netherlands, Sweden, and the UK) have
merely assessed how people perceive the campaign and its impact on their knowl-
edge but were not able to assess if people changed their attitude or behaviors in the
intended direction.
behavior, such as images and associations or the observed behavior of others. Since
certain industries try to use these cues in their own interest, the term “industrial
epidemics” has been coined for obesity, tobacco, and alcohol use (Jahiel and Babor
2007). Public regulation and market intervention are seen as the only evidence-
based mechanisms to prevent the harm caused by commodity industries (Moodie
et al. 2013). But efforts to create protective and positive school and family climates
also belong to environmental prevention. Their modus operandi is not persuasion
but positive “scaffolding” in the sense of providing opportunities, stimuli, and
encouragement for change in confined contexts.
policies on tobacco smoking were introduced, one might assume some link between
trends in the use of licit and illicit substances (Fig. 8.1).
Besides the perceived availability of substances, normative environmental aspects
such as cultural values, descriptive norms, and the social acceptance of use seem to
influence initiation into problem behavior and substance use (for more details on this,
see ▶ Chap. 9, “Regional and Cultural Aspects of Prevention” in this book). Kuntsche
and Jordan (2006) confirmed that close contact with substance-using peers is strongly
related to individual substance use. Students who saw others attending school while
intoxicated with cannabis, or taking cannabis on the school premises, used more
cannabis themselves and had more cannabis-using peers. Similar relations were not
found for alcohol. The authors suggest establishing an overarching environment of
disapproval as an effective means of preventing cannabis use by adolescents.
Normative beliefs are important factors in the success or failure of interventions,
and prevention work needs to address them (McAlaney et al. 2011). While several
studies confirm that behavioral change is mediated by descriptive norms, the social
norms approach has to be used with caution as social groups may also develop
minority norms that deliberately deviate from the healthy descriptive norm that is
being promoted. According to optimal distinctiveness theory, people adhere to
social norms of highly valued groups that can simultaneously satisfy their needs
to belong and to be different. For instance, messages that portray nonusers as a large
and undifferentiated majority may not be as successful as messages that emphasize
the uniqueness of nonusers (Comello 2011).
confirmed this prevention paradox for adolescent boys and girls for measures of
annual consumption and heavy episodic drinking; similar results were found in
Brazil. There is also some evidence for the validity of this phenomenon for other
substances. Stockwell et al. (2004) confirmed it for regular tobacco, alcohol, and
cannabis use among 15- to 16-year-olds. Still, there are limitations to this concept.
A minority of people with frequent heavy episodic drinking accounted for a large
proportion of all problems in one study (Danielsson et al. 2012), and Stockwell
et al. (2004) found that most illicit drug use occurred in the high-risk group, 15 % of
the sample.
The practical consequence of the prevention paradox is that all available
approaches should be used: environmental and universal prevention strategies
should aim to reduce initiation and overall levels of substance use, and targeted
strategies should address particularly vulnerable subgroups and individuals,
addressing harm related to early-age drug use or frequent cannabis use.
In summary, there is evidence for the beneficial effects of environmental
prevention at the macro level (the state), at the meso level (recreational
settings and schools), and above all at the microlevel (in families); and there are
beneficial effects beyond substance use alone. More elements of environmental
prevention should therefore be used to complement and support persuasive
prevention strategies. It should be noted, however, that vulnerable subgroups and
individuals also need targeted interventions, which will be described in the
following sections.
The concepts of universal, selective, and indicated prevention are used to
classify different preventive approaches in the following sections, based on differ-
ences in the vulnerability (and risk) of the target group. For universal prevention, all
members of the population are assumed to share the same general risk for substance
use problems, although the risk may vary greatly between individuals. Selective
prevention applies social and demographic indicators that roughly indicate
increased levels of vulnerability among some groups such as marginalized ethnic
minorities, youth in deprived neighborhoods, young (drug law) offenders, vulner-
able families, or some settings (such as clubbing environments). While these, often
readily available, institutional or demographic indicators can help to identify
groups where problem drug use is more likely to be concentrated, they cannot tell
us anything about the vulnerability of any individual in such a group. In indicated
prevention, however, vulnerable individuals are screened and needs have to be
defined on the basis of “properly diagnosed” risk conditions, such as attention
deficit disorder or conduct disorder.
vulnerable groups as being young (drug law) offenders, youth in deprived neighbor-
hood, homeless youth, some ethnic minorities and immigrant groups, school drop-
outs, students who are failing academically, and vulnerable families. These
vulnerable groups are mostly identified using social, demographic, or environmental
risk factors known to be associated with SUD. Targeted subgroups may be defined
by family status or place of residence, such as living in deprived neighborhoods or
areas with high drug use or trafficking. This means that prior to providing the
intervention, the situation and vulnerability pattern of a given target group has to
be studied. This clearly differs from universal prevention, where universal risk
factors are addressed. Since this vulnerability assessment relies on social and demo-
graphic characteristics at the group level, individual risk cannot be assessed.
Implementing experimental evaluation designs with groups that are often hard to
reach is extremely difficult and frequently impossible. For this reason, evidence for
the effectiveness for selective prevention is currently limited. However, the Amer-
ican cross-site evaluation of interventions for high-risk youth, together with Euro-
pean (Jones et al. 2006; Roe and Becker 2005) and American (Hansen et al. 2007;
Sussman et al. 2004) reviews of the evidence, allowed effective elements of such
interventions with vulnerable populations to be identified.
Effective elements include changing access within the environment, promoting
the development of personal and social skills, promoting positive relations in
families, addressing social influences, providing social support and helping partic-
ipants to develop goals and alternatives, developing positive schools, and enhanc-
ing motivation to avoid substance use (Hansen et al. 2007). The effective
components in selective prevention – inside and outside school settings – seem to
be virtually the same as in universal prevention. Interventions that do not solely
address drug use, adapt to young people’s experiences, and avoid rigid abstinence-
oriented messages have proven to be more effective. They address social needs
connected to drug use, rather than drug use behavior (Steiker 2008). After all, drug
use in these populations should be considered as just one of several expressions of
behavioral maladjustment. The specific challenge lies in targeting the right group
with the right type of prevention intervention and delivering the effective compo-
nents in appropriate ways. Vulnerable groups are often not so easily “available” as
pupils in schools and typically do not approach public services.
In summary, prevention that targets vulnerable people may moderate the effect
of an early developmental disadvantage, its translation into social marginalization,
and progression into substance abuse. Several research studies have shown that
interventions delivered during the early school years that aimed to improve educa-
tional environments and reduce social exclusion also had a moderating effect on
later substance use (Toumbourou et al. 2007), without specifically targeting youth
who experiment with drugs.
Although often unacknowledged, outcomes of the prevention programs
described here can also be beneficial in behavioral domains beyond substance
use, such as the prevention of violence, delinquency, academic failure, teenage
pregnancies, and unprotected sex. Substance use prevention professionals are often
unaware that smoking, drinking, safe sex, and healthy nutrition among adolescents
8 Prevention Strategies and Basics 129
Many parents in the Western world tend to assume that a close, warm, and open
relationship with their children is protective against SUD, by providing them with
a space to test their own boundaries. Recent research has provided considerable
support for the idea that not only parental support but also monitoring and control
are strong determinants of lower prevalence levels of adolescent risk behavior.
There is now a plethora of studies on the relationship between parental styles and
their offspring’s drug use. They classify parental behavior on two axes,
warm–distant and strict–lenient. Research indicates that the authoritative style
(strict and warm) is the most protective against substance use, while the neglectful
style (lenient and distant) increases the risk of drug use; research on the authori-
tarian and permissive styles is as yet inconclusive. Factors beyond parenting style,
such as parents’ drug use, emotional support and warmth, family structure, and
influence of culture, need to be taken into consideration (Becoña et al. 2012).
For instance, Van der Vorst et al. (2006) suggest that clear rules about alcohol
drinking in families are protective, while talking about alcohol and its risks proved
130 G. Burkhart and R. Simon
to alcohol use and harmful use in a very similar way, but adult-supervised alcohol
use resulted in higher levels of harmful alcohol consequences. This challenges the
assumption that supervised alcohol use or early-age alcohol use would reduce
the development of adolescent alcohol problems. Both Mediterranean drinking
cultures and Danish drinking parties where parents organize and supervise
alcohol consumption among their teenage offspring are based on this rationale.
A large European study (Kuntsche and Kuendig 2006) confirmed that the percep-
tion of excessive drinking in a family is more closely related to both frequent and
excessive drinking than to family structure, but family bonding was even more
closely related than drinking perception. The findings underline – for European
contexts – the importance of factors related to family life and support that minimize
the risk of frequent and excessive drinking despite given risk factors (Kuntsche and
Kuendig 2006).
In terms of prevention practice, the question again arises of how parental control,
warmth, rules, and monitoring can be increased or strengthened by interventions
and how these interventions should be delivered and to which families. The analysis
by Hemovich et al. (2011), for example, found that single-parent families and those
with lower incomes provided less monitoring, which was related to more drug use,
but not less warmth. This leads back to the importance of distinguishing between
universal family-based approaches that target all parents and those selective ones
designed for the more vulnerable families that have fewer financial, personal, and
time resources.
Most of the effective family-based programs contain elements of monitoring,
rule-setting, and contingency management. Some of them – such as the Strength-
ening Families Program (SFP) – were originally designed for the most vulnerable
families. In systematic reviews (Foxcroft and Tsertsvadze 2011b; Petrie
et al. 2007), the SFP was considered effective in preventing substance
use – including over the long term – and other problem behaviors. It seems to be
the only program to demonstrate in randomized control trials improvements in the
outcomes for the children, in addition to improved parenting skills and reductions in
child maltreatment. Particularly, selective family-level interventions might not
demonstrate benefits where they are applied more universally to include families
with very low rates of problems at child or family level. However, addressing all
families using a universal prevention approach might allow more vulnerable fam-
ilies to adopt educational, normative, and behavior models from the more conven-
tional families in the same group, so that often the more vulnerable families profit
most from such programs. Depending on how they are delivered, some universal
programs might predominantly attract the well-off, low-risk families; however,
effective (often selective) programs tackle this imbalance by offering transporta-
tion, child-care, and food at the venues – elements that might be essential for
families in need.
A systematic review (Broening et al. 2012) of programs for substance-affected
families found interventions to be effective when their duration was longer than
10 weeks and when they involved children’s, parenting, and family skills training
components. Proximal outcomes (e.g., knowledge, coping skills, family relations)
132 G. Burkhart and R. Simon
showed better results than more distal outcomes (e.g., self-worth and substance use
initiation). Apart from a few studies, the long-term effects on young people’s
substance use, delinquency, mental health, physical health, and school performance
have rarely been assessed in the evaluations.
The need to break intergenerational cycles of poor parenting practices was
addressed by Hill et al. (2010), who examined the extent to which interactions
between behavioral disinhibition, behavioral inhibition, and family management
during adolescence (from age 10) predict alcohol abuse and alcohol dependence at
age 27. Young people who were high in behavioral disinhibition were at increased
risk of later alcohol abuse and dependence, but only in consistently poorly managed
family environments, while in consistently well-managed families, high levels of
behavioral disinhibition did not increase the risk of later alcohol abuse or
dependence.
Overall, across universal and selective interventions, there is good evidence
from Cochrane Reviews that family-based prevention interventions are effective
in reducing young people’s alcohol, tobacco, and drug use (Foxcroft and
Tsertsvadze 2011a; Gates et al. 2007).
8.3 Conclusion
Prevention has developed and made some progress in recent years, but there is still
quite a lot of room for improvement. Overall, universal prevention seems to be
dominated by interventions that might attract public attention but are not likely to
be effective in preventing drug use. Policy interest in selective prevention has
increased in the same period, but this has not translated into more interventions
for vulnerable youth or more evaluation research. Finally, there has been some
recent interest in indicated prevention in Europe. Here, well-designed evaluation
studies have taken place, but the intervention coverage as such is still limited to
only a few countries. Too many prevention interventions continue to appeal to
cognitive processes only, namely, information provision, regardless of the negative
evidence that has been reported about such interventions.
With the arrival of the phenomenon of “legal highs” and continuously innovat-
ing synthetic psychoactive substances offered on a globalized market, this weakest
8 Prevention Strategies and Basics 135
of all prevention paradigms has been revived, and once again decision makers seem
to be convinced that prevention funds are best spent in detecting, assessing, and
warning youth about the dangers of these new substances. Policymakers and pro-
fessionals have only reluctantly begun to acknowledge that social norms and their
perception (environmental prevention) as well as impulse control (indicated pre-
vention) are powerful determinants of adolescent behavior. The potential for using
emotional and unconscious processes in prevention is virtually unacknowledged,
while implicit cognition is regularly used in advertisement and marketing in order
to boost consumption. Reviews found the largest effect sizes in studies that assessed
implicit semantic associations employed word association measures and focused on
marijuana use, suggesting that implicit cognition is a reliable predictor of substance
use (Rooke et al. 2008). Only a few prevention approaches, particularly in the
alcohol field, use techniques that aim to reverse the influence of the
abovementioned unconscious cues by attempts to change learned associations,
attention biases, and implicit attitudes.
In terms of gender differences, a number of program evaluations found, overall,
less or no effects for girls (Kumpfer et al. 2008; Poduska et al. 2008; Vigna-
Taglianti et al. 2009). One possible explanation might be a lower vulnerability at
baseline, which could also reflect the fact that neurobehavioral disinhibition is
found more frequently in boys. Alternative hypotheses are that these interventions
are less appealing to girls or that the timing of delivery with regard to their
cognitive, social, and emotional development is less appropriate, since girls mature
earlier (Vigna-Taglianti et al. 2009). Kelly et al. (2011) found that girls’ alcohol use
was – compared to boys – more influenced by high-risk peer networks, while
parental disapproval was less protective for them, compared to boys. So girls
who, overall, use psychoactive substances less and have fewer problems might
also gain less from existing prevention programs.
Reflecting the criticism that prevention is only abstinence oriented and is inap-
propriate to contemporary youth’s need to acquire risk competence, the term “risk
reduction” has been coined as a viable alternative for vulnerable or drug-using youth,
as an analogy to what harm reduction would be in relation to treatment. However, the
evidence, intervention examples, and theoretical frameworks discussed in this chap-
ter show that “risk reduction” is intrinsically included in all prevention measures.
Most prevention intervention in fact do not simply strive for abstinence but try to
delay initiation, achieve generally better behavioral control and adequate socializa-
tion, or avoid rapid escalation from experimental use into SUD or even addiction,
hence reducing risk and harms. Risk reduction can hardly be seen as separated from
prevention, while such “harm reduction” approaches within prevention might only be
effective and acceptable when targeted at older adolescents (over the age of 14) but
not for younger adolescents (Poulin and Nicholson 2005).
As described above, there are still a number of limitations in the evidence behind
prevention interventions. Nevertheless, given the limited number of options available
for tackling addiction problems, one cannot only rely on treatment and harm reduc-
tion. Recent discussions about “recovery,” in particular, bring us back to approaches
that target a life free from the negative impacts of addictive substances and behaviors.
136 G. Burkhart and R. Simon
While treatment is based on the informed consent of the treated person, preven-
tion interventions are usually the result of a unilateral decision taken by experts or
policymakers, based on their assumption that an intervention will have positive
effects on the targeted person and/or the social environment. While parents and
teachers might take such a decision “on behalf” of their children and pupils,
for adult target groups the responsibility clearly lies with experts and policymakers.
As has been shown for mass media campaigns, the question of responsibility and
consent is not an academic one, as iatrogenic effects of preventive interventions are
possible. It is crucial, therefore, that decision makers take a well-informed position
on behalf of their citizens in such instances.
As has been seen, especially in selective and indicated prevention, there is
a considerable overlap between treatment and prevention. In many cases prevention
offers an improved understanding of an individual’s situation, a self-examination, or
test, which might lead to treatment. A good example of this is treatment programs for
cannabis users offered via the Internet, which frequently start as self-tests and may
end up with a one-to-one treatment arrangement. Motivational interviewing can be
used as a tool helping to bridge the gap between prevention and treatment.
While prevention has been traditionally linked to school curricula, TV, and
information campaigns, the range of media and approaches now available has wid-
ened considerably. Web series, avatars, contacts, and information provided via SMS
or Twitter are no longer considered new approaches and have now become part of the
toolbox for prevention specialists. At the same time – also based on neuropsycholog-
ical findings – prevention has become more unified, and a number of problematic
behaviors, including destructive and violent behavior, substance use, and patholog-
ical use of computer games and the Internet, are today targeted with the same
interventions. The need for a strong evidence base, critical reflection of practice,
and adequate training of the staff involved remains central to all these approaches.
As we have seen in various sections of this chapter, social norms have a strong
influence on behavior, suggesting that the effect of informal social control and
social sanctions (from family and peers) may be more important than the certainty
and severity of formal sanctions. These examples illustrate that comprehensive
prevention policies ought not only to address individual vulnerabilities and illicit
drug use. Informal social norms have a major but largely underestimated influence
on initiation and level of substance use and related behaviors.
References
Agrawal A, Madden PAF, Martin NG, Lynskey MT (2013) Do early experiences with cannabis
vary in cigarette smokers? Drug Alcohol Depend 128(3):255–259
Becoña E, Martı́nez U, Calafat A, Juan M, Fernández-Hermida JR, Secades-Villa R (2012)
Parental styles and drug use: a review. Drugs Educ Prev Policy 19(1):1–10
Bellis MA, Hughes K, Morleo M, Tocque K, Hughes S, Allen T et al (2007) Predictors of risky
alcohol consumption in schoolchildren and their implications for preventing alcohol-related
harm. Subst Abuse Treat Prev Policy 2:15
8 Prevention Strategies and Basics 137
Berman G (2012) A thousand small sanities – crime control lessons from New York. Centre for
Justice Innovation, London
Binnie I, Kinver A, Lam P (2006) Know the score – cocaine wave 3–2005 post-campaign
evaluation. Scottish Executive, Edinburgh
Bolier L, Voorham L, Monshouwer K, Hasselt NV, Bellis M, Van Hasselt N (2011) Alcohol and
drug prevention in nightlife settings: a review of experimental studies. Subst Use Misuse
46(13):1569–1591
Broening S, Kumpfer K, Kruse K, Sack PM, Schaunig-Busch I, Ruths S et al (2012) Selective
prevention programs for children from substance-affected families: a comprehensive system-
atic review. Subst Abuse Treat Prev Policy 7(1):23
Bronfenbrenner U (1979) The ecology of human development: experiments by nature and design.
Harvard University Press, Cambridge, MA
B€uhler A (2008) The role of life skills promotion in substance abuse prevention: a mediation
analysis. Health Educ Res 23(4):621
B€
uhler A, Kröger C (2008) Prevention of substance abuse. EMCDDA and BZGA, Luxembourg
Calafat A, Juan M, Duch MA (2009) Preventive interventions in nightlife: a review. Adicciones
21(4):387–413
Carney T, Myers B (2012) Effectiveness of early interventions for substance-using adolescents:
findings from a systematic review and meta-analysis. Subst Abus Treat Prev Policy
7(1747–597X):25
Castellanos N, Conrod P (2006) Brief interventions targeting personality risk factors for adoles-
cent substance misuse reduce depression, panic and risk-taking behaviours. J Ment Health
15(16):645–658
Clark HK, Shamblen SR, Ringwalt CL, Hanley S (2012) Predicting high risk adolescents’
substance use over time: the role of parental monitoring. J Prim Prev 33(2–3):67–77
Comello MLG (2011) Characterizing drug non-users as distinctive in prevention messages:
implications of optimal distinctiveness theory. Health Commun 26(4):313–322
Conrod PJ, O’Leary-Barrett M, Newton N, Topper L, Castellanos-Ryan N, Mackie C, Girard
A (2013) Effectiveness of a selective, personality-targeted prevention program for adolescent
alcohol use and misuse: a cluster randomized controlled trial. JAMA Psychiatry 70:1–9
Crano WD (2010) Applying established theories of persuasion to problems that matter: on
becoming susceptible to our own knowledge. In: Forgas JP, Cooper J, Crano WD (eds) The
psychology of attitudes and attitude change. Psychology Press, New York
Creemers HE, Verhulst FC, Huizink AC (2009) Temperamental risk factors for adolescent
cannabis use: a systematic review of prospective general population studies. Subst Use Misuse
44(13):1833–1854
Danielsson A-K, Wennberg P, Hibell B, Romelsjö A (2012) Alcohol use, heavy episodic drinking
and subsequent problems among adolescents in 23 European countries: does the prevention
paradox apply? Addiction 107(1):71–80
De Looze M, Van den Eijnden R, Verdurmen J, Vermeulen-Smit E, Schulten I, Vollebergh W, Ter
Bogt T (2012) Parenting practices and adolescent risk behavior: rules on smoking and drinking
also predict cannabis use and early sexual debut. Prev Sci 13(6):594–604
De Wit H, Phillips TJ (2012) Do initial responses to drugs predict future use or abuse? Neurosci
Biobehav Rev 36(6):1565–1576
Faggiano F, Vigna-Taglianti FD, Versino E, Zambon A, Borraccino A, Lemma P (2008) School-
based prevention for illicit drugs use: a systematic review. Prev Med 46(5):385–396
Faggiano F, Vigna-Taglianti F, Burkhart G, Bohrn K, Cuomo L, Gregori D et al (2010) The
effectiveness of a school-based substance abuse prevention program: 18-month follow-up of
the EU-Dap cluster randomized controlled trial. Drug Alcohol Depend 108(1–2):56–64
Ferri M, Allara E, Bo A (2013) Media campaigns for the prevention of illicit drug use in young
people, Cochrane Database Syst Rev CD009287
Foxcroft DR, Tsertsvadze A (2011a) Universal school-based prevention programs for alcohol
misuse in young people. Cochrane Database Syst Rev 5:CD009113
138 G. Burkhart and R. Simon
Foxcroft DR, Tsertsvadze A (2011b) Universal family-based prevention programs for alcohol
misuse in young people. Cochrane Database Syst Rev 9:CD009308
Galvan A, Hare TA, Parra CE, Penn J, Voss H, Glover G, Casey BJ (2006) Earlier development of
the accumbens relative to orbitofrontal cortex might underlie risk-taking behavior in adoles-
cents. J Neurosci 26(25):6885–6892
Gates S, McCambridge J, Smith LA, Foxcroft DR (2007) Interventions for prevention of drug use
by young people delivered in non-school settings (Review), Cochrane Database Syst Rev (2)
CD005030
Glantz MD, Anthony JC, Berglund PA, Degenhardt L, Dierker L, Kalaydjian A et al (2009) Mental
disorders as risk factors for later substance dependence: estimates of optimal prevention and
treatment benefits. Psychol Med 39(1469–8978 (Electronic)):1365–1377
Gordon RS (1983) An operational classification of disease prevention. In: Steinberg JA, Silverman
MM (eds) Public health reports. Department of Health and Human Services, Washington, DC,
pp 107–109
Guralnick MJ (2008) International perspectives on early intervention: a search for common
ground. J Early Interv 30(2):90–101
Hale DR, Viner RM (2012) Policy responses to multiple risk behaviours in adolescents. J Public
Health 34(Suppl 1):i11–i19
Hansen WB, Dusenbury L, Bishop D, Derzon JH (2007) Substance abuse prevention program
content: systematizing the classification of what programs target for change. Health Educ Res
22(3):351–360
Hemovich V, Lac A, Crano WD (2011) Understanding early-onset drug and alcohol outcomes
among youth: the role of family structure, social factors, and interpersonal perceptions of use.
Psychol Health Med 16(3):249–267
Hill KG, Hawkins JD, Bailey JA, Catalano RF, Abbott RD, Shapiro VB (2010) Person-
environment interaction in the prediction of alcohol abuse and alcohol dependence in adult-
hood. Drug Alcohol Depend 110(1–2):62–69
Hornik R, Jacobsohn L, Orwin R, Piesse A, Kalton G (2008) Effects of the national youth anti-drug
media campaign on youths. Am J Public Health 98(12):2229–2236
Hughes K, Quigg Z, Eckley L, Bellis M, Jones L, Calafat A et al (2011) Environmental factors in
drinking venues and alcohol-related harm: the evidence base for European intervention.
Addiction 106(Suppl (1360–0443 (Electronic))):37–46
Huizink AC, Levälahti E, Korhonen T, Dick DM, Pulkkinen L, Rose RJ, Kaprio J (2010) Tobacco,
cannabis, and other illicit drug use among finnish adolescent twins: causal relationship or
correlated liabilities? J Stud Alcohol Drugs 71(1):5–14
Humensky JL (2010) Are adolescents with high socioeconomic status more likely to engage in
alcohol and illicit drug use in early adulthood? Subst Abuse Treat Prev Policy 5(1):19
Jahiel RI, Babor TF (2007) Industrial epidemics, public health advocacy and the alcohol industry:
lessons from other fields. Addiction 102(9):1335–1339
Jones L, Sumnall HR, Witty K, Wareing M, McVeigh J, Bellis MA (2006) A review of
community-based interventions to reduce substance misuse among vulnerable and
disadvantaged young people. Centre for Public Health, Liverpool John Moores University,
Liverpool
Kam JA, Middleton AV (2013) The associations between parents’ references to their own past
substance use and youth’s substance-use beliefs and behaviors: a comparison of Latino and
European American Youth. Hum Commun Res 39(2):208–229
Kelly AB, O’flaherty M, Toumbourou JW, Connor JP, Hemphill SA, Catalano RF (2011) Gender
differences in the impact of families on alcohol use: a lagged longitudinal study of early
adolescents. Addiction 106(1360–0443):1427–1436
Koning IM, Verdurmen JEE, Engels RCME, Van den Eijnden RJJM, Vollebergh WAM
(2012) Differential impact of a Dutch alcohol prevention program targeting adolescents and
parents separately and simultaneously: low self-control and lenient parenting at baseline
predict effectiveness. Prev Sci 13(3):278–287
8 Prevention Strategies and Basics 139
Korhonen T, Latvala A, Dick DM, Pulkkinen L, Rose RJ, Kaprio J, Huizink AC (2012) Genetic
and environmental influences underlying externalizing behaviors, cigarette smoking and illicit
drug use across adolescence. Behav Genet 42(4):614–625
Koutakis N, Stattin H, Kerr M (2008) Reducing youth alcohol drinking through a parent-targeted
intervention: the orebro prevention program. Addiction 103(10):1629–1637
Kumpfer KL, Smith P, Summerhays JF (2008) A wakeup call to the prevention field: are
prevention programs for substance use effective for girls? Subst Use Misuse 43(8–9):978–1001
Kuntsche EN, Jordan MD (2006) Adolescent alcohol and cannabis use in relation to peer and
school factors. Results of multilevel analyses. Drug Alcohol Depend 84(2):167–174
Kuntsche EN, Kuendig H (2005) Do school surroundings matter? Alcohol outlet density, percep-
tion of adolescent drinking in public, and adolescent alcohol use. Addict Behav 30(1):151–158
Kuntsche EN, Kuendig H (2006) What is worse? A hierarchy of family-related risk factors
predicting alcohol use in adolescence. Subst Use Misuse 41(1):71–86
Kurtz SP, Surratt H, Buttram ME, Levi-Minzi M, Chen M (2013) Interview as intervention: the
case of young adult multidrug users in the club scene. J Subst Abuse Treat 44(3):301–308
Lac A, Crano WD (2009) Monitoring matters: meta-analytic review reveals the reliable linkage of
parental monitoring with adolescent marijuana use. Perspect Psychol Sci 4(6):578–586
Legleye S, Beck F, Khlat M, Peretti-Watel P, Chau N (2012) The influence of socioeconomic
status on cannabis use among French adolescents. J Adolesc Health 50(4):395–402
Malmberg M, Kleinjan M, Vermulst AA, Overbeek G, Monshouwer K, Lammers J, Engels RCME
(2012) Do substance use risk personality dimensions predict the onset of substance use in early
adolescence? A variable- and person-centered approach. J Youth Adolesc 41(11):1512–1525
Markham W, Young R, Sweeting H, West P, Aveyard P (2012) Does school ethos explain the
relationship between value-added education and teenage substance use? A cohort study. Soc
Sci Med 75(1):69–76
Martinus T, Melson AJ, Davies JB, Mclaughlin A (2012) The “social norms” approach to alcohol
misuse prevention: testing transferability in a Scottish secondary school context. Drugs Educ
Prev Policy 19(2):111–119
Mayet A, Legleye S, Chau N, Falissard B (2010) The mediation role of licit drugs in the influence
of socializing on cannabis use among adolescents: a quantitative approach. Addict Behav
35(10):890–895
McAlaney J, Bewick B, Hughes C (2011) The international development of the “Social Norms”
approach to drug education and prevention. Drugs Educ Prev Policy 18(2):81–89
McCambridge J, Strang J (2004) The efficacy of single-session motivational interviewing in
reducing drug consumption and perceptions of drug-related risk and harm among young
people: results from a multi-site cluster randomized trial. Addiction 99(1):39–52
McCambridge J, Day M, Thomas BA, Strang J (2011) Fidelity to motivational interviewing and
subsequent cannabis cessation among adolescents. Addict Behav 36(1873–6327
(Electronic)):749–754
McCrystal P, Percy A, Higgins K (2007) The cost of drug use in adolescence: young people,
money and substance abuse. Drugs Educ Prev Policy 14(1):19–28
McMorris BJ, Catalano RF, Kim MJ, Toumbourou JW, Hemphill SA (2011) Influence of family
factors and supervised alcohol use on adolescent alcohol use and harms: similarities between
youth in different alcohol policy contexts. J Stud Alcohol Drugs 72(3):418–428
Midford R (2010) Drug prevention programmes for young people: where have we been and where
should we be going? Addiction 105(10):1688–1695
Miller BA, Holder HD, Voas RB (2009) Environmental strategies for prevention of drug use and
risks in clubs. J Subst Use 14(1):19–38
Moodie R, Stuckler D, Monteiro C, Sheron N, Neal B, Thamarangsi T et al (2013) Profits and
pandemics: prevention of harmful effects of tobacco, alcohol, and ultra-processed food and
drink industries. The Lancet 381(9867):670–679
Mrazek PJ, Haggerty RJ (1994) Reducing risks for mental disorders: frontiers for preventive
intervention research. National Academy Press, Washington, DC
140 G. Burkhart and R. Simon
Paternoster R (1987) The deterrent effect of the perceived certainty and severity of punishment:
a review of the evidence and issues. Justice Q 4(2):173–217
Peters LWH, Wiefferink CH, Hoekstra F, Buijs GJ, Ten Dam GTM, Paulussen TGWM
(2009) A review of similarities between domain-specific determinants of four health behaviors
among adolescents. Health Educ Res 24(2):198–223
Petrie J, Bunn F, Byrne G (2007) Parenting programmes for preventing tobacco, alcohol or drugs
misuse in children <18: a systematic review. Health Educ Res 22(2):177–191
Plunk AD, Cavazaos-Rehg P, Bierut LJ, Grucza RA (2013) The persistent effects of minimum
legal drinking age laws on drinking patterns later in life. Alcohol Clin Exp Res 37(3):463–469
Poduska JM, Kellam SG, Wang W, Brown CH, Ialongo NS (2008) Impact of the good behavior
game, a universal classroom-based behavior intervention, on young adult service use for
problems with emotions, behavior, or drugs or alcohol. Drug Alcohol Depend 95(Suppl 1):
S29–S44
Poulin C, Nicholson J (2005) Should harm minimization as an approach to adolescent substance
use be embraced by junior and senior high schools? Int J Drug Policy 16(6):403–414.
doi:10.1016/j.drugpo.2005.11.001
Racz SJ, McMahon RJ (2011) The relationship between parental knowledge and monitoring and
child and adolescent conduct problems: a 10-year update. Clin Child Fam Psychol Rev
14(4):377–398
Roe S, Becker J (2005) Drug prevention with vulnerable young people: a review. Drugs Educ Prev
Policy 12(2):85–99
Romer D, Duckworth AL, Sznitman S, Park S (2010) Can adolescents learn self-control? Delay of
gratification in the development of control over risk taking. Prev Sci 11(3):319–330
Rooke SE, Hine DW, Thorsteinsson EB (2008) Implicit cognition and substance use: a meta-
analysis. Addict Behav 33(10):1314–1328
Scarscelli D, Altopiedi R, Dameno R, Verga M (2012) Does fear of sanctions or sanctions
discourage drug use? The point of view of a sample of illegal drug users in Italy. Drugs
Educ Prev Policy 19(6):484–494
Skager R (2007) Replacing ineffective early alcohol/drug education in the United States with
age-appropriate adolescent programmes and assistance to problematic users. Drug Alcohol
Rev 26(6):577–584
Skenderian JJ, Siegel JT, Crano WD, Alvaro EE, Lac A (2008) Expectancy change and adoles-
cents’ intentions to use marijuana. Psychol Addict Behav 22(4):563–569
Sloboda Z, Glantz MD, Tarter RE (2012) Revisiting the concepts of risk and protective factors for
understanding the etiology and development of substance use and substance use disorders:
implications for prevention. Subst Use Misuse 47(1532–2491 (Electronic)):944–962
Smedslund G, Berg RC, Hammerstrøm KT, Steiro A, Leiknes KA, Dahl HM Karlsen K (2011)
Motivational interviewing for substance abuse. Cochrane Database Syst Rev CD008063
(online, Wiley)
Steiker LKH (2008) Making drug and alcohol prevention relevant. Adapting evidence-based
curricula to unique adolescent cultures. Fam Commun Health 31(Supp 1):852–860
Steinberg L (2008) A social neuroscience perspective on adolescent risk-taking. Dev Rev
28(0273–2297):78–106
Stockwell T, Toumbourou JW, Letcher P, Smart D, Sanson A, Bond L (2004) Risk and protection
factors for different intensities of adolescent substance use: when does the prevention paradox
apply? Drug Alcohol Rev 23(1):67–77
Stockwell T, Auld MC, Zhao J, Martin G (2012) Does minimum pricing reduce alcohol consump-
tion? The experience of a Canadian province. Addiction 107(5):912–920
Sussman S, Earleywine M, Wills T, Cody C, Biglan T, Dent CW, Newcomb MD (2004) The
motivation, skills, and decision-making model of “drug abuse” prevention. Subst Use Misuse
39(10–12):1971–2016
Toumbourou JW, Stockwell T, Neighbors C, Marlatt GA, Sturge J (2007) Interventions to reduce
harm associated with adolescent substance use. Lancet 369(9570):1391–1401
8 Prevention Strategies and Basics 141
Van der Vorst H, Engels RCME, Meeus W, Deković M (2006) The impact of alcohol-specific
rules, parental norms about early drinking and parental alcohol use on adolescents’ drinking
behavior. J Child Psychol Psychiatry 47(12):1299–1306
Vega WA, Gil AG (2005) Revisiting drug progression: long-range effects of early tobacco use.
Addiction 100(9):1358–1369
Vigna-Taglianti F, Vadrucci S, Faggiano F, Burkhart G, Siliquini R, Galanti MR (2009) Is
universal prevention against youths’ substance misuse really universal? Gender-specific effects
in the EU-Dap school-based prevention trial. J Epidemiol Community Health 63(9):722–728
Waddell GR (2010) Adolescent drug use and the deterrent effect of school-imposed penalties.
Forschungsinstitut Zuk Arb Inst Stud Labor IZA 31(5047):961–969
Wagenaar AC, Toomey TL (2002) Effects of minimum drinking age laws: review and analyses of
the literature from 1960 to 2000. J Stud Alcohol Suppl (14):206–225
Wagenaar AC, Tobler AL, Komro KA (2010) Effects of alcohol tax and price policies on
morbidity and mortality: a systematic review. Am J Public Health 100(11):2270–2278
Wakefield MA, Loken B, Hornik RC (2010) Use of mass media campaigns to change health
behaviour. Lancet 376(9748):1261–1271
Young R, Macdonald L, Ellaway A (2013) Associations between proximity and density of local
alcohol outlets and alcohol use among Scottish adolescents. Health Place 19(null):124–130
Zonnevylle-Bender MJS, Matthys W, Van de Wiel NMH (2007) Preventive effects of treatment of
disruptive behavior disorder in middle childhood on substance use and delinquent behavior.
J Am Acad Child Adolesc Psychiatry 46(1):33–39
Further Reading
EMCDDA (2008) Selected Issue: vulnerable groups of young people. Publications Office of the
European Union, Luxembourg, Retrieved from http://www.emcdda.europa.eu/publications/
selected-issues/vulnerable-young
EMCDDA (2009) Polydrug use: patterns and responses. Publications Office of the European
Union, Luxembourg, Retrieved from http://www.emcdda.europa.eu/publications/selected-
issues/polydrug-use
Strang J, Babor T, Caulkins J, Fischer B, Foxcroft D, Humphreys K (2012) Drug policy and the
public good: evidence for effective interventions. Lancet 379(9810):71–83
UNODC (2009) Guide to implementing family skills training programmes for drug abuse preven-
tion. United Nations, New York
Regional and Cultural Aspects of
Prevention 9
Roland Simon and Gregor Burkhart
Contents
9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
9.1.1 Culture and Substance Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
9.1.2 Implementation of Interventions and Cultural Conditions . . . . . . . . . . . . . . . . . . . . . . 145
9.2 International Perspectives and Trends . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
9.2.1 Mass Media Campaigns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
9.2.2 Environmental Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
9.2.3 Universal Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
9.2.4 Selective Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
9.2.5 Family-Based Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150
9.2.6 Indicated Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
9.3 Transfer of Prevention Technologies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
9.3.1 Examples of Successful Transfer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
9.3.2 The Role of Social Capital . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
9.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
Abstract
Drug use and prevention has to be understood within its cultural environment
and conditions.
There is increasing evidence that cultural values, descriptive norms, and the
social acceptability of use influence people’s initiation into substance use and
problem behavior directly as well as indirectly through parenting practices.
It has been argued that especially inconsistency between parenting style and
culture can cause harm to adolescents’ mental health.
Cultural and contextual differences between regions can also affect the
implementation, acceptance, and effectiveness of prevention interventions.
9.1 Introduction
Burkhart and Simon (# in this publication #) have shown that collective behavior
and perceived norms have a significant influence on substance use behavior. This
has implication for interventions, their effectiveness, and cultural acceptance. Most
universal and selective prevention strategies only target individual behavior and
decision-making, putting the onus of responsibility for behavioral control entirely
on the individual and disregarding the influence of network and collective behavior
(Szmigin et al. 2011).
societies, for example, tend to be more collective and authoritarian than Western
societies, with higher levels of emotional and financial connectedness and some-
times collective monitoring alongside parental monitoring. This higher level of
adolescent–family connectedness has been associated with better mental health
among adolescents in eight Arab societies (Dwairy 2006), indicating that authori-
tarian parenting within an authoritarian culture does not harm adolescents’ mental
health as this would be the case within Western liberal societies. The authors
hypothesize that it is the inconsistency between parenting style and culture that
causes harm to adolescents’ mental health. This suggests that education has to be
understood within its cultural environment and conditions.
Mass media campaigns continue to be popular both in the Americas and in Europe,
although they are evaluated more often in the USA. However, over a third of
European countries have reduced or abandoned mass media campaigns on illicit
drugs because of concerns about possible iatrogenic effects of such interventions
and a lack of funds to implement them. Some countries, such as Bulgaria, the Czech
Republic, Italy, Spain, France, and Romania, still use local and national mass media
campaigns. It is possible that mass media campaigns still have a wider role to play
in comprehensive social marketing strategies, such as those trying to change social
norms.
that work to reduce and maintain lower levels of drug use. Prevention programs and
interventions targeting specific problems or drugs are less often used in these
countries.
Guidelines for the creation of better environments in recreational settings, such
as the “safer dancing” guidelines in the UK, were developed since the end of the
1990s as simple but important environmental prevention tools to reduce the
occurrence of problems related to drugs and alcohol. They include access to
free drinking water, rules on glassware, noise, and staff training. Additional
elements are policies on and monitoring of interior space in respect of risky
sexual or aggressive behavior, training staff for medical emergencies related to
intoxicated patrons, and policies for serving alcohol and handling drug-related
problems. The strategies that are applied in Sweden and the USA (Miller
et al. 2009) add more repressive elements, such as monitoring interior space for
drug use and drug-related problems, training staff to detect drug-impaired
patrons, and excluding “problem” patrons (drug dealers, drug users, those carry-
ing weapons). While between 2004 and 2009 the number of EU countries that
reported the existence of such guidelines increased from 3 to 12, only half of them
appeared to monitor and enforced their implementation. In practice, even free
drinking water – a core requirement for safe clubbing to counter the effects of
dehydration and high temperatures while dancing – was available in the majority
of relevant nightclubs in only 11 EU countries (2009 data).
Of the four main drug prevention strategies in Europe, universal prevention pre-
dominates and is probably the most commonly implemented, particularly in schools
and families. The objective of delivering prevention interventions of the best
possible quality in the context of increased financial pressures due to the economic
downturn in Europe has led some countries to focus on improving the quality of
their prevention programs and professionals. The Czech Republic, for example, has
centralized the government’s prevention funds and has introduced Europe’s first
accreditation system, under which funding is available only to certified programs.
The certification of professionals is designed to improve the quality of delivery and
to ensure that public funds are spent efficiently.
In comparison with the Americas, very few countries in Europe have
implemented “manualized” programs (with the program details published in
a manual which facilitates implementation according to set standards and rules),
even if most of the available evidence on school-based prevention originates from
them. The manuals provide material and guidance for teachers and pupils on the
content of each of the sessions, promote discussions, and enable implementation
and behavioral changes to be evaluated. The most important program is Unplugged,
the only multisite randomized controlled trial (RCT) on prevention in Europe to
date. This comprehensive social influence program consists of twelve 1-h
interactive sessions delivered by class teachers and has proven its effectiveness in
148 R. Simon and G. Burkhart
a cluster randomized trial involving 7,079 pupils aged 12–14 in seven European
countries (www.eudap.net). Drunkenness and cannabis use showed reductions
after six 6 and 18 months; there was a reduced prevalence of all behavioral
outcomes related to problematic drug and alcohol use among boys, but not
among girls (Faggiano et al. 2010). Participation in the program was associated
with decreases in drunkenness, intention to get drunk, and alcohol-related problem
behaviors among adolescents from a low socioeconomic level. After this first
European multisite prevention trial, Unplugged was implemented in more eastern
European and Asian countries, in some cases replicating the initial promising
outcomes.
One unusual school-based prevention approach deserves special mention.
The Good Behavior Game (GBG) is not a typical lessons-based classroom
prevention program but rather a way of managing whole primary school classes
during regular lessons and socializing children to be self-controlled, emphasiz-
ing the role of significant others (teachers and peers) in children’s social adjust-
ment in school. Divided into teams, children systematically learn over a period
of one school year to respect basic class rules through a well-designed process
providing team rewards for respecting rules. RCTs reported a beneficial impact
up to the middle school years and even young adulthood. These effects included
reductions in alcohol and drug dependency disorders; antisocial personality
disorder; delinquency and imprisonment; regular smoking; suicidal ideation
and attempts; use of services for behavioral, drug, emotional, and school learn-
ing problems; and risky sexual activity such as unprotected sex. Substances and
substance use are not explicit themes in GBG; instead, it focuses on socializa-
tion, and the children themselves define the behaviors that will be rewarded.
GBG has been or is being implemented in at least four EU Member States. In
a similar modus operandi, the Smokefree Class competition is an evaluated and
effective program implemented in some European countries that works predom-
inantly by setting alternative peer norms about smoking and stimulates their
reinforcement by the peers themselves, but without mentioning the dangers or
risks of smoking.
While these are excellent examples of more developed concepts and their
implementation in Europe, the everyday practice of universal prevention in
European schools still seems to focus primarily on nonevidence-based
components – information days about drugs, visits by police officers, lectures
from experts or former drug addicts, and interventions providing information
(with no skills training) on the risks of drugs. There has, though, been a slight
increase in manualized multi-session programs like Unplugged. These include
training in communication skills and in the ability to handle conflict, stress, and
frustration. They also try to correct normative misperceptions about drug use. This
area, called “normative education,” is still quite underdeveloped despite positive
evidence (Martinus et al. 2012; Sussman et al. 2004). Many other manualized
programs, though, still have information provision as the key component, with
frontal (as opposed to interactive) delivery.
9 Regional and Cultural Aspects of Prevention 149
Compared to other parts of the world, Europe seems to have invested much
political effort in addressing the problems of vulnerable groups, and since 2004,
an increasing number of EU Member States have indicated vulnerable groups as
primary targets for prevention interventions. However, in real terms, the reported
level of intervention provision has only increased for two subgroups: young
offenders and pupils with academic and social problems. The latter might be
due to some Member States shifting attention in general to young people with
academic problems and school dropouts, who share many risk factors with
problem drug users. Young offenders as a group are easy to identify, but inter-
ventions provided are often not appropriate for them. While almost all EU
Member States offer alternatives to imprisonment or penal sanctions for underage
drug law offenders, treatment is not particularly tailored for them. They may be
treated alongside more problematic drug users and/or dealt with as though they
are themselves problematic drug users, increasing the risk of further marginali-
zation and deviant behavior. In many cases, more suitable interventions would
have clear and structured protocols, be of adequate duration, and be provided in
neutral settings. The manualized program for young offenders (FreD) takes this
approach. Developed at the national level, it has been expanded to and adapted by
one-third of EU Member States.
Some countries have reacted specifically to the increased vulnerability to drug
use found among pupils in vocational schools, for example, with tailored programs
to generally improve literacy and numeracy levels among disadvantaged students.
At the community level, municipalities in northern Europe and in Italy aim to
combine drug and alcohol policies, action plans, and youth work through binding
cooperation agreements between local authorities and nongovernmental organiza-
tions. Combining norm-setting environments and individual counselling
approaches in this way might avoid segregating vulnerable young people into
specific interventions for high-risk youth, which has the potential to cause further
harm, as described above. Municipalities have closer contact with citizens and can
better coordinate the different services involved. The strengthening of local respon-
sibility for prevention has fostered community plans and interagency work, partic-
ularly in northern European countries.
Early intervention approaches, in the original meaning of the term, provide
social, emotional, and learning support to children in the early years of life (this
is distinct from the recent use of the term “early intervention” to mean “early in the
career of substance use”; see below). It can delay or prevent future problems
(including substance misuse) more effectively and economically than intervening
only when problems appear. Parenting programs at a local level would be an
essential part of early intervention, but proactive parental work and training is
still an exception.
The content of interventions presented as “selective prevention” is often unclear,
and problems in defining the scope of the concept make monitoring difficult.
150 R. Simon and G. Burkhart
and tools helps to improve prevention interventions and to assure their effectiveness
in replication trials, as well as making them easy to apply. Their implementation is
more likely to be set out in a manual (i.e., manualized) to assure accuracy of
implementation and to allow trained staff who may not be prevention experts to
implement them. Such programs are also more likely to have been pretested
(to confirm the validity of their theory base), to have been checked for unintentional
(iatrogenic) effects, and to prove positive outcomes. Such interventions could be
considered “high-tech prevention,” as their development and partly also their
implementation require specific know-how, research, repeated refinement proce-
dures, quality control, proof of effectiveness, replication studies, and some certainty
that they do not harm. In medicine, most people would naturally expect such a level
of “technology assessment,” especially of medications, before they can be distrib-
uted to the population.
In Europe such high-tech programs are rare, especially outside classrooms.
Prevention strategies mainly consist of varying combinations of policies for
vulnerable populations; isolated or combined activities for school-aged youth to
raise their awareness, self-competence, social skills, risk perception, and/or
autonomy; events and advice for parents; and youth work and counselling inter-
ventions for those with existing risky substance use patterns. Such approaches
have to make use of the existing services and infrastructure, and they allow for
innovation and adaption to local needs and perceptions. However, they are
sometimes based on little more than common sense and often lack evidence of
both effectiveness and possible iatrogenic effects. While Europe has a range of
innovative and pragmatic selective prevention interventions for vulnerable
groups, many of them are not rigorously evaluated. Few indicated prevention
programs are running, even though some well-evaluated and effective programs
exist.
In broad terms, it seems that the relative lack of prevention infrastructure in
the USA has led to more prevention research and program development. Europe,
on the other hand, relies on a more elaborate infrastructure but spends much
less energy on ensuring that the many different existing services deliver preven-
tion work of a specific quality. However, there are examples in Europe that do
control the quality of programs. In the Czech Republic, quality control is carried
out through an accreditation system and through regulating training of the
professionals involved. Recently developed European drug prevention quality
standards might help to steer prevention policies in the EU as a whole in new
directions.
Well-developed programs from North America have been culturally adapted to suit
other parts of the world. Using a preexisting program means that the resources,
manuals, and methodologies are ready for immediate use, facilitating
implementation.
154 R. Simon and G. Burkhart
9.4 Conclusion
not effective in preventing drug use. Interest in selective prevention has increased
during this period, but this has not translated into more interventions for vulnerable
youth or more evaluation research. Finally, there has been some interest in indi-
cated prevention in Europe, and effective evaluation studies have been carried out,
but these types of intervention are still limited to only a few countries. Too much
prevention in Europe and seemingly elsewhere – apart from North
America – continues to appeal to cognitive processes only, namely, information
provision. And too often interventions only target individual behavior, ignoring the
fact that it is culturally embedded.
Findings from country-level ecological analyses on the health of young people
(Viner et al. 2012) show that the strongest determinants of adolescent health
worldwide are structural factors such as national wealth, income inequality, and
access to education. As a consequence, safe and supportive families and schools,
together with positive and supportive peers, are crucial in addressing risk and
building protective factors. These are not limited to the neurobiological factors
outlined at the beginning – childhood trajectories towards health and well-being
are also modified by economic and social factors within countries, leading to
inequalities. But there is evidence that effective prevention programs can
reduce the effects of social inequality on behavioral outcomes. In fact, some
universal prevention programs have shown differentially better effects on
more vulnerable children (Kellam et al. 2008); some selective family-based
programs seem to be more effective the more vulnerable the targeted families
are (Kumpfer et al. 2008); and indicated programs can bring the most behaviorally
difficult children to better social functioning. Most importantly, almost all
interventions have positive spin-off effects beyond substance use disorder on
aggressive behavior and on mental health. Despite this, these tools are still
underused.
As we have seen at various parts of this chapter, social norms have a strong
influence on behavior, suggesting that the effect of informal social control and
social sanctions (from family and peers) may be more important than the certainty
and severity of formal sanctions (Paternoster 1987). These examples illustrate that
comprehensive prevention policies ought not only to address individual vulnera-
bilities and illicit drug use. Informal social norms have a major but largely
underestimated influence on initiation and level of substance use and related
behaviors.
There is a limited number of prevention programs with well-proven evidence of
effectiveness that are relatively easy to implement through manuals and other
supporting materials. Better use could be made of these interventions, which have
often been developed in North America. A number of successful examples have
shown that this approach is worthwhile and promising. While cultural conditions
cannot be ignored, it is possible to successfully adapt programs developed in one
cultural environment to another culture. This approach should be pursued further,
especially at a time when it is unlikely that substantial new investments in preven-
tion research will be made.
9 Regional and Cultural Aspects of Prevention 157
References
B€uhler A, Kröger C (2008) Prevention of substance abuse. EMCDDA and BZGA, Luxembourg
Conrod PJ, O’Leary-Barrett M, Newton, N, Topper L, Castellanos-Ryan N, Mackie C, Girard
A (2013) Effectiveness of a selective, personality-targeted prevention program for adolescent
alcohol use and misuse: a cluster randomized controlled trial. JAMA Psychiatry, 70, 334–342
Cunningham JA (2007) Implications of the normative fallacy in young adult smokers aged 19–24
years. Am J Pub Health 97(8):1399–1400
Dwairy M (2006) Parenting styles, individuation, and mental health of Arab adolescents: a third
cross-research study. J Cross Cult Psychol 37(3):262–272
Eriksen M, Mackay J, Ross H (2012) The tobacco atlas (fourth). American Cancer Society,
Atlanta, Retrieved from http://tobaccoatlas.org/
Faggiano F, Vigna-Taglianti FD, Versino E, Zambon A, Borraccino A, Lemma P (2008) School-
based prevention for illicit drugs use: a systematic review. Prev Med 46(5):385–396
Faggiano F, Vigna-Taglianti F, Burkhart G, Bohrn K, Cuomo L, Gregori D et al (2010) The
effectiveness of a school-based substance abuse prevention program: 18-month follow-up of
the EU-Dap cluster randomized controlled trial. Drug Alcohol Depend 108(1–2):56–64
Foxcroft DR, Tsertsvadze A (2011a) Universal school-based prevention programs for alcohol
misuse in young people. Cochrane Database Syst Rev 5:CD009113
Foxcroft DR, Tsertsvadze A (2011b) Universal family-based prevention programs for alcohol
misuse in young people. Cochrane Database Syst Rev 9
Foxcroft DR, Tsertsvadze A (2011c) Universal multi-component prevention programs for alcohol
misuse in young people. Cochrane Database Syst Rev 9:CD009307
Fukuyama F (2001) Social capital, civil society and development. Third World Q 22(1):7–29
Gates S, McCambridge J, Smith LA, Foxcroft DR (2007) Interventions for prevention of drug use
by young people delivered in non-school settings (review). Cochrane Database Syst Rev (2)
Hawkins JD, Catalano RF, Arthur MW, Egan E, Brown EC, Abbott RD, Murray DM (2008) Test-
ing communities that care: the rationale, design and behavioral baseline equivalence of the
Community Youth Development Study. Prev Sci 9(3):178–190
Hublet A, Schmid H, Clays E, Godeau E, Gabhainn SN, Joossens L, Maes L (2009) Association
between tobacco control policies and smoking behaviour among adolescents in 29 European
countries. Addiction 104(11):1918–1926
Kellam SG, Brown CH, Poduska JM, Ialongo NS, Wang W, Toyinbo P et al (2008) Effects of
a universal classroom behavior management program in first and second grades on young adult
behavioral, psychiatric, and social outcomes. Drug Alcohol Depend 95:S5–S28
Kellam SG, Mackenzie AC, Brown CH, Poduska JM, Wang W, Petras H, Wilcox HC (2011) The
good behavior game and the future of prevention and treatment. Addict Sci Clin Pract
6(1):73–84
Kumpfer KL, Pinyuchon M, De Melo AT, Whiteside H (2008) Cultural adaptation process for
international dissemination of the strengthening families program. Eval Health Prof
31(2):226–239
Kumpfer KL, Xie J, O’Driscoll R (2012) Effectiveness of a culturally adapted strengthening
families program 12–16 years for high-risk Irish families. Child Youth Care For 41(2):173–195
Kuntsche EN, Jordan MD (2006) Adolescent alcohol and cannabis use in relation to peer and
school factors. Results of multilevel analyses. Drug Alcohol Depend 84(2):167–174
Martinus T, Melson AJ, Davies JB, Mclaughlin A (2012) The “social norms” approach to alcohol
misuse prevention: testing transferability in a Scottish secondary school context. Drugs Educ
Prev Policy 19(2):111–119
Midford R (2010) Drug prevention programmes for young people: where have we been and where
should we be going? Addiction 105(10):1688–1695
Miller BA, Holder HD, Voas RB (2009) Environmental strategies for prevention of drug use and
risks in clubs. J Subst Use 14(1):19–38
158 R. Simon and G. Burkhart
Molgaard VK, Spoth RL, Redmond C (2000) The strengthening families program for parents and
youth 10–14. Washington, DC: Office of Juvenile Justice and Delinquency Prevention. Juv Just
Bull August:1–12
Olds RS, Thombs DL, Tomasek JR (2005) Relations between normative beliefs and initiation
intentions toward cigarette, alcohol and marijuana. J Adolesc Health 37(1):75
Paternoster R (1987) The deterrent effect of the perceived certainty and severity of punishment:
a review of the evidence and issues. Justice Q 4(2):173–217
Petrie J, Bunn F, Byrne G (2007) Parenting programmes for preventing tobacco, alcohol or drugs
misuse in children <18: a systematic review. Health Educ Res 22(2):177–191
Ringwalt C, Vincus AA, Ennett ST, Hanley S, Bowling JM, Yacoubian GS, Rohrbach LA
(2008) Random drug testing in US public school districts. Am J Public Health 98(5):826–828
Sloboda Z, Glantz MD, Tarter RE (2012) Revisiting the concepts of risk and protective factors for
understanding the etiology and development of substance use and substance use disorders:
implications for prevention. Subst Use Misuse 47(1532–2491 (Electronic)):944–962
Spinney L (2007) Public smoking bans show signs of success in Europe. Lancet
369(9572):1507–1508
Sussman S, Earleywine M, Wills T, Cody C, Biglan T, Dent CW, Newcomb MD (2004) The
motivation, skills, and decision-making model of “drug abuse” prevention. Subst Use Misuse
39(10–12):1971–2016
Szmigin I, Bengry-Howell A, Griffin C, Hackley C, Mistral W (2011) Social marketing, individual
responsibility and the culture of intoxication. Eur J Mark 45(5):759–779
Szobot CM, Rohde LA, Bukstein O, Molina BSG, Martins C, Ruaro P, Pechansky F (2007) Is
attention-deficit/hyperactivity disorder associated with illicit substance use disorders in male
adolescents? A community-based case-control study. Addiction 102(7):1122–1130
Viner RM, Ozer EM, Denny S, Marmot M, Resnick M, Fatusi A, Currie C (2012) Adolescence and
the social determinants of health. Lancet 379(9826):1641–1652
Wilkinson R, Picket K (2010) The spirit level: why equality is better for everyone. Penguin,
London
Winters KC, Fahnhorst T, Botzet A, Lee S, Lalone B (2012) Brief intervention for drug-abusing
adolescents in a school setting: outcomes and mediating factors. J Subst Abuse Treat
42(3):279–288
Section II
Screening and Early Interventions
Abstract
This introduction describes the chapters published in Sect. II on “Diagnosis,
Detection and Early Intervention for Substance Use Disorders”. The first chapter
provides an overview of the hierarchy of diagnoses employed in the substance
use disorders field and presents the diagnostic criteria for the central disorders of
repetitive substance use. Following this there are two chapters on screening tools
and brief intervention approaches for alcohol use disorders and drug (including
nicotine) use disorders respectively. A detailed literature review on early and
brief interventions of substance use disorders follows. The final two chapters are
concerned with biological markers of alcohol and laboratory techniques for
identification of drug use respectively.
This section is concerned with the diagnoses that apply to substance use disorders
and how these disorders can be identified at an earlier or milder stage and appro-
priate advice and treatment provided. The aim of early detection and brief inter-
vention is to both reduce harm that would otherwise occur were substance use to
continue unchecked and to prevent the progression to substance dependence
(addiction) which would otherwise be a likely consequence of continued use.
Current definitions and diagnostic criteria for substance use disorders form
the opening chapter of this section. Written by John Saunders and Noeline Latt,
the chapter begins with a reflection on the importance of a common language
by which human disorders and problems can be communicated amongst addiction
specialists and other health professionals and in a way that can be understood
and appreciated by patients with these disorders. A historical review of the
various concepts of substance use and its disorders follows. It will be seen that
many different concepts have been promoted over recent human history and by
different professional groups. Some of the concepts and definitions disagree as
to the nature and also etiology of substance use problems, and these
competing concepts are reviewed to provide a background to currently employed
diagnoses.
A key development was the description, based on detailed clinical investiga-
tions, of the substance dependence syndrome by Edwards and Gross (1976). This
concept initially applied to the alcohol dependence syndrome and has been subse-
quently accepted as the core syndrome for nearly all types of psychoactive sub-
stance that have abuse and addictive potential. The substance dependence
syndrome is an atheoretical and non-etiological concept, purely descriptive but
emphasizing the essential syndromal nature of substance dependence in which
clusters of symptoms, experiences, and physiological features tend to occur in
combination with each other in the affected person at around the same time and
repeatedly so.
The substance dependence syndrome has been powerfully influential. It was
the basis for the definitions and diagnostic criteria for substance dependence in
two successive versions of the Diagnostic and Statistical Manual of Mental and
Behavioral Disorders of the American Psychiatric Association, namely,
DSM-IIIR (published in 1987) and DSM-IV (published in 1994). It also forms
the basis for the understanding of substance use disorders amongst the literature
developed by the World Health Organization, including the 10th revision of
the International Classification of Diseases, ICD 10. Rather surprisingly, the
concept of dependence has been aggregated with that of substance abuse in
the latest DSM revision, DSM-5. The central diagnosis in DSM-5 of substance
use disorder is a looser rather disaggregated concept, and although empirically
based on questionnaire data, its value to guide clinical practice remains to be
established.
Comprehensive clinical assessment of substance use disorders, with a particular
emphasis on alcohol, is a subject of the following chapter by Teresa Bobes-Bascáran
(▶ Chap. 14, “Clinical Assessment of Alcohol Use Disorders”). Clinical assessment
of substance use disorders, like that in most medical practice, is based primarily on
the clinical interview, supplemented by findings on observation and examination
and importantly in many cases of substance dependence on collateral and corrobo-
rative information. Clinical assessment is also complemented by results from labo-
ratory tests, but these are the subjects of two separate chapters in this section.
This second chapter outlines the areas necessary for exploration in the clinical
interview, including the (i) assessment of the use (intake) of the particular
10 Screening and Early Interventions: An Introduction 163
References
Edwards G, Gross MM (1976) Alcohol dependence: provisional description of a clinical
syndrome. Br Med J 1:1058–1061
Diagnostic Definitions, Criteria and
Classification of Substance Use Disorders 11
John B. Saunders and Noeline C. Latt
Contents
11.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
11.2 Diagnoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
11.2.1 The Range of Addictive Substances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
11.2.2 Excessive Use and Repeated Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170
11.2.3 Mechanisms Underlying Repetitive Substance Use . . . . . . . . . . . . . . . . . . . . . . . . . 171
11.2.4 Concepts of Substance Use Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172
11.2.5 Substance Use Diagnoses in DSM-IV, DSM-5, and ICD-10 . . . . . . . . . . . . . . . 174
11.2.6 Substance Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
11.2.7 Substance Withdrawal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
11.2.8 Nondependent Repetitive Substance Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
11.2.9 Broadening the Definition: Substance Use Disorder in DSM-5 . . . . . . . . . . . . . 180
11.2.10 Other Definitions of Addiction or Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
11.2.11 Other Forms of Repetitive Substance Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
11.2.12 Substance-Induced Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
Abstract
Diagnostic terms exist to identify forms of substance use which are causing
clinical impairment or risk and to distinguish them from normality. Acute intox-
ication refers to a state caused by the acute pharmacological effects of the
substance. Repetitive substance use which confers the risk of harmful conse-
quences is termed “hazardous” or “risky” use. Substance abuse is a DSM-IV
term which denotes a maladaptive and repetitive pattern of substance use which
causes essentially social and personal problems. “Harmful use” is an ICD-10 term
which denotes repetitive substance use which is actually causing physical or
psychiatric harm. At the top of the hierarchy of disorders in both DSM-IV and
ICD-10 is the substance dependence syndrome. This is defined as a psychobio-
logical syndrome that comprises impaired control over substance use, tolerance,
and withdrawal symptoms and is characterized by continued use of the substance
despite harmful consequences. Underlying the dependence syndrome is a set of
enduring neurobiological changes in brain reward, stress, salience, and control
systems. These result in an internal “driving force” to use and continue to use
a particular substance (or group of substances) in a self-perpetuating way. The
recently published DSM-5 has changed the diagnostic landscape as it has deleted
the diagnoses of substance dependence and substance abuse and replaced them
with a broader condition of “substance use disorder.” DSM-5 also classifies as
“substance-induced disorders” the conditions of intoxication and withdrawal. In
addition to these diagnoses are the numerous mental, neurocognitive, and physical
complications. They include substance-induced mental disorders such as depres-
sive disorders, anxiety disorders, psychotic disorders, bipolar and related disor-
ders, obsessive–compulsive and related disorders, sleep disorders, sexual
dysfunctions, delirium, and neurocognitive disorders. ICD-10 has comprehensive
coverage of all physical disorders induced by psychoactive substance use. How-
ever, DSM-5 essentially neglects the significant medical/physical complications
of alcohol and other substance use and has abandoned the multiaxial system,
which included (as Axis III) associated physical conditions.
Diagnosis is based on a set of specific diagnostic criteria which reflect the
particular pattern of substance use and the psychophysiological attributes and
mental and other consequences of the condition. The key diagnoses in DSM-IV,
DSM-5, and ICD-10 are reviewed in this chapter. Clinical diagnosis of these
disorders is based on clinical knowledge and training. In addition there are
several diagnostic interview schedules, together with screening and assessment
instruments, which contribute to the diagnosis.
11.1 Introduction
situations. Illicit drugs, such as cannabis (marijuana), may have functional value to
some people, and there may be a threshold of use for some beneath which little
harm occurs. However, all these substances have an inherent capacity to cause
intoxicating effects, dependence (addiction), and a range of physical,
neurocognitive, psychological, and social harms.
Diagnoses are made to facilitate communication between different health-care
providers and to provide a basis for some form of intervention. The intellectual
process underlying diagnosis also serves to distinguish the patient’s condition from
normality. Some diagnoses indicate forms of substance use that confer the risk of
harmful consequences in the future, others indicate current clinical illness or impair-
ment, and yet others indicate syndromal disorders. A coherent system of diagnosis
and classification provides a vital structure for the practice of addiction medicine.
The present time is a period of considerable change in diagnostic concepts and
terminology. One of the principal diagnostic systems, the Diagnostic and Statistical
Manual of Mental and Behavioural Disorders, has recently published its fifth
edition (DSM-5) (American Psychiatric Association 2013). Substance use disorders
have been radically restructured within it, and this will be described below. At the
present time, the International Classification of Diseases, which is the international
basis for disease, morbidity, and mortality coding, is undergoing revision, with the
11th revision (ICD-11) being scheduled for publication in 2015. Changes to the
diagnostic criteria of addictive disorders are contemplated, but the essential diag-
nostic concepts may be similar to the current version ICD-10 (World Health
Organization 1992). Many addiction specialists in North America and elsewhere
adopt the diagnostic concepts and criteria developed by the American Society of
Addiction Medicine and the International Society of Addiction Medicine. The
conceptual understanding of substance disorders is rather different in these formu-
lations and the diagnostic criteria have only passing resemblance to those employed
in the DSM and ICD systems. A further contrast is provided by the emphasis in the
fields of epidemiology and public health on quantification of substance use and not
to define specific behavioral or psychophysiological disorders.
It will be apparent from the foregoing comments that a synthesis of diagnostic
concepts in the current classification systems is not possible. In this chapter we shall
present a history of common concepts of substance use disorders and then review
the key diagnoses in the current international diagnostic systems. Before this we
shall briefly review the range of addictive (dependence-inducing) and potentially
harmful psychoactive substances and also the patterns of substance use that need to
be captured by a diagnostic classification system.
11.2 Diagnoses
There are many thousands of naturally occurring and synthetic substances that have
the capacity to induce addiction, and new ones are continually being synthesized.
170 J.B. Saunders and N.C. Latt
Substances with addictive potential tend to have acute psychological effects which
consumers find pleasant, at least initially and in the majority of cases. They tend to
cause euphoria and, in many cases, a sense of relaxation. Certain substances are
valued because they relieve pain or sickness and therefore are described as having
a medicinal effect as opposed to a primary hedonic one. The pharmacokinetic
properties of the substance influence its addictive potential, with the rapidity of
absorption (and therefore action), ease of penetrating the blood/brain barrier, and
duration of action influencing the likelihood of recurrent self-administration and
therefore addiction. Addictive potential is also influenced by the mode of admin-
istration, with the smoking and intravenous injecting routes inducing more rapid
addiction than oral ingestion. Addictive substances tend to have a biphasic action,
whereby the hedonic effect is typically followed by negative symptoms consequent
on declining blood and tissue levels of the substance. The neurobiological changes
which occur in this phase could be regarded as “restorative,” with the aim of
returning neuronal systems to their normal functioning state.
The propensity of psychoactive substances to induce addiction therefore
ranges considerably depending on the mode of administration, the substance’s
pharmacodynamic and pharmacokinetic properties, and also the social setting in
which the substance is taken. Caffeine as occurs in coffee, tea, and certain soft
drinks and once considered a minor stimulant at the lowest end of the addiction
spectrum is listed in modern systems such as DSM-5 (American Psychiatric
Association 2013). Certain other substances have psychoactive properties and
are harmful, but are not or only rarely addictive. These include most of the
hallucinogens, where the acute psychoactive effects (often of a psychedelic or
psychotomimetic nature) commonly result in clinical presentations but where
addiction/dependence is very uncommon. Other substances such as sugar and
certain commercial soft drinks exist in a borderline area where addiction is
described, but is not typical and is often rare. Substances in this last domain
will not be further considered in the present chapter.
Many prescribed and proprietary (“over the counter”) medications have addic-
tive potential. Because of the commercial value of these medications, there is
controversy as to whether they should be termed addictive substances as opposed
to their inducing physiological dependence. In the medical community there is
a divergence of opinion between those who would exclude medication use when it
is being prescribed through a prescription or advised by a medical practitioner and
those authorities who regard the occurrence of a desire for repeated administration
of such medications and the occurrence of withdrawal symptoms to indicate that
addictive processes are present in the individual.
There are numerous psychological and social influences which determine whether
a substance with psychoactive properties is actually used, periodically or repeat-
edly, and may potentially lead to harmful consequences and addiction. An impor-
tant determinant is the availability of a particular substance in a society, and this is
in turn may be determined by whether it is of plant origin and requires particular
climatic conditions or level of rainfall to grow. Other substances are chemically
synthesized and require a corresponding level of knowledge and technical equip-
ment to produce.
Psychological mechanisms are involved in substance use becoming repetitive
use, and classical conditioning theory, operant conditioning theory, and social
learning theory all contribute to our understanding of how this eventuates. The
reader is referred to suitable reviews for further reference.
Neurobiological mechanisms come into play in particular when a pattern of
repetitive substance use has developed and result in that repetitive use tending to
become more stereotyped and self-perpetuating, being driven by internal cues
rather than external circumstances. The essential result of the neurobiological
mechanisms of addiction is the generation of an internal driving force, which is
enduring and which promotes further substance use even in the absence of
external cues and continues to do so even when circumstances are inappropriate
for substance use and the person may actually be experiencing harm as a result of
that use. The driving force of what is termed substance dependence or addiction
results in substance use occupying a more and more central role in the person’s
life, with other interests, enjoyments, activities, and responsibilities being rele-
gated to the periphery. Much has been learned about the neurobiological
172 J.B. Saunders and N.C. Latt
processes, and it appears there are interlinked neurocircuits which are “re-set” in
a person with addiction. These subserve reward, alertness (excitation), and
salience on behavioral control.
In summary, in the early period of psychoactive substance use, that use is
influenced strongly by external circumstances and also by the person’s mood
state. As repeated use continues and dependence develops, the repetitive use
reflects more the internal neurobiological mechanisms that have developed. It is
these mechanisms that result in repetitive substance use becoming more and more
syndromal and to produce the clinical disorders we recognize as addiction.
the dependence syndrome is subsumed under substance use disorder or alcohol use
disorder (American Psychiatric Association 2013).
Although many different systems of diagnosis and classification have been pro-
posed for substance use disorders over the years, two have international recogni-
tion. They are the Diagnostic and Statistical Manual of Mental Disorders (DSM) of
the American Psychiatric Association, Fourth and Fifth Editions (DSM-IV and
DSM-5 respectively) (American Psychiatric Association 1994, 2000, 2013),
11 Diagnostic Definitions, Criteria and Classification of Substance Use Disorders 175
which covers only mental and behavioral disorders, and the International
Classification of Diseases (ICD) of the World Health Organization (World Health
Organization 1992), now in its Tenth Revision (ICD-10), which is a classification of
all diseases, injuries, and causes of death.
The substance withdrawal syndrome refers to a state which may occur in persons with
the dependence syndrome (ICD-10; DSM-IV) and (in a smaller proportion) with
substance use disorder (DSM-5). The substance withdrawal syndrome refers to
a state seen in persons with the dependence syndrome when use is curtailed. It is
an important manifestation of the neurobiological changes that underpin dependence.
In general the features of the withdrawal syndrome are opposite to those of the
acute pharmacological effects of the substance. In contrast to dependence, the
withdrawal syndrome varies appreciably according to the substance. Psychostimulant
withdrawal is very different to withdrawal from sedative/hypnotics.
176 J.B. Saunders and N.C. Latt
Table 11.1 Diagnostic criteria for dependence/alcohol use disorder/substance use disorder in
ICD-10, DSM-IV, and DSM-5
DSM-5 alcohol use
disorder/substance use
ICD-10 dependence DSM-IV dependence disorder
Stem A maladaptive pattern of A problematic pattern of
substance use, leading to alcohol (other substance)
clinically significant use leading to clinically
impairment or distress, as significant impairment or
manifested by 3 or more of distress, as manifested by
the following occurring at at least two of the
anytime in the same following occurring within
12-month period a 12-month period
1. New in A strong desire or sense of No equivalent Craving or a strong desire
DSM-5 compulsion to take the criterion – mentioned in or urge to use alcohol
psychoactive substance text (or other substance)
(craving or compulsion)
2. No equivalent criterion but There is persistent desire There is persistent desire
text states that the or unsuccessful attempts to or unsuccessful efforts to
subjective awareness of cut down or control cut down or control
compulsion is most substance use alcohol (or other
commonly seen during substance) use
attempts to stop or control
substance use
3. Difficulties in controlling The substance is often Alcohol (or other
substance-taking behavior taken in larger amounts or substance) is often taken in
in terms of its onset, over a longer period of larger amounts or over
termination, or levels of time than was intended a longer period than was
use (loss of control) intended
4. Progressive neglect of Important social, Recurrent alcohol
alternative pleasures occupational, or (or other substance) use
because of psychoactive recreational activities are resulting in a failure to
substance use or increased given up or reduced fulfil major role
amount of time necessary because of drinking or obligations at work,
to obtain or take the psychoactive substance school, or home
substance or to recover use
from its effects
5. Subsumed in above A great deal of time is A great deal of time is
criterion spent in activities spent in activities
necessary to obtain the necessary to obtain
substance, use the alcohol(or other
substance, or recover from substance), use alcohol
its effects (or other substance), or
recover from its effects
(continued)
11 Diagnostic Definitions, Criteria and Classification of Substance Use Disorders 177
Repetitive substance use which does not fulfill the criteria for the dependence
syndrome is still of clinical significance. It is handled differently in the two systems.
In ICD-10 the term harmful use applies to repetitive use of a psychoactive sub-
stance which has caused physical or mental harm to that person. In DSM-IV the
11 Diagnostic Definitions, Criteria and Classification of Substance Use Disorders 179
Table 11.2 Diagnostic criteria for substance withdrawal in ICD-10 and DSM-IV and for alcohol
withdrawal in DSM-V
ICD-10 substance withdrawal DSM-IV (TR) substance DSM-5 alcohol withdrawal
syndrome withdrawal syndrome syndrome
1. Clear evidence of recent (A) The development of (A) Cessation of (or reduction
cessation or reduction of a substance-specific syndrome in) alcohol use that has been
substance use after repeated due to cessation of, or heavy and prolonged
and usually prolonged and/or reduction in, substance use
high dose use of that that has been heavy and
substance. One of the main prolonged
indicators of the dependence
syndrome
2. Symptoms and signs (B) The substance-specific (B) Two (or more) of the
compatible with the known syndrome causes clinically following developing within
features of a withdrawal state significant distress or several hours to a few days
from the particular substance impairment in social, after cessation of
or substances. Physical occupation, or other important
(or reduction in) alcohol use
symptoms vary according to areas of functioning described in criterion A:
the substance being used. 1. Autonomic hyperactivity
Psychological disturbances (e.g., sweating, PR > 100 bpm)
(e.g., anxiety, depression, 2. Increased hand tremor
sleep disorders) are also
3. Insomnia
common features of
withdrawal. Typically the 4. Nausea or vomiting
patient reports that 5. Transient visual, tactile, or
withdrawal symptoms are auditory hallucinations or
relieved by further illusions
substance use 6. Psychomotor agitation
7. Anxiety
8. Generalized tonic–clonic
seizures
3. The features are not (C) The symptoms are not due (C) The signs and symptoms
accounted for by a medical to a general medical condition in criterion B cause clinically
disorder unrelated to the and are not better accounted significant distress or
substance use and not better for by another mental disorder impairment in social,
accounted for by another occupational, or in other
mental or behavioral disorder important areas of functioning
The two systems that have most impact internationally are the ICD and the DSM,
under the auspices of the World Health Organization and the American Psychiatric
Association (APA) respectively. Several professional organizations have developed
definitions for use by their own members/fellows (the APA is a national profes-
sional organization, but the DSM has such international reach that it is more
appropriately classified as an international system). Foremost of these other orga-
nizations is the American Society of Addiction Medicine (ASAM). It employs the
term addiction rather dependence or “use disorders.” The ASAM definition of
addiction (American Society of Addiction Medicine 2011) is as follows:
Addiction is a primary, chronic disease of brain reward, motivation, memory and related
circuitry. Dysfunction in these circuits leads to characteristic biological, psychological,
social and spiritual manifestations. This is reflected in an individual pathologically pursu-
ing reward and/or relief by substance use and other behaviours.
Addiction is characterized by inability to consistently abstain, impairment in
behavioural control, craving, diminished recognition of significant problems with one’s
behaviours and interpersonal relationships, and a dysfunctional emotional response. Like
other chronic diseases, addiction often involves cycles of relapse and remission. Without
treatment or engagement in recovery activities, addiction is progressive and can result in
disability or premature death.
treatment programs and residential recovery programs. The definition has been
adopted, on a temporary basis, by the International Society of Addiction Medicine
and the Canadian Society of Addiction Medicine.
In the remaining part of this chapter, we shall describe the common substance-
induced mental disorders, with a brief comment only on substance-induced physical
disorders.
and fully within six months. The diagnosis is excluded if the psychotic state
is a manifestation of substance withdrawal syndrome. According to DSM-IV,
a substance-induced psychotic disorder is defined by (i) prominent hallucinations
or delusions developing during, or within a month of, substance intoxication or
withdrawal, (ii) the phenomenon is etiologically related to the disturbance, and (iii)
that the disturbance is not accounted for by a psychotic disorder that is not
substance-induced (American Psychiatric Association 2000).
In DSM-5 (Table 11.5) substance/medication-induced psychotic disorders, is
mentioned in the Chapter on Schizophrenia Spectrum and Other Psychotic Disor-
ders with the psychotic disorder associated with alcohol, cannabis, phencyclidine,
other hallucinogens, inhalants, sedative/hypnotic/anxiolytic, amphetamine
(or other stimulant), cocaine, and other unknown substance. The psychotic symp-
toms are thought to be a physiological consequence of a drug of abuse (medication
or toxin) and cease after removal of the agent. The onset of psychotic disorder
during intoxication of a substance is differentiated from that with onset during
withdrawal of the substance.
For psychostimulants such as amphetamines and cocaine, there is a dose–response
relationship, with psychosis occurring especially in those who have been using high
doses and/or over a lengthy period. According to ICD-10, a diagnosis of psychotic
disorder should not be made merely on the basis of perceptual distortions or hallu-
cinatory experiences when substances having primary hallucinogenic effects (e.g.,
lysergic acid (LSD), mescaline, and cannabis in high doses) have been taken. In such
cases, and also for confusional states, a possible diagnosis of acute intoxication
should be considered. DSM-IV has no such exclusion.
186 J.B. Saunders and N.C. Latt
11.2.12.3 Delirium
Delirium is an uncommon feature of substance misuse, although sometimes the
diagnosis is made in persons with acute intoxication. Substance intoxication with
delirium is an accepted diagnosis in DSM (American Psychiatric Association 1994,
2000, 2013), but not in ICD-10 (World Health Organization 1992). Most commonly
it is seen in those with a severe withdrawal syndrome from alcohol or sedative/
hypnotic drugs. The classical disorder is delirium tremens (DTs) (Saunders and
Janca 2000), which is a short-lived but occasionally life-threatening toxic-
confusional state with accompanying somatic disturbances. It is usually
a consequence of absolute or relative cessation of alcohol in severely dependent
drinkers with a long history of use. Its onset may be preceded by features of simple
withdrawal and/or by withdrawal convulsions. A similar withdrawal delirium is
seen after cessation of benzodiazepines and other sedative/hypnotics although with
less tremor. In DSM-5 substance intoxication delirium is differentiated from sub-
stance withdrawal delirium in the Chapter on Neurocognitive Disorders (American
Psychiatric Association 2013).
events are usually evident, as are difficulties in learning new material. Confabulation
may be marked, but is not invariably present and should not be regarded as
a prerequisite for diagnosis. Importantly, other cognitive functions are usually rela-
tively well preserved; the amnesic defects are therefore out of proportion to other
disturbances. Personality changes, often with apparent apathy and loss of initiative,
and tendency towards self-neglect may be present, but is not regarded as necessary
for diagnosis. The amnesic syndrome is not specified as such in DSM-5, but is listed
under substance/medication-induced major or mild neurocognitive disorder.
References
American Psychiatric Association (1952) Diagnostic and statistical manual for mental disorders.
American Psychiatric Association, Washington, DC
American Psychiatric Association (1968) The diagnostic and statistical manual of mental disor-
ders, second edition (DSM-II). American Psychiatric Association, Washington, DC
American Psychiatric Association (1994) The diagnostic and statistical manual of mental disor-
ders, fourth edition (DSM-IV). American Psychiatric Association, Washington, DC
American Psychiatric Association (2000) The diagnostic and statistical manual of mental
disorders, fourth edition, text revision (DSM-IV-TR). American Psychiatric Association,
Washington, DC
American Psychiatric Association (2013) The diagnostic and statistical manual of mental disor-
ders, fifth edition (DSM-5). American Psychiatric Association, Washington DC
American Society of Addiction Medicine (2011) Public policy statement: definition of addiction.
American Society of Addiction Medicine, Chevy Chase
Ball D (2008) Addiction science and its genetics. Addiction 103:360–367
Bandura A (1977) Social learning theory. Prentice-Hall, Eaglewood Cliffs
Bertholet N, Daeppen J-B, Wietlisbach V, Fleming M, Burnand B (2005) Reduction of
alcohol consumption by brief alcohol intervention in primary care. Arch Intern Med 165:986–995
Dawson DA (2000) Alcohol consumption, alcohol dependence and all-cause mortality. Alcohol
Clin Exp Res 24:72–81
Dawson DA, Grant BF, Li T-K (2005) Quantifying the risks associated with exceeding
recommended drinking limits. Alcohol Clin Exp Res 29:902–908
Degenhardt L, Lynskey M, Coffey C, Patton G (2002) ‘Diagnostic orphans’ among young adult
cannabis users: persons who report dependence symptoms but do not meet diagnostic criteria.
Drug Alcohol Depend 67:205–212
Edwards G, Gross MM (1976) Alcohol dependence: provisional description of a clinical syn-
drome. Br Med J 1:1058–1061
Edwards G, Arif A, Hodgson R (1981) Nomenclature and classification of drug and alcohol-
related problems: a WHO memorandum. Bull World Health Organ 59:255–242
Eng MY, Schuckit MA, Smith TL (2003) A five-year prospective study of diagnostic orphans for
alcohol use disorders. J Stud Alcohol 64:227–234
Feingold A, Rounsaville B (1995) Construct validity of the dependence syndrome as measured by
DSM-IV for different psychoactive substances. Addiction 90:1661–1669
Jellinek EM (1960) The disease concept of alcoholism. Hillhouse Press, New Brunswick
Kaner EF, Dickinson HO, Beyer F, Pienaar E, Schlesinger C, Campbell F, Saunders JB,
Burnand B, Heather N (2009) The effectiveness of brief alcohol interventions in primary
care settings: a systematic review. Drug Alcohol Rev 28:301–323
Krabman PB, Saunders JB (1996) Diagnostic criteria for substance misuse and dependence. In:
Rommelspacher H, Schuckit MA (eds) Bailliere’s Clinical Psychiatry, vol 21. Baillière
Tindall, London, pp 375–404
Latt N, Conigrave KM, Saunders JB, Marshall EJ, Nutt DJ (2009) Oxford specialist handbook of
addiction medicine. Oxford University Press, Oxford
Ledermann S (1960) Alcool, alcoolism, alcoolisation: données scientifiques de caractère
physiologique, économique et social. Presses Universitaires de France, Institut National
d’Etudes Demographiques, Paris
Lejoyeux M, McLoughlin M, Ades J (2000) Epidemiology of behavioural dependence: literature
review and results of original studies. Eur Psychiatry 15:129–134
11 Diagnostic Definitions, Criteria and Classification of Substance Use Disorders 189
National Institute on Alcohol Abuse and Alcoholism (2005) Helping patients who drink too much:
a clinician’s guide. National Institute on Alcohol Abuse and Alcoholism, Rockville
Nelson CB, Rehm J, Ust€ € un TB, Grant B, Chatterji S (1999) Factor structures for DSM-IV
substance disorders criteria endorsed by alcohol, cannabis, cocaine and opiate users: results
from the WHO reliability and validity study. Addiction 94:843–855
Owen RT, Tyrer P (1983) Benzodiazepine dependence: a review of the evidence. Drugs
25:385–398
Potenza MN (2006) Should addictive disorders include non-substance related conditions? Addic-
tion 101(s1):142–151
Room R (1989) Drugs, consciousness and self-control: popular and medical conceptions. Int Rev
Psychiatry 1:63–70
Roy A, Pandey SC (2002) The decreased cellular expression of neuropeptide Y protein in rat brain
structures during ethanol withdrawal after chronic ethanol exposure. Alcohol Clin Exp Res
26:796–803
Russell M, Light JM, Gruenewald PJ (2004) Alcohol consumption and problems: the relevance of
drinking patterns. Alcohol Clin Exp Res 28:921–930
Saha TD, Chou PS, Grant BF (2006) Toward an alcohol use disorder continuum using item
response theory: results from the National epidemiologic survey on alcohol and related
conditions. Psychol Med 36:931–941
Saha TD, Stinson FS, Grant BF (2007) The role of alcohol consumption in future classification of
alcohol use disorders. Drug Alcohol Depend 89:82–92
Saunders JB (1982) Alcoholism: new evidence for a genetic contribution. Br Med
J 284:1137–1138
Saunders JB (2006) Substance dependence and non dependence in the diagnostic and statistical
manual of mental disorders (DSM) and the international classification of diseases (ICD): can an
identical conceptualization be achieved? Addiction 101(s1):49–59
Saunders JB, Janca A (2000) Delirium tremens: its aetiology, natural history and treatment.
Current Opinion Psychiatry 13:629–633
Sobell MB, Sobell LC (1993) Problem drinkers: guided self-change treatment. Guilford Press,
New York/London
Teesson M, Lynskey M, Manor B, Baillie A (2002) The structure of cannabis dependence in the
community. Drug Alcohol Depend 68:266–262
Volkow ND, Fowler JS, Wang GJ (2004) The addicted brain viewed in the light of imaging
studies: brain circuits and treatment strategies. Neuropharmacology 47:3–13
World Health Organization (1992) The ICD-10 classification of mental and behavioural disorders:
clinical descriptions and diagnostic guidelines. World Health Organization, Geneva
World Health Organization (2004) Neuroscience of psychoactive substance use and dependence.
World Health Organization, Geneva
Y€ucel M, Lubman DI (2007) Neurocognitive and neuroimaging evidence of behavioural
dysregulation in human drug addiction: implications for diagnosis, treatment and prevention.
Drug Alcohol Rev 26:33–39
Further Reading
Koob GF (2006) The neurobiology of addiction: a neuroadaptational view relevant for diagnosis.
Addiction 101(s1):24–31
Lessov CN, Martin NG, Statham DJ, Todorov AA, Slutske WS, Bucholz KK, Heath AC, Madden
PAF (2004) Defining nicotine dependence for genetic research: evidence from Australian
twins. Psychol Med 34:865–879
Sartorius N, Kaelber CT, Cooper JE, Roper NT, Rae DS, Gulbinat W, Ust€ € un TB, Regier DA
(1993) Progress toward achieving a common language in psychiatry: the clinical guidelines
accompanying the WHO classification of mental and behavioural disorders in ICD-10. Arch
Gen Psychiatry 50:115–124
Screening, Early Detection and Brief
Intervention for Alcohol Use Disorders 12
John B. Saunders and Noeline C. Latt
Contents
12.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192
12.1.1 Broadening the Spectrum of Intervention for Alcohol Use Disorders . . . . . . . 192
12.2 Screening and Brief Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
12.2.1 The Spectrum of Hazardous Consumption and Alcohol Use Disorders . . . . . 193
12.2.2 Development of the AUDIT and Other Screening Instruments . . . . . . . . . . . . . . 195
12.2.3 Brief Interventions: Background and Evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
12.2.4 Implementation of Screening and Brief Intervention in
Clinical Practice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
12.2.5 Brief Intervention in Practice: The Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202
12.2.6 Development of Electronic Screening and Brief Intervention . . . . . . . . . . . . . . . . 202
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
Abstract
Self-recognition of an alcohol use disorder is often late in the natural history of
this condition. Because of this and the limited impact of treatment for patients
with late-stage complications of their alcohol problem, there has been consider-
able effort made to identify alcohol consumption where it has reached a hazard-
ous or risky stage or is starting to cause problems, before dependence becomes
12.1 Introduction
Kristenson et al. (1983) and Heather et al. (1987). Since those early days, there has
been a substantial effort to develop screening instruments, such as the Alcohol Use
Disorders Identification Test (AUDIT) and the development of brief structured ther-
apies designed to be used at the time hazardous and harmful alcohol use is identified.
This approach has been endorsed by many authorities. In 1990, an influential
report from the US Institute of Medicine recommended that healthcare responses
should extend beyond the provision of treatment for people with established alcohol
dependence (or “alcoholism”) to encompass early detection and treatments in
primary care and in other non-specialist settings. It noted the evidence accumulat-
ing for the effectiveness of opportunistic screening and brief intervention for
hazardous and harmful alcohol consumption. In the United Kingdom, the National
Institute for Health and Clinical excellence in 2010 supported the widespread
implementation of brief intervention approaches.
Screening and brief intervention is analogous to screening for asymptomatic
hypertension and hyperlipidemia and indeed screening for a range of medical,
mental, and social disorders. It is predicated on the basis that early detection and
treatment of a disorder in its developmental stage has advantages over treatment of
the established disorder in terms of reduced morbidity, better and more guaranteed
response to treatment, and the avoidance of the costs of treating the advanced
disorder and prevention of premature mortality.
This chapter will (1) review the current criteria for hazardous/unhealthy alcohol
consumption, (2) examine the available screening instruments (focusing on instru-
ments specifically derived to screen for a range of hazardous consumption and
alcohol use disorders), (3) review the evidence for the effectiveness of brief
interventions, (4) examine the implementations of such interventions in healthcare
systems, and (5) conclude with an outline of the key therapeutic components of
brief interventions. Mention will also be made of electronic screening and brief
intervention which has been developed to further broaden the access of people with
hazardous or unhealthy patterns of alcohol consumption to information and advice,
who otherwise might not be engaged in the healthcare system.
Alcohol use and misuse exist as a continuum, and an important realization is that
harm can occur at many points along this continuum. Accidents can occur due to
a single episode of excessive consumption, and they are more likely to occur with
repeated bouts of drinking; social problems can arise due to intoxicated behaviors,
and acute medical disorders may also arise from periodic binges. Many chronic
disease states are linked to regular consumption of alcohol that may not reflect
alcohol dependence. Although the risks of all these are multiplied on people who
194 J.B. Saunders and N.C. Latt
have alcohol dependence, and it is right that much attention be paid to this group, it
is important to capture a broad range of consumption patterns and alcohol disorders.
The risk of harm is related to the level of alcohol consumption and the frequency
and duration of consumption. For many harmful consequences, there appears to be
a threshold of consumption below which harm is not seen or occurs only infre-
quently. In many countries, national authorities have defined hazardous (or risky or
unhealthy) alcohol use. Some examples are as follows:
(a) United States: for women, more than seven drinks per week or more than three
drinks per occasion and, for men, more than 14 drinks per week or more than
four drinks per occasion (one drink being approximately 13 g of alcohol)
(US Preventive Services Task Force 2013).
(b) United Kingdom: for men, over 40 g alcohol (five units) per day or 21 units per
week and, for women, over 24 g alcohol (three units) per day or 14 units per week
(one unit approximately equivalent to 8 g alcohol) (SIGN Guidelines 2003).
(c) Australia: more than two standard drinks on any day (for both men and women)
or more than four standard drinks on a single occasion (one standard drink being
approximately 10 g of alcohol). For those under the age of 16 years or if
a woman is pregnant or planning to become pregnant or breastfeeding, the
safest option is not to drink alcohol (NH & MRC 2009).
The term alcohol use disorders is typically used to denote a repetitive pattern of
alcohol consumption. It may be facilitated by external factors such as cultural
norms and practices, peer pressure, work culture, and work pressure or internal
factors such as the person’s feelings and mental state or desire to experience the
euphoria and state of intoxication that alcohol can cause. Non-dependent alcohol
use disorders include ICD 10 harmful alcohol use, DSM-IV alcohol abuse, and part
of the spectrum of the recently defined DSM-V alcohol use disorder. DSM-IV
alcohol abuse is defined as a maladaptive pattern of alcohol use over a twelve-
month period, leading to clinically significant failure to fulfill major obligations at
work, school, or home; legal problems; or interpersonal problems, or when it is
physically hazardous. “Unhealthy alcohol use” is a term referring to that spectrum
of alcohol use that can result in health consequences and broadly covers hazardous/
harmful drinking, alcohol abuse, or alcohol dependence (Saitz 2005; Saitz
et al. 2013).
Alcohol dependence is a psychobiological syndrome and is best understood as
a disorder where there is a persistent internal drive to consume alcohol such that
alcohol increasing takes “center stage” in the person’s life and other enjoyments,
activities and responsibilities are pushed to the periphery. It reflects enduring
changes in key neurocircuits that subserve reward, alertness, response control,
and salience in the ventral tegmental area of the midbrain, the nucleus accumbens,
and related structures of the lower forebrain and with projections to and from the
prefrontal gyrus and the circulate gyrus of the cortex. It is more “disease-like” than
any other form of repetitive alcohol use and tends to be self-perpetuating and to run
true when active at different periods in the person’s life.
For this spectrum of hazardous alcohol use and alcohol use disorder, there is
a need for reliable methods of screening and intervention. The term “screening and
12 Screening, Early Detection and Brief Intervention for Alcohol Use Disorders 195
The modern era of screening for hazardous alcohol consumption and alcohol
use disorders began with the development of the Alcohol Use Disorders Identifi-
cation Test (AUDIT) (Saunders and Aasland 1987; Saunders et al. 1993; Babor
et al. 1992). Prior to the development of the AUDIT, alcohol screening instruments
focused on the detection of alcoholism. They were not designed to detect the
range of alcohol use disorders or hazardous/unhealthy alcohol consumption,
the reason being that these concepts had not gained general acceptance at the
time the older instruments were introduced. These older instruments include
the Michigan Alcoholism Screening Test (MAST), developed in 1971 and
which exists in several versions including brief ones and the four-item CAGE
(Ewing 1984).
The AUDIT has its origins in the WHO collaborative work that was initiated by
the Expert Committee and was derived from findings in a World Health Organiza-
tion collaborative study. The AUDIT was developed from the empirical selection of
items contained in a WHO assessment instrument, comprising more than 150 ques-
tions. Participating centers from six countries around the world (which represented
different cultures, healthcare systems, stages of economic development and polit-
ical systems) were involved. The ten items which formed the AUDIT were those
which had the following characteristics:
1. They had the highest or comparably high item-to-total correlations with the
domains they represented.
2. Individually and collectively they had the greatest discriminatory value between
patients who had hazardous consumption and/or alcohol use disorders and those
who did not.
3. The questions not only conformed to the then bi-dimensional concept of alcohol
dependence and its consequences but extended it to a tridimensional concept
of (i) intake measures, (ii) measures of the urge or drive to consume alcohol
(and putative dependence), and (iii) direct or proxy measures of alcohol-related
consequences.
4. The sensitivity and specificity and positive and negative predictive values for the
AUDIT in clinical and also epidemiology populations indicated a high degree of
accuracy of classification and therefore practical utility.
5. Likewise the sensitivity and specificity of questions in the three individual
domains were psychometrically acceptable.
6. The questionnaire as a whole and questions within the three domains had
acceptable psychometric performance as judged by measures such as
Cronbach’s Alpha Coefficient.
196 J.B. Saunders and N.C. Latt
7. Each individual question had high face validity and the meaning of the question
was clear and it explicitly mentioned the link with alcohol consumption.
8. Each question was suitable in providing a means of exploring further the
patient’s experiences with alcohol and the questionnaire as a whole was suitable
as a framework for intervention.
9. The individual questions could be translated readily and accurately (both
grammatically and idiomatically) into major world languages.
Subsequent studies showed that the AUDIT Questions:
1. Performed as a stand-alone questionnaire as it did when the questions were
embedded in a general health screening instrument
2. Had high acceptance among populations being screened
3. Could be adapted easily to electronic format including interactive media where
feedback on the AUDIT score and on responses to individual questions could be
provided
The AUDIT questionnaire offers a simple and systematic way of assessing alcohol
intake (Questions 1–3), alcohol dependence (Questions 4–6), and alcohol-related
harm (Questions 7–10). The questionnaire may be self-administered while the patient
is awaiting the consultation or may be used by the clinician during the assessment.
Responses in the AUDIT are quantified from 0 (far left column) to 4 (far right column)
for Questions 1–8 and 0, 2, and 4 for Questions 9–10. The AUDIT score may range
from 0 (for an abstainer of alcohol) to 40. A presumptive diagnosis of hazardous or
harmful consumption is made if the AUDIT score is 8 or above. More severe harm and
dependence are likely when the score is 13 or more and to be extremely likely if the
score is 20 or more. The scores on the AUDIT can also point to the intervention
required, if any. Scores of 0 and 1–7 may result in some feedback but otherwise no
specific intervention. A score of 8 or more merits a brief intervention, with scores of
13 or more (and certainly 20 or more) alerting the clinician to the need for detoxifi-
cation and referral for specialist treatment. Assessment by completion of the AUDIT
questionnaire itself is reported to reduce hazardous drinking (Kypri et al. 2007)
Several derivatives of the AUDIT have been published over the years. The most
popular of these is the AUDIT-C, which comprises simply the first three questions
of consumption measures. The shorter three-item AUDIT-C has been shown to be
a more convenient and effective instrument for diagnosing alcohol use disorders in
a primary care setting, viz.:
1. How often do you have a drink containing alcohol?
2. How many standard drinks containing alcohol do you have on a typical drinking
day?
3. How often do you have four drinks (for women) and six drinks (for men) or more
on one occasion?
Scores of 3 or more in women and 4 or more in men have a sensitivity of 73 %
and 86 % and a specificity of 91 % and 89 %, respectively. (Bradley et al. 2007)
A score of 7–10 or more indicates alcohol dependence (Rubinsky et al. 2010).
At a minimum, one question on the quantity of alcohol consumed can be asked.
“How many times in the past year have you had five (for men) or four (for women)
or more drinks in a day?” (a positive test was considered to be a response >0) was
12 Screening, Early Detection and Brief Intervention for Alcohol Use Disorders 197
found to be useful in primary care (Smith et al. 2009). In the FAST, the consump-
tion question is “How often do you have eight (or for women six) or more standard
drinks on one occasion?” A response of monthly or more is considered a positive
answer. Three further questions make up the FAST (Hodgson et al. 2002) with
a score of three or more indicating hazardous alcohol drinking.
Some alcohol screening instruments have been developed to identify hazardous
consumption and alcohol use disorders within specific populations such as women,
pregnant women, adolescents, and the elderly. These include the TWEAK to screen
for alcohol use during pregnancy (Russell et al. 1991).
Another relevant screening test is the WHO Alcohol, Smoking and Substance
Involvement Screening Test (ASSIST). ASSIST is a combined screen for drug and
alcohol misuse and is available for self-completion while the patient is in the
waiting room or hospital clinic. It is designed to inquire about alcohol use in
context of health inquiries to detect problem or risky alcohol and other substance
use in primary health care. It is linked to a brief intervention based on the acronym
FRAMES and incorporates motivational interviewing (WHO ASSIST Working
Group 2002; Newcombe et al. 2005).
In 2001, a smoking, nutrition, alcohol, and physical activity (SNAP)
framework developed by the Australian government Department of Health and
Aging (SNAP 2001) was found to fit well with general practice consultations
(Harris et al. 2005).
Once a person has been identified, through screening or clinical inquiry, as having
an alcohol use disorder, a brief, focused form of therapy is beneficial. The usual
term to describe this is “brief alcohol intervention.” As described above, brief
intervention aims to engage with people who have hazardous or harmful alcohol
consumption, using the DSM terms alcohol abuse (DSM-IV) or alcohol use disor-
der (DSM-V). The focused advice and therapy is provided before the person has
developed alcohol dependence or severe physical, mental, or personal problems.
Brief intervention is therefore a proactive strategy comprising provision of brief
advice on the consequences of hazardous/harmful drinking or alcohol abuse,
feedback of harm and relating this to the patient’s excess drinking, setting goals
for safe levels of drinking, outlining benefits obtained from cutting down drinking,
and setting strategies to overcome “at-risk” times. The intervention may take only
4–5 mins.
There is a wealth of evidence attesting to the effectiveness of brief alcohol
interventions in reducing alcohol intake and alcohol-related problems in persons
with alcohol use disorders. Approximately 50 randomized controlled trials of
various forms of brief intervention compared with no intervention or an alternative
form of intervention have been published. Furthermore, several meta-analyses have
been published since the early 2000s. A Cochrane Collaboration review of 23 trials
of a number of interventions, most commonly brief interventions, for preventing
198 J.B. Saunders and N.C. Latt
identified. Combining that with the NNT of 5–6 for alcohol consumption leads to
the result that on average 45 patients in primary care will need to be screened for
each person with hazardous alcohol consumption to become a low-risk drinker.
This indicates the degree of effort required to provide brief intervention in practice
although information on alcohol consumption is relevant to much of the health care
when other issues such as the potential for interactions with medications and advice
needed for pregnant women and people with a range of chronic medical disorders
are taken into consideration.
Screening and early detection therefore has a greater role than leading to a brief
intervention. Early detection can often result in the correct diagnosis being expe-
dited, with the patient being spared unnecessary investigations. Equally important,
knowledge of the alcohol use disorder may prevent months or indeed years of
inappropriate or ineffective treatment for patients who have disorders that may be
related to alcohol consumption, such as hypertension, esophagitis and gastritis,
anxiety, depression, and recurrent headache. It can also often provide an answer for
patients who have multiple nonspecific and seemingly unconnected symptoms.
Efforts to facilitate the implementation of screening and brief intervention in
primary care began with the original WHO collaborative study. When evidence
became available for the effectiveness of brief alcohol interventions in this collab-
orative study, thoughts were directed to how these interventions could be
implemented in the primary care system. Phase III of the collaborative study
included analyses of barriers to intervention and approaches that would facilitate
the implementation of these interventions. This work, described above, led to
controlled studies of implementation techniques (Saunders and Wutzke 1996;
Gomel et al. 1998; and Funk et al. 2005). These studies examined the effectiveness
of different promotional approaches to elicit interest in general practitioners in
receiving materials to undertake screening and brief intervention. These studies
conducted in six countries showed that direct mail techniques elicited a request for
brief intervention materials among approximately half of general practitioners
while telephone marketing and personal marketing (similar to pharmaceutical
company academic detailing) had uptake rates of around 80 %. Thus, promotional
techniques familiar to the commercial world could be adapted to the dissemination
of brief alcohol interventions.
The next component of this work was to examine the effect of various training
and support techniques in the actual provision of these interventions. Several such
techniques were compared, with the end point being the proportion of patients with
hazardous alcohol consumption who actually underwent screening and received an
appropriate brief intervention. Results showed that among general practices where
on-site training had been provided but where there was no subsequent training or
support, approximately one-third of patients with hazardous consumption had
received a brief intervention over the three-month period the study was being
undertaken. On-site training followed by various levels of telephone-based support
and personal contact resulted in up to 70 % of patients with hazardous consumption
receiving an appropriate alcohol intervention.
Findings such as these would suggest that the widespread provision of training
and subsequent support would be a successful means of incorporating screening and
brief intervention into primary care. However, when an assessment was undertaken
a year later, much of the screening and brief intervention had ceased. Medical
practitioners typically reported they found the work interesting and they appreci-
ated being involved in the study. However, in the absence of structural and
contractual supports for brief interventions, their provision naturally tailored off
and only approximately 10 % of practitioners were still providing them in any
systematic way 1 year later.
12 Screening, Early Detection and Brief Intervention for Alcohol Use Disorders 201
1. FLAGS:
Feedback: Problems experienced or likely to occur and link this with
unhealthy drinking.
Listen: Listen to the patient’s response and assess his/her readiness to change
(use motivational interviewing techniques as required) (Prochaska et al; 1992).
Advice: Give clear advice to change and/or reduce unhealthy levels of
drinking; list the benefits of change.
Goals: Negotiate goals to reduce drinking to recommended limits.
Strategies: Discuss practical methods and strategies, for example, how to
determine at-risk times, and develop coping strategies.
References
American Psychiatric Association (DSM IV TR) (2000) Diagnostic and statistical manual of
mental disorders, Text revision 1V. American Psychiatric Association, Washington, DC
American Psychiatric Association (DSM V) (2013) Diagnostic and statistical manual of mental
disorders, 5th edn. American Psychiatric Association, Washington DC/London
Babor TF, Grant M (eds) (1992) W.H.O. Project on identification and management of alcohol-
related problems. World Health Organization, Geneva
Beich A, Thorsen T, Rollnick S (2003) Screening in brief intervention trials targeting excessive
drinkers in general practice: systematic review and meta-analysis. BMJ 327(7414):536–542
Bien TH, Miller WR, Tonigan JS (1993) Brief interventions for alcohol problems: a review.
Addiction 88(3):315–335
BMJ Practice Guidelines (2011) Diagnosis, assessment, and management of harmful drinking and
alcohol dependence: summary of NICE guidance. BMJ 342:d700
Bradley KA, DeBenedetti AF, Volk RJ et al (2007) AUDIT C as a brief screen for alcohol misuse
in primary care. Alcohol Clin Exp Res 31:1208
Conigrave KM, Davies P, Haber P, Whitfield J (2003) Traditional markers of excessive alcohol
use. Addiction 98(Suppl 2):31
Cuijpers P, Riper H, Lemmets L (2004) Effects on mortality of brief interventions for problem
drinking: a meta-analysis. Addiction 99(7):839–845
Dinh-Zarr TB, Goss CW, Heitman E et al (2009) Interventions for preventing injuries in problem
drinkers. Cochrane Injury Group, The Cochrane Library. http://onlinelibrary.wiley.com/doi/
10.1002/14651858.pub2/full
Drummond C, Coulton S, James D et al (2009) Effectiveness and cost effectiveness of a stepped
care intervention for alcohol use disorders in primary care: pilot study. Br J Psychiatry
195:448–456
Ewing J (1984) Detecting alcoholism (the CAGE questionnaire). J Am Med Assoc
252:11905–11907
Funk M, Wutzke S, Kaner E, Anderson P, Pas L, McCormick R, Gual A, Barford S, Saunders J
(2005) A multicountry controlled trial of strategies to promote dissemination and implemen-
tation of brief alcohol intervention in primary health care: findings of a World Health
Organization collaborative study. J Stud Alcohol 66:379–388
Gomel MK, Wutzke SE, Gardcastle DM, Lapsley H, Reznik RB (1998) Cost-effectiveness of
strategies to market and train primary health care physicians in brief intervention techniques
for hazardous alcohol use. Soc Sci Med 47:203–211
Harris MF, Hobbs C, Powell Davies G et al (2005) Implementation of a SNAP intervention in two
divisions of general practice: a feasibility study. Med J Aust 183(10):S54–S58
Havard A et al (2008) Systematic review and meta-analysis of strategies targeting alcohol
problems in emergency department: interventions reduce alcohol related injuries. Addiction
103:368–376
Heather N, Campion P, Neville R, Maccabe D (1987) Evaluation of a controlled drinking Minimal
intervention for problem drinkers in general practice (the DRAMS scheme). J R Coll Gen Pract
37:358–363
Hodgson R, Alwyn T, John B et al (2002) The FAST alcohol screening test. Alcohol Alcohol
37(1):61–66
IOM (Institute of Medicine), Division of Mental Health and Behavioural Medicine (1990) Broad-
ening the base of treatment for alcohol problems. National Academy Press, Washington, DC
Kaner EF, Dickinson HO, Beyer FR, Pienaar ED, Campbell F, Schlesinger C, Heather N, Saunders
JB, Burnand B (2007) Effectiveness of brief alcohol interventions in primary care populations.
Cochrane Database Syst Rev (2). Article no. CD004148
Kaner EF, Dickinson HO, Beyer F, Pienaar E et al (2007a) The effectiveness of brief alcohol
interventions in primary care settings: a systematic review. Drug Alcohol Rev 28(3):301–323
12 Screening, Early Detection and Brief Intervention for Alcohol Use Disorders 205
Smith PC, Schmidt SM, Allensworth-Davies D, Saitz R (2009) Primary care validation of a single
question alcohol screening rest. J Gen Intern Med 24:783
Smoking, nutrition, alcohol, physical activity (SNAP) framework for general practice. Canberra:
Australian Government Department of Health & Ageing. 2001. http://www.health.gov.au/
internet/wcm,s/Publishing.nsf/Content/health-pubhlth-about-gp-snap-cnt.htm
US Preventive Service Task Force (2004) Screening and behavioral counseling interventions in
primary care to reduce alcohol misuse. Ann Intern Med 140:554–556
US Preventive Services Task Force (2013) http://www.uspreventiveservicestaskforce.org/
Whitlock EP, Polen MR, Green CA et al (2004) Behavioural counselling interventions in primary
care to reduce risky/harmful alcohol use by adults: a summary of the evidence for the US
Preventive Services Task Force. Ann Intern Med 140:557–568
WHO ASSIST Working Group (2002) Working group: alcohol, smoking and substance
involvement screening test (ASSIST): development, reliability and feasibility. Addiction
97:1183–1194
World Health Organization (1992) The ICD 10 Classification of mental and behavioural
Disorders: clinical descriptions and diagnostic guidelines. WHO, Geneva
Wutzke SE, Conigrave KM, Saunders JB, Hall WD (2002) The long-term effectiveness of brief
interventions for unsafe alcohol consumption: a 10-year follow-up. Addiction 97:665–675
Screening for Nicotine and Drug Use
Disorders 13
Sawitri Assanangkornchai and J. Guy Edwards
Contents
13.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208
13.2 Facets of Drug Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208
13.2.1 Screening in Different Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208
13.2.2 Primary Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
13.2.3 Secondary Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
13.2.4 Medicolegal Practice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
13.2.5 Some General Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
13.2.6 Screening Instruments for Tobacco and Drug Use Disorders . . . . . . . . . . . . . . . 212
13.2.7 Instruments Enquiring About Different Drug Types in a
Disaggregated Form . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212
13.2.8 Instruments Enquiring About Drug Use in an Aggregated Form . . . . . . . . . . . 218
13.2.9 Instruments Specific to One Drug . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
13.2.10 The Fagerström Test for Nicotine Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
13.2.11 Instruments Enquiring About Multiple Problems, Including
Comorbidity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
13.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
Abstract
Screening aims at detecting substance use, ideally at an early stage, with a view
of providing subsequent treatment if required. It is most productively employed
in populations in whom there is a high prevalence of use, such as general and
S. Assanangkornchai (*)
Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
e-mail: [email protected]
J.G. Edwards
Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
Department of Psychiatry, Royal South Hants Hospital, Southampton, UK
e-mail: [email protected]
emergency medical patients, those attending clinics for pain or sexually trans-
mitted disorders, and people who have come into conflict with the law. It is of
less value in well-staffed facilities that already routinely enquire about substance
use during comprehensive clinical assessments.
Numerous screening instruments have been designed – those that screen
for different substances in an aggregated or disaggregated way, those for one
specific substance, and those for substance-related problems – but relatively few
have satisfactory psychometric properties. Examples of instruments that
screen for nicotine or drug use disorders or for multiple substances are the
Alcohol, Smoking, and Substance Involvement Screening Test, CAGE-AID
(mnemonic for items Cut down, Annoyed, Guilty, Eye-opener-Adapted to
Include Drugs), Drug Abuse Screening Test, and the Fagerström Test
for Nicotine Dependence. The choice of an instrument should depend on its
psychometric properties, the population being screened, availability of staff to
use it properly, and the practicality of introducing it into the facility.
Ethical aspects of the use of the instruments are important. Outside
purely research settings, screening will have limited value unless follow-on
treatment is available, and substance misusers are encouraged to accept it and
adhere to it. The best test of the true value of screening will be in the prevention of
Longer-term medical and psychosocial consequences of substance misuse.
13.1 Introduction
Screening for substance use and use disorders helps identify people who have
suffered the consequences of using one or more substances or are at risk of future
harm if they continue to use the substance(s). It aims to detect problems at an early
stage and can be followed by treatment if indicated. Screening instruments for drug
misuse have been evaluated in the community and health-care facilities and in
relation to the law.
Patients do not go to their doctors to be screened or rated, but to talk about their
problems, to be listened to, and to receive treatment. In an ideal world, it should not
be necessary to screen for substance use, because there would be adequately trained
staff to carry out a comprehensive assessment that would “automatically” take all
aspects of substance use into consideration. However, in the imperfect world in
which we live – a world in which the demand for services greatly outstrips supply
and conveyor-belt medicine is forced on us – screening offers a useful helping hand.
It can also help educate personnel unfamiliar with substance misuse on the most
important questions to ask and serve as an aide memoir for those who are already
familiar with them.
Primary care deals with a wide range of people and an equally wide range of
lifestyles and disorders, including substance misuse disorders. Its workers are
usually seen as trustworthy, and it provides an excellent opportunity for early
identification. We therefore endorse WHO recommendations on screening in
general practice, with consideration given to the use of the Alcohol, Smoking,
and Substance Involvement Screening Test (ASSIST; World Health Organization
2012) when time and/or staffing permits. Otherwise, shorter, simpler instruments
should be used.
departments and concluded that for cannabis this single question was sufficient: “In
the past year, how often have you used cannabis?” with the response categories,
“Once or less” or “Two or more times.” The same question, reworded to screen for
other drugs, might therefore be sufficient for them also (Newton et al. 2011).
13.2.5.1 Ethics
Even when using a simple screening instrument, it is important that we remain
aware of the concerns and sensitivities of our patients/clients, concerns such as
embarrassment or fear of the legal and other social consequences of drug use. It is
essential that honesty and transparency are central to our dealings with patients.
Patient’s anxieties can be allayed by emphasizing that the decision to reveal
information in response to questions asked by the instrument is theirs and theirs
alone. In health-care settings, the patient should be assured that anything revealed
will be treated in strict confidence and not disclosed to others without their permis-
sion. In the justice system, the extent to which information will be disclosed to others
will need to be made explicit. Doing this is particularly important in medicolegal
work, whether in civil or criminal cases, and especially so when dealing with
delinquent youngsters to help gain their trust, confidence, and cooperation.
Screening instruments for substance use disorders are categorized into four groups:
instruments that enquire about different types of drugs in a disaggregated way,
enquire about drug use in an aggregated way, are specific to one drug, and enquire
about multiple problems, including comorbidity (Table 13.1).
Examples in this group include the WHO Alcohol, Smoking, and Substance
Involvement Screening Test (ASSIST) and its modified forms and the Drug History
Questionnaire (DHQ).
13.2.7.1 ASSIST
The ASSIST is a screening instrument developed by a group of WHO researchers to
help detect substance use and related problems in primary and general medical care.
It can help health workers identify the level of risk for each substance identified. It
seeks information on the use of all types of psychoactive substances, including
tobacco, alcohol, cannabis, cocaine, amphetamine-type stimulants, sedatives, hal-
lucinogens, inhalants, and opioids. It asks if any of these have ever been used and, if
so, the frequency of use during the past three months; if the respondents have had
a strong desire or urge to use the substance; the frequency of any problems they
Table 13.1 Screening instruments for drug use and drug use disorders
13
Approx. time
Instrument Full name References Population studied Time frame No. of items Administered by required Score
(a) Instruments enquiring about different drug types in a disaggregated form
ASSIST Alcohol, Smoking World Health Adults Lifetime 8 items Clinician- 10 min for 0–3: low risk, no
and Substance Organization Past administered administration, intervention (0–10
Involvement (2002) 3 months interview 5 min for for alcohol)
Screening Test Computer- scoring 4–26: moderate
administered risk, brief
format available intervention (11–26
Adolescent for alcohol)
version available 27+: high risk,
more intensive
intervention
DHQ Drug History Sobell et al. Adults Lifetime 5 items Self-administered 5–10 min No specific cutoff
PDHQ Questionnaire (1995) Past
Psychoactive 6 months
Screening for Nicotine and Drug Use Disorders
Drug History
Questionnaire
(b) Instruments enquiring about drug use in an aggregated form
CAGE-AID Cut down, Annoyed, Brown and Adolescent; Lifetime 4 items Self-administered 5 min Range: 0–4
Guilty, Eye-opener- Rounds patients with Cutoff score 1 or
Adapted to Include (1995) comorbidity; more for drug
Drugs adults dependence
CRAFFT Car, Relax, Alone, Knight Adolescents Lifetime 6 items Interviewed, self- 5 min Range: 0–6
RAFFT Forget, Friends, et al. (1999) American Indian/ Past year administered, Cutoff score of 2
Trouble native Alaskans computerized for risky use
DAST Drug Abuse Skinner Adults Lifetime 10, 20, 28 Self-administered 5–10 min Range: 0–10, 20, 28
Screening Test (1982) College students; items Adolescent version DAST-28: cutoff 6
pregnant women (DAST-A) DAST-20: cutoff 6
available DAST-10: cutoff 2
213
(continued)
214
TICSa Two-Item Conjoint Brown Adults Past year 2 items Self-administered 5 min Cutoff: 1
Screen for Alcohol (1997)
and Other Drug
Problems
UNCOPE Use, Neglected, Hoffmann Adults Lifetime 6 items Interviewer 5–10 min Cutoff: 2
Cut down, Objection, et al. (2003) Past year administered
Preoccupied,
Emotional
discomfort
(c) Instruments specific to one drug
CAST Cannabis Abuse French Adolescents Lifetime 6 items Self-administered 5 min Range: 0–6
Screening Test Monitoring Score 4:
Center for problematic
Drug and cannabis use
Drug
Addictions
(2013)
Screening for Nicotine and Drug Use Disorders
CUDIT Cannabis Use Adamson Adults; Past 10 items Self-administered 5–10 min Range: 0–40
CUDIT-R Disorders et al. (2010), adolescents 6 months 5-point Likert Cutoff:8
Identification Test Adamson and Current scale
Sellman
(2003)
CUPIT Cannabis Use Bashford Adolescents; Lifetime 16 items Self-administered 5 min Range: 0–82
Problems (2010) adults Past Cutoff: 12
Identification Test 12 months
MSI Marijuana Screening Alexander Adults Lifetime 31 items Self-administered 5–10 min Range: 0–31
Inventory (2003) Past year Cutoff: 3
PUM Problematic Use Piontek et al. General adult Lifetime 8 items Self-administered Range: 0–8
of Marijuana (2008) population Cutoff: 2
CDS-12 Cigarette Etter Adults Lifetime 12 & 5 items Self-administered 10 min Range: CDS-12,
CDS-5 Dependence Scale et al. (2003) Adolescents Current 12–60; CDS-5, 5-25
215
(continued)
216
co-occurring
clients
POSIT Problem-Oriented Rahdert Adolescents Lifetime 139 items, Self-administered 20–30 min Cutoff scores
Screening Instrument (1991) 10 problem indicating low,
for Teenagers areas medium, or high
risk for each of the
10 problem areas
a
Copyright information unavailable
b
Fee required for use; other instruments free in public domain
217
218 S. Assanangkornchai and J.G. Edwards
have had; if the substance has interfered with their responsibilities; if anyone has
expressed concern about their substance use; if they have tried to decrease or
discontinue use; and if they have ever used any substance by injection (WHO
ASSIST Working Group 2002).
There are modified forms of the ASSIST – the NMASSIST (National Institute on
Drug Abuse (NIDA)-modified ASSIST) (National Institute on Drug Abuse 2013);
ASSIST-Lite (ultrarapid ASSIST) (Ali et al. 2013); ASSIST-Y for use in children
and adolescents aged 10–17 years; and the electronic eASSIST (Drug and Alcohol
Services South Australia (DASSA) 2012).
In a validation study among 1,047 participants in drug treatment and primary
health-care settings in Australia, Brazil, India, Israel, Thailand, the UK, the
USA, and Zimbabwe, the ASSIST showed high construct and concurrent valid-
ity and positive correlation with similar instruments ranging from 0.48 to 0.88
(p < 0.001) (Humeniuk et al. 2008). The sensitivity in the study ranged from
54 % to 97 %, specificity 50–96 %, depending on the drug type. The instrument
was later tested in 214 patients with first episode psychoses and revealed
satisfactory concurrent validity (r ¼ 0.41–0.63; p < 0.001), with a sensitivity
of 63–81 % and specificity of 62–76 % (Hides et al. 2009). Both studies also
showed high validity in discriminating between nonproblematic use, abuse, and
dependence and between those with and without illicit drug problems. A high
internal consistency and good-to-excellent test–retest reliability (kappa,
0.58–0.90) were also reported (WHO ASSIST Working Group 2002). In
a diagnostic accuracy study among 2,082 adults recruited from general medical
and specialist mental health/addiction treatment services in nine countries, the
ASSIST-LITE also showed high sensitivity (0.8–1.0) and specificity (0.7–0.8)
(Ali et al. 2013).
13.2.8.1 CRAFFT
CRAFFT is a mnemonic, based on its individual items: Car, Relax, Alone, Forget,
Friends, and Trouble (Knight et al. 1999). It is the best studied instrument for
screening for alcohol and drug use and related problems in adolescents (Pilowsky
and Wu 2013). The six items are preceded by three preliminary questions that ask
about the use of alcohol, cannabis, and other drugs. It evaluates certain lifetime
events and behaviors, irrespective of when they occurred. The items were devel-
oped from the Problem-Oriented Screening Test for Teenagers (POSIT), Drug and
Alcohol Problem (DAP) Quick Screen, and RAFFT questionnaire (Relax, Alone,
Forget, Friends, Trouble). The CRAFFT was examined in several populations,
including patients seen in hospital-based, sexually transmitted disease and sub-
stance use clinics, primary care, emergency departments, and the general popula-
tion. The instrument was found to be suitable for distinguishing between alcohol
and substance use, and problem use, abuse, and dependence, with a sensitivity
ranging from 0.61 to 1.00, specificity from 0.33 to 0.97 (Dhalla et al. 2011).
Apart from instruments used to screen for alcohol, those most readily available are
for cannabis, tobacco, and opioid use. Short instruments designed specifically for
cannabis screening that have satisfactory psychometric properties and have been
used in various populations include the Cannabis Abuse Screening Test (CAST),
Cannabis Use Disorders Identification Test (CUDIT), and Problematic Use of
Marijuana (PUM) (Piontek et al. 2008). The Fagerström Test for Nicotine Depen-
dence (FTND) is the instrument most widely used to screen for nicotine use, while
other available instruments are the Cigarette Dependence Scale (CDS) and Tobacco
Dependence Screener (TDS). For opioids, most instruments, such as the Current
220 S. Assanangkornchai and J.G. Edwards
Opioid Misuse Measure (COMM), Opioid Risk Tool (ORT), and Opioid Assess-
ment for Patients with Pain (SOAPP), were designed to elicit information to
identify patients with chronic pain who are at risk of problems caused by their
long-term analgesic treatment.
The Fagerström Test for Nicotine Dependence (FTND) is also known as the
Fagerström Test for Cigarette Dependence (FTCD), a revision of the Fagerström
Tolerance Questionnaire (FTQ). It was designed to provide an ordinal measure of
nicotine dependence. It contains six items that seek information on the number of
cigarettes smoked, compulsion to smoke, and dependence. It provides a severity
rating that can be used to help plan treatment and assess the prognosis. Its brevity
and ease of scoring make it an efficient way of obtaining clinically meaningful
information. It can be incorporated into general health and lifestyle screening
questionnaires for use in clinical and nonclinical settings.
A modified version of the scale (modified Fagerström Tolerance Questionnaire,
mFTQ) has been adapted for use in adolescents. The FTND was found to be reliable
for evaluating smokers in different settings. It had a test–retest reliability ranging
from 0.58 to 0.91, with the lowest value in smokers with schizophrenia, and
a sensitivity of 0.75 and specificity of 0.80 in a study among patients with cancer
in Japan. There was a weak (r ¼ 0.19) to satisfactory (r ¼ 0.59) correlation between
the FTND score and breath carbon monoxide and saliva cotinine levels (Meneses-
Gaya et al. 2009).
mental health-care staff, and staff working in substance use disorder treatment
programs. The POSIT has been found to have strong internal consistency in several
of its subscales and good test–retest reliability and overall validity (Knight
et al. 2001, 2003).
13.3 Conclusion
Because of the high and increasing prevalence of substance use disorders and
related comorbidity, screening for substances is important in many medical, psy-
chiatric, and forensic services. There is a higher prevalence of use in some patient
groups than others, such as those attending accident and emergency departments
and pain clinics, and those who come into conflict with the law. Numerous
screening instruments have been designed and validated. Factors that determine
the choice of an instrument are not only its psychometric properties but also the
practicality of employing it. The enormous pressures of working in a busy clinical
unit often preclude the use of the lengthier instruments without special assistance. It
should not be forgotten that screening is only the first step on a very long journey
towards providing a successful outcome. It will be of limited value without the
provision of treatment opportunities and encouraging substance users to accept and
then adhere to any treatment offered. Finally, it is important to determine the
success rate of using the instruments in terms of discontinuation or at least
decreased use of substances compared with standard practice and to assess what
effect they have in reducing long-term complications.
References
ADAI Library (2013) Screening and assessment instruments.http://lib.adai.washington.edu/instru-
ments/. Accessed 24 May 2013
Adamson SJ, Sellman JD (2003) A prototype screening instrument for cannabis use disorder: the
Cannabis Use Disorders Identification Test (CUDIT) in an alcohol-dependent clinical sample.
Drug Alcohol Rev 22(3):309–315
Adamson SJ, Kay-Lambkin FJ, Baker AL, Lewin TJ, Thornton L, Kelly BJ, Sellman JD (2010) An
improved brief measure of cannabis misuse: The Cannabis Use Disorders Identification Test-
Revised (CUDIT-R). Drug Alcohol Depend 110(1–2):137–143
Alexander D (2003) Clinical pilot experiences using the Marijuana Screening Inventory (MSI-X):
screening guidelines and case illustrations. J Soc Work Pract Addict 3(4):29–51
Ali R, Meena S, Eastwood B, Richards I, Marsden J (2013) Ultra-rapid screening for substance-use
disorders: the alcohol, smoking and substance involvement screening test (ASSIST-Lite). Drug
Alcohol Depend 132(1–2):352–361
Babor TF, McRee BG, Kassebaum PA, Grimaldi PL, Ahmed K, Bray J (2007) Screening, brief
Intervention, and referral to treatment (SBIRT): toward a public health approach to the
management of substance abuse. Subst Abus 28(3):7–30
Bashford J, Flett R, Copeland J (2010) The Cannabis Use Problems Identification Test (CUPIT):
development, reliability, concurrent and predictive value among adolescents and adults.
Addiction 105(4):615–625
222 S. Assanangkornchai and J.G. Edwards
Berman AH, Bergman H, Palmstierna T, Schlyter F (2005) Evaluation of the Drug Use Disorders
Identification Test (DUDIT) in criminal justice and detoxification settings in a Swedish
population sample. Eur Addict Res 11(10):22–31
Brown RL, Rounds LA (1995) Conjoint screening questionnaires for alcohol and other drug abuse:
criterion validity in a primary care practice. Wis Med J 94(3):135–140
Brown RL, Leonard T, Saunders LA, Papasouliotis O (1997) A two-item screening test for alcohol
and other drug problems. J Fam Pract 44(2):151–160
Butler SF, Budman SH, Fernandez K, Jamison RN (2004) Validation of a screener and opioid
assessment measure for patients with chronic pain. Pain 112(1–2):65–75
Butler SF, Budman SH, Fernandez KC, Houle B, Benoit C, Katz N, Jamison RN (2007) Devel-
opment and Validation of the Current Opioid Misuse Measure. Pain 130:144–156
Center for Substance Abuse Treatment (ed) (1998) Screening and assessing adolescents for
substance use disorders. Treatment improvement protocol (TIP) series, No. 31. HHS publica-
tion no. (SMA) 12–4079. Substance Abuse and Mental Health Services Administration,
Rockville
Dhalla S, Zumbo BD, Poole G (2011) A review of the psychometric properties of the CRAFFT
instrument: 1999–2010. Curr Drug Abuse Rev 4(1):57–64
Drug and Alcohol Services South Australia (DASSA) (2012) Alcohol, Smoking and Substance
Involvement Screening Test (ASSIST). http://www.dassa.sa.gov.au/site/page.cfm?u¼477.
Accessed 30 Oct 2012
Etter J, Le Houezec J, Perneger TV (2003) A self-administered questionnaire to measure depen-
dence on cigarettes: the Cigarette Dependence Scale. Neuropsychopharmacology 28:359–370
French Monitoring Centre for Drugs and Drug Addiction (OFDT) (2013) Detection of problem
cannabis use: the Cannabis Abuse Screening Test. http://www.ofdt.fr/BDD/publications/docs/
eisasst9.pdf. Accessed 7 June 2014
Grant C, Marsh R, Sheridan J, Wheeler A, Suaalii-Sauni T, Black S, Butler R (2007) The
Substances and Choices Scale (SACS) – the development and testing of a new alcohol and
other drug screening and outcome measurement instrument for young people. Addiction
102(9):1390–1398
Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO (1991) The Fagerstrom Test for
Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict
86(9):1119–1127
Hides L, Cotton SM, Berger G, Gleeson J, O’Donnell C, Proffitt T, McGorry PD, Lubman DI
(2009) The reliability and validity of the Alcohol, Smoking and Substance Involvement
Screening Test (ASSIST) in first-episode psychosis. Addict Behav 34(10):821–825
Hoffmann NG, Hunt DE, Rhodes WM, Riley KJ (2003) UNCOPE: a brief substance dependence
screen for use with arrestees. J Drug Issues 33(1):29–44
Humeniuk R, Ali R, Babor TF, Farrell M, Formigoni ML, Jittiwutikarn J, de Lacerda RB, Ling W,
Marsden J, Monteiro M, Nhiwatiwa S, Pal H, Poznyak V, Simon S (2008) Validation of the
Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Addiction
103(6):1039–1047
Inciardi J (1994) Screening and assessment for alcohol and other drug abuse among adults in the
criminal justice system; Treatment Improvement Protocol (TIP) series 7 DHHS publication
no. (SMA) 94B2076. Center for Substance Abuse Treatment of the Substance Abuse and
Mental Health Services Administration (SAMHSA), Rockville
Kawakami N, Takatsuka N, Inaba S, Shimizu H (1999) Development of a screening questionnaire
for tobacco/nicotine dependence according to ICD-10, DSM-IIIR, and DSM-IV. Addict Behav
24(2):155–166
Knight J, Shrier L, Bravender T, Farrell M, Vander Bilt J, Shaffer H (1999) A new brief screen for
adolescent substance abuse. Arch Pediatr Adolesc Med 153(6):591–596
Knight JR, Goodman E, Pulerwitz T, DuRant RH (2001) Reliability of the Problem Oriented
Screening Instrument for Teenagers (POSIT) in adolescent medical practice. J Adolesc Health
29(2):125–130
13 Screening for Nicotine and Drug Use Disorders 223
Knight JR, Sherritt L, Harris SK, Gates EC, Chang G (2003) Validity of brief alcohol screening
tests among adolescents: a comparison of the AUDIT, POSIT, CAGE, and CRAFFT. Alcohol
Clin Exp Res 27(1):67–73
Mdege ND, Lang J (2011) Screening instruments for detecting illicit drug use/abuse that could be
useful in general hospital wards: a systematic review. Addict Behav 36(12):1111–1119
Meneses-Gaya IC, Zuardi AW, Loureiro SR, Crippa JA (2009) Psychometric properties of the
Fagerstrom Test for Nicotine Dependence. J Bras Pneumol 35(1):73–82
National Institute on Drug Abuse (2013) NIDA-Modified ASSIST- V2.0. http://www.drugabuse.
gov/nidamed/screening/nmassist.pdf. Accessed 25 April 2013
Newton AS, Gokiert R, Mabood N, Ata N, Dong K, Ali S, Vandermeer B, Tjosvold L, Hartling L,
Wild TC (2011) Instruments to detect alcohol and other drug misuse in the emergency
department: a systematic review. Pediatrics 128(1):e180–192
Pilowsky D, Wu L (2013) Screening instruments for substance use and brief interventions
targeting adolescents in primary care: a literature review. Addict Behav 38:2146–2153
Piontek D, Kraus L, Klempova D (2008) Short scales to assess cannabis-related problems: a
review of psychometric properties. Subst Abuse Treat Prev Policy 3(25). doi:10.1186/1747-
597x-3-25
Prokhorov AV, Koehly LM, Pallonen UE, Hudmon KS (1998) Adolescent nicotine dependence
measured by the modified Fagerstrom tolerance questionnaire at two time points. J Child
Adolesc Subst Abuse 7(4):35–47
Rahdert E (ed) (1991) The adolescent assessment/referral system manual. HHS publication
no. (ADM) 91–1735. U.S. Department of Health and Human Services, ADAMHA, National
Institute on Drug Abuse, Rockville
Schwartz RH, Wirtz PW (1990) Potential substance abuse detection among adolescent patients.
Using the Drug and Alcohol Problem (DAP) quick screen, a 30-item questionnaire. Clin
Pediatr 29:38–43
Skinner HA (1982) The drug abuse screening test. Addict Behav 7(4):363–367
Sobell LC, Kwan E, Sobell MB (1995) Reliability of a Drug History Questionnaire (DHQ). Addict
Behav 20(2):233–241
Solanki DR, Koyyalagunta D, Shah RV, Silverman SM, Manchikanti L (2011) Monitoring opioid
adherence in chronic pain patients: assessment of risk of substance misuse. Pain Physician
14(2):E119–E131
Tiet QQ, Finney JW, Moos RH (2008) Screening psychiatric patients for illicit drug use disorders
and problems. Clin Psychol Rev 28(4):578–591
Webster LR, Webster RM (2005) Predicting aberrant behaviors in opioid-treated patients:
preliminary validation of the Opioid Risk Tool. Pain Med 6(6):432–442
WHO ASSIST Working Group (2002) The Alcohol, Smoking and Substance Involvement
Screening Test (ASSIST): development, reliability and feasibility. Addiction 97(9):1183–1194
World Health Organization (2012) The WHO ASSIST Phase IV (2008–2011). http://www.who.
int/substance_abuse/activities/assist_phase_IV/en/index.html. Accessed 25 Sep 2012
Yudko E, Lozhkina O, Fouts A (2007) A comprehensive review of the psychometric properties of
the Drug Abuse Screening Test. J Subst Abuse Treat 32(2):189–198
Clinical Assessment of Alcohol Use
Disorders 14
Teresa Bobes-Bascarán, Teresa Bascarán, Paz Garcı́a-Portilla, and
Julio Bobes
Contents
14.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226
14.2 Comprehensive Assessment of Alcohol Use and Related Problems . . . . . . . . . . . . . . . . . . . 227
14.2.1 Evaluation of Alcohol Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
14.2.2 Psychiatric Comorbidity Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
14.2.3 Neuropsychological Performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
14.2.4 Psychosocial Functioning and Quality of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
14.3 Cross-References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
Abstract
Clinical assessment of alcohol use disorders involves both a detailed initial inter-
view and examination and monitoring of the patient’s progress. There are no
specific instruments to diagnose alcohol misuse, and so diagnostic assessment
involves taking an accurate history from the patient and a meticulous clinical
T. Bobes-Bascarán (*)
CIBERSAM, University of Valencia, Valencia, Comunidad Valenciana, Spain
e-mail: [email protected]
T. Bascarán
CIBERSAM, University of Oviedo, Oviedo, Principado de Asturias, Spain
e-mail: [email protected]
P. Garcı́a-Portilla
CIBERSAM, University of Oviedo, Oviedo, Principado de Asturias, Spain
Psychiatry Department, University of Oviedo, Oviedo, Spain
e-mail: [email protected]
J. Bobes
Department of Medicine - Psychiatry, University of Oviedo, Centro de Investigación Biomédica
en Red de Salud Mental (CIBERSAM), Oviedo, Spain
e-mail: [email protected]
14.1 Introduction
• Alcohol consumption:
• Historical and recent patterns of drinking
• Dependence and withdrawal symptomatology
• Alcohol craving and impulsiveness
• Alcohol-related problems (i.e., legal, economic, occupational)
• Self-efficacy and confidence in relapse prevention
• Readiness to change
• Other drug misuse, including prescribed and under-the-counter medication
• Comorbid mental health disorders
• Comorbid physical health conditions
• Neurocognitive performance
• Social and personal functioning
• Quality of life and disability
This information may be obtained by a precise clinical interview, but standard-
ized tools and measures may be administered as well (see Table 14.1).
This chapter will enumerate and briefly describe the most relevant psychometric
instruments to evaluate alcohol use disorders and related problems, psychiatric
comorbid symptomology, neurocognitive performance, and social functioning and
quality of life issues. The reader is recommended to consult the companion
▶ Chap. 12, “Screening, Early Detection and Brief Intervention for Alcohol Use
Disorders” and ▶ Chap. 15, “Drug Testing” for further information about comple-
mentary methods of assessment. Regarding physical and mental health comorbidities,
Section VIII is an exhaustive revision on ▶ Medical Disorders and Complications of
Alcohol and Other Drugs, Pain and Addiction, and Section IX addresses ▶ Psychiatric
Comorbidities and Complications of Alcohol and Other Drugs.
15 scales: 9 primary scales (related to main problem areas) and 6 secondary scales
(perceived support and conflicts with partner, family, and friends) (McLellan
et al. 1980). There is a follow-up version (ASI-FU follow-up) designed to monitor
patients’ evolution and treatment outcomes and several adaptations to adolescent
population: Teen-ASI (Kaminer et al. 1989) and T-ASI-2 (Brodey et al. 2008).
14.2.1.3 Craving/Impulsiveness
The Obsessive Compulsive Drinking Scale
The OCDS is a 14-item scale developed to reflect obsession and compulsion related
to craving and drinking behavior such as drinking-related thoughts, urges to drink,
230 T. Bobes-Bascarán et al.
and the ability to resist those thoughts and urges (Anton et al. 1995). The OCDS has
been shown to be a reliable and sensitive as a monitoring tool and has proved
content and predictive validity for relapse drinking. There is an adolescent version,
the A-OCDS (Deas et al. 2001), which discriminates between problem drinkers and
experimenters and detects functional impairment associated with alcohol abuse.
Individuals with alcohol use disorders often suffer from one or more psychiatric
disorders. This frequent phenomenon indicates the necessity of specific assessment
and treatment in the field of addictive behaviors, which, historically, has been narrowed
and focused on the addiction per se. This section yields over basic instruments to assess
psychiatric comorbidity in patients with alcohol problems (see Table 14.2). For further
information on psychiatric comorbidity, consult section IX of this book, ▶ Psychiatric
Comorbidities and Complications of Alcohol and Other Drugs.
Studies have long established that excessive alcohol use is associated with damage
and impairment of brain structure and function, yielding to poor cognitive perfor-
mance and behavior disturbances. Assessment of neuropsychological performance
(and intervention where necessary) is fundamental, given that it determines assimi-
lation and understanding of information, reasoning, and problem solving (in order to
prevent relapse) and capacity to remember therapeutic guidelines, learn new skills,
maintain abstinence, and develop more adaptive behaviors. This section enumerates
the most relevant tests to evaluate neuropsychological performance (see Table 14.3).
Alcohol and other drug use disorders are increasingly viewed as chronic conditions.
It is therefore important to assess their impact on the patient’s overall well-being.
From this perspective, the management of addictive behaviors should aim for the
broad goal of recovery, which is defined as abstinence plus improved quality of life
and psychosocial functioning. Assessing these social parameters is essential in
treatment planning and outcome assessment as they represent the abilities and skills
of the individual to function independently in the community.
14.2.4.1 Disability
Disability Assessment Schedule 2.0
The WHODAS 2.0 was developed through a collaborative international approach,
with the aim of developing a single generic instrument for assessing health status
and disability across different cultures and settings (World Health Organization
2010). It is short, simple, and easy to administer and one first-level general
14 Clinical Assessment of Alcohol Use Disorders 233
14.2.4.3 Functioning
Global Assessment of Function
The GAF is a 100-point tool rating overall psychological, social, and occupational
functioning of people over 18 years of age and older (American Psychiatric
Association 1994, 2013). It excludes physical and environmental impairment.
This scale is included in the fourth edition of the Diagnostic and Statistical Manual
of Mental Disorders (DSM-IV). However, in DSM-5, the multiaxial system and
GAF assessment have been abandoned.
14.3 Cross-References
▶ Drug Testing
▶ Medical Disorders and Complications of Alcohol and Other Drugs, Pain and
Addiction: An Introduction
▶ Motivational Interviewing and Behaviour Change in Addiction Treatment
▶ Psychiatric Comorbidities and Complications of Alcohol and Other Drugs:
An Introduction
▶ Screening, Early Detection and Brief Intervention for Alcohol Use Disorders
References
Aldrich FK, Wilson B (1991) Rivermead behavioural memory test for children (RBMT-C):
a preliminary evaluation. Br J Clin Psychol 30(Pt 2):161–168
American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders,
4th edn. American Psychiatric Association, Washington, DC
American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders,
5th edn. American Psychiatric Association, Arlington
Anton RF, Moak DH, Latham P (1995) The obsessive compulsive drinking scale: a self-rated
instrument for the quantification of thoughts about alcohol and drinking behavior. Alcohol Clin
Exp Res 19:92–99
Barratt ES (1959) Anxiety and impulsiveness related to psychomotor efficiency. Percept Mot
Skills 9(2):191–198
Bechara A, Damasio A, Tranel D, Anderson S (1994) Insensitivity to future consequences
following damage to human prefrontal cortex. Cognition 50:7–15
236 T. Bobes-Bascarán et al.
Beck AT, Weissman A, Lester D, Trexler L (1974) The measurement of pessimism: the hope-
lessness scale. J Consult Clin Psychol 42(6):861–865
Beck AT, Kovacs M, Weissman A (1979) Assessment of suicidal intention: the scale for suicide
ideation. J Consult Clin Psychol 47(2):343–352
Beck AT, Steer RA, Ball R, Ranieri W (1996) Comparison of beck depression inventories -IA and
-II in psychiatric outpatients. J Pers Assess 67(3):588–597
Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS et al (1995) The
development of a clinician-administered PTSD scale. J Trauma Stress 8(1):75–90
Brodey BB, McMullin D, Kaminer Y, Winters KC, Mosshart E, Rosen CS et al (2008) Psychometric
characteristics of the teen addiction severity index-two (T-ASI-2). Subst Abus 29(2):19–32
Brown SA, Christiansen BA, Goldaman MS (1987) The alcohol expectancy questionnaire: an
instrument for the assessment of adolescent and adult alcohol expectancies. J Stud Alcohol
48:483–491
Cacciola JS, Alterman AI, Habing B, McLellan AT (2011) Recent status scores for version 6 of the
addiction severity index (ASI-6). Addiction 106(9):1588–1602
Clayton AH, McGarvey EL, Clavet GJ (1997) The changes in sexual functioning questionnaire
(CSFQ): development, reliability, and validity. Psychopharmacol Bull 33(4):731–745
Conners CK, Erhardt D, Sparrow E (1999) Conners’ adult ADHD rating scales. Multi-Health
Systems, North Tonawanda
Cooper Z, Cooper PJ, Fairburn CG (1989) The validity of the eating disorder examination and its
subscales. Br J Psychiatry 154:807–812
Cyders MA, Smith GT, Spillane NS, Fischer S, Annus AM, Peterson C (2007) Integration of
impulsivity and positive mood to predict risky behavior: development and validation of
a measure of positive urgency. Psychol Assess 19(1):107–118
Deady M (2009) A review of screening, assessment and outcome measures for drug and alcohol
settings. Network of Alcohol & other Drug Agencies, New South Wales
Deas D, Roberts J, Randall C, Anton R (2001) Adolescent obsessive-compulsive drinking scale: an
assessment tool for problem drinking. J Natl Med Assoc 93(3):92–103
Derogatis LR (1997) The derogatis interview for sexual functioning (DISF/DISF-SR): an intro-
ductory report. J Sex Marital Ther 23(4):291–304
Derogatis LR, Cleary PA (1977) Factorial invariance across gender for the primary symptom
dimensions of the SCL-90. Br J Soc Clin Psychol 16(4):347–356
Derogatis LR, Melisaratos N (1979) The DSFI: a multidimensional measure of sexual functioning.
J Sex Marital Ther 5(3):244–281
DiClemente CC, Carbonari JP, Montgomery RPG, Hughes SO (1994) The alcohol abstinence self-
efficacy scale. J Stud Alcohol 55:141–148
Endicott J, Nee J, Harrison W, Blumenthal R (1993) Quality of life enjoyment and satisfaction
questionnaire: a new measure. Psychopharmacol Bull 29(2):321–326
Eysenck HJ, Eysenck SBG (1975) Manual of the eysenck personality questionnaire. Hodder and
Stoughton, Londres
Eysenck SBG, Eysenck HJ, Barrett P (1985) A revised version of the psychoticism scale. Pers
Indiv Differ 6(1):21–29
Flannery BA, Volpicelli JR, Pettinati HM (1999) Psychometric properties of the Penn alcohol
craving scale. Alcohol Clin Exp Res 23(8):1289–1295
Folstein MF, Robins LN, Helzer JE (1983) The mini-mental state examination. Arch Gen
Psychiatry 40(7):812
Garner DM, Olmsted MP (1986) Scoring the eating disorder inventory. Am J Psychiatry
143(5):680–681
Golden CJ (1976) Identification of brain disorders by the stroop color and word test. J Clin Psychol
32(3):654–658
Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL et al (1989) The
Yale-brown obsessive compulsive scale. I. Development, use, and reliability. Arch Gen
Psychiatry 46(11):1006–1011
14 Clinical Assessment of Alcohol Use Disorders 237
Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32(1):50–55
Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62
Hasin DS, Trautman KD, Miele GM, Samet S, Smith M, Endicott J (1996) Psychiatric research
interview for substance and mental disorders (PRISM): reliability for substance abusers.
Am J Psychiatry 153(9):1195–1201
Horn JL, Wanberg KW, Foster FM (1987) Guide to the alcohol Use inventory (AUI).
Minneapolis, MN
Kaminer Y, Bukstein O, Tarter R (1989) Teen addiction severity index (T-ASI): clinical and
research implications: a preliminary report. NIDA Res Monogr 95:363
Kaplan E, Goodglass H, Weintraub S (1983) Boston naming test. Lea & Febiger, Philadelphia
Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for
schizophrenia. Schizophr Bull 13(2):261–276
Kessler RC, Adler L, Ames M, Demler O, Faraone S, Hiripi E et al (2005) The world health
organization adult ADHD self-report scale (ASRS): a short screening scale for use in the
general population. Psychol Med 35(2):245–256
Lezak MD (1995) Neuropsychological assessment. Oxford University Press, New York
Loranger AW (1988) Personality disorder examination. DV Communications, Yonkers
Mc Kinley JC, Hathaway SR, Meehl PE (1948) The Minnesota multiphasic personality inventory;
the K scale. J Consult Psychol 12(1):20–31
McConnaughy EA, Prochaska JO, Velicer WF (1983) Stages of change in psychotherapy: mea-
surement and sample profiles. Psychother Theor Res Prac 20:368–375
McLellan AT, Luborsky L, Woody GE, O’Brien (1980) An improved diagnostic evaluation
instrument for substance abusers: The Addiction Severity Index. J Nerv Ment Dis
168:26–33
McLellan AT, Cacciola JC, Alterman AI, Rikoon SH, Carise D (2006) The addiction severity
index at 25: origins, contributions and transitions. Am J Addict 15(2):113–124
McMahon J, Jones BT (1993a) The negative alcohol expectancy questionnaire. J Assoc Nurs Subst
Abuse 12:17
McMahon J, Jones BT (1993b) Negative expectancy and motivation. Addicti Res 1:145–155
Miller WR, Marlatt GA (1984) Comprehensive drinker profile. Psychological Assessment
Resources, Odessa
Miller WR, Tonigan JS (1996) Assessing drinkers’ motivations for change. The stages of change
readiness and treatment eagerness scale (SOCRATES). Psychol Addict Behav 10(2):81–89
Millon T (1983) Millon clinical multiaxial inventory manual. National Computer Systems, Minneapolis
Millon T, Millon C, Davis R (2004) Millon clinical multiaxial inventory - III manual. National
Computer Systems, Minneapolis
Morosini PL, Magliano L, Brambilla L, Ugolini S, Pioli R (2000) Development, reliability
and acceptability of a new version of the DSM-IV social and occupational functioning
assessment scale (SOFAS) to assess routine social functioning. Acta Psychiatr Scand
101(4):323–329
Nelson HE (1976) A modified card sorting test sensitive to frontal lobe defects. Cortex
12(4):313–324
Nelson HE (1982) National adult reading test. NFER-Nelson, Windsor
Nelson HE, Willison JR (1991) The revised national adult reading test- test manual. NFER-
Nelson, Windsor
Organization WH (2010) World health organization disability assessment scale 2.0 (WHODAS
2.0). WHO, Geneva
Overall JE, Gorham DR (1962) The brief psychiatric rating scale. Psychol Rep 10:790–812
Patton JH, Stanford MS, Barratt ES (1995) Factor structure of the Barratt impulsiveness scale.
J Clin Psychol 51(6):768–774
Power M, Harper A, Bullinger M (1999) The world health organization WHOQOL-100: tests of
the universality of quality of life in 15 different cultural groups worldwide. Health Psychol
18(5):495–505
238 T. Bobes-Bascarán et al.
Contents
15.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
15.2 Drug Testing Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
15.2.1 Drug Testing Technologies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
15.2.2 Chromatographic Techniques for Detecting Drugs of Abuse . . . . . . . . . . . . . . . 244
15.2.3 Pharmacokinetics and Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
15.2.4 Amphetamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
15.2.5 Benzodiazepines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
15.2.6 Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
15.2.7 Alprazolam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
15.2.8 Bromazepam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
15.2.9 Clobazam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
15.2.10 Clonazepam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
15.2.11 Diazepam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
15.2.12 Flunitrazepam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
15.2.13 Lorazepam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
15.2.14 Midazolam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
15.2.15 Nitrazepam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
15.2.16 Oxazepam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252
15.2.17 Temazepam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252
15.2.18 Triazolam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252
15.2.19 Immunoassay Detection of Benzodiazepines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252
15.2.20 Cannabinoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252
15.2.21 Opiates and Opioids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
15.2.22 Cocaine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
Abstract
Drug testing involves the analysis of urine or other body fluids for the presence
of prescription drugs, illicit substances, and sometimes other toxins, together
P. Paull
Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Camperdown, Australia
e-mail: [email protected]
with their metabolites, for the purpose of diagnosis and monitoring of progress
and/or treatment in human subjects. Typically it is employed for clinical,
medicolegal, or forensic purposes. This chapter reviews the approach to drug
assays that would be undertaken in a hospital biochemistry or toxicology
laboratory, where typically a sample of urine has been obtained from the patient.
It does not specifically cover “benchtop” or “ward” testing, for which purpose
a range of commercial dipstick-type tests have been introduced. The capacity of
urine drug screening to determine the recent use of a psychoactive substance is
often misunderstood by clinicians, and careful interpretation of the results is
needed and should be undertaken in consultation with laboratory staff. The
chapter reviews the techniques available for detecting the main classes of
drugs including opioids, benzodiazepines, cannabinoids, and psychostimulants.
15.1 Introduction
A range of body fluids or tissues can be assayed for the presence of drugs. No single
assay technology or assay strategy will detect all drugs of possible interest.
Comprehensive broad-spectrum analyses for drugs are labor-intensive. For this
reason, most clinical laboratories that perform drug testing adopt a limited testing
strategy that is designed to satisfy specific clinical needs. If this strategy is to
succeed, it is essential that there is good communication between clinicians and
laboratorians.
Clinicians should understand the technical limitations of the assay technology
used in particular laboratories.
This chapter will discuss the pharmacokinetics of drugs of abuse and what assay
technologies are available in the detection of these drugs in body fluids.
A common term used in a request to the laboratory is for a “drug screen.” There
is no single process that can identify all drugs. Screening processes will attempt to
identify commonly abused substances, but many drugs and toxicants are not
identified by “screening.” Sometimes these drugs/toxicants will not be identified
unless there is prior suspicion of their use and “targeted” assays are performed.
Drug screening is done in a number of different contexts. Some of these contexts
are listed below:
1. Hospital toxicology
2. Workplace drug testing
3. Forensic toxicology
4. Postmortem toxicology
5. Sports toxicology
6. Drug-facilitated sexual assault
7. Drugs of abuse testing
Hospital toxicology is the investigation of deliberate or accidental overdose of
prescription drugs or illicit substances and other toxins, in order to identify the
toxicant so that “rational” therapy may be given to the patient. This was the raison
15 Drug Testing 241
d’être for drug screening when this testing was first introduced into clinical labora-
tories in the 1970s. Interest in drug screening of this kind has receded over the years,
and presently there is an emphasis on supportive therapy while the drug is
metabolized and eliminated. The exceptions to this approach are when a specific
antidote is available.1
Workplace drug testing is done to detect possible impairment of performance of
tasks that are performed in the workplace. This testing is of particular importance
when the occupation includes operation of dangerous equipment or the operation of
vehicles, boats, and aircraft. A special case is the impairment of health-care
practitioners who have access to drugs. Addicted individuals use potent synthetic
opioids, such as fentanyl. Fentanyl is not detected in conventional screening
protocols.
Forensic toxicology is done to provide evidence of a medicolegal nature where
poisoning is alleged and may lead in evidence in criminal prosecutions.
Postmortem toxicology is toxicology done to help determine the cause of death.
Sports toxicology is drug testing done to detect the use of performance-
enhancing drugs such as anabolic steroids and erythropoietin.
Investigation of drug-facilitated sexual assault involves targeted analysis of
some toxicants that are not usually detected in broad-spectrum screening. These
drugs include gamma-hydroxybutyrate and ketamine.
Drugs of abuse testing is a term used to indicate testing for the presence of drugs
that have a potential for addiction. Sometimes this testing includes assays for drugs
used in substitution therapy, such as methadone or buprenorphine, to assess
compliance with prescribed therapy.
These different kinds of “drug screening” result in analytical protocols that vary
according to the context. Most hospital-based laboratories have protocols that are
a combination of “hospital toxicology” and “drugs of abuse testing.” Most hospital
laboratories do not document chain of custody of sample nor adhere to the rigorous
practice demanded for medicolegal testing. Thus, testing that is done for “clinical
purposes” does not satisfy the regulatory requirements applied to medicolegal
testing.
Drugs of abuse include amphetamine and amphetamine derivatives, benzodiaz-
epines, cocaine, cannabis, and opiates.
The presence of drugs can be determined in a variety of body fluids such as
urine, blood, oral fluid, sweat, meconium, and vitreous humor. Drugs can also be
detected in hair and body tissues (especially hepatic and renal tissue). All of these
matrices offer various advantages and disadvantages.
Urine is the most commonly used matrix for drug detection. Urine samples can
be obtained by noninvasive means. Urine offers a longer detection window com-
pared to blood and oral fluid.
1
Examples are paracetamol and digoxin overdose and methanol or ethylene glycol poisoning. In
the case of paracetamol and digoxin toxicity, measurement of the concentration of the drug in
serum is more useful than detection in urine.
242 P. Paull
Urine has the disadvantage that it may be adulterated or substituted at the time of
collection. If the testing is to be reliable, the collection should be done under
observation. The collection should be done in an area where there are no water
sources such as taps and where a dye has been added to cistern water. The
temperature of the urine should be tested immediately after collection to determine
that the sample has been freshly voided. The creatinine concentration, pH, and the
presence of oxidizing agents should also be tested to determine dilution or adulter-
ation that can interfere with testing. Surreptitious adulteration with ammonia
solution, bicarbonate, limewater, salt, vinegar, soap, detergents, and bleach can
all interfere with immunoassays for drugs of abuse.
Drug testing technology can be classified into two major categories: immunoassay
and chromatographic techniques of analysis. The chromatographic techniques of
analysis may be further classified into thin-layer chromatography, gas chromatog-
raphy, and liquid chromatography.
15.2.1.1 Immunoassay
The majority of clinical laboratories use immunoassay on high-capacity automated
analyzers as first-line screening. All immunoassays are based on an antibody
directed against the drug of interest. Binding of drug in the test sample to the
antibody modulates an indicator system. The indicator system produces a signal
that is a measure of the amount of drug in the sample. There a number of
commercial immunoassays that vary in the indicator system used to indicate drug
binding. A further variable is the specificity of the antibody. The cross-reactivity of
the antibody to other structurally similar drugs and to drug metabolites is variable
for different assay vendors.
The popularity of immunoassays is that most of them can be run on the same
analyzers that are used to measure biochemical parameters in a routine biochem-
istry laboratory. The assays are rapid, do not require sample pretreatment, are
supplied as “off-the-shelf” kits, are automated, and use a small volume of raw
urine. The assays are validated by the manufacturer.
Four variations of immunoassays are in common use. These assays are:
• Enzyme multiplied immunoassay technique (EMIT, a Siemens trademark)
• Fluorescence polarization immunoassay (FPIA, an Abbott trademark)
• Cloned enzyme donor immunoassay (CEDIA, a Thermo trademark)
• Kinetic interaction of microparticles in solution (KIMS, a technique associated
with Roche Abuscreen)
In Australasian laboratories, the CEDIA assays are the most commonly used
immunoassays. In the CEDIA assay, ß-galactosidase is present as two inactive
enzyme fragments which can reassociate to form the functional enzyme.
15 Drug Testing 243
One of the inactive fragments is conjugated with drug (this fragment is desig-
nated as the “enzyme donor” fragment). If drug is present in the sample, it binds to
the drug antibody and the enzyme fragment is free to associate and form the active
enzyme. If drug is not present in the sample, the enzyme-drug fragment binds to the
antibody and the fragment is not available to form an active enzyme.
Active enzyme cleaves chlorophenol red-ß-D-galactopyranoside to yield free
chlorophenol red that can be detected photometrically.
Immunoassays for drugs suffer from the same disadvantages as any immunoas-
say. False-positive results for particular drugs of abuse can arise because of poor
specificity for the drug. One of the popular assay systems uses an antibody to detect
amphetamine that cross-reacts with pseudoephedrine.
The antibody used in screening assays for opiate drugs cannot distinguish
between the presence of morphine and the presence of codeine. Thus, it is possible
to have a positive opiate urine from the ingestion of a popular over-the-counter
combination analgesic (paracetamol and codeine).
There is a commercial assay for methadone in urine that is specific for the parent
drug and with limited cross-reactivity for the metabolites of methadone (EDDP and
EMDP). There is a different assay from the same vendor that is specific for EDDP
with low cross-reactivity for the parent drug methadone. This allows detection of
a practice in where dispensed methadone was sold to other users. The person
on-selling would spike their urine with pharmaceutical methadone to indicate that
they had taken methadone and were compliant with the prescribed pharmacother-
apy. Testing this urine for the presence of methadone metabolite would yield
a negative result and thus rule out that the methadone in the urine resulted from
ingestion of the prescribed drug.
Sometimes interpretation of a result depends on knowledge of the antibody
specificity and metabolism of the drug.
The initial phase of drug excretion in the urine may have a higher proportion of
parent drug than later phases of excretion where drug metabolites may predominate.
Different individual may metabolize drug differently to others. Given that anti-
bodies from different manufacturers have different specificities for parent drug and
metabolites, any attempt to determine a quantitative result from immunoassay is
fraught with difficulty. Further urine can range from dilute to concentrated
depending on the state of hydration of individuals.
Clinicians should be aware that immunoassay screening is typically reported as
a “negative” or “positive” result. A positive result means that the drug was detected
at a concentration that exceeds a threshold concentration (often referred to as
a “cutoff” concentration). A negative result does not mean that the drug is absent,
rather that the concentration is less than the threshold concentration.
Cutoff concentrations are mandated in a range of jurisdictions, and there is some
variability in the concentrations specified. There is an Australian and New Zealand
Standard for Drugs of Abuse Testing in urine. The standard is jointly published by
Standards Australia and Standards New Zealand and has the formal title of AS/NZS
4308:2008 Procedures for specimen collection and the detection and quantitation
of drugs of abuse in urine.
244 P. Paull
2
There is a variation on this procedure that is called solid-phase extraction; this technique will not
be discussed here.
246 P. Paull
Mass spectrometry involves the formation of charged ion(s) from the drug mole-
cule. These charged ions can be sorted in the mass spectrometer and the mass of each
ion determined. Hard ionization, such as that produced by subjecting the drug molecule
to a beam of electrons, results in extensive fragmentation of the drug molecule. Soft
ionization, such that produced using an electrospray ion source,3 produces limited
fragmentation. Different drugs give rise to a distinctive ion “fingerprint.”
There is now a trend to the use of “tandem mass spectrometry.” In tandem mass
spectrometry, one of the ions generated in the ion source is selectively introduced in
a collision cell where it collides with inert gas molecules. These collisions induce
further fragmentation. The daughter ions produced from the selected precursor ion
can be separated and characterized. The two stages of fragmentation of the drug
molecule in a tandem mass spectrometer provide greater specificity in the identi-
fication of the drug. Thus, drugs are identified based on the time it takes to elute the
drug from the chromatographic column (retention time) and the pattern of ions
formed after ionization of the drug molecule.
Gas chromatography has the highest resolution of all these modes of chroma-
tography and can typically resolve 100 or more compound in a single
chromatographic run. The disadvantage of GC is that it can only be applied to
volatile substances so that most drugs have to be derivatized before they can be
chromatographed. This is a labor-intensive process.
LC can be used for nonvolatile drugs and does not require chemical derivatiza-
tion. LC lacks some of the resolving power of GC. Ionization of drugs in the liquid
phase results in soft ionization with limited fragmentation, and for this reason
tandem mass spectrometry is usually required to give the desired specificity to
the analysis. LC-TMS analyzers double the cost of GC-MS analyzers.
15.2.4 Amphetamine
3
Electrospray ionization occurs when solvent is eluted from a chromatographic column and
nebulised from a jet, maintained at a high voltage, into a heated gas stream.
15 Drug Testing 247
Acidic urine inhibits tubular reabsorption and promotes net excretion of amphet-
amine because the drug is charged at an acidic pH and less likely to diffuse back
across the plasma membrane of the tubular epithelium. When the pH of urine is
uncontrolled, about 30 % of the drug is excreted unchanged in the first 24 h; if the
urine is acidified, this rises to 75 %, and if the urine is alkalinized, the amount
excreted unchanged can fall to less than 5 %.
The plasma half-life of amphetamine can vary from 4 h (acidic urine) to 12 h
(uncontrolled urinary pH).
The major route of metabolism is oxidative deamination to form phenylacetone
which is then hydroxylated to benzoic acid which in turn is converted to hippuric
acid. When urine pH is not manipulated, about 50 % of the dose is excreted in the
urine as benzoic and hippuric acids.
There are many compounds that are structurally related to amphetamine that
have psychoactive properties. These include methamphetamine (crystal meth),
methylenedioxyamphetamine (MDA), and methylenedioxymethylamphetamine
(MDMA or Ecstasy).
Methamphetamine is the molecule formed when the amino group of amphet-
amine is substituted with a methyl group to form a secondary amine. MDMA is the
molecule formed when there is a methylenedioxy bridge attached to the benzene
ring on carbon atoms 3 and 4.
Historically, immunoassays for amphetamines in urine were prone to interfer-
ence from a range of other drugs including over-the-counter drugs such as pseudo-
ephedrine. The more recent formulations of these kits are less likely to exhibit these
cross-reactions. When there is doubt about the veracity of a laboratory result,
enquiry should be made of the individual laboratories to determine the performance
characteristics of the particular assay that is used.
There is some variation in the performance of immunoassays for amphetamines
and related compounds. The most common immunoassay system used in Australia
offers two versions of the assay to detect these psychoactive amines. Both versions
give 100 % cross-reactivity with amphetamine but have different cross-reactivity
for the analogues of amphetamine.
One of the assay systems shows 100 % reactivity for methamphetamine, 2 %
reactivity for MDA, and 70 % reactivity for MDMA. The alternate assay system
shows 80 % reactivity for methamphetamine, 115 % reactivity for MDA, and 200 %
reactivity for MDMA. Assays from other vendors have different patterns of reactivity.
Despite all of these variables, amphetamine and related compounds should be
detected in the urine for 48 h after administration of the drug.
15.2.5 Benzodiazepines
The variety of chemical structures that possess these properties is extensive. This
chapter will restrict discussion to the 12 compounds of this class that are used
clinically in Australia. They are shown in Table 15.1.
The chemical structures of these compounds are shown in Fig. 15.1.
All of these compounds include a benzene ring fused with a diazepine ring.
A diazepine ring is a 7-member heterocyclic compound that contains two nitrogen
atoms. The atoms of the diazepine ring are numbered 1–5 starting with the nitrogen
atom closest to the benzene ring (atoms involved in the fusion of the two rings are
not counted).
In all of these compounds, the nitrogen atoms are located at positions 1 and
4 (called a 1, 4-benzodiazepine). The exception is clobazam where the nitrogen
atoms are in positions 1 and 5 (a 1, 5-benzodiazepine).
With the exception of bromazepam, all of these benzodiazepines have an aryl
substituent attached to position 5 in the diazepine ring. Bromazepam is substituted
at position 5 with a pyridine ring.
Midazolam includes a fused diazolo ring. A diazolo ring is a five-member
heterocyclic ring that includes two nitrogen atoms.
Alprazolam and triazolam include a fused triazolo ring. A triazolo ring is a five-
member heterocyclic ring that includes three nitrogen atoms.
All of these benzodiazepines include substitution of a carbon atom in the fused
benzene ring. This carbon atom is the para position relative to the carbon closest to
the nitrogen in the diazepine ring. This position is sometimes numbered as carbon
7, sometimes as carbon 8, and sometimes as carbon 9.
This carbon is variously numbered because of the convention in numbering
atoms in fused ring systems.
In six of the benzodiazepines, this “para” carbon atom is numbered as atom
7 (bromazepam, clobazam, clonazepam, diazepam, oxazepam, and temazepam).
In three of the benzodiazepines, this carbon atom is numbered as atom 8 (alpraz-
olam, midazolam, and triazolam).
Table 15.1
Benzodiazepine Duration of action4
Alprazolam Intermediate acting
Bromazepam Intermediate acting
Clobazam Long acting
Clonazepam Long acting
Diazepam Long acting
Flunitrazepam Long acting
Lorazepam Intermediate acting
Midazolam Short acting
Nitrazepam Long acting
Oxazepam Intermediate acting
Temazepam Intermediate acting
Triazolam Short acting
15 Drug Testing 249
H3C N
N
N H O O
N H O
N N
Cl N
Br N Cl N O2 N N
O
N Cl
H3C N
CH3
O H3C H
N O O N
N N
OH N
Cl N O2N N N
Cl
Cl
F
F Cl
O N
CH3 N
HN H O O
N N
N
N OH OH
Cl N Cl N Cl N
O2 N
Cl
Fig. 15.1
15.2.6 Metabolism
NH
O
R2
R3
Aminobenzophenone
15.2.7 Alprazolam
The two major metabolites are a-hydroxyalprazolam (where the methyl substituent
of the triazolo ring is hydroxylated) and 4-hydroxyalprazolam where carbon 4 of the
diazepine ring is hydroxylated. Both metabolites are active. The
a-hydroxyalprazolam represents 15 % of the dose of the parent drug and the
4-hydroxyalprazolam represents about 60 % of the dose. The remainder is made up
of minor metabolites such as the benzophenone derivative and desmethylalprazolam.
15.2.8 Bromazepam
The two major metabolites are 3-hydroxybromazepam (30 %) and the benzophe-
none derivative (40 %). These two metabolites are extensively conjugated.
15.2.9 Clobazam
15.2.10 Clonazepam
15.2.11 Diazepam
15.2.12 Flunitrazepam
15.2.13 Lorazepam
15.2.14 Midazolam
15.2.15 Nitrazepam
15.2.16 Oxazepam
15.2.17 Temazepam
15.2.18 Triazolam
15.2.20 Cannabinoids
Table 15.2 Specificity of the CEDIA ® Benzodiazepine Assay for various benzodiazepines and
their metabolitesa
Percent cross-reactivity without Percent cross-reactivity with
Drug/metabolite ß-glucuronidase treatment ß-glucuronidase treatment
7-aminoflunitrazepam Not tested 99
7-aminonitrazepam Not tested 83
a-Hydroxyalprazolam 188 167
a-Hydroxytriazolam 193 155
Alprazolam 205 220
Alprazolam glucuronide Not tested 100
Bromazepam 110 104
Clobazam 62 59
Clonazepam 140 71
Desalkylflurazepam 210 173
Diazepam 247 154
Flunitrazepam 135 109
Lorazepam 122 115
Lorazepam glucuronide 1 45
Aminoclonazepam Not tested 96
Nitrazepam 100 100
Desmethyldiazepam 211 173
Oxazepam 107 125
Oxazepam glucuronide 1 25
Temazepam 144 93
Temazepam glucuronide 1 25
Triazolam 191 217
a
Adapted from the Thermo Scientific Benzodiazepine Assay Package Insert dated November 2002
reliability of the assessment. Stringent criteria will give a high probability of a true
positive result, whereas less stringent criteria may detect more recidivist behavior but
at the risk of false-positive results (Identifying New Cannabis Use with Urine
Creatinine-Normalized THCCOOH Concentrations and Time Intervals between
Specimen Collections, M. L. Smith, A. J. Barnes, and M. A. Huestis, Journal of
Analytical Toxicology, volume 33, May 2009, page 185). Clinicians should contact
their local provider of laboratory testing to determine an appropriate testing strategy
for the care of their patients.
Opium is the dried sap that is exuded when the seedpods of the opium poppy
(Papaver somniferum) are scored. Crude opium contains about 25 alkaloids.
Alkaloids are plant products that are bases because they contain
a heterocyclic ring that includes a nitrogen atom. Many alkaloids have
pharmacological activity. The main alkaloids in opium are morphine, codeine,
and thebaine.
Morphine can be isolated in pure form from opium. Both licit and illicit sources of
morphine are derived from the cultivation of poppies. The term opiates is used to
describe drug substances that are purified from opium or are simple derivatives of the
opium alkaloids: this includes morphine, codeine, and heroin. The term opioids
includes all substances that have a morphine-like activity whether they are naturally
occurring alkaloids, semisynthetic drugs such as hydrocodone and hydromorphone,
or synthetic drugs that include buprenorphine, fentanyl, methadone, and oxycodone.
The morphine molecule consists of five fused rings. There is a benzene ring fused to
a cyclohexane ring (6 carbon unsaturated ring) which in turn is fused to a cyclohexene
ring (6 carbon unsaturated ring). The benzene ring and the cyclohexene ring are joined
by a tetrahydrofuran ring (5 atom ring containing an oxygen atom). These four fused
rings form a rigid structure in one plane; above this plane is a piperidine ring
(6-membered ring containing a nitrogen atom). Piperidine shares carbon atoms with
the four ring systems at positions 9, 13, and 14 (see the structure below).
Morphine has two hydroxyl groups, one at position 3 and one at position
6. These two hydroxyl groups can react with acetic acid (or acetic anhydride) so
that two acetyl groups are added to the molecule via an ester link. The resulting
15 Drug Testing 257
• If the total morphine concentration in the urine sample is greater than 1,000 mg/L
and the ratio of the morphine concentration to the codeine concentration is l < 2,
then poppy seeds can be excluded as the sole source for the positive opiate test
result.
• If the total morphine concentration in the urine sample is greater than 1,000 mg
per ml and no codeine is detected, then it is likely that the positive opiate result is
due to the use of morphine or heroin (The Clinical Toxicology Laboratory, Page
87, AACC Press, 2001).
Table 15.3 shows the cross-reactivity of a commercial reagent system for
detection of opiates (Cedia Opiates, Thermo Scientific).
The assay is calibrated to morphine, and codeine shows 125 % cross-reactivity,
whereas diacetylmorphine and other morphine metabolites show a cross-reactivity
between 48 % and 57 % (Table 15.3). It should be noted that some semisynthetic
opiate agonists such as pethidine, oxymorphone, and oxycodone show minimal
activity in the immunoassay system, whereas other semisynthetic agonists show
50–57 % cross-reactivity.
Thus, a “negative” screen for “opiates” does not exclude abuse of a number
of opiates and opioids. If this is an issue of concern, practitioners should
enquire of their service provider to determine the specificity of
the immunoassay used.
It should be noted that a number of assay vendors offer immunoassays that are
directed at a particular opiate or opioid and are relatively specific for the compound
of interest. These assays may not be offered by hospital biochemistry laboratories
on a routine basis. The sample may need to be forwarded to a specialist drug assay
laboratory. Such opioids include buprenorphine, pethidine, oxycodone, tramadol,
and methadone.
The general rule is that opiates that react in screening assay can be detected for
2 days after a single occasion of use.
Table 15.3
Drug/metabolite Cross-reactivity
Morphine 100
Codeine 125
Diacetylmorphine 53
Dihydrocodeine 50
Hydrocodone 48
Hydromorphone 57
Morphine-3-glucuronide 81
Morphine-6-glucuronide 47
6-Monoacetylmorphine 81
Pethidine (meperidine) 0
Oxymorphone 2
Oxycodone 3
15 Drug Testing 259
15.2.22 Cocaine
5
6
4
3
Cocaine has a methyl ester attached at carbon 2 of the tropane ring and a benzoyl
ester attached to carbon 3. A trivial name for cocaine is methylbenzoylecgonine.
The metabolism of cocaine involves hydrolysis of the two ester bonds in the
drug. The major metabolite is benzoylecgonine formed when the methyl ester is
hydrolyzed to yield a carboxyl on carbon 2 of the tropane ring. About 45 % of the
dose is excreted in the urine as benzoylecgonine.
260 P. Paull
Table 15.4
Drug/metabolite Cross-reactivity
Benzoylecgonine 100
Cocaine 54
Ecgonine 1
Methylecgonine 0
Table 15.4 shows the specificity of a commonly used immunoassay for cocaine.
The assay is calibrated to the major metabolite, benzoylecgonine. There is limited
reaction to cocaine (54 %) and virtually no reaction to the minor metabolites of
cocaine.
The cutoff concentration for immunoassay screening is specified as 300 mg/L of
“cocaine metabolite”; given the specificity of most assays and the pattern of urinary
excretion of metabolites, this equates to a concentration of 300 mg/L of
benzoylecgonine.
The standard specifies a lower cutoff concentration for chromatographic confir-
matory assays. The confirmatory test is reported as positive if benzoylecgonine is
detected at a concentration 150 mg/L or if methylecgonine is detected at a con-
centration 150 mg/L.
Benzoylecgonine can be detected in the urine after a single occasion of use for
about 72 h.
Biological State Marker for Alcohol
Consumption 16
Friedrich Martin Wurst, Natasha Thon, Wolfgang Weinmann,
Michel Yegles, and Ulrich W. Preuss
Contents
16.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262
16.2 Direct Ethanol Metabolites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
16.2.1 Ethyl Glucuronide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
16.2.2 Ethyl Sulfate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 266
16.2.3 Fatty Acid Ethyl Esters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
16.2.4 Phosphatidylethanol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268
16.2.5 Hair Analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
16.2.6 The Value of Ethanol Metabolites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272
16.3 Traditional Biomarkers for Alcohol Consumption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
16.3.1 Gamma-Glutamyl Transferase (g-GT) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
16.3.2 Mean Corpuscular Erythrocyte Volume (MCV) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
16.3.3 Carbohydrate-Deficient Transferrin (CDT) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
Abstract
Alcohol-related disorders are common, expensive in their entire course, and
often underdiagnosed. To facilitate early diagnosis and therapy of alcohol-
related disorders and thus prevent later complications, questionnaires and bio-
markers are useful. Indirect state markers like gamma-glutamyl transpeptidase
(GGT), mean corpuscular volume (MCV), and carbohydrate deficiency trans-
ferrin (CDT) are influenced by age, gender, various substances, and non-alcohol-
related illnesses and do not cover the entire timeline for alcohol consumption.
Direct state markers as ethyl glucuronide (EtG), phosphatidylethanol (PEth), and
fatty acid ethyl esters (FAEEs) have gained enormous interest in the last decades
as they are metabolites of alcohol becoming only positive in the presence of
alcohol. As biomarkers with high sensitivity and specificity covering the com-
plimentary timeline, they are already routinely in use and contribute to new
perspectives in prevention, interdisciplinary cooperation, diagnosis, and therapy
of alcohol-related disorders.
16.1 Introduction
Alcohol-related disorders are in the top ten of the most common diseases worldwide
(World Health Organization (WHO) 2011). The point prevalence for alcohol
dependence in Germany, as in other comparable countries, is 5 % and the lifetime
prevalence is 10 % (Mann 2002). Worldwide, approximately 4 % of deaths are
attributable to alcohol, greater than deaths caused by HIV, violence, or tuberculosis
(World Health Organization (WHO) 2011). The yearly costs attributable to alcohol
in Europe are approximately 270 billion € and in Germany 26.7 billion € (DHS).
The costs include medical care; decreased productivity caused by illness, accidents,
and death; and the social burden, e.g., in the family (World Health Organization
(WHO) 2011).
In general hospitals, a rate of up to 20 % of all inpatients having an alcohol use
disorder was found; in surgical departments rates from 16 % to 35 % in patients
with multiple trauma were described (Tonnesen and Kehlet 1999; Spies et al. 2001).
These patients have a prolonged hospital stay (Tonnesen and Kehlet 1999; Spies
et al. 2001; Rubinsky et al. 2012); they have to be treated 1.5 days longer in ICUs
16 Biological State Marker for Alcohol Consumption 263
(Rubinsky et al. 2012) and are twice likely to return to OR due to complications
(Rubinsky et al. 2012). The post-traumatic lethality is up to four times higher in
individuals with alcohol use disorders (Tonnesen and Kehlet 1999; Spies
et al. 2001). Of all alcohol-dependent individuals, 80 % are treated by general
practitioners and only 34 % in general hospitals (Mann 2002). Thus, alcohol-related
disorders are common, expensive in their entire course (Rehm et al. 2009), and
often underdiagnosed (Moore et al. 1989).
To facilitate early diagnosis and therapy of alcohol-related disorders and thus
prevent later complications, questionnaires like the CAGE questionnaire (Ewing
1984) or the Alcohol Use Disorders Identification Test (AUDIT) (Saunders
et al. 1993) and biomarkers are useful.
Indirect state markers as well as direct state markers are routinely used to detect
alcohol. The indirect state markers like gamma-glutamyl transpeptidase (GGT),
mean corpuscular volume (MCV), and carbohydrate deficiency transferrin (CDT)
are influenced by age, gender, various substances, and non-alcohol-related illnesses
and do not cover the entire timeline for alcohol consumption (Conigrave et al. 2002;
Laposata 1999; Helander 2003a; Hannuksela et al. 2007; Niemelä 2007; Allen
et al. 2009).
Direct state markers have gained enormous interest in the last decades as they
are metabolites of alcohol becoming only positive in the presence of alcohol. As
biomarkers with high sensitivity and specificity covering the complimentary time-
line, they are already routinely in use and contribute to new perspectives in
prevention, interdisciplinary cooperation, diagnosis, and therapy of alcohol-related
disorders.
• Fatty acid ethyl ester (FAEEs) especially in hair (Auwärter et al. 2001; Pragst
et al. 2001; Appenzeller et al. 2007a; Pragst and Yegles 2007)
Direct ethanol metabolites are detectable in serum for hours, in urine for up to
7 days, in whole blood over 2 weeks, and in hair over months.
16.2.1.2 Limitations
In recent years, the potential in vitro formation and degradation of EtG and EtS
have gained attention (Helander et al. 2009; Helander and Dahl 2005; Baranowski
et al. 2008; Halter et al. 2009): At first, hydrolysis of EtG caused by microbes in
urinary tract infections, especially E. coli, was reported (Helander and Dahl 2005).
Complete degradation of EtG within 3–4 days by E. coli and C. sordellii was
confirmed by Baranowski et al. (2008). In contrast, the stability of EtS for up to
11 days could be shown (Baranowski et al. 2008). Further studies with standardized
test procedures for biodegradation showed that EtS in closed bottle test (OECD
301 D) remained stable for even longer periods, whereas in the context of a higher
bacterial density such as in the Manometric Respiratory Test (MRT), a reduction
after 6 days was detected (Halter et al. 2009). This problem could be countered by
cooling and the addition of stabilizers.
Furthermore, a recent study reported that the bacterial degradation of EtG by E. coli
can be prevented by the use of dried urine on filter paper (Redondo et al. 2012).
Ethyl sulfate (EtS) presents a secondary elimination pathway for alcohol and is
usually detectable in varying interindividual concentrations. An immunochemical
detection test is currently not commercially available for EtS. For combined detection
of EtS and EtG, the use of rapid LC/MS-MS procedures is routinely applied.
The formation is effected by sulfonyl transferase and the breakdown by sulfa-
tases. The molecular weight is 126 g/mol and the molecular formula C2H5SO4H.
16 Biological State Marker for Alcohol Consumption 267
Ethyl sulfate formed through conjugation of activated sulfate and ethanol in rat
liver was described by Boström and Vestermark in 1960 (Boström and Vestermark
1960). Its detection in rat urine was conducted after application of 35S-sulfate and
ethanol on rats, with thin slice chromatography and autoradiographic proof on
radiographic film (Boström and Vestermark 1960).
Schneider and Glatt (2004) developed a liquid chromatography-tandem mass
spectrometry method with 2-propylsulfates as internal standard. Helander and Beck
(2004) used liquid chromatography-electrospray ionization-mass spectrometry
(LC-ESI-MS) in a single-quadrupole modus and D5-ethylsulfate as internal
standards for the quantification of EtS in urine samples. The disadvantage of this
method is a longer period of chromatographic separation. Furthermore, the exclu-
sive monitoring of de-protonated molecules in a single MS does not meet forensic
standards (Aderjan et al. 2000; Society of Forensic Toxicologists and American
Academy of Forensic Sciences and SOFT/AAFS 2006). At any rate, an additional
fragment ion would be required for the verification analyses according to forensic
guidelines (Society of Forensic Toxicologists and American Academy of Forensic
Sciences and SOFT/AAFS 2006). Even when this requirement from forensic
guidelines must not be met in clinical diagnostic, it is still in demand
in workplace drug testing in the USA (SAMHSA. Mandatory Guidelines for
Federal Workplace Drug Testing. Federal Register 2004). In this context, an
LC-tandem-MS method with penta-deuterium EtS as internal standard and two
ion transitions (Dresen et al. 2004), which can be used in forensic and medicolegal
cases as well as in clinical routine (Skipper et al. 2004a), raises particular interest.
In summary, a cutoff of 0.05 mg/l for repeated alcohol intake was suggested
(Albermann et al. 2012b). As for ethyl glucuronide, there is evidence of prolonged
elimination in reduced renal function (Høiseth et al. 2013).
In recent years, the existence of fatty acid ethyl esters, non-oxidative metabolic
products of ethanol in blood and various organs with reduced or deficient capacity
to oxidize ethanol after consumption has been proven. Since these esters were
proven to cause damage to subcellular structures, they were postulated to be
mediators of organ damage.
Two enzymes catalyze the formation of FAEE: acetyl-coenzyme A:ethanol
o-acyltransferase (AEAT) and fatty acid ethyl ester-synthase. FAEE synthase can
be isolated from rabbit myocardium, human brain, and rat fat tissue. Two of these
FAEE synthases were shown to be identical to rat liver carboxyl esterase (Tsujita
and Okuda 1992; Bora et al. 1996). Furthermore, pancreatic lipase, lipoprotein
lipase, and glutathione transferase were shown to possess FAEE synthase activity
(Tsujita and Okuda 1992; Bora et al. 1996; Bora et al. 1989).
Fatty acid ethyl esters are formed in the presence of ethanol from free fatty acids,
triglycerides, lipoproteins, or phospholipids affected by specific cytosolic or micro-
somal FAEE synthases or through acyl-coenzyme A-ethanol o-acyltransferase.
268 F.M. Wurst et al.
Detectable levels are found in blood shortly after alcohol consumption and remain
positive for more than 24 h (Borucki et al. 2005).
Of 15 different FAEEs in the hair, the sum of four of these (ethyl stearate, ethyl
oleate, ethyl myristate, and ethyl palmitate) is shown to function as a marker in hair
analysis (Pragst and Yegles 2007). With a cutoff of 0.5 ng/ml, a sensitivity
and a specificity of 90 % were reported. A differentiation between abstinent, social,
and excessive drinkers appears possible (Yegles et al. 2004; González-Illán
et al. 2011). However, the complex GC/MS method lacks practicability for
routine use.
16.2.4 Phosphatidylethanol
16.2.4.2 Limitations
In blood and tissues containing ethanol, the formation of PEth under certain
conditions may be feasible. Without influencing the PEth levels, blood samples
can be stored in refrigerators for up to 72 h or frozen at 80 C.
In vitro formation of PEth in erythrocytes has been reported after addition of
ethanol (Varga and Alling 2002). Further experimental studies in rats showed that
ceramide is able to block the activity of phospholipase- D and inhibits the synthesis
of PEth (Pragst and Yegles 2008).
Hair analysis has been established to assess ethanol intake. FAEE and ethyl
glucuronide (EtG), two metabolic by-products of ethanol, are gaining attention as
alcohol markers in hair (Auwärter et al. 2001; Pragst et al. 2001; Appenzeller
et al. 2007a; Pragst and Yegles 2007; Yegles et al. 2004; Wurst et al. 2004b; Pragst
and Yegles 2008; Pragst 2006).
The time frame for the detection of alcohol consumption is longer in hair
compared to blood or urine. Due to head hair growth of 1 cm per month, depending
on the hair length, evidence of alcohol consumption can be found for the respective
time period. The deposit of lipophilic FAEE in hair occurs in sebum (Auwärter
et al. 2004), whereas hydrophilic EtG is incorporated through perspiration and/or
from blood (Pragst and Yegles 2007).
Measurement of FAEE and EtG allows differentiation between chronic
excessive and moderate alcohol consumption as well as abstinence or very low
levels of alcohol consumption.
270 F.M. Wurst et al.
In summary, specific ethanol metabolites are available which can detect the spec-
trum between short-term intake of small amounts and long-term use of large
amounts of alcohol (Table 16.1). Cutoff values and influencing factors are summa-
rized in Tables 16.2 and 16.3.
Appropriate methods of analysis and pre-analytics are crucial for a valid and
reliable detection of markers. For ethyl glucuronide (EtG), the most frequently used
marker, the best method for detection is chromatographic approach which is
considered a standard method especially in forensic cases. A commercial test
kit is available and contributed to wide distribution of the test. Of course, lab
values always require critical reappraisal. However, EtG is detectable in urine
using LC-MS/Ms even after an ingestion of low amounts of alcohol (1 g), which
also occurs in some foods, drugs, and disinfectants. Individuals with the motiva-
tion to or obligation for abstinence have to be informed about these “hidden
contents” to avoid involuntary intake of alcohol. For forensic purposes, the
current cutoff value of 0.1 mg/L should be adapted to exclude cases of involuntary
alcohol use. With respect to differences in formation and degradation, EtG
and ethyl sulfate (EtS) should be analyzed together, if possible. In the
absence of known influencing factors, EtG in the hair can be recommended as
a marker for alcohol intake for the last 3 months. Further, guidelines for inter-
pretations of values from international society (SOHT) are available. While
positive urine values of EtG and EtS can be in accord with innocent/unintentional
alcohol intake, positive values of PEth are related to previous intoxications of
0.5 % and more.
The use of dried blood spots is promising and may facilitate sample taking,
storage, distribution, and decrease of infection risk.
Table 16.1 Clinically relevant options for the determination of direct biomarkers, with respect to
amount and duration of alcohol intake (Modified according to Thon et al. (2013))
Duration of consumption Amount of consumption
>1 g/d >40–60 g/d
<1 day Serum, urine: Serum and urine: EtOH, EtG, EtS; PEth in whole
EtOH, EtG, EtS blood and dried blood spots (LC-MS/MS)
>1 day Serum, urine: Serum and urine: EtOH, EtG, EtS; PEth in whole
EtOH, EtG, EtS blood and dried blood spots (LC-MS/MS)
>14 days Serum, urine: Serum and urine: EtOH, EtG, EtS; PEth in whole
EtOH, EtG, EtS blood and dried blood spots (HPLC LC-MS/MS)
Weeks to months Serum, urine: Serum and urine: EtOH, EtG, EtS; PEth in whole
EtOH, EtG, EtS blood and dried blood spots (HPLC LC-MS/MS),
EtG and FAEEs in hair
EtOH ethanol, EtG ethyl glucuronide, EtS ethyl sulfate, PEth phosphatidylethanol, FAEE fatty
acid ethyl esters
16 Biological State Marker for Alcohol Consumption 273
Table 16.2 Clinically relevant options for the determination of direct biomarkers, with respect to
amount and duration of alcohol intake (Modified according to Thon et al. (2013))
Biomarkers Amount of consumption Cutoff Reference
EtG in hair Abstinence and low intake <7 pg/mg Society of Hair Testing
(<10 g alc/d) (2009)
Social consumption 7–30 pg/mg
(20–40 g/d)
Excessive drinking (>60 g/d) >30 pg/mg
FAEEs in Repeated alcohol intake 200 pg/mg Society of Hair Testing
hair Excessive intake 500 pg/mg (2009)
EtG in urine Total abstinence 0.1 mg/L Thierauf
- Unintentional intake 0.1 mg/l–0.5 mg/L et al. (2009a, b)
- Recent alcohol use
- Longer back-dated alcohol
intake in larger amounts
Unintentional intake 0.5–1 mg/L
unlikely, but possible, active
alcohol intake probable
EtS in urine Total abstinence 0.05 mg/L Weinmann et al. (2004)
PEth >40 g/d, more than 2 weeks HPLC: 0.22 mM, LC/MS- Varga et al. (1998),
of alcohol intake at least once MS: 20/30 ng/ml PEth Gnann et al. (2012),
with 1 % detectable 16:0/18:1 or 0.05 mM Aradóttir et al. (2004)
EtG ethyl glucuronide, FAEEs fatty acid ethyl esters in hair, EtS ethyl sulfate, PEth
phosphatidylethanol
Table 16.3 Detection of direct biomarker, with respect to amount and duration of alcohol intake
(Modified according to Thon et al. (2013))
Direct biomarkers Potential influencing factor Influence Reference
EtG in urine E. coli, dried urine spots No Redondo et al. (2012)
Grade of liver disease, No Wurst et al. (2004a), Stewart
smoking, BMI, body water et al. (2013)
content reduced kidney
function
EtS in urine E. coli, dried urine spots No Hoiseth et al. (2012)
PEth Liver disease No Stewart et al. (2009)
Hypertension No
Storage of ethanol blood No Aradóttir et al. (2004)
samples
Refrigerator temperature,
80 C
EtG in hair Hairsprays with ethanol, No Ferreira et al. (2012), Kulaga
hair color, melanin et al. (2009), Appenzeller
content, age, gender, BMI et al. (2007b), Kharbouche
et al. (2010)
EtG in urine E. coli, C. sordellii Decrease Helander and Dahl (2005),
Baranowski et al. (2008)
Reduced kidney function Longer Wurst et al. (2004a), Hoiseth
detection et al. (2012)
Chloral hydrate False Arndt et al. (2009)
positives
EtS in urine Reduced kidney function Longer Hoiseth et al. (2012)
detection
Closed bottle test (OECD 28 days stable Halter et al. (2009)
301 D) detection,
Manometer Respiratory depletion after
Test (MRT) 6 days
FAEEs in hair Aggressive alkaline False negative Sampson et al. (1997)
hairsprays
Hairsprays with ethanol False
positives
PEth Ethanol-containing blood Increase Aradóttir et al. (2004)
samples, storage of ethanol
blood samples at RT and
20 C
EtG in hair Hairspray with EtG Increase Sporkert et al. (2012)
Reduced kidney function Increase Høiseth et al. (2013)
Bleaching, hair styling False negative Yegles et al. (2004), Morini
products et al. (2010b)
EtG ethyl glucuronide, FAEE fatty acid ethyl esters, EtS ethyl sulfate, PEth phosphatidylethanol,
BMI body mass index, RT room ambient temperature, E. coli Escherichia coli, C. sordellii
Clostridium sordellii
16 Biological State Marker for Alcohol Consumption 275
normal values (according to Szasz, 4–18 U/l in women and, 6–28 U/l in men) requires
the chronic, daily alcohol intake over at least four to six weeks. A short-term, higher
alcohol burden causes no such increase (Haffner et al. 1988). Nevertheless, Anton
et al. (1998) showed that the drinking intensity has more influence on g-GT than
drinking frequency. In absolute alcohol abstinence, normalization of the values
occurs within three weeks to 60 days (Haffner et al. 1988).
The sensitivity of g-GT varies, according to age, gender, and body weight, from
35 % to 85 % (von Herbay and Strohmeyer 1994). Puukka et al. (2006a) showed
that g-GT increased with age in heavy alcohol drinkers as well as moderate
drinkers. In contrast, in young adults less than 30 years, even when these are
alcohol dependent, the sensitivity of the markers is very low (Bisson and
Milford-Ward 1994). Chan et al. (1989) traced this back to higher resistance in
younger patients to damaging alcohol effects. In addition, the higher vulnerability
of women to alcohol-associated liver diseases is well known (Puukka et al. 2006b).
Other studies have shown a relationship between being overweight (BMI > 25) and
an increase in g-GT (Puukka et al. 2006b). g-GT levels can also be increased by
various other causes, for example, the effect of medication (such as enzyme-
inducing drugs, e.g., phenytoin) and teratogens, obesity, diabetes, and cholestatic
or inflammatory liver diseases. Accordingly, the specificity of 63–85 % is only
relatively satisfactory, and g-GT, in spite of its practicality as single indicator of
chronic alcohol misuse and current liver diseases, is a relatively poor alcohol
biomarker (Cushman et al. 1984; Neumann and Spies 2003).
Transferrin is the most important iron transport molecule in humans; its synthesis and
glycolization occur in hepatocytes. Depending on the iron load as well as the number
276 F.M. Wurst et al.
liver diseases makes the comparison with other traditional markers difficult. In
selected, clinical patient groups, various test methods with specificity between
90 and 100 % with high sensitivity (50–90 %) were reported (Stibler 1991b;
Kwoh-Gain et al. 1990; Stowell et al. 1997a, b).
In WHO/ISBRA Study, the sensitivity of CDT with 60 % in men was slightly less
than that of g-GT; in women the sensitivity reached only 29 % (Laposata 1999)
(Conigrave et al., 2002b). False-positive increased CDT values can occur in biliary
cirrhotic, autoimmune hepatitis, genetically determined transferrin variants, or the
autosomal recessive inherited CDG syndrome (Stibler 1991b; Salaspuro 1999). Most
patients with liver diseases have insignificantly increased CDT values so that the
specificity, especially in comparison to other state markers, must be stated exceptionally
high and usually reach at least 90 %. Thus, CDT could be used for detection of chronic
alcohol consumption and changes in drinking patterns in these patients (Bortolotti
et al. 2006; Helander and Tabakoff 1997). With a half-life of 14 days and normalization
of CDT values in abstinence, evidence of drinking relapses in the post-acute phase after
alcohol withdrawal treatment can be obtained (Stibler 1991b; Niemelä 2002).
Increases in HDL cholesterol and apoprotein I/II are described in many studies as
specific and sensitive indicators of chronic alcohol strain; by contrast triglycerides
278 F.M. Wurst et al.
and total cholesterol are nutritionally influenced. Alcohol leads to an increase in the
concentrations of cholesterol and phospholipids within the HDL particles and
causes a shift to bigger portions of phospholipids in richer and larger HDL2
particles (Goldberg et al. 1995; Lucas et al. 2005).
Studies showed this phenomenon to be the basic principle for the observed
cardioprotective character of moderate alcohol consumption (Clemens
et al. 1986; Moore and Pearson 1986). Chronic alcohol load causes an increase in
HDL over 50 mg/dl; after withdrawal and with continuing abstinence, the values
normalize within 1–4 weeks (Goldberg et al. 1995; Gilg et al. 1995). The
pathogenic cause for alcohol-related HDL and apoprotein increases is postulated
to be an enzyme induction as well as increased lipoprotein lipase activity
(Gilg et al. 1995; Hannuksela et al. 2004).
Increased HDL levels without alcohol can occur under the influence of medica-
tion (sedatives, lovastatin), pronounced underweight, and physical strain. Still, the
specificity of this marker is highly esteemed; moreover, it proved itself to be
practicable (Hannuksela et al. 1992a). Particularly in patients without liver damage,
HDL and apoprotein I/II can be used for monitoring abstinence since changes in
alcohol consumption would be accurately reflected.
16.3.7 b-Hexosaminidase
be 91–98 %; the sensitivity is 69–94 % (Stowell et al. 1997b; Taracha et al. 2001).
According to studies by Kärkkäinen and Salaspero (1991), b-hexosaminidase
activity reflects recent alcohol consumption, while b-hexosaminidase in urine
remains increased for longer periods after alcohol consumption.
appear less convincing than methanol as alcohol markers because increased acetone
levels also result from metabolic disorders like ketosis in hunger, diabetes, cooling,
and heavy physical strain.
16.3.10.2 Alc-Index
By combining methanol, acetone/isopropanol, g-GT, and CDT in a logistic regres-
sion formula, Brinkmann et al. (2000) developed the so-called Alc-index to differ-
entiate between alcohol-dependent patients and nondrinkers. The basic principle for
the investigations was the hypothesis that each of these alcohol markers shows
overlap in values in the collective with none or low alcohol consumption and
alcoholics. From the results, an Alc-index of 1.7 as cutoff was defined with
a specificity of 100 % and a sensitivity of 90 % to differentiate between
alcohol-dependent and non-alcohol-dependent individuals. The advantage of this
index is the single cutoff point instead of four different cutoff points for individual
markers.
100%
90%
90%
80%
70%
60%
Sensitivity
63%
50% 58%
50%
40% 45% 47%
30%
20%
10%
0%
γ-GT MCV CDT ASAT ALAT γ-CDT
Fig. 16.1 Comparison of sensitivities of conventional markers with g-CDT (Modified from
Niemelä 2007)
10
9
8
7
Weeks
6
5
4
3
2
1
0
Methanol CDT HDL-Chol. γ -GT MCV
Fig. 16.2 Depiction of alcohol markers in appropriate timelines (Modified from Gilg et al. 1995)
16.4 Conclusion
References
Aderjan R, Babel B, Briellmann T et al (2000) Anlage zu den Richtlinien der GTFCh zur
Qualitätssicherung bei forensisch-toxikologischen Untersuchungen. Anhang A: Anforderung
an einzelne Analysenmethoden. Toxichem Krimtech 67:13–16
Albermann ME, Musshoff F, Aengenheister L et al (2012a) Investigations on the influence of
different grinding procedures on measured ethyl glucuronide concentrations in hair determined
with an optimized and validated LC-MS/MS method. Anal Bioanal Chem 403(3):769–776
Albermann ME, Musshoff F, Doberentz E et al (2012b) Preliminary investigations on
ethyl glucuronide and ethyl sulphate cut-offs for detecting alcohol consumption on the basis
16 Biological State Marker for Alcohol Consumption 283
of an ingestion experiment and on data from withdrawal treatment. Int J Legal Med
126(5):757–764
Allen JP, Litten RZ, Anton RF, Cross GM (1994) Carbohydrate deficient transferrin as a measure
of immoderate drinking: remaining issues. Alcohol Clin Exp Res 18:799–812
Allen JP, Marques P, Wurst F (2009) Biomarkers of alcohol use: their nature, strengths, and
limitations. Mil Med 173(8):v–viii
€
Alling C, Gustavsson L, Anggård E (1983) An abnormal phospholipid in rat organs after ethanol.
FEBS Lett 152:24–28
Alt A, Janda I, Seidl S et al (2000) Determination of ethyl glucuronide in hair samples. Alcohol
Alcohol 35:313–314
Anton RF, Moak DH (1994) Carbohydrate-deficient transferrin and gamma-glutamyltransferase as
markers of heavy alcohol consumption: gender differences. Alcohol Clin Exp Res 18:747–754
Anton RF, Stout RL, Roberts JS, Allen JP (1998) The effect of drinking intensity and frequency on
serum carbohydrate-transferrin and gamma-glutamyl transferase levels in outpatient alco-
holics. Alcohol Clin Exp Res 22:1456–1462
Anton RF, Dominick C, Bigelow M, Westby C (2001) Comparison of Bio-Rad % CDT TIA and
CDTect as laboratory markers of heavy alcohol use and their relationships with gamma-
glutamyltransferase. Clin Chem 47:1769–1775
Appenzeller BMR, Agirman R, Neuberg P et al (2007a) Segmental determination of ethyl
glucuronide in hair: a pilot study. Forensic Sci Int 173:87–92
Appenzeller BM, Schuman M, Yegles M (2007b) Ethyl glucuronide concentration in hair is not
influenced by pigmentation. Alcohol Alcohol 42:326–327
Aradóttir S, Seidl S, Wurst FM et al (2004) Phosphatidylethanol in human organs and blood:
a study on autopsy material and influences by storage conditions. Alcohol Clin Exp Res
28(11):1718–1723
Aradottir S, Asanovska G, Gjerss S et al (2006) Phosphatidylethanol (PEth) concentrations in
blood are correlated to reported alcohol intake in alcohol-dependent patients. Alcohol Alcohol
41:431–437
Arndt T (2001) Carbohydrate-deficient transferrin as a marker of chronic alcohol abuse: a critical
review of preanalysis, analysis, and interpretation. Clin Chem 47:13–27
Arndt T (2003) Asialotransferrin–an alternative to carbohydrate-deficient transferrin? Clin Chem
49:1022–1023
Arndt T, Gierten B, G€ ussregen B et al (2009) False-positive ethyl glucuronide immunoassay
screening associated with chloral hydrate medication as confirmed by LC-MS/MS and
self-medication. Forensic Sci Int 184:27–29
Auwärter V, Sporkert F, Hartwig S et al (2001) Fatty acid ethyl esters in hair as markers of alcohol
consumption. Segmental hair analysis of alcoholics, social drinkers, and teetotalers. Clin Chem
47:2114–2123
Auwärter V, Kiessling B, Pragst F (2004) Squalene in hair- a natural reference substance for the
improved interpretation of fatty acid ethyl ester concentrations with respect to alcohol misuse.
Forensic Sci In 145:149–159
Baranowski S, Serr A, Thierauf A (2008) In vitro study of bacterial degradation of ethyl
glucuronide and ethyl sulphate. Int J Leg Med 122:389–393
Bean P, Kleaver E, Roberts B, Harasymiw J (2001) A new century approach for alcohol screen in
the insurance industry. J Insur Med 33:183–188
Bianchi V, Ivaldi A, Raspagni A et al (2011) Pregnancy and variations of carbohydrate-deficient
transferrin levels measured by the candidate reference HPLC method. Alcohol Alcohol
46(2):123–127
Bisson JI, Milford-Ward A (1994) A comparison of carbohydrate deficient transferrin with other
markers of alcohol misuse in male soldiers under the age of thirty. Alcohol Alcohol
29:315–321
Bora PS, Spilburg CA, Lange LG (1989) Metabolism of ethanol and carcinogens by glutathione
transferases. Proc Natl Acad Sci U S A 86:4470–4473
284 F.M. Wurst et al.
Bora PS, Guruge DG, Miller DD et al (1996) Purification and characterization of human heart fatty
acid ethyl ester synthase/carboxylesterase. J Mol Cell Cardiol 28:2027–2032
Bortolotti F, De Paoli G, Tagliaro F (2006) Carbohydrate-deficient transferrin (CDT) as a marker
of alcohol abuse: a critical review of the literature 2001–2005. J Chromatogr B Analyt Technol
Biomed Life Sci 841:96–109
Borucki K, Schreiner R, Dierkes J et al (2005) Detection of recent ethanol intake with new markers:
comparison of fatty acid ethyl esters in serum and of ethyl glucuronide and the ratio of
5-hydroxytryptophol to 5-hydroxyindole acetic acid in urine. Alcohol Clin Exp Res 29:781–787
Boström H, Vestermark A (1960) Studies on ester sulphates. 7. On the excretion of sulphate
conjugates of primary aliphatic alcohols in the urine of rats. Acta Physiol Scand 48:88–94
Böttcher M, Beck O, Helander A (2008) Evaluation of a new immunoassay for urinary ethyl
glucuronide testing. Alcohol Alcohol 43:46–48
Brinkmann B, Köhler H, Banaschak S, Berg A, Eikelmann B, West A, Heinecke A (2000) ROC
analysis of alcoholism markers – 100 % specificity. Int J Legal Med 113:293–299
Burroughs AK, Sabin CA, Rolles K et al (2006) 3-month and 12-month mortality after first liver
transplant in adults in Europe: predictive models for outcome. Lancet 367:225–232
Chan AW, Leong FW, Schanley DL, Welte JW, Wieczorek W, Rej R, Whitney RB
(1989) Transferrin and mitochondrial aspirate aminotransferase in young adult alcoholics.
Drug Alcohol Depend 23:13–18
Chen J, Conigrave KM, Macaskill P, Whitfield JB, Irwig L (2003) Combining carbohydrate-
deficient transferrin and gamma-glutamyltransferase to increase diagnostic accuracy for
problem drinking. Alcohol Alcohol 38:574–582
Clemens MR, Scied HW, Waller HD (1986) Serumlipide von Alkoholikern vor und nach
Abstinenz: Bedeutung f€ ur das “Koronarrisiko”. J Clin Chem Clin Biochem 24:369–374
Conigrave KM, Degenhardt LJ, Whitfield B et al (2002) On behalf of the WHO/ISBRA study on
biological state and trait markers of alcohol use and dependence investigators. CDT, GGT, and
AST as markers of alcohol use: the WHO/ISBRA collaborative project. Alcohol Clin Exp Res
26:332–339
Conigrave KM, Davies P, Haber P, Whitfield JB (2003) Traditional markers of excessive alcohol
use. Addiction 98(Suppl 2):31–43
Costantino A, Digregorio EJ, Korn W et al (2006) The effect of the use of mouthwash on
ethylglucuronide concentration in urine. J Anal Toxicol 30:659–662
Cushman P, Jacobson G, Barboriak JJ, Anderson AJ (1984) Biochemical markers for alcoholism:
sensitivity problems. Alcohol Clin Exp Res 8:245–257
Dahl H, Stephanson N, Beck O et al (2002) Comparison of urinary excretion characteristics of
ethanol and ethyl glucuronide. J Anal Toxicol 26:201–204
Dahl H, Voltaire Carlsson A, Hillgren K et al (2011a) Urinary ethyl glucuronide and ethyl sulphate
testing for detection of recent drinking in an outpatient treatment program for alcohol and drug
dependence. Alcohol Alcohol 46(3):278–282
Dahl H, Hammarberg A, Franck J et al (2011b) Urinary ethyl glucuronide and ethyl sulphate
testing for recent drinking in alcohol-dependent outpatients treated with acamprosate or
placebo. Alcohol Alcohol 46(5):553–557
DHS http://www.dhs.de/datenfakten/alkohol.html [Zugriff am 11 Oct 2013]
DiMartini A, Day N, Dew MA et al (2006) Alcohol consumption patterns and predictors of use
following liver transplantation for alcoholic liver disease. Liver Transpl 12:813–820
Dresen S, Weinmann W, Wurst FM (2004) Forensic confirmatory analysis of ethyl
sulphate – a new marker for alcohol consumption – by liquid chromatography/electrospray
ionisation/tandem mass spectrometry. J Am Soc Mass Spectrom 15:1644–1648
Erim Y, Bottcher M, Dohmen U et al (2007) Urinary ethyl glucuronide testing detects alcohol con-
sumption in alcoholic liver disease patients awaiting liver transplantation. Liver Transpl 13:757–761
Ewing JA (1984) Detecting alcoholism: the CAGE questionnaire. JAMA 252:1905–1907
Faller A, Richter B, Kluge M et al (2011) LC-MS/MS analysis of phosphatidylethanol in dried
blood spots versus conventional blood specimens. Anal Bioanal Chem 401(4):1163–1166
16 Biological State Marker for Alcohol Consumption 285
Ferreira LM, Binz T, Yegles M (2012) The influence of ethanol containing cosmetics on ethyl
glucuronide concentration in hair. Forensic Sci Int 218:123–125
Fleming MF, Anton RF, Spies CD (2004) A review of genetic, biological, pharmacological and
clinical factors that affect carbohydrate-deficient transferrin levels. Alcohol Clin Exp Res
28:1347–1355
Foti RS, Fisher MB (2005) Assessment of UDP-glucuronosyltransferase catalyzed formation of
ethyl glucuronide in human liver microsomes and recombinant UGTs. Forensic Sci Int
153(2):109–116
Fulop M, Ben-Ezra J, Bock J (1986) Alcoholic ketosis. Alcohol Clin Exp Res 10:610–615
Gilg T, Soyka MV, Meyer L, Ora I (1989) Methanol und Isopropanol als biochemische
Alkoholismusmarker – psychiatrische und forensische Aspekte. Nervenheilkunde 8:105–113
Gilg T, Deinl I, Grundner H, Soyka M (1995) Stellenwert von Begleitstoffanalytik (Methanol,
Isopropanol) und CD-Transferrin (CDT) in der Alkoholismusdiagnostik. In: Soyka M (ed)
Biologische Alkoholismusmarker. Chapman and Hall, London/Glasgow/Weinheim/New
York/Tokyo/Melbourne/Madras, pp 45–91
Gitto S, Micco L, Conti F et al (2009) Alcohol and viral hepatitis: a mini-review. Dig Liver Dis
41:67–70
Gnann H, Weinmann W, Engelmann C et al (2009) Selective detection of phosphatidylethanol
homologues in blood as biomarkers for alcohol misuse by LC-ESI-MS/MS. J Mass Spectrom
44(9):1293–1299
Gnann H, Engelmann C, Skopp G et al (2010) Identification of 48 homologues of phosphatidy-
lethanol in blood by LC-ESI-MS/MS. Anal Bioanal Chem 396:2415–2423
Gnann H, Weinmann W, Thierauf A (2012) Formation of phosphatidylethanol and its subsequent
elimination during an extensive drinking experiment over 5 days. Alcohol Clin Exp Res
36(9):1507–1511
Goldberg DM, Hahn SE, Parkes JG (1995) Beyond alcohol: beverage consumption and cardio-
vascular mortality. Clin Chim Acta 237:155–187
González-Illán F, Ojeda-Torres G, Dı́az-Vázquez LM et al (2011) Detection of fatty acid ethyl
esters in skin surface lipids as biomarkers of ethanol consumption in alcoholics, social drinkers,
light drinkers, and teetotallers using a methodology based on microwave-assisted extraction
followed by solid-phase microextraction and gas chromatography mass spectrometry. J Anal
Toxicol 35(4):232–237
Gustavsson L, Alling C (1987) Formation of phosphatidylethanol in rat brain by phospholipase
D. Biochem Biophys Res Commun 142:958–963
Hackler R, Arndt T, Helwig-Rolig A, Kropf J, Steinmetz A, Schaefer JR (2000) Investigation
by isoelectric focusing of the initial carbohydrate-deficient transferrin (CDT) and non-CDT
transferrin isoform fractionation step involved in determination of CDT by the
ChronAlcoI.D. assay. Clin Chem 46:483–492
Haffner HT, Krämer M, Zink P (1988) Veränderungen der Leberenzymwerte im Verlauf einer
36st€undigen Alkoholbelastung. Blutalkohol 25:116–126
Haffner HT, Banger M, Graw M, Besserer K, Brink T (1997) The kinetics of methanol elimination
in alcoholics and the influence of ethanol. Forensic Sci Int 89:129–136
Hagström H, Stål P, Stokkeland K et al (2012) Alcohol consumption in patients with primary
sclerosing cholangitis. World J Gastroenterol 18:3105–3111
Hahn JA, Dobkin LM, Mayanja B et al (2012a) Phosphatidylethanol (PEth) as a biomarker of
alcohol consumption in HIV-positive patients in sub-Saharan Africa. Alcohol Clin Exp Res
36(5):854–862
Halter CC, Dresen S, Auwaerter V et al (2008) Kinetics in serum and urinary excretion of
ethyl sulphate and ethyl glucuronide after medium dose ethanol intake. Int J Legal Med
122:123–128
Halter CC, Laengin A, Al-Ahmad A et al (2009) Assessment of the stability of the
ethanol metabolite ethyl sulphate in standardised degradation tests. Forensic Sci Int
186(1):52–55
286 F.M. Wurst et al.
Hannuksela M, Marcel YL, Kesäniemi YA, Savolainen MJ (1992a) Reduction in the concentration
and activity of plasma cholesteryl ester transfer protein by alcohol. J Lipid Res 33:737–744
Hannuksela M, Kesäniemi YA, Savolainen MJ (1992b) Evaluation of plasma cholesteryl ester
transfer protein (CETP) activity as a marker of alcoholism. Alcohol Alcohol 27:557–562
Hannuksela M, Liisanantti MK, Savolainen MJ (2002) Effect of alcohol on lipids and lipoproteins
in relation to atherosclerosis. Crit Rev Clin Lab Sci 39:225–283
Hannuksela M, Rämet ME, Nissinen AE, Liisanantti MK, Savolainen MJ (2004) Effects of ethanol
on lipids and atherosclerosis. Pathophysiol 10:93–103
Hannuksela ML, Liisanantti MK, Nissinen AE et al (2007) Biochemical markers of alcoholism.
Clin Chem Lab Med 45:953–961
Harasymiw J, Bean P (2007) The early detection of alcohol consumption (EDAC) test shows better
performance than gamma-glutamyltransferase (GGT) to detect heavy drinking in a large
population of males and females. Med Sci Monit 13:PI 19–24
Harasymiw J, Vinson DC, Bean P (2000) The early detection of alcohol consumption (EDAC)
score in the identification of heavy and at-risk-drinkers from routine blood tests. J Addict Dis
19:43–59
Harasymiw J, Seaberg J, Bean P (2004) Detection of alcohol abuse using a routine test panel.
Alcohol Alcohol 39:325–328
Hartmann S, Aradottir S, Graf M et al (2007) Phosphatidylethanol as a sensitive and specific
biomarker – comparison with gamma glutamyl transpeptidase, mean corpuscular volume and
carbohydrate-deficient transferrin. Addict Biol 12:81–84
Hartwig S, Auwärter V, Pragst F (2003) Effect of hair care and hair cosmetics on the concentra-
tions of fatty acid ethyl esters in hair as markers of chronically elevated alcohol consumption.
Forensic Sci Int 131:90–97
Helander A (2003a) Biological markers in alcoholism. J Neural Transm 66:15–32
Helander A (2003b) Carbohydrate-deficient transferrin (CDT): adding sensitivity and specificity to
alcohol abuse testing. Dade Behring J 13–15
Helander A, Beck O (2004) Mass spectrometric identification of ethyl sulphate as an ethanol
metabolite in humans. Clin Chem 5:936–937
Helander A, Dahl H (2005) Urinary tract infection: a risk factor for false-negative urinary ethyl
glucuronide but not ethyl sulphate in the detection of recent alcohol consumption. Clin Chem
51(9):1728–1730
Helander A, Tabakoff B (1997) Biochemical markers of alcohol use and abuse: experiences
from the pilot study of the WHO/ISBRA collaborative project on state and trait markers of
alcohol. International society for biomedical research on alcoholism. Alcohol Alcohol
32:133–144
Helander A, Zheng Y (2009) Molecular species of the alcohol biomarker phosphatidylethanol in
human blood measured by LC-MS. Clin Chem 55(7):1395–1405
Helander A, Fors M, Zakrisson B (2001) Study of axis-shield new %CDT immunoassay for
quantification of carbohydrate-deficient transferrin (CDT) in serum. Alcohol Alcohol
36:406–412
Helander A, Husa A, Jeppsson JO (2003) Improved HPLC method for carbohydrate-deficient
transferrin in serum. Clin Chem 49:1881–1890
Helander A, Hagelberg CA, Beck O et al (2009) Case report. Unreliable alcohol testing in
a shipping safety programme. Forensic Sci Int 189:e45–e47
Hietala J, Koivisto H, Anttila P, Niemelä O (2006) Comparison of the combined marker
GGT-CDT and the conventional laboratory markers of alcohol abuse in heavy drinkers,
moderate drinkers and abstainers. Alcohol Alcohol 41:528–533
Hoiseth G, Nordal K, Pettersen E et al (2012) Prolonged urinary detection times of EtG and EtS in
patients with decreased renal function. Alcohol Clin Exp Res 36(7):1148–1151
Høiseth G, Morini L, Polettini A, Christophersen A, Mørland J (2009) Blood kinetics of ethyl
glucuronide and ethyl sulphate in heavy drinkers during alcohol detoxification. Forensic Sci Int
188:52–56
16 Biological State Marker for Alcohol Consumption 287
Høiseth G, Morini L, Ganss R et al (2013) Higher levels of hair ethyl glucuronide in patients with
decreased kidney function. Alcohol Clin Exp Res 37(Suppl 1):E14–E16
Hultberg B, Isaksson A, Berglund M, Moberg AL (1991) Serum b-hexosaminidase isoenzyme:
a sensitive marker for alcohol abuse. Alcohol Clin Exp Res 15:549–552
Humaloja K, Salaspero M, Roine R (1997) Biliary excretion of dolichols and beta-
hexosaminidase – effect of ethanol and glucagon. Lipids 32:1169–1172
Huseby NE, Nilssen O, Erfurth A, Wetterling T, Kanitz RD (1997) Carbohydrate-deficient
transferrin and alcohol dependency: variation in response to alcohol intake among different
groups of patients. Alcohol Clin Exp Res 21:201–205
Iffland R (1993) CDT, GGT und Methanol als Alkoholismusindikatoren in Blutproben alkoholauf-
fälliger Kraftfahrer. Fortschr Diagnost 4. Praxisreport 5:17–22
Iffland R, Staak M (1990) Methanol und Isopropanol als Alkoholismusmarker. Beitr Gerichtl Med
48:173–177
Iffland R, Kaschade W, Heesen D, Mehne P (1984) Untersuchungen zur Bewertung hoher
Methanolspiegel bei Begleitalkohol-Analysen. Beitr Gerichtl Med 42:231–236
Iffland R, Balling MP, Börsch G, Herold C, Kaschade W, Löffler T, Schmidtmann U, Stettner
J (1994) Zur Wertung erhöhter Spiegel von GGT, CDT, Methanol, Aceton und Isopropanol im
Blut alkoholauffälliger Kraftfahrer – Alkoholismusindikatoren anstelle medizinisch-
psychologischer Untersuchungen? Blutalkohol 3:287–314
Isaksson A, Walther L, Hansson T et al (2011) Phosphatidylethanol in blood (B-PEth): a marker
for alcohol use and abuse. Drug Test Anal 3:195–200
Jeppsson JO, Kristensson H, Fimiani C (1993) Carbohydrate-deficient transferrin quantified by
HPLC to determine heavy consumption of alcohol. Clin Chem 39:2115–2120
Joya X, Friguls B, Ortigosa S et al (2012) Determination of maternal-fetal biomarkers of prenatal
exposure to ethanol: a review. J Pharm Biomed Anal 69:209–222
Junghanns K, Graf I, Pfl€ uger J et al (2009) Urinary ethyl glucuronide (EtG) and ethyl sulphate
(EtS) assessment: valuable tools to improve verification of abstention in alcohol-dependent
patients during in-patient treatment and at follow-ups. Addiction 104:921–926
Kärkkainen P, Salaspero M (1991) Beta-hexosaminidase in the detection of alcoholism and heavy
drinking. Alcohol Alcohol Suppl 1:459–464
Kärkkainen P, Jokelainen K, Roine R, Suokas A, Salaspuro M (1990) The effects of moderate drinking
and abstinence on serum and urinary betahexosaminidase levels. Drug Alcohol Depend 25:35–38
Kaufmann E, Alt A (2008) Detection of ethyl glucuronide in dried human blood using LC-MS/MS.
Int J Legal Med 122:245–249
Kelly M, Chick J, Gribble R et al (2006) Predictors of relapse to harmful alcohol after orthotopic
liver transplantation. Alcohol Alcohol 41:278–283
Kenan N, Larsson A, Axelsson O et al (2011) Changes in transferrin glycosylation during
pregnancy may lead to false-positive carbohydrate-deficient transferrin (CDT) results in testing
for riskful alcohol consumption. Clin Chim Acta 412(1):129–133
Kharbouche H, Steiner N, Morelato M et al (2010) Influence of ethanol dose and pigmentation on
the incorporation of ethyl glucuronide into rat hair. Alcohol 44(6):507–514
Kip MJ, Spies CD, Neumann T et al (2008) The usefulness of direct ethanol metabolites in
assessing alcohol intake in non-intoxicated male patients in an emergency room setting.
Alcohol Clin Exp Res 32:1284–1291
Koivisto H, Hietala J, Anttila P, Parkkila S, Niemelä O (2006) Long-term ethanol consumption
and macrocytosis: diagnostic and pathogenic implications. J Lab Clin Med 147:191–196
Kronstrand R, Brinkhagen L, Nyström FH (2012) Ethyl glucuronide in human hair after daily
consumption of 16 or 32 g of ethanol for 3 months. Forensic Sci Int 215(1):51–55
Kulaga V, Velazquez-Armenta Y, Aleksa K et al (2009) The effect of hair pigment on the
incorporation of fatty acid ethyl esters (FSEE). Alcohol Alcohol 44:287–292
Kwoh-Gain I, Fletcher LM, Price J, Powell LW, Halliday JW (1990) Desialylated transferrin and
mitochondrial aspartate aminotransferase compared as laboratory markers of excessive alcohol
consumption. Clin Chem 36:841–845
288 F.M. Wurst et al.
Laposata M (1999) Assessment of ethanol intake – current tests and new assays on the horizon.
Am J Clin Pathol 112:443–450
Lesch OM, Walter H, Antal J, Heggli DE, Kovacz A, Leitner A, Neumeister A, Stumpf I,
Sundrehagen E, Kasper S (1996) Carbohydrate-deficient transferrin as a marker of alcohol
intake: a study with healthy subjects. Alcohol Alcohol 31:265–271
Lewis GD, Laufmann KA, McAnalley BH, Garriott JC (1984) Metabolism of acetone to isopropyl
alcohol in rats and humans. J Forensic Sci 29:541–549
Liniger B, Nguyen A, Friedrich-Koch A, Yegles M (2010) Abstinence monitoring of suspected
drinking drivers: ethyl glucuronide in hair versus CDT. Traffic Inj Prev 2:123–126
Loftus N, Barnes A, Ashton S et al (2011) Metabonomic investigation of liver profiles of nonpolar
metabolites obtained from alcohol-dosed rats and mice using high mass accuracy MSn
analysis. J Proteome Res 10(2):705–713
Lucas DL, Brown RA, Wassef M, Giles TD (2005) Alcohol and the cardiovascular system
research challenges and opportunities. J Am Coll Cardiol 45:1916–1924
Magrinat G (1973) Ethanol and methanol metabolites in alcohol withdrawal. Nature 244:234–235
Mani JC, Pietruszko R, Theorell H (1970) Methanol activity of alcohol dehydrogenase from
human liver, horse liver and yeast. Arch Biochem Biophys 140:52–59
Mann K (2002) Neue ärztliche Aufgaben bei Alkoholproblemen: von der Behandlungskette zum
€
Behandlungsnetz. Deutsches Arzteblatt 99(10):632–644
Marques P, Tippets S, Allen JP et al (2010) Estimating driver risk using alcohol biomarkers,
interlock BAC tests and psychometric assessments. Addiction 105(2):226–239
Marques P, Hansson T, Isaksson A et al (2011) Detection of phosphatidylethanol (PEth) in the
blood of drivers in an alcohol ignition interlock program. Traffic Inj Prev 12(2):136–141
Martensson O, Harlin A, Brandt R, Seppa K, Sillanaukee P (1997) Transferrin isoform distribu-
tion: gender and alcohol consumption. Alcohol Clin Exp Res 21:1710–1715
McDonell MG, Howell DN, McPherson S et al (2012) Voucher-based reinforcement for alcohol
abstinence using the ethyl-glucuronide alcohol biomarker. J Appl Behav Anal 45(1):161–165
Mitchell JM, Teague CH, Kayser AS et al (2012) Varenicline decreases alcohol consumption in
heavy-drinking smokers. Psychopharmacology (Berl) 223(3):299–306
Montalto NJ, Bean P (2003) Use of contemporary biomarkers in the detection of chronic alcohol
use. Med Sci Monit 9:285–290
Moore RD, Pearson TA (1986) Moderate alcohol consumption and coronary artery
disease – a review. Medicine 65:242–267
Moore RD, Bone LR, Geller G et al (1989) Prevalence, detection, and treatment of alcoholism in
hospitalized patients. JAMA 261:403–407
Morgan MY, Camilo ME, Luck W, Sherlock S, Hoffbrand AV (1981) Macrocytosis in alcohol-
related liver disease: its value for screening. Clin Lab Haematol 3:35–44
Morini L, Groppi A, Marchei E et al (2010a) Population Baseline of Meconium Ethyl Glucuronide
and Ethyl Sulphate Concentrations in Newborns of Nondrinking Women in 2 Mediterranean
Cohorts. Ther Drug Monit [Epub ahead of print]
Morini L, Zucchella A, Polettini A et al (2010b) Effect of bleaching on ethyl glucuronide in hair:
an in vitro experiment. Forensic Sci Int 198:23–27
Mundle G, Munkes J, Ackermann K, Mann K (2000) Sex differences of carbohydrate-deficient
transferrin, gamma-glutamyltransferase and mean corpuscular volume in alcohol-dependent
patients. Alcohol Clin Exp Res 24:1400–1405
Nalesso A, Viel G, Cecchetto G et al (2011) Quantitative profiling of phosphatidylethanol
molecular species in human blood by liquid chromatography high resolution mass spectrom-
etry. J Chromatogr A 1218(46):8423–8431
Neumann T, Spies C (2003) Use of biomarkers for alcohol use disorders in clinical practice.
Addiction 98(Suppl 2):81–91
Niemelä O (2002) Serum diagnosis of alcoholic liver disease and markers of ethanol intake. In:
Shermann DIN, Preedy V, Watson RR (eds) Ethanol and the liver, 1st edn. Taylor and Francis,
New York/London, pp 411–449
16 Biological State Marker for Alcohol Consumption 289
Saunders JB, Aasland OG, Babor TF et al (1993) Development of the alcohol use disorders
identification test (AUDIT): WHO collaborative project on early detection of persons with
harmful alcohol consumption – II. Addiction 88:791–804
Savolainen MJ, Hannuksela M, Seppänen S, Kervinen K, Kesäniemi YA (1990) Increased high-
density lipoprotein cholesterol concentration in alcoholics is related to low cholesteryl ester
transfer protein activity. Eur J Clin Invest 20:593–599
Schlögel H, Dresen S, Spaczynski K et al (2005) Stability of ethyl glucuronide in urine, post-
mortem tissue and blood samples. Int J Legal Med 30:1–6
Schmitt G, Aderjan R, Keller T et al (1995) Ethyl-glucuronide: an unusual ethanol metabolite in
humans. Synthesis, analytical data, and determination in serum and urine. J Anal Toxicol 19:91–94
Schneider H, Glatt H (2004) Sulfo conjugation of ethanol in humans in vivo and by individual
sulfotransferase forms in vitro. Biochem J 383:543
Sillanaukee P, Olsson U (2001) Improved diagnostic classification of alcohol abusers by
combining carbohydrate-deficient transferrin and gamma-glutamyltransferase. Clin Chem
47:681–685
Sillanaukee P, Strid N, Allen JP, Litten RZ (2001) Possible reasons why heavy drinking increases
carbohydrate-deficient transferrin. Alcohol Clin Exp Res 25:34–40
Sillanaukee P, van der Gaag MS, Sierksma A, Hendriks HF, Strid N, Pönniö M, Nikkari ST
(2003) Effect of type of alcoholic beverages on carbohydrate-deficient transferrin, sialic acid
and liver enzymes. Alcohol Clin Exp Res 27:57–60
Skipper GE, Schaefer P, Thierauf A et al (2004a) Detection of surreptitious alcohol use among
health professionals recovering from substance-related disorders using a new marker, ethyl
glucuronide. Alcohol Alcohol 39:445–459
Skipper GE, Weinmann W, Thierauf A, Schäfer P, Wiesbeck G, Allen J, Miller M, Wurst FM
(2004b) Ethyl glucuronide: a biomarker to identify alcohol use by health professionals
recovering from substance use disorders. Alcohol Alcohol 39(5):445–449
Society of Forensic Toxicologists and American Academy of Forensic Sciences, SOFT/AAFS
(2006) Forensic toxicology laboratory guidelines. http://www.soft-tox.org/index.php?
option¼com_content&view¼article&id¼55&Itemid¼62. Accessed 22 July 2012
Society of Hair Testing (2009) Consensus of the society of hair testing on hair testing for chronic
excessive alcohol consumption. http://soht.org/pdf/Consensus_EtG_2009.pdf. Zugriff am
22 Juli 2012
Spies C, Tonnesen H, Andreasson S et al (2001) Perioperative morbidity and mortality in chronic
alcoholic patients. Alcohol Clin Exp Res 25(5):164S–170S
Sporkert F, Kharbouche H, Augsburger MP (2012) Positive EtG findings in hair as a result of
a cosmetic treatment. Forensic Sci Int 218(1):97–100
Stade B, Ali A, Bennett D et al (2009) The burden of prenatal exposure to alcohol: revised
measurement of cost. Can J Clin Pharmacol 16(1):e91–e102
Stauber RE, Jauk B, Fickert P, Hausler M (1996) Increased carbohydrate-deficient transferrin
during pregnancy: relation to sex hormones. Alcohol Alcohol 31:389–392
Stewart SH, Reuben A, Brzezinski WA et al (2009) Preliminary evaluation of phosphatidylethanol
and alcohol consumption in patients with liver disease and hypertension. Alcohol Alcohol
44(5):464–467
Stewart SH, Law TL, Randall PK et al (2010) Phosphatidylethanol and alcohol consumption in
reproductive age women. Alcohol Clin Exp Res 34(3):488–492
Stewart SH, Koch DG, Burgess DM et al (2013) Sensitivity and specificity of urinary ethyl
glucuronide and ethyl sulphate in liver disease patients. Alcohol Clin Exp Res 37(1):150–155
Stibler H (1991a) Carbohydrate-deficient transferrin in serum: a new marker of potentially harmful
alcohol consumption reviewed. Clin Chem 37:2029–2037
Stibler H (1991b) Carbohydrate-deficient transferrin in serum: a new marker of potentially
harmful alcohol consumption reviewed. Clin Chem 37:2029–2037
Stibler H, Kjellin KG (1976) Isoelectric focusing and electrophoresis of the CSF proteins in tremor
of different origins. J Neurol Sci 30:269–285
16 Biological State Marker for Alcohol Consumption 291
Wurst FM, Thon N (2012) WeinmannWet al. Characterization of sialic acid index of plasma
apolipoprotein J and phosphatidylethanol during alcohol detoxification – a pilot study. Alcohol
Clin Exp Res 36(2):251–257
Wurst FM, Kempter C et al (1999a) Ethyl glucuronide – a marker of alcohol consumption and
a relapse marker with clinical and forensic implications. Alcohol Alcohol 34:71–77
Wurst FM, Kempter C, Seidl S et al (1999b) Can ethyl glucuronide be determined in post mortem
body fluids and tissues? Alcohol Alcohol 34:262–263
Wurst FM, Vogel R, Jachau K et al (2003a) Ethyl glucuronide detects recent alcohol use in
forensic psychiatric inpatients. Alcohol Clin Exp Res 27:471–476
Wurst FM, Skipper GE, Weinmann W (2003b) Ethyl glucuronide – the direct ethanol metabolite
on the threshold from science to routine use. Addiction 98(Suppl 2):51–61
Wurst FM, Wiesbeck GA, Metzger JW et al (2004a) On behalf of the WHO/ISBRA study on
biological state and trait markers of alcohol use and dependence. On sensitivity, specificity and
the influence of various parameters on ethyl glucuronide levels in urine – results from the
WHO/ISBRA Study. Alcohol Clin Exp Res 28:1220–1228
Wurst FM, Alexson S, Wolfersdorf M et al (2004b) Concentration of fatty acid ethyl esters in hair
of alcoholics: comparison to other biological state markers and self reported ethanol intake.
Alcohol Alcohol 39:33–38
Wurst FM, Dresen S, Allen JP et al (2006) Ethyl Sulphate: A Direct Ethanol Metabolite Reflecting
Recent Alcohol Consumption. Addiction 101:204–211
Wurst FM, Kelso E, Weinmann W (2008a) Measurement of direct Ethanol metabolites suggests
higher rate of alcohol use among pregnant women than found with the AUDIT – a pilot study in
a population-based sample of Swedish women. Am J Obstet Gynecol 198(4):407.e1–5
Wurst FM, D€ursteler-MacFarland KM, Auwaerter V et al (2008b) Assessment of alcohol use
among methadone maintenance patients by direct ethanol metabolites and self-reports. Alcohol
Clin Exp Res 32:1552–1557
Wurst FM, Yegles M, Alling C et al (2008c) Measurement of direct ethanol metabolites in a case
of a former driving under influence (DUI) of alcohol offender, now claiming abstinence. Int
J Legal Med 122:235–239
Wurst FM, Haber PS, Wiesbeck G et al (2008d) Assessment of alcohol consumption among
hepatitis C positive people receiving opioid maintenance treatment using direct ethanol
metabolites and self report – a pilot study. Addict Biol 13:416–422
Wurst FM, Thon N, Aradottir S et al (2010) Phosphatidylethanol: normalization during detoxifi-
cation, gender aspects and correlation with other biomarkers and self-reports. Addict Biol
15(1):88–95
Wurst FM, Thon N, Yegles M et al (2011) Optimizing heroin-assisted treatment (HAT): assess-
ment of the contribution of direct ethanol metabolites in identifying hazardous and harmful
alcohol use. Drug Alcohol Depend 115(1):57–61
Wymer A, Becker DM (1990) Recognition and evaluation of red blood cell macrocytosis in the
primary care setting. J Gen Intern Med 5:192–197
Xin Y, Lasker JM, Lieber CS (1995) Serum carbohydrate-deficient transferrin: mechanism of
increase after chronic alcohol intake. Hepatology 22:1462–1468
Yegles M, Labarthe A, Auwärter V et al (2004) Comparison of ethyl glucuronide and fatty acid
ethyl ester concentrations in hair of alcoholics, social drinkers and teetotallers. Forensic Sci Int
145:167–173
Zelner I, Hutson JR, Kapur BM et al (2012) False-positive meconium test results for fatty acid
ethyl esters secondary to delayed sample collection. Alcohol Clin Exp Res 36(9):1497–1506
Zheng Y, Beck O, Helander A (2011) Method development for routine liquid chromatography-
mass spectrometry measurement of the alcohol biomarker phosphatidylethanol (PEth) in
blood. Clin Chim Acta 412:1428–1435
Brief Intervention for Illicit Drug Users
17
Jennifer Harland, Linda Gowing, and Robert Ali
Contents
17.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294
17.2 Providing Effective Brief Interventions for Illicit Drug Users . . . . . . . . . . . . . . . . . . . . . . . . . 294
17.2.1 Nature of Brief Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294
17.2.2 Effectiveness of Brief Interventions for Alcohol and Smoking Cessation . . . 295
17.2.3 Effectiveness of Brief Interventions for Illicit Drug Users . . . . . . . . . . . . . . . . . . . 296
17.2.4 Settings for Brief Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
17.2.5 Key Principles in Conducting a Brief Intervention with an
Illicit Drug User . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
17.2.6 International Perspectives and Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . 307
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 308
Abstract
Screening and brief intervention is an effective public health measure for the early
detection and management of substance use disorders. There is a range of validated
screening tools designed for use in various settings and contexts. This chapter provides
anoverviewoftheprocessthatisafundamentalnextstepfollowingscreening,namely,
the provision of an effective and targeted brief intervention for illicit drug users.
It includes an overview of the evidence related to brief interventions for people
using cannabis, amphetamines, cocaine, or opiates. Although research in this area
is somewhat limited, the chapter will draw on the empirical evidence for effective
brief intervention in a range of areas and suggest practical approaches to engage
illicit drug users. There are many possible settings (primary care, emergency
department, and mental health) and various ways of presenting brief interventions,
such as via a computer. As illicit drug use is rarely limited to one substance,
implications for polydrug users are addressed. Practical steps and examples are
provided, based on the principles of motivational interviewing, to demonstrate
how effective brief interventions can be implemented.
Some of the common barriers to implementing brief interventions in practice
will be explored. Practical solutions will be offered as a guide to overcoming
both real and perceived barriers to conducting targeted and effective brief
interventions in practice.
17.1 Introduction
The combination of physical, psychological, and social dimensions makes drug depen-
dence a complex condition (Gowing et al. 2001). Addressing substance misuse is a high
priority for health policy, and there are clear public health and economic benefits from
the early detection of an emerging problem to prevent its escalation. Screening
combined with brief intervention provides a comprehensive, integrated, public health
approach across the full spectrum of substance misuse (Babor et al. 2007).
Most people with clinically significant (low-moderate severity) problems relat-
ing to their substance use will not seek help from specialist addiction treatment
services (Humeniuk et al. 2012). General health-care professionals therefore play
an important role in the early detection of substance misuse. Any health-care visit
presents an opportunity for screening and brief intervention, and routine practice
should include asking about and documenting substance use (Saitz 2010).
There is strong evidence for the effectiveness of brief interventions in primary
care settings for alcohol (Kaner et al. 2008) and tobacco and growing evidence that
brief interventions are effective for cannabis (Copeland et al. 2001; Copeland and
Swift 2009), benzodiazepines (Bashir et al. 1994; Heather et al. 2004), amphet-
amines (Baker et al. 2001; 2003), opiates (Saunders et al. 1995), and cocaine use
(Stotts et al. 2001). Research has shown that screening and brief intervention has
led to a reduction in mortality (Cuijpers et al. 2004), health-care costs (Kaner
et al. 2008), criminal justice involvement, and societal costs (Sullivan
et al. 2011). The present chapter should be read in conjunction with the companion
▶ Chaps. 12, “Screening, Early Detection and Brief Intervention for Alcohol Use
Disorders” and ▶ 13, “Screening for Nicotine and Drug Use Disorders.”
The definition of brief intervention varies throughout the literature and is often used
as an overarching term to include related, but slightly different, types of interven-
tions such as brief motivation and brief motivational enhancement (Ager
17 Brief Intervention for Illicit Drug Users 295
et al. 2011). Overall, the goals of brief intervention are to assess and identify
substance use behavior in clients, provide advice on these behaviors, facilitate
behavior change with regard to substance use, and motivate the client to receive
further treatment if necessary (Bien et al. 1993; Miller and Rollnick 2013). For the
purpose of this chapter, brief intervention is defined as:
A practice that aims to explore real or potential problems with substance use and
help strengthen an individual’s motivation to change. Brief cminterventions are
generally of short duration (5–30 min) and may extend over one to four sessions (Gowing
et al. 2001).
Screening and brief intervention provided in acute care settings is associated with
modest changes in self-reported recent illicit drug use (Woodruff et al. 2013).
A review of randomized controlled trials of motivational interviewing among
drug-abusing or drug-dependent individuals found that 14 of the 17 trials identified
reported positive treatment effects (Miller et al. 2003). Among US college students,
a brief intervention reduced alcohol, cannabis, and other drug use at 3 months, with
greatest effects among heaviest users (McCambridge and Strang 2004); however,
findings were not maintained at 12 months.
A randomized controlled trial conducted by Shetty (2011) found that a culturally
competent, motivational intervention integrated into the care of vulnerable patients
with facial injury reduced illicit drug use behaviors. Participants received an
individualized behavioral intervention via two counseling sessions, the first shortly
after their injury and the second 4–6 weeks later (Shetty 2011).
Although there is limited research on the effectiveness of brief interventions
with specific illicit substances, an overview of the available evidence on cannabis,
amphetamines, opiates, and prescription medications is presented below.
17.2.3.1 Cannabis
Brief interventions have shown promise among both adult and adolescent cannabis
users with research to date finding brief interventions effective in reducing the
quantity and frequency of use and a number of cannabis-associated problems
(Carroll et al. 2006; Copeland et al. 2001; Dennis et al. 2004; Kamon et al. 2005;
Stephens et al. 2000). These studies have typically compared a brief intervention
(from one to six sessions) to a delayed treatment control (DTC) condition and are
largely based on cognitive behavior therapy (CBT) and motivational enhancement
therapy (MET).
An Australian study by Martin and Copeland (2008) found that individuals who
received a single assessment session combined with a feedback session based on
MET had greater reductions in cannabis use and the number of DSM-IV criteria
endorsed for cannabis dependence in comparison to those in a delayed treatment
control condition.
A meta-analysis of brief interventions for cannabis by the UK National Institute
for Health and Clinical Excellence (NICE) found a significant increase in the
likelihood of abstinence associated with brief intervention treatment (relative risk
3.33, 95 % CI 1.99–5.56) (National Collaborating Centre for Mental Health 2007).
Among samples of adolescents attending emergency departments, a brief interven-
tion with booster sessions, delivered by peers, was effective in preventing cannabis
use and “days high” at 12 months (Beralnstein et al. 2009). McCambridge
et al. (2008) found that there was no difference in outcome between motivational
interviewing and drug information and advice at either the 3- or 6-month follow-up
study interval. There was, however, substantial evidence of variability in outcomes
by practitioner, regardless of the intervention being delivered, including in relation
17 Brief Intervention for Illicit Drug Users 297
17.2.3.2 Amphetamines
In a randomized controlled trial of regular amphetamine users, Baker et al. (2001)
reported that a brief intervention (n ¼ 32) consisting of either a two-session
intervention of motivational interviewing and cognitive behavioral therapy or
a four-session intervention consisting of a motivational interview and skills training
in avoidance of high-risk situations, coping with cravings, and relapse prevention
was feasible among regular users of amphetamine when compared with the control
group (n ¼ 32) who received a self-help booklet. The main finding was that more
people in the intervention condition abstained from amphetamines at 6-month
follow-up compared to the controlled condition (Baker et al. 2001).
In a follow-up study, Baker and Dawe (2005) reported a significant increase in
the likelihood of abstinence from amphetamines among those receiving two or
more treatment sessions. Reduction in amphetamine use was accompanied by
significant improvements in stage of change, benzodiazepine use, tobacco smoking,
polydrug use, injecting risk-taking behavior, criminal activity level, and psychiatric
distress and depression level.
From the findings, Baker and Dawe (2005) recommend a stepped-care approach.
A basic intervention would consist of a structured assessment of amphetamine use and
related problems, self-help material, and regular monitoring of amphetamine use and
related harms. Baker and Dawe (2005) suggest offering two sessions of CBT at the
outset for regular amphetamine users with further treatment offered depending on
response.
17.2.3.3 Cocaine
Benefits have been shown after two sessions of motivational interviewing for
cocaine users with low initial motivation to change (Rohsenow et al. 2004). Platt
(1997), from a review of cocaine misuse, concluded that a nonconfrontational,
empathic, and mutually respective therapeutic relationship is more likely to engage
those more entrenched users who are unwilling to accept that they have a problem.
17.2.3.4 Heroin
Research into brief interventions with heroin users is limited; however, a study
conducted by Saunders et al. (1995) concluded that brief motivational interventions
were a useful adjunct to clients on methadone programs. They found that over
298 J. Harland et al.
Primary care settings provide the best context and opportunity for change over
time, since patients have an expectation of preventive care and often have a long-
term and trusting relationship with a clinician (Saitz et al. 2010). There is research
evidence supporting the effectiveness of brief interventions that target either alco-
hol use or smoking in primary health-care settings (Kaner et al. 2008). Brief
interventions for substances other than alcohol have also been shown to be effective
in primary care settings, if culturally appropriate intervention procedures are
developed (Humeniuk et al. 2003).
An annual cross-sectional study of approximately 1,000 general practitioners
throughout Australia has been provided since 1998 by the Bettering the Evalu-
ation and Care of Health (BEACH) program. Frewen et al. (2008) analyzed the
BEACH data between April 2000 and March 2007 and showed that general
practitioners addressed illicit drug use approximately 55,000 times per year
and of these, cannabis made up 3.2 % of all encounters which specified an illicit
drug. The most common response was to offer counseling (approximately 52.7 %
of cannabis encounters) and referral (approximately 22.5 % of cannabis encoun-
ters), while recommending a medication for a specific cannabis-related problem
was less common (approximately 9.3 % of cannabis encounters) (Frewen
et al. 2008).
Patients view primary care as a credible source of advice about health risks
including substance use (Humeniuk et al. 2003). Nurses comprise the greatest
proportion of health-care workers and serve in a variety of settings, often in roles
that are focused on health promotion and patient education. This makes practice
nurses ideal providers of screening and brief intervention (Puskar et al. 2013).
findings, opportunities and implications for screening and brief intervention for
illicit substance use via computer tablets are currently being explored.
The use of a phone application or ‘app’ is seen to be less confrontational than
face-to-face communication, particularly if the person is uncertain whether their
substance use is a problem. In Australia, the ‘Night Coach’ phone app developed by
the Australian National Council on Drugs, offers screening via the ASSIST and a
brief intervention based on the persons responses and risk category. The person is
able to track the amount of money they have spent on their substance use and links
are provided to specialist support and treatment services.
The stages of change model can be used to match interventions with a person’s
readiness to take in information and change their substance use (Fig. 17.1).
be nonjudgmental and respectful of the client’s choice but at the same time raise
awareness and provide relevant information (Naegle and D’Avanzo 2000). Raising
doubt is an effective approach as it increases the client’s perception of risks and
problems with their current behavior. The overall strategy is to maintain a low
intensity of interaction so the individual does not feel overwhelmed or pressured to
change (Miller and Rollnick 2002).
Contemplation is a very paradoxical stage of change as, although the person is
aware of a problem, they have not made a significant commitment to change (Miller
and Rollnick 2002). Individuals at the contemplation stage are aware of the harms
of use and the benefits of changing but are still ambivalent about changing. This can
be expressed as “I don’t believe how much I am spending on drugs, but I really like
it” (DiClemente et al. 2004).
During a brief intervention, the clinician can be quite influential at this stage as
they encourage the client to explore the risks of continued use versus the benefits of
changing. The clinician can help the client “tip the balance” in favor of the most
positive behavior. It is important to note that responsibility for change lies with
the client and that the clinician reinforces the advantages of change and promotes
self-efficacy of the client. For clinicians, it is important that they recognize
ambivalence as a vital part of the contemplation stage of change. It must also be
recognized that contemplation does not mean commitment (DiClemente and
Velasquez 2002).
The individual has entered the preparation stage when they have decided to
take action in the near future and are making plans and developing motivation to
engage in change activities. This is often expressed as “I want to know how to give
up” or “I am ready to try cutting down.” The person may be confused about the best
way forward and may seek advice of professional, friends, family, and people who
have been through a similar experience to learn from their experience.
Individuals at the preparation stage have often sought treatment previously and
may have tried and failed to change in the past. Yet, they have often learned
valuable lessons from past change attempts (DiClemente and Velasquez 2002). It
is important in the preparation stage to assist the client in finding the best course of
action. This can be done by offering a menu of options, cocreating a plan, goal
setting, demystifying the change process, and inspiring realistic hope (Prochaska
et al. 1992). People at this stage may benefit from validation and reinforcement in
respect to their reasons for change and assistance in planning strategies to bring
about change. The overall strategy at this stage is to help the client determine the
best course of action to take in seeking change.
The next stage is action and this is when people most overtly modify their
behavior. During this stage, the person makes the move and actually implements
the plan for which they have been preparing (DiClemente and Velasquez 2002).
It is important that the clinician help the client to take steps toward change
such as monitoring progress, reinforcing incremental success to increase
self-efficacy, and helping to problem-solve as issues arise (Naegle and
D’Avanzo 2000).
304 J. Harland et al.
People at the action stage may benefit from problem-solving and goal-setting
skills to assist with implementing and integrating change. They may require an
introduction to the significant potential of relapse and mapping of change processes,
including adjustment to the impact of change on self-identity (WHO 2004).
In the next stage, maintenance, the person works to consolidate the gains
attained during the action stage and fights to prevent relapse. Without a strong
commitment to maintenance, there will be a short lapse or relapse to the old
behavior. Although traditional therapies view maintenance as a static stage, the
stages of change model sees it as a critically important continuation that can last
from as little as 6 months to as long as a lifetime (DiClemente and Velasquez 2002).
The maintenance stage is characterized by a substantial and sustained change of
behavior and by attempts to prevent relapse or consolidate previous gains
(Migneault et al. 2005). People at this stage may require assessment of the strategies
that they have found useful in changing and assistance in dealing with any potential
problems with sustaining the gains. They may also benefit from reinforcement of
relapse prevention strategies, including returning to self-management strategies
before a relapse occurs (Miller and Rollnick 2002).
The stages of change model recognizes that relapse is possible, and likely, when
trying to change behavior. People often cycle through the stages many times before
reaching their goal (Migneault et al. 2005). Therefore, a lapse should not be
considered a failure but rather a minor setback. After a relapse, individuals often
regress to an earlier stage and then begin progressing through the stages again.
Often, people who relapse have a better chance of success the next time as they
have learnt new ways to deal with old behaviors and they have history of partial
success to build on (DiClemente and Velasquez 2002).
Therefore, a relapse should not be wasted as it is an opportunity for the client to
refine self-management skills (DiClemente and Velasquez 2002). People who
relapse need to analyze events leading up to the lapse and post-relapse impacts.
Relapse is often typified by self-blame which only intensifies the impact and
possible duration of the setback.
FRAMES
Feedback The provision of personally relevant feedback is a key component
of brief intervention and generally follows a thorough assessment of drug use
and related problems. Feedback can include information about the individ-
ual’s drug use and problems from a screening instrument such as the ASSIST,
information about personal risks associated with current drug use patterns,
and general information about substance-related risks and harms. If the
person’s presenting complaint could be related to substance use, it is impor-
tant to inform then about the link as part of the feedback. Feedback may also
include a comparison between the person’s substance use patterns and prob-
lems and the average patterns and problems experienced by other similar
people in the population.
Responsibility A key principle of intervention with substance users is to
acknowledge that they are responsible for their own behavior and that they
can make choices about their substance use. The message that “ultimately the
choice is yours” enables the person to retain personal control over their
behavior and its consequences. This sense of control has been found to be
an important element in motivation for change and to decrease resistance.
Advice The central component of effective brief interventions is the
provision of clear advice regarding the harms associated with continued
use. People are often unaware that their current pattern of substance use
could lead to health or other problems or make existing problems worse.
Providing clear advice that cutting down or stopping substance use will
reduce their risk of future problems will increase their awareness of their
personal risk and provide reasons to consider changing their behavior.
Menu of options Effective brief interventions provide the person with
a range of alternative strategies to cut down or stop their substance use. This
allows the person to choose the strategies which are most suitable for their
situation and which they feel will be most helpful. Providing choices rein-
forces the sense of personal control and responsibility for making change and
can help to strengthen the patient’s motivation for change. Giving informa-
tion or guides to cutting down or stopping is a good first start and can be used
alone or in conjunction with several options.
Empathy A consistent component of effective brief interventions is
a warm, reflective, empathic, and understanding approach by the person
delivering the intervention. Use of a warm, empathic style is a significant
factor in the person’s response to the intervention.
Self-Efficacy The final component of effective brief interventions is to
encourage the person to have confidence in their ability to make changes in
17 Brief Intervention for Illicit Drug Users 307
their substance use behavior. People who believe that they are likely to make
changes are much more likely to do so than those who feel powerless or
helpless to change their behavior. It is particularly helpful to elicit self-
efficacy statements from patients as they are likely to believe what they
hear themselves say.
References
Ager RD, Roahen-Harrisn S, Toriello PJ, Kissinger P, Morse P, Morse EV, Rice J (2011)
Predictors of adopting motivational enhancement therapy. Res Soc Work Pract 21:65–76
Babor TF, McRee BG, Kassebaum PA, Grimaldi PL, Ahmed K, Bray J (2007) Screening, Brief
Intervention, and Referral to Treatment (SBIRT): toward a public health approach to the
management of substance abuse. Subst Abus 28(3):7–30
Baker A, Dawe D (2005) Amphetamine use and co-occurring psychological problems: review of
the literature and implications for treatment. Aust Psychol 40:88–95
Baker A, Boggs TG, Lewin TJ (2001) Randomised controlled trial of brief cognitive-behavioural
interventions among regular users of amphetamine. Addiction 96:1279–1287
Baker A, Lewin T, Reichler H, Clancy R, Carr V, Garrett R, Sly K, Devir H, Terry M (2002)
Evaluation of a motivational interview for substance use within psychiatric in-patient services.
Addiction 97(10):1329–1337
17 Brief Intervention for Illicit Drug Users 309
Miller WR, Yahne CE, Tonigan JS (2003) Motivational interviewing in drug abuse services:
a randomized trial. J Consult Clin Psychol 71:754–763
Naegle M, D’Avanzo C (2000) Addiction and substance abuse strategies for advanced practice
nursing. Prentice Hall Health, Upper Saddle River
National Collaborating Centre for Mental Health (2007) Drug misuse: psychosocial interventions’
(NICE clinical guideline 51). National Institute for Health and Care Excellence, UK
Navarro H, Shakeshaft A, Doran C (2011) The cost-effectiveness of GP screening and brief
intervention. Addict Behav 36:1191–1198
Newton A (2013) Brief emergency department interventions for youth who use alcohol and other
drugs. Paediatr Emerg Care 29(5):673–684
Night Coach http://nightcoach.org/ancd/screen/home.action
Ondersma SJ, Gerkin ER, Svikis DS (2011) The potential for substance use during prediction of
computer-delivered brief intervention response. Subst. Use Misuse 46:77–86
Platt JJ (1997) Cocaine addiction: theory, research and treatment. Harvard University Press,
Cambridge, MA
Prochaska JO, Goldstein MG (1991) Process of smoking cessation. Implications for clinicians.
Clin Chest Med 12:727–735
Prochaska JA, DiClemente CC, Norcross JC (1992) In search of how people change. Applications
to addictive behaviour. Am Psych 47:1102–1114
Proudfoot J, Goldberg D, Mann A (2003) Computerized, interactive, multimedia cognitive-
behavioural program for anxiety and depression in general practice. Psychol Med 33:217–227
Puskar K, Gotham H, Terhorst L, Hagle H, Mitchell A, Braxter B, Fioravanti M, Kane I, Talcott K,
Woomer G, Burns H (2013) Effects of Screening, Brief Intervention, and Referral to Treatment
(SBIRT) education and training on nursing students’ attitudes toward working with patients
who use alcohol and drugs. Subst Abus 34(2):122–128
Rohsenow DJ, Monti PM, Martin RA, Colby SM, Myers MG, Gulliver SB, Brown RA, Mueller TI,
Gordon A, Abrams DB (2004) Motivational enhancement and coping skills training for
cocaine abusers: effects on substance use outcomes. Addiction 99:862–874
Saitz R, Alford DP, Berstein J, Chang DM, Samet J, Palfai T (2010) Screening and brief
intervention for unhealthy drug use in primary care settings: randomized trials are needed.
J Addict Med 4(3):123–130
Saunders B, Wilkinson C, Phillips M (1995) The impact of a brief motivational intervention with
opiate users attending a methadone programme. Addiction 90:415–424
Shakeshaft A, Fawcett J, Mattick (2006) Patient driven computers in primary care: demonstrating
their use and feasibility. Health Educ 106:400–411
Shanahan M, Shakeshaft A, Mattick RP (2006) Modelling the costs and outcomes of changing
rates of screening for alcohol misuse by general practitioners in the Australian context. Appl
Health Econ Health Policy 5:155–166
Shetty V (2011) Motivational intervention integrated into care of facial injury patients may reduce
illicit drug use behaviours. J Oral Maxiofac Surg 69:2396–2411
Stead LF, Bergson G, Lancaster T (2008) Physician advice for smoking cessation. Cochrane
Database Syst Rev 2:CD000165. doi:10.1002/14651858.CD000165.pub3
Stephens RS, Roffman RA, Curtin L (2000) Comparison of extended versus brief treatments for
marijuana use. J Consult Clin Psychol 68:898–908, American Psychological Association
(ISSN: 0022-006X)
Stotts AL, Schmitz JM, Rhoades HM, Grabowski J (2001) Motivational interviewing with
cocaine-dependent patients: a pilot study. J Consult Clin Psychol 69(5):858–862
Sullivan LE, Tetrault JM, Braithwaite RS, Turner BJ, Fiellin DA (2011) A meta-analysis of the
efficacy of nonphysician brief interventions for unhealthy alcohol use: implications for the
patient-centered medical home. Am J Addict 20:343–356
Tait RJ, Hulse GK, Robertson SI, Sprivulis PC (2005) Emergency department-based intervention
with adolescent substance users: 12-month outcomes. Drug Alcohol Depend 79:359–363
312 J. Harland et al.
Walton MA, Bohnert K, Resko S, Barry K, Chermack ST, Zucker RA, Zimmerman MA,
Booth BM, Blow FC (2013) Computer and therapist based brief interventions among
cannabis-using adolescents presenting to primary care: one year outcomes. Drug Alcohol
Depend 132(3):646–653 In press, Available online 25 May 2013
WHO ASSIST Working Group (2002) The Alcohol, Smoking and Substance Involvement
Screening Test (ASSIST): development, reliability and feasibility. Addiction 97:1183–1194
Winters KC, Leitten W (2007) Brief intervention for drug-abusing adolescents in a school setting.
Psychol Addict Behav 21(2):249–254. doi:10.1037/0893-164X.21.2.249
Woodruff S, Eisenberg K, McCabe C, Clapp J, Hohman M (2013) Evaluation of California’s
alcohol and drug screening and brief intervention project for emergency department patients.
West J Emerg Med 14(3):263–270
World Health Organization (2004) Global status report on alcohol 2004. WHO, Geneva
Section III
Drugs of Abuse and
Pharmacotherapies for
Substance Disorders
Abstract
Drug abuse continues being a public health problem. Old drugs such as alcohol,
tobacco, opioids, and cannabis; newer drugs such as cocaine, amphetamines,
hallucinogens, sedatives, and anabolic steroids; and the newest drugs such as the
synthetic cannabinoids are producing devastating medical and psychosocial
consequences among people of all ages and in most countries of the world.
This section provides an overview of the pharmacological and psychosocial
effects of the most common drugs of abuse as well as the state-of-the-art
treatments of the addictive disorders that may result from their compulsive
use. The section also includes chapters that highlight some specific therapeutic
approaches, special issues related to the implementation of some treatments in
some countries, and topics related to the research of new pharmacotherapies for
drug addictions. In addition, this section offers a unique international perspec-
tive to these topics, which is consistent with the global nature of the drug abuse
problem and responds to the need of going beyond country boundaries to
effectively tackle this worldwide epidemic.
It is our pleasure to introduce the Section III of the textbook, which is titled Drugs
of Abuse and Pharmacotherapies for Substance Disorders. The field of Addiction
Medicine is rapidly transforming. For the most part of the last century, people with
addictions were considered morally flawed and lacking in willpower. Recently,
Contents
19.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320
19.2 Pharmacological Treatment Options . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
19.2.1 Disulfiram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
19.2.2 Naltrexone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
19.2.3 Acamprosate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
19.2.4 Nalmefene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
19.2.5 Topiramate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
19.2.6 Baclofen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
19.2.7 Combining Anticraving Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
19.2.8 Additional Psychosocial Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
Abstract
The acute and long-term consequences of alcohol use disorders are very well
known. Multiple treatments for these disorders have been investigated, and some
of them have received approval by regulatory agencies. Disulfiram blocks the
natural degradation of alcohol. It inhibits the acetaldehyde dehydrogenase, and
the accumulation of acetaldehyde in the body results in unpleasant symptoms
such as rush, nausea, headache, diarrhea, vomiting, and a drop in blood pressure.
Disulfiram should only be prescribed once the patient has been detoxified and is
free of alcohol and without withdrawal symptoms. Naltrexone is a competitive
opiate antagonist with high affinity to the m-receptor and lower affinity to the
d- and k-receptors and is approved to treat alcohol dependence in individuals
who are not opioid dependent. Acamprosate binds to NMDA receptors and thus
dampens the glutamate-mediated excitability and is approved for the treatment
of alcohol dependence in people who already established a state of alcohol
abstinence. Nalmefene is the most recent medication approved for use in alcohol
dependence. It was approved by the European Medicines Agency in 2012 for
a reduction of heavy drinking days and/or total alcohol consumption. Nalmefene
is a selective opioid ligand with an equally high affinity to the m- and k-receptors
and medium affinity to the d-receptor. It acts as an antagonist at the m- and
d-receptor, but different from naltrexone, it is a co-agonist at the k-receptor. The
official indication for nalmefene is to reduce alcohol consumption. The chapter
will discuss these and other medications that are being investigated for the
treatment of alcohol use disorders.
19.1 Introduction
19.2.1 Disulfiram
19.2.1.1 Pharmacology
As mentioned above, the potential of disulfiram (tetraethylthiuram disulfide) to
modify alcohol consumption was found by serendipity. After disulfiram had been
identified as the substance which caused the change in drinking habits, further
research revealed the mechanism of action (Martensen-Larsen 1948). Disulfiram
blocks the natural degradation of alcohol. Specifically it irreversibly inhibits the
acetaldehyde dehydrogenase for 2–5 days, a condition which is only terminated by
de novo synthesis of the enzyme. The accumulation of acetaldehyde in the body
results in unpleasant symptoms such as rush, nausea, headache, diarrhea, vomiting,
and a drop in blood pressure. Similar symptoms can be seen in about 50 % of
the Asian population with a genetically determined lack of an ISO-enzyme of the
acetaldehyde dehydrogenase which again leads to an accumulation of acetaldehyde
when alcohol is consumed.
19.2.1.4 Efficacy
An early meta-analysis showed the superiority of disulfiram over placebo (Agosti
1995). However, this result was questioned by a large randomized trial in the USA
where no significant benefit was found (Fuller et al. 1986). While this trial was very
influential in some parts of the world, it did not convince clinicians who had long
worked with this drug especially after some of the earlier safety issues had been
resolved (Chick 1999). In Germany, disulfiram witnessed a renaissance after
a group at Göttingen University published a long-term study with extremely ill
patients who had been coming into the clinic literally every day for supervised
intake for more than a year (Krampe et al. 2006). So far we have only limited
evidence on disulfiram from head-to-head comparisons with other anticraving
medications. Some publications point to a superiority over other approved medi-
cations such as acamprosate and naltrexone (Besson et al. 1998; De Sousa 2004;
Laaksonen et al. 2008). This was reflected in several meta-analyses as well
(i.e., Berglund et al. 2003).
19.2.2 Naltrexone
Naltrexone is the second drug which was approved for the long-term treatment of
alcoholism. Based on observations in monkeys (Altshuler et al. 1980), two clinical
trials were undertaken in the USA which showed a benefit over placebo (Volpicelli
et al. 1992; O’Malley et al. 1992) and convinced the FDA to grant a rapid approval.
19.2.2.1 Pharmacology
Naltrexone is a competitive opiate antagonist with high affinity to the m-receptor
and lower affinity to the d- and k-receptors. The consumption of alcohol increases
the release of brain endorphin (Gianoulakis et al. 1996) and subsequently of
dopamine which results in the positive reinforcing effects of alcohol. A specific
blockade of the m-receptors and thus of the positive reinforcement of alcohol is the
most likely explanation of naltrexone’s clinical efficacy (Sinclair et al. 2002; Heilig
et al. 2011). Although the plasma half-life of naltrexone and its active metabolite
19 Pharmacological Long-Term Treatment of Alcohol Use Disorders 323
ß-naltrexol is only about 10–12 h, its m-receptor occupancy shown with PET studies
lasts for about 48–72 h (Lee et al. 1988). For the specific impact of a polymorphism
of the m opiate receptor gene, see below.
19.2.2.4 Efficacy
The two pivotal trials (Volpicelli et al. 1992; O’Malley et al. 1992) were followed
by many more studies around the world (Mann 2004). More than half of them
showed significant superiority over placebo. Those which did not were often not
powered well enough, were done in difficult to treat patients (Krystal et al. 2001), or
had a very high placebo response (Gastpar et al. 2002; Mann et al. 2013). Recent
meta-analyses and a Cochrane analysis conclude that there is a clear benefit of
naltrexone in the treatment of alcoholism (Rösner et al. 2010a, b). A genetic
component in treatment response was first demonstrated in a post hoc analysis of
three independent trials (Oslin et al. 2003). Patients were genotyped looking for
carriers of the Asp40 allele (A/G, G/G) versus individuals carrying the Asn40 allele
(A/A). The positive treatment effect was confined to patients who carried at least
one G allele. This finding has been replicated several times (Anton 2008) but
remains somewhat controversial due to negative studies (Gelernter et al. 2007).
19.2.3 Acamprosate
19.2.3.1 Pharmacology
Acamprosate is the calcium salt of N-acetyl homotaurine, a small, highly flexible
molecule with similarities to many amino acids, most notably glutamate, gamma-
aminobutyric acid, aspartate, glycine, and taurine (Spanagel and Zieglgänsberger
1997; Spanagel and Kiefer 2008). Its mechanism of action seems to be linked to
324 K. Mann and F. Kiefer
19.2.3.4 Efficacy
There have been a large number of randomized controlled trials worldwide testing
acamprosate against placebo (Kiefer and Mann 2010). The majority showed
a significant benefit of acamprosate. This is corroborated by Cochrane analyses,
the latest of which was published in 2012 (Rösner et al. 2010a, b). However, there
were several negative studies as well such as the large COMBINE study in the USA
(Anton et al. 2006) and more recently by Mann et al. (2013). Based on its potential
mechanism of action described above (dampening of a hyper-glutamatergic state) it
was speculated that acamprosate could be more beneficial in severely affected
patients who are more likely to suffer from an upregulated glutamate system
(Spanagel and Kiefer 2008). Our own study with a head-to-head comparison of
two cohorts of patients who differed in severity measures did not support this
assumption (Mann et al. 2013). Another idea according to which acamprosate
19 Pharmacological Long-Term Treatment of Alcohol Use Disorders 325
would be more beneficial to individuals who relapse for the negative reinforcing
effect of alcohol (Verheul et al. 1999; Mann et al. 2009; Heilig et al. 2011) still
awaits empirical support. The first studies aiming to associate acamprosate’s
efficacy with genetic markers suggest an involvement of a single-nucleotide poly-
morphism located in the GATA binding protein 4 (GATA4) gene (Kiefer
et al. 2011). GATA4 represents a factor regulating the transcription of ANP and
showed an association with alcohol dependence in two independent genome-wide
association studies on alcohol dependence (Treutlein et al. 2009; Edenberg
et al. 2010).
19.2.4 Nalmefene
Nalmefene is the most recent medication approved for use in alcohol dependence. It
was approved by the European Medicines Agency in 2012 for a reduction of heavy
drinking days and/or total alcohol consumption.
19.2.4.1 Pharmacology
Nalmefene is a selective opioid ligand with an equally high affinity to the m- and
k-receptors and medium affinity to the d-receptor. It acts as an antagonist at the
m- and d-receptors, but different from naltrexone, it is a co-agonist at the k-receptor
(Bart et al. 2005). Studies in rodents seem to show that the difference compared
with naltrexone concerning the action at the k-receptor might be of relevance
lending the drug higher potency in animals with more severe dependence
(Walker et al. 2011). However, this finding needs to be replicated in humans.
Nalmefene has several metabolites which have much less affinity to the
m-receptors than the parent substance. Only nalmefene 3-O-sulfate contributes to
the pharmacological effect, but this metabolite is only present in low concentra-
tions. Nalmefene has a plasma half-life of 10–12 h. Blockade of brain receptors
with nalmefene lasts between 48 and 72 h.
The mechanism of action is mainly based on its antagonistic properties at the
m-receptor. This counteracts the reinforcement driven by an alcohol-triggered
mesolimbic dopamine release which is facilitated by the release of ß-endorphins.
In studies with animal models, an additional effect based on nalmefene’s role as
a partial k-receptor agonist (Walker et al. 2011) was observed. This is currently
being investigated in humans.
19.2.4.4 Efficacy
Several earlier studies indicated its efficacy in reducing consumption in alcohol-
dependent patients (Mason et al. 1999; Karhuvaara et al. 2007). One study did not
show a significant effect (Anton et al. 2004). Recently three large-scale phase III
studies were conducted in Europe which showed efficacy over placebo in reducing
heavy drinking days and total alcohol consumption; all three studies are published
(Mann et al. 2013; Gual et al. 2013; van den Brink et al. 2013).
19.2.5 Topiramate
This medication is approved for the treatment of epilepsy. Its use in alcoholism has
been tested because of indications that it reduces the reinforcing effects of alcohol
and inhibits glutamatergic pathways in the corticomesolimbic system (Johnson
2005; White et al. 2004). A first positive single-site trial (Johnson et al. 2003)
was followed by a larger multisite trial (Johnson et al. 2007). This latter showed
a significant effect over placebo in reducing alcohol consumption. Patients did not
have to be abstinent to participate which was different from many other studies
referred to in this chapter (with the exception of the nalmefene trials, see above).
The effect size was considerable, but undesired effects were as important as
expected. Therefore, the medication had to be carefully titrated from week 0 to
week 5. Undesired effects were paresthesia, headache, taste perversion, fatigue, and
difficulty with concentration and memory. A smaller and more recent study did not
show a significant effect (Likhitsathian et al. 2013). However, as expected the first
meta-analysis comes to a positive overall effect of the drug (Arbaizar et al. 2010).
In conclusion, off-label use may be worth trying but only with a titration of the dose
and under very careful consideration and monitoring of these side effects (Aubin
and Daeppen 2013).
19.2.6 Baclofen
differed between trials, patients treated with baclofen (30 mg) experienced
higher rates of abstinence from alcohol than those taking placebo in the majority
of case series and two of the randomized controlled trials (Addolorato et al. 2002,
2007). Data suggest that baclofen was safe in patients with alcohol dependence,
including those with moderate to severe liver cirrhosis and may provide benefi-
cial anxiolytic effects. However, the largest available randomized controlled trial
by Garbutt et al. (2010) failed to show a benefit for 30 mg baclofen in assessing
the efficacy and safety in terms of weekly heavy drinking days and percentage of
abstinent days or for the secondary outcomes of craving, for example, depres-
sion. Again, baclofen was well tolerated with no significant reported adverse
events.
Taken together, positive effects from using baclofen for the treatment of alcohol
dependence can be surmised; however, the small number of studies currently does
not allow a final conclusion. Larger trials that include higher dosages of baclofen
(up to 270 mg daily) are currently ongoing.
References
Addolorato G, Caputo F, Capristo E et al (2002) Baclofen efficacy in reducing alcohol craving and
intake: a preliminary double-blind randomized controlled study. Alcohol Alcohol 37:504–508
Addolorato G, Leggio L, Ferrulli A et al (2007) Effectiveness and safety of baclofen for mainte-
nance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: a randomized,
double-blind, controlled study. Lancet 370(9603):1915–1922
Addorolato G, Leggio L (2010) Safety and efficacy of baclofen in the treatment of alcohol-
dependent patients. Curr Pharm Des 16(19):2113–2117
Agosti V (1995) The efficacy of treatments in reducing alcohol consumption: a meta-analysis. Int
J Addict 30:1067–1077
Altshuler HL, Phillips PE, Feinhandler DA (1980) Alteration of ethanol self-administration by
naltrexone. Life Sci 26:679–688
Anton RF (2008) Genetic basis for predicting response to naltrexone in the treatment of alcohol
dependence. Pharmacogenomics 9(6):655–658
Anton RF, Pettinati H, Zweben A, Kranzler HR, Johnson B, Bohn MJ, McCaul ME, Anthenelli R,
Salloum I, Galloway G, Garbutt J, Swift R, Gastfriend D, Kallio A, Karhuvaara S (2004)
A multi-site dose ranging study of nalmefene in the treatment of alcohol dependence. J Clin
Psychopharmacol 24:421–428
Anton RF, O’Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, Gastfriend DR,
Hosking JD, Johnson BA, LoCastro JS, Longabaugh R, Mason BJ, Mattson ME, Miller WR,
Pettinati HM, Randall CL, Swift R, Weiss RD, Williams LD, Zweben A, COMBINE Study
Research Group (2006) Combined pharmacotherapies and behavioral interventions for alcohol
dependence: the COMBINE study: a randomized controlled trial. JAMA 295:2003–2017
Arbaizar B, Diersen-Sotos T, Gómez-Acebo I, Llorca J (2010) Topiramate in the treatment of
alcohol dependence: a meta-analysis. Actas Esp Psiquiatr 38:8–12
Aubin HJ, Daeppen JB (2013) Emerging pharmacotherapies for alcohol dependence: a systematic
review focusing on reduction in consumption. Drug Alcohol Depend. doi:pii: S0376-8716(13)
00154-3. 10.1016/j.drugalcdep. Epub ahead of print
Bart G, Schluger JH, Borg L, Ho A, Bidlack JM, Kreek MJ (2005) Nalmefene induced elevation in
serum prolactin in normal human volunteers: partial kappa opioid agonist activity? Neuropsy-
chopharmacology 30:2254–2262
Berglund M, Thelander S, Salaspuro M, Franck J, Andréasson S, Ojehagen A (2003) Treatment of
alcohol abuse: an evidence-based review. Alcohol Clin Exp Res 27:1645–1656
Besson J, Aeby F, Kasas A, Lehert P, Potgieter A (1998) Combined efficacy of acamprosate and
disulfiram in the treatment of alcoholism: a controlled study. Alcohol Clin Exp Res
22:573–579
Brennan JL, Leung JG, Gagliardi JP, Rivelli SK, Muzyk AJ (2013) Clinical effectiveness of
baclofen for the treatment of alcohol dependence: a review. Clin Pharmacol 5:99–107
Brewer C (1993) Long-term, high-dose disulfiram in the treatment of alcohol abuse.
Br J Psychiatry 163:687–689
Br€
ueck G, Mann K (2006) Alkoholismusspezifische Psychotherapie: Manual mit Behandlungs-
smodulen. (Alcoholism-specific psychotherapy: manual with treatment modules). Deutscher
€
Arzteverlag, Köln
Chick J (1999) Safety issues concerning the use of disulfiram in treating alcohol dependence. Drug
Saf 20:427–435, Review
Cowen MS, Adams C, Kraehenbuehl T, Vengeliene V, Lawrence AJ (2005) The acute anti-
craving effect of acamprosate in alcohol-preferring rats is associated with modulation of the
mesolimbic dopamine system. Addict Biol 10:233–242
De Sousa A (2004) A one-year pragmatic trial of naltrexone vs disulfiram in the treatment of
alcohol dependence. Alcohol Alcohol 39:528–531
Edenberg HJ, Koller DL, Xuei X, Wetherill L, McClintick JN, Almasy L, Bierut LJ, Bucholz KK,
Goate A, Aliev F, Dick D, Hesselbrock V, Hinrichs A, Kramer J, Kuperman S, Nurnberger JI Jr,
19 Pharmacological Long-Term Treatment of Alcohol Use Disorders 329
Rice JP, Schuckit MA, Taylor R, Todd Webb B, Tischfield JA, Porjesz B, Foroud T (2010)
Genome-wide association study of alcohol dependence implicates a region on chromosome 11.
Alcohol Clin Exp Res 34:840–852
Edwards G (2000) Alcohol: the world’s favorite drug. St. Martin’s Press, New York, p 118
Edwards G (2005) History of prevention of relapse. In: Spanagel R, Mann K (eds) Drugs for
relapse prevention of alcoholism. Birkhäuser Verlag, Switzerland
Fuller RK, Branchey L, Brightwell DR, Derman RM, Emrick CD, Iber FL, James KE, Lacoursiere
RB, Lee KK, Lowenstam I et al. (1986) Disulfiram treatment of alcoholism. A Veterans
Administration Cooperative Study. JAMA 256:1449–1455
Garbutt JC, Kampov-Polevoy AB, Gallop R, Kalka-Juhl L, Flannery BA (2010) Efficacy and
safety of baclofen for alcohol dependence: a randomized, double-blind, placebo-controlled
trial. Alcohol Clin Exp Res 34:1–9
Gastpar M, Bonnet U, Böning J, Mann K, Schmidt LG, Soyka M, Wetterling T,
Kielstein V, Labriola D, Croop R (2002) Lack of efficacy of naltrexone in the prevention of
alcohol relapse: results from a German Multicenter Study. J Clin Psychopharmacol
22:592–598
Gelernter J, Gueorguieva R, Kranzler HR, Zhang H, Cramer J, Rosenheck R, Krystal JH, VA
Cooperative Study #425 Study Group (2007) Opioid receptor gene (OPRM1, OPRK1, and
OPRD1) variants and response to naltrexone treatment for alcohol dependence: results from
the VA Cooperative Study. Alcohol Clin Exp Res 31(4):555–563
Gianoulakis C, de Waele JP, Thavundayil J (1996) Implication of the endogenous opioid system in
excessive ethanol consumption. Alcohol 13:19–23
Gual A, He Y, Torup L, van den Brink W, Mann K, for the ESENSE 2 Study Group
(2013) A randomised, double-blind, placebo-controlled, efficacy study of nalmefene,
as-needed use, in patients with alcohol dependence. Eur Neuropsychopharmacol. doi:pii:
S0924-977X(13)00075-8. 10.1016/j. Epub ahead of print
Harris BR, Prendergast MA, Gobson DA, Rogers DT, Blanchard JA, Holley RC, Fu MC, Hart SR,
Pedigo NW, Littleton JM (2002) Acamprosate inhibits the binding and neurotoxic effects of
trans-ACPD, suggesting a novel site of action at metabotropic glutamate receptors. Alcohol
Clin Exp Res 26:1779–1793
Heilig M, Goldman D, Berrettini W, O’Brien CP (2011) Pharmacogenetic approaches to the
treatment of alcohol addiction. Nat Rev Neurosci 12:670–684
Johnson BA (2005) Recent advances in the development of treatments for alcohol and cocaine
dependence: focus on topiramate and other modulators of GABA or glutamate function. CNS
Drugs 19:873–896, Review
Johnson BA, Ait-Daoud N, Bowden CL, DiClemente CC, Roache JD, Lawson K, Javors MA, Ma
JZ (2003) Oral topiramate for treatment of alcohol dependence: a randomised controlled trial.
Lancet 361:1677–1685
Johnson BA, Rosenthal N, Capece JA, Wiegand F, Mao L, Beyers K, McKay A, Ait-Daoud N,
Anton RF, Ciraulo DA, Kranzler HR, Mann K, O’Malley SS, Swift RM (2007) Topiramate for
treating alcohol dependence: a randomized controlled trial. JAMA 298:1641–1651
Karhuvaara S, Simojoki K, Virta A, Rosberg M, Löyttyniemi E, Nurminen T, Kallio A, Mäkelä R
(2007) Targeted nalmefene with simple medical management in the treatment of heavy
drinkers: a randomized double-blind placebo-controlled multicenter study. Alcohol Clin Exp
Res 31:1179–1187
Kiefer F, Mann K (2010) Acamprosate: how, where, and for whom does it work? Curr Pharm Des
16(19):2098–2102
Kiefer F, Jahn H, Tarnaske T, Helwig H, Briken P, Holzbach R, Kämpf P, Stracke R, Baehr M,
Naber D, Wiedemann K (2003) Comparing and combining naltrexone and acamprosate in
relapse prevention of alcoholism: a double-blind, placebo-controlled study. Arch Gen Psychi-
atry 60:92–99
Kiefer F, Witt SH, Frank J, Richter A, Treutlein J, Lemenager T, Nöthen MM, Cichon S, Batra A,
Berner M, Wodarz N, Zimmermann US, Spanagel R, Wiedemann K, Smolka MN, Heinz A,
330 K. Mann and F. Kiefer
Rietschel M, Mann K (2011) Involvement of the atrial natriuretic peptide transcription factor
GATA4 in alcohol dependence, relapse risk and treatment response to acamprosate. Pharmaco-
genomics J 11:368–374
Krampe H, Stawicki S, Wagner T, Bartels C, Aust C, R€ uther E, Poser W, Ehrenreich H (2006)
Follow-up of 180 alcoholic patients for up to 7 years after outpatient treatment: impact of
alcohol deterrents on outcome. Alcohol Clin Exp Res 30:86–95
Krystal JH, Cramer JA, Krol WF, Kirk GF, Rosenheck RA (2001) Naltrexone in the treatment of
alcohol dependence; Veterans Affairs Naltrexone Cooperative Study 425 Group. N Engl J Med
345:1734–1749
Laaksonen E, Koski-Jännes A, Salaspuro M, Ahtinen H, Alho H (2008) A randomized,
multicentre, open-label, comparative trial of disulfiram, naltrexone and acamprosate in the
treatment of alcohol dependence. Alcohol Alcohol 43:53–61
Lee MC, Wagner HN Jr, Tanada S, Frost JJ, Bice AN, Dannals RF (1988) Duration of occupancy
of opiate receptors by naltrexone. J Nucl Med 29:1207–1211
Lewin L (1931) Phantastica: narcotic and stimulating drugs. Kegan Paul/Trench and Trubner, London
Lhuintre JP, Daoust M, Moore ND, Chretien P, Saligaut C, Tran G, Bosimare F, Hillemand B
(1985) Ability of calcium bis acetyl homotaurine, a GABA agonist, to prevent relapse in
weaned alcoholics. Lancet 1:1014–1016
Likhitsathian S, Uttawichai K, Booncharoen H, Wittayanookulluk A, Angkurawaranon C,
Srisurapanont M (2013) Topiramate treatment for alcoholic outpatients recently receiving
residential treatment programs: a 12-week, randomized, placebo-controlled trial. Drug Alcohol
Depend. doi:pii: S0376-8716(13)00251-2. Epub ahead of print
Mann K (2004) Pharmacotherapy of alcohol dependence: a review of the clinical data. CNS Drugs
18:485–504
Mann K, Lehert P, Morgan MY (2004) The efficacy of acamprosate in the maintenance of
abstinence in alcohol-dependent individuals: results of a meta-analysis. Alcohol Clin Exp
Res 28:51–63
Mann K, Kiefer F, Spanagel R, Littleton JM (2008) Acamprosate: recent findings and future
research directions. Alcohol Clin Exp Res 32:1105–1110
Mann K, Kiefer F, Smolka M, Gann H, Wellek S, Heinz A (2009) Searching for responders to
acamprosate and naltrexone in alcoholism treatment: rationale and design of the PREDICT
study. Alcohol Clin Exp Res 33:674–683
Mann K, Bladström A, Torup L, Gual A, van den Brink W, The ESENSE 1 Study Group
(2013) Extending the treatment options for patients with alcohol dependence – a randomised
controlled study of nalmefene. Biol Psychiatry 73:706–713
Marie C (1955) A propos d’un nouveau mode de traitement de l’alcoolisme chronique par
implantation de disulfure de tétraéthylthiourame. (A new way of treating chronic alcoholism
by implanting tetraethylthiuran disulfat) Thèse, Paris
Martensen-Larsen O (1948) Treatment of alcoholism with a sensitizing drug. Lancet 25:6539
Mason BJ, Salvato FR, Williams LD, Ritvo EC, Cutler RB (1999) A double-blind, placebo-
controlled study of oral nalmefene for alcohol dependence. Arch Gen Psychiatry 56:719–724
Morley KC, Teesson M, Reid SC, Sannibale C, Thomson C, Phung N, Weltman M, Bell JR,
Richardson K, Haber PS (2006) Naltrexone versus acamprosate in the treatment of alcohol
dependence: a multi-centre, randomized, double-blind, placebo-controlled trial. Addiction
101:1451–1462
O’Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B (1992) Naltrexone
and coping skills therapy for alcohol dependence. A controlled study. Arch Gen Psychiatry
49:881–887
Oslin DW, Berrettini W, Kranzler HR, Pettinati H, Gelernter J, Volpicelli JR, O’Brien CP
(2003) A functional polymorphism of the mu-opioid receptor gene is associated with naltrex-
one response in alcohol-dependent patients. Neuropsychopharmacology 28:1546–1552
Pettinati HM, Weiss RD, Miller WR, Donovan D, Ernst DB, Rounsaville BJ
(2004) volume 2. Medical management treatment manual: a clinical research guide for
19 Pharmacological Long-Term Treatment of Alcohol Use Disorders 331
medically trained clinicians providing pharmacotherapy as part of the treatment for alcohol
dependence. DHHS publication no. (NIH) 04-5289. NIAAA, Bethesda
Pierrefiche O, Daoust M, Naassila M (2004) Biphasic effect of acamprosate on NMDA but not on
GABAA receptors in spontaneous rhythmic activity from the isolated neonatal rat respiratory
network. Neuropharmacology 47:35–45
Rösner S, Hackl-Herrwerth A, Leucht S, Lehert P, Vecchi S, Soyka M (2010a) Acamprosate for
alcohol dependence. Cochrane Database Syst Rev 9, CD004332
Rösner S, Hackl-Herrwerth A, Leucht S, Vecchi S, Srisurapanont M, Soyka M (2010b) Opioid
antagonists for alcohol dependence. Cochrane Database Syst Rev 12:CD001867
Sinclair JD, Alho H, Shinderman M (2002) Naltrexone for alcohol dependence. N Engl J Med
346:1329–1331
Spanagel R, Kiefer F (2008) Drugs for relapse prevention of alcoholism: ten years of progress.
Trends Pharmacol Sci 29(3):109–115
Spanagel R, Mann K (eds) (2005) Drugs for relapse prevention in alcoholism. Birkhäuser Verlag,
Basel
Spanagel R, Zieglgänsberger W (1997) Anti-craving compounds for ethanol: new pharmacolog-
ical tools to study addictive processes. Trends Pharmacol Sci 18:54–59
Starosta AN, Leeman RF, Volpicelli JR (2006) The BRENDA model: integrating psychosocial
treatment and pharmacotherapy for the treatment of alcohol use disorders. J Psychiatr Pract
12:80–89
Treutlein J, Cichon S, Ridinger M, Wodarz N, Soyka M, Zill P, Maier W, Moessner R, Gaebel W,
Dahmen N, Fehr C, Scherbaum N, Steffens M, Ludwig KU, Frank J, Wichmann HE,
Schreiber S, Dragano N, Sommer WH, Leonardi-Essmann F, Lourdusamy A, Gebicke-
Haerter P, Wienker TF, Sullivan PF, Nöthen MM, Kiefer F, Spanagel R, Mann K,
Rietschel M (2009) Genome-wide association study of alcohol dependence. Arch Gen Psychi-
atry 66:773–784
van den Brink W, Aubin HJ, Bladström A, Torup L, Gual A, Mann K (2013) Efficacy of nalmefene
as-needed in alcohol dependent patients with at least high drinking risk level: results from
a subgroup analysis of two randomised controlled 6-month studies. Alcohol & Alcohol, ahead
of print
Verheul R, van den Brink W, Geerlings P (1999) A three-pathway psychobiological model of
craving for alcohol. Alcohol Alcohol 34:197–222
Volpicelli JR, Alterman AI, Hayashida M, O’Brien CP (1992) Naltrexone in the treatment of
alcohol dependence. Arch Gen Psychiatry 49:876–880
Walker BM, Zorrilla EP, Koob GF (2011) Systemic k-opioid receptor antagonism by
nor-binaltorphimine reduces dependence-induced excessive alcohol self-administration in
rats. Addict Biol 16:116–119
White HS, Brown SD, Woodhead JH, Skeen GA, Wolf HH (2004) Topiramate modulates GABA-
evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism. Epilepsia
41(Suppl 1):S17–S20
Witte P, Bachteler D, Spanagel R (2005) Acomprasate: preclinical data. In: Spanagel and Mann
(eds) Drugs for Relapse Prevention of Alcoholism. Birkhäuser Verlag, Basel, Boston, Berlin,
2005:73–84
World Health Organization (WHO) (2000) International guide for monitoring alcohol consump-
tion and related harm. WHO/MSD/MSB/00.4. 2000 http://whqlibdoc.who.int/hq/2000/
who_msd_msb_00.4.pdf
Enzymatic Aspects of Alcoholism-ADH
and ALDH 20
Mitsuru Kimura, Akira Yokoyama, Sachio Matsushita, and
Susumu Higuchi
Contents
20.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334
20.2 Polymorphisms of Alcohol Metabolizing Enzymes and Alcoholism . . . . . . . . . . . . . . . . . . 334
20.2.1 Alcohol Dehydrogenase (ADH) and Alcoholism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334
20.2.2 Aldehyde Dehydrogenase (ALDH) and Alcoholism . . . . . . . . . . . . . . . . . . . . . . . . . . 336
20.2.3 ALDH2 and ADH1B Polymorphism and Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337
20.2.4 ADH1B and ALDH2 Polymorphism and Physical Diseases . . . . . . . . . . . . . . . . . 339
20.2.5 Clinical Characteristics of Alcoholics with Inactive
ALDH2 and Super-Active ADH1B . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339
20.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 340
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 340
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342
Abstract
Most ethanol taken into the body is converted to acetaldehyde by alcohol
dehydrogenase (ADH), and then from acetaldehyde to acetic acid by aldehyde
dehydrogenase (ALDH). However, polymorphisms exist in the genes of these
enzymes. A super-active form of ADH1B and an inactive form of ALDH2 have
preventive effects against alcoholism. In addition, several reports have
suggested an association between polymorphisms in ADH1C, ADH4, and
ALDH1A1 and alcoholism. Moderate to heavy drinkers with inactive ALDH2
and less-active ADH1B have a much higher risk of gastrointestinal tract
cancer compared with those with active ALDH2 and super-active ADH1B.
The ADH1B and ALDH2 polymorphisms are associated with various physical
diseases such as liver disease, pancreatitis, and diabetes mellitus. Alcoholics
with inactive ALDH2 have unique clinical characteristics; for example, they
20.1 Introduction
Most alcohol taken into the body is eliminated in the liver; first, ethanol is converted
to acetaldehyde by alcohol dehydrogenase (ADH), and then acetaldehyde is
converted to acetic acid by aldehyde dehydrogenase (ALDH). These enzymes have
genetic polymorphisms that can alter the activity of alcohol and acetaldehyde metab-
olism. These polymorphisms are known to have a great effect on drinking behavior in
healthy people as well as on the risk of alcohol dependence. Moreover, variations in
metabolic enzymes are associated with the risk of physical diseases, including
gastrointestinal tract cancer and liver cirrhosis, in moderate to heavy drinkers. Several
studies have suggested that the clinical characteristics and disease course of alcohol
dependence differ between the ADH and ALDH genotypes. In this chapter we review
variations in alcohol-metabolizing enzymes and alcoholism.
More than 90 % of alcohol taken into the body is eliminated via the liver. Three
mechanisms mediate the oxidation from ethanol to acetaldehyde: ADH, the micro-
somal ethanol oxidizing system (MEOS), and catalase. ADH works at low to high
concentrations of alcohol and plays a major role in alcohol metabolism. MEOS
works only at high concentrations of alcohol. Catalase is considered to have a minor
effect on alcohol metabolism.
There are five classes of ADH (class I–V), encoded by seven genes (ADH1A,
ADH1B, ADH1C, and ADH4–7). Class I ADH consists of homo- or heterodimers
of a-, b-, and g-subunits encoded by ADH1A, ADH1B, and ADH1C, respectively.
Class I ADH enzymes have high affinity for ethanol and contribute the most to
ethanol metabolism in the liver. Class II ADH, which is a homodimer of two p
subunits encoded by the ADH4 gene, has a higher Km (the Michaelis constant) for
ethanol than class I ADH, but is still believed to play some role in ethanol
elimination, although the effect seems weaker than that of class I ADH enzymes.
Class III (ADH5) and class IV ADH (ADH6) seem to have little involvement in
ethanol oxidation. Class V ADH (ADH7) is abundant in the stomach and consid-
ered to contribute during the early stage of alcohol metabolism in the stomach
20 Enzymatic Aspects of Alcoholism-ADH and ALDH 335
causes higher acetaldehyde production, which in turn leads to adverse effects that
suppress drinking behavior. However, there is no evidence of an accumulation of
acetaldehyde after alcohol intake in humans who have the ADH1B*2 allele.
The g-subunit encoded by ADH1C has a polymorphisc loci at the
272 (rs1693482) and 350 (rs698) amino acid position in high linkage equilibrium:
ADH1C*1 with 272Arg-350Ile and ADH1C*2 with 272Gln-350Val. The subunit
encoded by ADH1C*2 allele has less activity during ethanol elimination. Several
studies reported that the ADH1C*2 allele is associated with a higher risk of alcohol
dependence than the ADH1C*1 allele (Zintzaras et al. 2006). It is suggested that
this association might be due to the linkage equilibrium between ADH1C*1 and
ADH1B*2; however, the association is detected even in a population that rarely has
the ADH1B*2 variant (Montane-Jaime et al. 2006).
Some studies have also suggested that the variation of class II ADH encoded by
the ADH4 gene is associated with alcohol dependence. An analysis of SNP markers
at the ADH gene cluster on chromosome 4q22 found that the strongest association
with alcohol dependence was detected at the ADH4 gene region (Edenberg
et al. 2006), but the particular locus responsible for this association and its function
are still unclear.
Most acetaldehyde produced from ethanol by ADH and other oxidizing enzymes is
oxidized to acetic acid by ALDH in the liver. There are several ALDH family genes
in humans, but ALDH1 and ALDH2 are the most important for acetaldehyde
metabolism. It is considered that mitochondrial ALDH2 plays a major role in the
20 Enzymatic Aspects of Alcoholism-ADH and ALDH 337
Fig. 20.1 Alcohol consumption and the risk for esophageal squamous cell carcinoma according
to (a) ALDH2 genotype and (b) ADH1B genotype. The subjects were classified as never/rare
drinkers; current drinkers who consumed 1–8.9 units/week (light drinkers; 1 unit ¼ 22 g ethanol),
9–17.9 units/week (moderate drinkers), or 18+ units/week (heavy drinkers); or ex-drinkers. Odds
ratios were adjusted for age, frequency of drinking strong alcoholic beverages straight, pack-years
of smoking, frequency of intake of green and yellow vegetables, and frequency of fruit intake. The
vertical lines indicate the 95% confidence interval. *p<0.05, **p<0.01, and ***p<0.001
(Reprinted from Yokoyama et al. 2010)
The ADH1B and ALDH2 polymorphism are associated with various physical
diseases such as liver disease, pancreatitis, and diabetes mellitus. A recent large
survey of Japanese alcoholic men demonstrated that the age-adjusted odds ratio
for liver cirrhosis, chronic calcific pancreatitis, and diabetes mellitus was
higher in alcoholics with super-active ADH1B or active ALDH2 than in those
with less-active ADH1B or inactive ALDH2 (Yokoyama et al. 2013). Moreover,
the active form of ALDH2 was associated with hypertension. A meta-analysis
of East Asian case-control studies showed the same results; that is, less-active
ADH1B and active ALDH2 are associated with a high incidence of liver disease,
cirrhosis, and pancreatitis (Li et al. 2011, 2012). This association might be due
to differences in alcohol consumption in subjects due to variations in ADH1B
and ALDH2.
The variations of ADH1B and ALDH2 have been reported to affect clinical
characteristics and the disease course of alcohol dependence. A survey conducted
in Japan reported that alcoholic men with inactive ALDH2 developed incidents and
symptoms related to alcohol dependence more slowly than alcoholics with active
ALDH2 (Murayama et al. 1998). The onset of every symptom was delayed
1–5 years in the inactive ALDH2 group compared with the active ALDH2 group.
Interestingly, the onset of alcoholism was earlier in alcoholic women with inactive
ALDH2 than those with active ALDH2, which contrasts with the findings seen in
male alcoholics (Kimura et al. 2011). One of the reasons for these gender differ-
ences might be that the inactive ALDH2 group had psychiatric comorbid diseases
more frequently than the active ALDH2 group. In the same way as with ALDH2,
the development of alcohol dependence in alcoholic men with super-active ADH1B
was delayed compared with those with less-active ADH1B (Eriksson et al. 2001).
There is a difference in personality profile between alcoholics with active and
inactive ALDH2. A survey that assessed personality traits using Cloninger’s
Tridimensional Personality Questionnaire found that alcoholics with inactive
ALDH2 revealed higher novelty-seeking and lower harm-avoidance scores
compared with those with active ALDH2 (Kimura et al. 2009).
ADH1B polymorphism affects the severity of alcohol withdrawal syndrome.
A study using Japanese subjects suggested the prevalence of alcohol withdrawal
syndrome was higher in alcoholics with less-active ADH1B than in those with
super-active ADH1B (Suwaki et al. 2001). Although there was no difference in
alcohol consumption between the super-active and less-active ADH1B groups, the
less-active ADH1B group had significantly higher blood alcohol concentrations;
therefore, variation in alcohol metabolism may alter the severity of withdrawal
symptoms. There is also a report that demonstrates the association between ADH4
340 M. Kimura et al.
polymorphism and the severity of delirium tremens (Gizer et al. 2011). In contrast,
there is little evidence of the relation between ALDH2 polymorphism and the
severity of alcohol withdrawal syndrome.
20.3 Conclusion
References
Birley AJ, James MR, Dickson PA, Montgomery GW, Heath AC, Martin NG, Whitfield JB
(2009) ADH single nucleotide polymorphism associations with alcohol metabolism in vivo.
Hum Mol Genet 18(8):1533–1542
Boccia S, Hashibe M, Galli P, De Feo E, Asakage T, Hashimoto T, Hiraki A, Katoh T, Nomura T,
Yokoyama A, van Duijn CM, Ricciardi G, Boffetta P (2009) Aldehyde dehydrogenase 2 and
head and neck cancer: a meta-analysis implementing a Mendelian randomization approach.
Cancer Epidemiol Biomarkers Prev 18(1):248–254
Edenberg HJ, Xuei X, Chen HJ, Tian H, Wetherill LF, Dick DM, Almasy L, Bierut L, Bucholz
KK, Goate A, Hesselbrock V, Kuperman S, Nurnberger J, Porjesz B, Rice J, Schuckit M,
Tischfield J, Begleiter H, Foroud T (2006) Association of alcohol dehydrogenase genes with
alcohol dependence: a comprehensive analysis. Hum Mol Genet 15(9):1539–1549
Ehlers CL, Spence JP, Wall TL, Gilder DA, Carr LG (2004) Association of ALDH1 promoter
polymorphisms with alcohol-related phenotypes in southwest California Indians. Alcohol Clin
Exp Res 28(10):1481–1486
Eriksson CJ, Fukunaga T, Sarkola T, Chen WJ, Chen CC, Ju JM, Cheng AT, Yamamoto H,
Kohlenberg-Muller K, Kimura M, Murayama M, Matsushita S, Kashima H, Higuchi S, Carr L,
Viljoen D, Brooke L, Stewart T, Foroud T, Su J, Li TK, Whitfield JB (2001) Functional
relevance of human adh polymorphism. Alcohol Clin Exp Res 25(5 Suppl ISBRA):157S–163S
Gizer IR, Edenberg HJ, Gilder DA, Wilhelmsen KC, Ehlers CL (2011) Association of alcohol
dehydrogenase genes with alcohol-related phenotypes in a Native American community
sample. Alcohol Clin Exp Res 35(11):2008–2018
Goedde HW, Agarwal DP, Fritze G, Meier-Tackmann D, Singh S, Beckmann G, Bhatia K, Chen
LZ, Fang B, Lisker R et al (1992) Distribution of ADH2 and ALDH2 genotypes in different
populations. Hum Genet 88(3):344–346
Higuchi S, Matsushita S, Muramatsu T, Murayama M, Hayashida M (1996) Alcohol and aldehyde
dehydrogenase genotypes and drinking behavior in Japanese. Alcohol Clin Exp Res
20(3):493–497
20 Enzymatic Aspects of Alcoholism-ADH and ALDH 341
Further Reading
Higuchi S, Matsushita S, Masaki T, Yokoyama A, Kimura M, Suzuki G, Mochizuki H (2004)
Influence of genetic variations of ethanol-metabolizing enzymes on phenotypes of alcohol-
related disorders. Ann N Y Acad Sci 1025:472–480
Yokoyama A, Omori T, Yokoyama T (2010) Alcohol and aldehyde dehydrogenase polymor-
phisms and a new strategy for prevention and screening for cancer in the upper aerodigestive
tract in East Asians. Keio J Med 59(4):115–130
Benzodiazepine Abuse and Addiction
21
Annie Umbricht and Martha L. Velez
Contents
21.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345
21.2 Pharmacology of Benzodiazepine and Other BZD-Site Agonists . . . . . . . . . . . . . . . . . . . . 346
21.3 Clinical Uses of BZDs and Z-Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347
21.4 Pharmacokinetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348
21.5 Problems Related to the Long-Term Use of BZDs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348
21.6 BZDs Misuse, Abuse, and Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
21.7 Recreational BZD Abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
21.8 BZD Withdrawal Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
21.9 BZD Abuse in Specific Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352
21.10 Adolescents and Young Adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
21.11 Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 354
21.12 Women . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 354
21.13 Polysubstance Users . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
21.14 Drug-Facilitated Rape . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
21.15 Treatment of BZD Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 356
21.16 BZD Detoxification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 356
21.16.1 Gradual Tapering of the BZDs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 356
21.16.2 Switching to an Equivalent Dose of a Long Half-Life BZD Before
Tapering Withdrawal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357
21.16.3 Adjuvant Medication Treatment to Decrease BZD Withdrawal
Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 358
21.16.4 Pharmacologic Treatment of Underlying Conditions . . . . . . . . . . . . . . . . . . . . . . 358
21.16.5 Non-pharmacologic Treatment of BZD Addiction . . . . . . . . . . . . . . . . . . . . . . . . . 358
A. Umbricht (*)
Behavioral Pharmacology Research Unit, The Johns Hopkins University School of Medicine,
Baltimore, MD, USA
e-mail: [email protected]
M.L. Velez
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
e-mail: [email protected]
Abstract
Chlordiazepoxide’s sedative activity was serendipitously discovered by
Sternbach in 1955 in Basel, Switzerland, and this first benzodiazepine (BZD)
was introduced in 1960 for the treatment of anxiety and insomnia, followed
shortly by diazepam in 1963. Given their lower toxicity, BZDs soon replaced
barbiturates and other hypnotic drugs, and they became widely prescribed.
Although generally considered effective and safe for short-term use for
a wide range of conditions, the long-term use of BZDs is much more contro-
versial as they lose efficacy and have been associated with adverse reactions.
Problems associated with long-term use include rebound of the symptoms for
which they were prescribed, alteration of sleep architecture with loss of sleep
efficiency, nightmares, agitation, anterograde amnesia leading to cognitive
impairment, confusion, depression, psychomotor compromise with increased
risk of falls and motor vehicle accidents, withdrawal symptoms upon discon-
tinuation, and risk of dependence and abuse in special populations. In the late
1980s and early 1990s, a new group of GABAA receptor agonists at the
benzodiazepine receptor site, the Z-drugs, was introduced for the treatment of
insomnia, the most common being zaleplon, zolpidem, zopiclone, and its
s-enantiomer eszopiclone. Chemically distinct from the benzodiazepine
group, they have been promoted to be safer than traditional BZDs and gained
wide acceptance with the public and practitioners. However, given their site of
action at the benzodiazepine site of the GABAAR, complications are expected
to be similar. In fact, the FDA, on May 14, 2013, released a safety announce-
ment recommending a dose reduction for zolpidem extended release as well as
a warning not to operate a vehicle or machinery requiring complete mental
alertness on the day following the use of zolpidem due to residual psychomotor
impairment. Next day sedation, physical dependence and withdrawal, cognitive
and psychomotor problems are found in patients receiving Z-drugs. Abuse of
the Z-drugs is on the increase and studies suggest that Z-drugs may also increase
the risk of depression.
Clinicians prescribing sedatives should ensure short-term use to maximize
benefit while minimizing misuse and diversion. They can play a critical role in
identifying patients at risk to misuse or divert prescription drugs. Several
studies demonstrate that BZD discontinuation in patients with long-term use
and dependence is associated with improved quality of life. The management of
the patients with BDZ abuse and/or dependence and interventions for BZD
detoxification will be described.
21 Benzodiazepine Abuse and Addiction 345
21.1 Introduction
Benzodiazepine (BZD) and other BZD receptor agonists (so-called Z-drugs) remain
among the most widely prescribed drugs, in spite of recommendations to prescribe
SSRIs for long-term treatment of anxiety disorders and melatonin agonists for
insomnia. Alprazolam, zolpidem, diazepam, clonazepam, and lorazepam are listed
among the 200 most commonly prescribed medications in the United States
(Tan et al. 2011). Alprazolam is the tenth most often prescribed medication in the
United States, and the number of prescriptions increased from 41.4 million in 2007
to 49.1 million in 2011. Zolpidem follows as the 12th most prescribed drug with
34.5 million prescriptions in 2007 and increasing to 44.6 million prescriptions in
2011. The prevalence of regular BZD use is estimated between 2.2 % and 17.6 % in
the general population (Donoghue and Lader 2010; Lader 2011), and 5.4 % of the
population receive BZD agonist prescriptions for insomnia.
Public health problems associated with BZDs are mainly due to chronic prescrip-
tions for legitimate symptoms, diversion to other persons than the patients for whom
the prescription was initially ordered, and broader illegal trade for nonmedical use.
The nonmedical use of prescription drugs has soared in the last 20 years and become
a major public health threat. Due to the heterogeneity in individuals classified as
“misusers” or “abusers” of prescription medications, it is difficult to determine the true
magnitude and clinical significance of problems associated with any particular form of
inappropriate medication use (Barrett et al. 2008). However, sedatives are among
the medications most frequently used without prescription in the United States
(Manchikanti 2006). In one study, 84 % of 3,234 benzodiazepine users identified in
a study of 15 general practices were still using them 8 months later, and in the 1996
Australian National Health Survey, 58 % of the 359,300 benzodiazepine users had
been taking them for at least 6 months (Parr et al. 2009).
Although misuse and abuse of BZDs can be found at any age, they disproportion-
ately impact vulnerable populations, including the elderly, adolescents and young
adults, pregnant women, individuals subject to sexual victimization or dating vio-
lence, those with a history of mental illness, and those with a history of substance
abuse disorders. BZD misuse is among the most widespread forms of adolescent
prescription drug misuse. In population-based national surveys, 9.3 % and 9.5 % of
12th grade students report lifetime sedative and anxiolytic use for recreational purpose
(Johnston et al. 2009). In European countries, an average of 5.6 % of adolescents had
used tranquilizers/sedatives with prevalences ranging from 1.5 % in Ukraine and the
United Kingdom to about 13 % in Lithuania and France. In Brazil, adolescents have
a 5 % lifetime use of sedatives or tranquilizers; females and students attending private
schools are at increased risks of BZD use (Opaleye et al. 2013).
Long-term use of BZDs is prevalent among seniors in North America, Australia,
and Europe (Curran et al. 2003). Approximately 9–54 % of elderly adults have used
benzodiazepines in a given year (Llorente et al. 2000), and two thirds of the
prescriptions were inappropriate.
People who are mentally or physically vulnerable are more likely to misuse these
drugs. In 2009, at least 33 % of drug-related emergency department (ED) visits in
346 A. Umbricht and M.L. Velez
the United States were related to CNS depressants. ED visits involving benzodiaz-
epines more than doubled between 2004 and 2009. This demonstrates an alarming
increase in the abuse of BZDs and other non-BZD hypnotics. In addition, there is
a significant increase in the involvement of alprazolam, clonazepam, and zolpidem
in drug-related suicide cases since 2004, with a 148 % increase for zolpidem and
a 105 % increase for alprazolam.
Substance abuse treatment programs and emergency departments’ data indicate
that the combination of benzodiazepines and narcotic pain reliever abuse is com-
mon as 80 % of people who abused benzodiazepines also misused other drugs, most
commonly opioids. An estimated 3–41 % of alcoholics abused benzodiazepines.
The rehabilitation of patients who also abuse BZDs in combination to other drugs is
very challenging as they represent a treatment-resistant population.
The number of admissions to addiction treatment for abuse of BZDs nearly
tripled in the United States between 1998 and 2008, compared to an 11 % increase
in overall substance abuse admissions. The number of annual admissions for
combined abuse of benzodiazepine and narcotic pain reliever increased by 570 %
from 5,032 admissions in 2000 to 33,701 admissions in 2010. The majority of these
admissions were non-Hispanic white males between 18 and 34 years of age. Most
BZD abusers (95 %) reported abuse of another substance besides the BZD, with
82.1 % reporting primary abuse of another substance and 12.9 % reporting primary
abuse of BZD (SAHMSA Treatment Episode Data Set 2011).
The shorter the onset of action after drug taking, the more efficient is the learning of
the subjective effect associated to the drug. With BZDs of short onset of action
(30 min), the individual learns that relaxation, stress relief, or sleep is obtained by
taking a pill rather than by learning more effective practices of stress reduction
and a more structured lifestyle with regular sleep hygiene. Moreover, attempts to
discontinue medications after several weeks of regular intake are met with resur-
gence or rebound of the primary symptom of anxiety or insomnia, frustrating
the attempts, triggering further drug seeking, and leading to automatic and com-
pulsive drug-taking behaviors or the cycle of addiction. With chronic intake,
tolerance sets in to the effect and duration of the desired effect of the drug, requiring
increases in doses and frequency of doses. Tolerance to chronic benzodiazepine use
appears to result from neuroadaptive processes involving both desensitization of
inhibitory gamma-aminobutyric acid (GABA) receptors and sensitization of excit-
atory glutaminergic receptors (Ashton 2005).
When high-dose benzodiazepines or ethanol is abruptly discontinued, this
“downregulated” state of inhibitory transmission is unmasked, leading to charac-
teristic withdrawal symptoms of anxiety, insomnia, irritability, autonomic hyper-
activity, sweats, and, possibly, seizures.
Benzodiazepine drugs form a homogenous class of medications made of a benzene
ring and a diazepine ring. The differences between the different benzodiazepine drugs
are in their side chains. On the other hand, the non-benzodiazepine drugs (Z-drugs)
bind specifically to and activate the benzodiazepine site of GABAA receptors but they
are not chemically related to benzodiazepines. They are principally classified into three
groups of chemicals: (1) imidazopyridines (zolpidem, alpidem, necopidem, saripidem),
(2) pyrazolopyrimidines (zaleplon, divaplon, fasplon, indiplon, lorediplon, ociplon,
panadiplon, taniplon), and (3) cyclopyrrolones (eszopiclone, zopiclone, pagoclone,
pazinaclone, suproclone, suriclone). Given their specific binding and allosteric modu-
lation of GABAA, these drugs have similar long-term negative effects to benzodiaze-
pines including adverse cognitive (amnesia) and psychomotor effects, compromise in
balance, standing steadiness, night falls, and motor incoordination leading to driving
impairments. Due to their heterogeneous chemical classes, routine toxicology screens
for drugs of abuse do not include the Z-drugs sedatives, so that the extent of their impact
on emergency room visits and other societal costs remain underreported. In clinical
trials, these sedative hypnotics were found to more than double the risk of depression
compared to the groups taking placebo. Consequently, the long-term use of sedative
hypnotic drugs increase the suicide risk as well as overall mortality risk (partially due to
increase in risks of cancer and infections). The Z-drugs have similar risks of rebound
and withdrawal effects as benzodiazepine drugs.
In this section, we are first reviewing accepted indications for BZDs. BZDs and
other BZD-site agonists are indicated for short-term use and at the lowest effective
dose for these indications.
348 A. Umbricht and M.L. Velez
21.4 Pharmacokinetic
BZDs are well absorbed by the gastrointestinal tract after oral administration. After
intravenous administration, BZDs quickly distribute to the brain and central ner-
vous system. Only midazolam has reliable absorption after intramuscular adminis-
tration. The main difference between BZDs relates to the time to peak effect (onset
of action) and duration of action, depending on the metabolic half-life and the
presence or not of psychoactive metabolites. BZD characteristics predicting the
severity of the benzodiazepine withdrawal syndrome are higher dose, longer dura-
tion of treatment, shorter half-life, and more rapid taper. Clinical variables of BZD
withdrawal severity include severity of preexisting anxiety and/or depression,
personality disorder, panic disorder, and history of or concurrent substance use
disorder. Withdrawal from rapidly absorbed, short-acting drugs with no active
metabolites (e.g., alprazolam, triazolam) can start within hours of the last dose;
withdrawal from substances with long-acting metabolites (e.g., diazepam) may
have gradual onset with a peak within 1–10 days after the last dose.
The long-term clinical use of BZDs is much more controversial. Advocates of long-
term management with BZDs quote patients’ acceptability and widespread belief of
safety and efficacy. However, several academic and public health policies strongly
advise against long-term use of BZDs for PTSD, generalized anxiety, insomnia,
depression, and panic attacks due to the lack of evidence of demonstrated long-term
efficacy in the treatment of these conditions and their problematic effects
(Table 21.1).
Sedatives adversely affect cognitive (memory, attention) and psychomotor func-
tioning impacting daily activities. BZD-associated impairments in reaction time,
21 Benzodiazepine Abuse and Addiction 349
attention, and visuospatial skills increase vulnerability for motor vehicle accidents.
There is also a clear association between the use of BZDs in aged people and
increased risk of falls and fractures and of traffic accidents (Thomas 1998; Gunja
2013). Psychomotor impairment, falls, and hip fractures are more likely to occur
with Z-drugs that have longer half-lives.
Among war veterans, potential adverse consequences are BZD misuse and/or
addiction, especially among those patients with an already established substance
use disorder. Disinhibition has been described in patients with traumatic brain
injury; these two conditions are common and often underdiagnosed among veterans
with PTSD returning from Iraq and Afghanistan. In addition, it is becoming
apparent that BZDs have the potential to reduce the effectiveness of exposure-
based psychotherapy, which is considered a pillar in the treatment of veterans with
PTSD and requires effective short-term memory, as the mechanism underlying
effectiveness is a change in memory (Lund et al. 2013).
Evidence-based guidelines insist on BZD’s liability for physical dependence
which may occur even with appropriate therapeutic dose but for longer period of
time. The risk for negative effects such as abuse and dependence is minimized when
they are prescribed for short term (e.g., 2–4 weeks for intense grief reaction).
350 A. Umbricht and M.L. Velez
As stated earlier, because of rebound, i.e., exacerbation of symptoms for which the
medications were taken initially, a large proportion of BZD recipients become
chronic users, with ensuing development of tolerance and the potential for physical
and psychological dependence. The dilemma is the difficulty to prevent what is
anticipated for short-term therapy to become long-term misuse with no established
evidence of long-term benefit and the liability of dependence and negative psycho-
motor and cognitive side effects (Lader 2011).
Intentional abusers actively seek the sedatives because of their rewarding psycho-
active properties. Sedatives can be abused due to their ability to relax anxious
feelings and remove inhibitions (such as during social encounters), similar to the
euphoric feelings induced by alcohol or illegal drugs (Yu 2012).
The drugs are purchased from legal or illegal sources for recreational use or
obtained from friends or family members who have prescriptions. Other sources
include illicit sales of diverted supplies or the Internet. The modern everywhere
technology, such as the easy access to Internet, plays a significant role in this regard
by opening up a new source for access to drugs, explaining a portion of the increase
in their abuse. Illegal online pharmacies sell controlled substances, including
21 Benzodiazepine Abuse and Addiction 351
sedatives, over the Internet without regard for local laws, without a valid prescrip-
tion, and without medical guidance and supervision (Forman et al. 2006). Direct
marketing of medications to patients through media (especially television) may be
related to changed attitudes toward ingestion of psychotherapeutic agents.
Misuse of psychoactive medications, particularly in the case of individuals with
prescribed BZDs, may not only stem from the individual factors but from a lack of
quality health-care service. The fact that these drugs are considered “medication”
and are endorsed by physicians may give a false sense of safety. Health-care
providers may inadvertently play a role in misuse behaviors by failing to recognize
a patient’s potential for developing a substance abuse/dependence disorder,
misdiagnosing the patient, overprescribing the medication, or just due to time
pressure on the physician: it takes more time to refuse a patient’s request and
teach alternative behavioral strategies for anxiety or insomnia than to agree and
write the requested prescription.
Increased “medicalization” and pharmacotherapeutic management of common
symptoms such as insomnia and subsequent increase in prescription of BZDs or
Z-drugs have also led to more addiction and abuse problems. More worrisome, and
by no means rare, are those who are on chronic prescription of opiates and sedatives
for chronic pain, given the increased potential for respiratory depression and
cardiac arrest especially with comorbid diagnoses of COPD or obstructive sleep
apnea.
Finally, while doctor shoppers, physicians, and the Internet receive much of the
attention regarding diversion, data suggest that there are numerous active street
markets involving patients, Medicaid recipients, and pharmacies as well. Diversion
can occur in many ways, including the illegal sale of prescriptions by physicians
and those who are referred to on the street as “loose” pharmacists; “doctor shop-
ping” by individuals who visit numerous physicians to obtain multiple prescrip-
tions; theft, forgery, or alteration of prescriptions by health-care workers and
patients; robberies and thefts from manufacturers, distributors, and pharmacies;
and thefts of institutional drug supplies. Many of these individuals have conditions
that have been appropriately diagnosed and addressed with a proper course of
treatment but are selling their prescription drugs for profit or exchanging them for
illicit drugs. In addition, there are many individuals posing as legitimate patients for
the purposes of scamming physicians and pharmacists or otherwise defrauding the
system (Inciardi et al. 2007).
Withdrawal symptoms can sometimes occur after as little as 4 weeks of daily use of
BZDs but occur in about half of the patients treated daily for more than 4 months
(el-Guebaly et al. 2010), and may last for 6–8 weeks. In some protracted cases, it
can last for months. However, many patients will report more restorative sleep and
improved quality of life after a few weeks off the medications, due to improved
cognitive and psychomotor functioning (Salzman et al. 1992).
352 A. Umbricht and M.L. Velez
While in the past sedative medications traditionally have been prescribed to women
and older age groups, the growing problem of prescription drug abuse in the
beginning of the twenty-first century affects individuals of both genders and of all
ages, including middle school-aged children (ages 12–16) worldwide. For example,
in Canada, a national health survey showed the use of sedatives doubled between
1994 and 2003 with particular increase among men, individuals under 60 years of
age, and among obese men and underweight women (Vozoris and Leung 2011).
Usually, high prevalences among specific populations reflect the presence of
underlying conditions that can explain in part the known relationship between
sedatives and morbidity/mortality. This is the case of the greater odds of sedative
medication use found among morbidly obese men complicating obesity-related
21 Benzodiazepine Abuse and Addiction 353
sleep disruption (obstructive sleep apnea) and the associated cardiac mortality risk
that has been found to be increased in the presence of BZDs. The same is true with
chronic obstructive pulmonary disease, when the anxiety triggered by shortness of
breath is treated with BZDs.
The lifetime prevalence of anxiety ranges between 15 % and 20 % and the median
age of onset is 11 years of age, constituting one of the most common and earliest
type of psychopathology among children and adolescents (Mohr and Schneider
2013). Anxiety disorders are found in 5–19 % of all children and adolescents, and in
children younger than 12, prevalence ranges between 2.6 % and 5.2 %, with
separation anxiety as the most common disorder (Costello et al. 2004; Ford
et al. 2003). Children with an anxiety disorder are more likely to be engaged in
drug abuse activities as young adults at follow-up (Beesdo et al. 2009).
Sleep disorders are also very common in pediatric populations, with as many as
17 % of adolescents having unrestorative sleep (Roberts et al. 2002). However, sleep
problems among children often go unrecognized in general practice, in part because of
parents underreporting of sleep problems in their children or adolescents. Awareness
of the importance and potential consequences of sleep problems on academic perfor-
mance, neurocognitive function, and daytime behavioral problems has to be empha-
sized (Blunden et al. 2004). Children and adolescents are frequently sleeping less than
9 hours at night, the recognized minimum amount of sleep required in this age group.
Intrinsic contributors to inadequate sleep patterns in children and adolescents include
developmental changes causing a shift in circadian rhythm during puberty, delayed
sleep phase syndrome (7 % of adolescents), sleep-disordered breathing, and insomnia-
type symptoms found in up to 34 % of adolescents. Extrinsic factors include early
school start time and poor sleep habits (also called sleep hygiene) such as use of
electronic devices near or during bedtime and caffeine consumption, especially
problematic when undisclosed in soda or other foods (Tan et al. 2012). Anxiety,
poor academic performance, behavioral problems, and sleep problems have been
recognized as risk factors for substance use, abuse, and dependence.
The nonprescribed use of sedatives among adolescents and young adults is a cause
of concern in many countries. Fast brain development during this life stage, especially
the development of executive function and learning acquisition, implies that exposure
to amnesia-inducing drugs may stunt development and result in devastating neurobi-
ological changes and behavioral consequences such as missed educational milestones,
increased impulsivity (inversely correlated with short-term memory), and school
dropouts. Young people report using sedatives to relieve anxiety symptoms and to
sleep, with high percentage of teenagers and many of their parents believing that
prescription drugs, even taken nonmedically, are more safe than illegal drugs.
Uncharted societal changes exposing children and adolescents are increased
exposure to direct-to-consumer advertisement of medications since 1992, rushed
medical visits promoting fixing of problems via prescription while decreasing
354 A. Umbricht and M.L. Velez
21.11 Elderly
21.12 Women
Women are a vulnerable population for BZD drug abuse. First, women are more
likely than men to suffer from depression, anxiety, trauma, and victimization, all of
which are also associated with substance abuse. Second, women at different ages
report using drugs to cope with stressful situations in their lives. Third, studies
suggest that women are significantly more likely than men to be prescribed med-
ications with high abuse liability such as narcotics and anxiolytics and not rarely in
combination and for long periods of time.
BZDs cross the placenta and have the potential to accumulate in the embryo/fetus
and may consequently cause adverse problems (Iqbal et al. 2002). The general con-
sensus is that BZDs have low teratogenic potential but may be associated with an
increased risk of cleft palate. Current recommendations are that in order to minimize
risk if BZDs are absolutely needed, they should be prescribed at the lowest effective
dose for the shortest possible duration, avoiding use in the first trimester and avoiding
poly-pharmacotherapy use (Dell’osso and Lader 2013). Pregnant women on BZDs are
often tapered off their BZD treatment. However, there is a portion of BZD-dependent
pregnant women who are unable to discontinue their BZDs in spite of knowing the
associated risk of cleft palate and the potential harm of BZD on the developing brain.
21 Benzodiazepine Abuse and Addiction 355
Pregnant women substance users with BZD dependence are in general very
impaired, emotionally challenged with frequent relapses and issues of
noncompliance with treatment recommendations possibly due to underlying trust
issues. BZDs should never be used for pregnant women with other addictive
disorders as they increase impulsivity and prevent learning more adaptive coping
skills. Moreover, when BZDs are continued into the late pregnancy, neonatal
abstinence syndrome may occur in the baby and can be prolonged. This additional
stressor at the start of life is not only detrimental to the baby, as her irritability may
jeopardize bonding between the mother and child dyad, which may be very
significant given the preexisting vulnerabilities of the mother. Alternative
approaches to treating anxiety and stress during pregnancy are “desperately”
needed, and more should be done to validate the usefulness of integrative
approaches to improve self-regulation during pregnancy.
Ingestion of intoxicant during parties puts participants at risk for sexual assaults.
Studies on the prevalence of drug-facilitated sexual assaults have been conducted in
the United States. Of 1,179 urine samples from victims of sexual assault analyzed
356 A. Umbricht and M.L. Velez
For some long-term BZD user patients, minimal interventions such as brief con-
sultation or a letter with information about risks of long-term use of BZDs and the
recommendation for their discontinuation can be effective and do not produce
adverse effects (Cormack et al. 1994; Heather et al. 2004).
The management of BZD withdrawal syndrome includes, either independently
or in combination, (1) gradual tapering of the BZD, (2) switching to an equivalent
dose of a long half-life BZD before gradual tapering of the latter (Lader et al. 2009),
(3) the use of adjuvant medications, (4) treatment of the underlying conditions
(i.e., SSRIs for anxiety) prior to detoxification and continuing these medications
after BZD discontinuation (Rickels et al. 1990), and (5) non-pharmacologic
treatments of underlying conditions (Table 21.4).
The rate of BZD taper is different for each patient and needs to be individualized,
but there are some common recommendations depending on the type of BZD
21 Benzodiazepine Abuse and Addiction 357
diazepam substitution and taper over 2–3 weeks. Especially in this group, the use of
adjuvant antiepileptic medications is indicated (see below).
It is important to treat any underlying condition before, during, and after BZD
withdrawal treatment. SSRIs and other antidepressant with low stimulating poten-
tial (sertraline, paroxetine, citalopram, escitalopram, mirtazapine, trazodone) are
recommended for anxiety disorders, especially with concurrent depressive symp-
toms. Melatonin is recommended for insomnia.
Table 21.4 Steps recommended for BDZ discontinuation after long-term use
1. Send a letter or have a conversation with the patient explaining the negative consequences of
long-term use of BDZs. Explain the process of taper and the non-pharmacologic options to deal
with the symptoms related to BDZ discontinuation and/or underlying problems
2. Change to longer-acting medication and taper over a period of 6–12 weeks
3. If step 2 fails or the patient has a severe dependence with risk of seizures, use a medication to
suppress the withdrawal symptoms for several weeks before and after BDZ reduction
4. If step 3 fails or the patient is at risk for complications, use inpatient dose reduction of BDZ over
a period of 1–3 weeks
5. Consider the need for psychiatric or hypnotic medication different than BDZ to treat underlying
anxiety and/or insomnia
6. Refer for therapy (CBT, mindfulness-based therapy, support groups)
approaches to the treatment of anxiety and sleep disorders. Although the review of
these strategies is beyond the scope of this chapter, clinicians will benefit their
patients in developing familiarity with self-empowering strategies aimed at improv-
ing quality of life and health by reducing stress while minimizing risks associated
with pharmacologic management.
Historically, psychotherapy for anxiety disorders (panic, generalized
anxiety, social anxiety, phobias) was the first available treatment to provide relief
for anxiety symptoms. The initial long-term dynamic therapy has been replaced
by short-term intensive dynamic psychotherapy, cognitive behavioral therapy,
and other interventions such as exposure therapy and mindfulness-based therapies.
There are several promising therapies that have been used recently to treat
anxiety. Some of them are COPE (Creating Opportunities for Personal Empower-
ment) that is a brief-focused cognitive behavioral therapy-based intervention
that can be delivered to teens in school settings using a group format. Adolescents
who received this therapy reported significant decreases in depression and anxiety
on the Beck Youth Inventory as well as increases in personal beliefs about
managing negative emotions. Evaluations indicated that the group COPE inter-
vention was a positive experience for the teens (Mazurek Melnyk et al. 2013)
(Table 21.4).
A 12-session program of mindfulness-based stress reduction (MBSR) in seventh
and eighth graders at a small school for low-income urban boys resulted in less
anxiety, improved coping, and a possible attenuation of cortisol response to
academic stress, when compared with Health Education participants (Sibinga
et al. 2013).
Pathological worry is considered a central symptom of generalized anxiety
disorder but can be seen in other types of anxiety (e.g., excessive worry over future
panic attacks). For that reason, studies of interventions that reduce pathological
worry are considered very important. Results from a meta-analysis performed by
Covin et al. (2008) found that cognitive behavioral therapy (CBT) for GAD can be
a highly effective treatment for reducing pathological worry, especially for younger
adults. CBT was also effective for geriatric patients and the improvement was both
for the short term and over time.
360 A. Umbricht and M.L. Velez
Countries have created guidelines aiming at reducing the chronic use of BZD and
consequently the risks of misuse and abuse. Several academic (American Psychi-
atric Association (APA), the National Institute for Health and Care Excellence
(NICE), Royal Australian and New Zealand College of Psychiatrists (RANZCP),
the UK Committee on Safety of Medicines (1988)) and governmental agencies
(U.S. Department of Veterans Affairs (VA) and the U.S. Department of Defense (DoD),
21 Benzodiazepine Abuse and Addiction 361
the UK Department of Health via the Chief Medical Officer (2004)) have created
evidence-based guidelines describing indications and recommended length of
time for BZD use. Most of these guidelines emphasize selective serotonin
reuptake inhibitors (SSRI) as first-line treatment for generalized anxiety,
panic attacks, and post-traumatic stress disorder and generally discourage the
use of BZDs. However, primary and mental health-care providers frequently
continue prescribing BZDs in situations not included in the guidelines (Abrams
et al. 2013).
21.17.2 Screening
Due to the strong association between anxiety disorders and substance use, as well
as the strong association between drug abuse and prescription drug misuse, it is
imperative to include screening questions regarding alcohol, smoking, and sub-
stance use histories when pharmacologic options for treatment of anxiety or
insomnia are considered. Identifying at-risk individuals, considering alternative
treatments where appropriate, and education on the safe and effective use of
BZDs or Z-drugs may all decrease BZD diversion and misuse (McLarnon 2011).
Obtaining patient signature for a treatment contract and monitoring the duration of
therapy to limit at 2–6 weeks maximum are another way of preventing BZD-related
problems. In addition, a history of respiratory insufficiency such as chronic obstruc-
tive lung disease or obstructive sleep apnea should be a relative contraindication to
BZDs due to increased lethality in this group.
Education should highlight the side effects of BZDs, including their potential for
physical dependence; rebound symptoms upon discontinuation; adverse effect on
memory, cognition, and mood; the increased risk of falls; and accidents when
operating vehicles or machinery within 24 h of taking the medication.
Prescribers should educate patients and their guardians that a prescription is only
for the person who received the prescription, and inform about the risks of diversion
including making medications available to other persons living in the household.
Education should be provided regarding safe storage of medications in locked
cabinets or boxes. Leftover medications should be disposed appropriately and
returned to the pharmacist for environmentally safe disposal.
There is a need for widespread education regarding the importance of sleep in
children and adolescents and the timely recognition of poor sleep habits and/or
sleep problems (Blunden et al. 2004). Sleep hygiene interventions are beneficial in
improving sleep quality in children, adolescents, and adults. Combination of sleep
hygiene intervention, cognitive behavioral therapy (CBT), and stress reduction has
been used to improve sleep and decrease the risk of relapse among adolescents with
substance abuse problems (Bootzin and Stevens 2005).
362 A. Umbricht and M.L. Velez
21.18 Conclusion
While the true extent of benzodiazepines abuse and diversion is unknown, it is well
known that they are among the top most frequently prescribed medications in
Western countries and they are used and misused regularly or continuously for
insomnia and anxiety and as muscle relaxants. In addition, due to the adverse
effects on memory and cognition, BZDs may affect daily activities such as driving
or taking care of children. Benzodiazepine abuse leading to dependence is
a common and costly comorbidity among substance abuse patients and one for
which safe and effective treatments are greatly needed. BZD-related problems are
also found among adolescents, seniors, war veterans, and women. Health-care
providers and the society in general need to be aware not only of the large abuse
liability of these substances but also of the importance of individual differences in
risk for misuse and diversion. Detoxification from BDZs is usually a challenging
process and needs to be closely monitored by experienced and compassionate
providers due to the severe discomfort and the underlying problems that required
the medications. Non-pharmacologic therapies such as sleep hygiene, exercise,
outdoor activities, cognitive behavioral therapy, mindfulness skills training, or
other relaxation interventions have been shown to be as efficacious as pharmaco-
therapy for insomnia and anxiety. These interventions have the benefits of long-
term stress reduction, improvement of cognition and life satisfaction, and decrease
in disease burden.
21 Benzodiazepine Abuse and Addiction 363
References
Abrams TE, Lund BC, Bernardy NC, Friedman MJ (2013) Aligning clinical practice to PTSD
treatment guidelines: medication prescribing by provider type. Psychiatr Serv 64(2):142–148
Ashton H (2005) The diagnosis and management of benzodiazepine dependence. Curr Opin
Psychiatry 18:249–255
Barrett SP, Meisner JR, Stewart SH (2008) What constitutes prescription drug misuse? Problems
with current conceptualizations. Curr Drug Abuse Rev 1:255–262
Beesdo K, Knappe S, Pine DS (2009) Anxiety and anxiety disorders in children and adolescents:
developmental issues and implications for DSM-V. Psychiatr Clin North Am 32(3):483–524
Blackledge JT, Hayes SC (2001) Emotion regulation in acceptance and commitment therapy.
J Clin Psychol 57(2):243–255, Review
Blunden S, Lushington K, Lorenzen B, Ooi T, Fung F, Kennedy D (2004) Are sleep problems
under-recognized in general practice? Arch Dis Child 89:708–712
Bobes J, Rubio G, Terán A, Cervera G, López-Gómez V, Vilardaga I, Pérez M (2012) Pregabalin
for the discontinuation of long-term benzodiazepines use: an assessment of its effectiveness in
daily clinical practice. Eur Psychiatry 27(4):301–307
Bootzin RR, Stevens SJ (2005). Adolescents, substance abuse, and the treatment of insomnia and
daytime sleepiness. Clin Psychol Rev 25:629–644
Carroll KM, Schottenfeld R (1997) Nonpharmacologic approaches to substance abuse treatment.
Med Clin North Am 81(4):927–944
Cormack MA, Sweeney KG, Hughes J, Foot GA (1994) Evaluation of an easy cost-effective
strategy for cutting benzodiazepine use in general practice. Br J Gen Pract 44:5–8
Costello EJ, Egger HL, Angold A (2004) Developmental epidemiology of anxiety disorders. In:
Ollendick TH, March JS (eds) Phobic and anxiety disorders in children and adolescents:
a clinician’s guide to effective psychosocial and pharmacological interventions. Oxford
University Press, New York, pp 61–91
Covin R, Ouimet AJ, Seeds PM, Dozois DJA (2008) A meta-analysis of CBT for pathological
worry among clients with GED. J Anxiety Disord 22(2008):108–116
Croissant B, Grosshans M, Diehl A, Mann K (2008) Oxcarbazepine in rapid benzodiazepine
detoxification. Am J Drug Alcohol Abuse 34(5):534–540
Curran HV, Collins R, Fletcher S, Kee SC, Woods B, Iiiffe S (2003) Older adults and withdrawal
from benzodiazepine hypnotics in general practice: effects on cognitive function, sleep, mood
and quality of life. Psychol Med 33(7):1223–1237
Dell’osso B, Lader M (2013) Do benzodiazepines still deserve a major role in the treatment of
psychiatric disorders? A critical reappraisal. Eur Psychiatry 28(1):7–20
Donoghue J, Lader M (2010) Usage of benzodiazepines: a review. Int J Psychiatry Clin Pract 14:78–87
El-Guebaly N, Sareen J, Stein MB (2010) Are there guidelines for the responsible prescription of
benzodiazepines? Can J Psychiatry 55(11):709–714
ElSohly MA, Salamone SJ (1999) Prevalence of drugs used in cases of alleged sexual assault.
J Anal Toxicol 23:141–146
Epstein DH, Hawkins WE, Covi L, Umbricht A, Preston KL (2003) Cognitive-behavioral therapy
plus contingency management for cocaine use: findings during treatment and across 12-month
follow-up. Psychol Addict Behav 17(1):73–82
Foa EB, Hembree EA, Rothbaum BO (2007) Prolonged exposure therapy for PTSD: Emotional
processing of traumatic experiences. New York, NY: Oxford University Press
Ford T, Goodman R, Meltzer H (2003) The British child and adolescent mental health survey
1999: the prevalence of DSM-IV disorders. J Am Acad Child Adolesc Psychiatry
42(10):1203–1211
Forman RF, Marlowe DB, McLellan AT (2006) The internet as a source of drug of abuse. Curr
Psychiatry Rep 8:377–382
Glass J, Lanctot KL, Herrmann N et al (2005) Sedative hypnotics in older people with insomnia:
meta-analysis of risks and benefits. BMJ 331(7526):1169
364 A. Umbricht and M.L. Velez
Gunja N (2013) In the ZZZ zone: the effects of Z-drugs on human performance and driving. J Med
Toxicol 9(2):163–171
Heather N, Bowie A, Ashton H, McAvoy B, Spencer I, Brodie J, Giddings D (2004) Randomised
controlled trial of two brief interventions against long-term benzodiazepine use: outcome of
intervention. Addict Res Theory 12:141–154
Heikkinen AE, Moykkynen TP, Korpi ER (2009) Long-lasting modulation of glutamatergic
transmission in VTA dopamine neurons after a single dose of benzodiazepine agonists.
Neuropsychopharmacology 34:290–298
Holden JD, Hughes IM, Tree A (1994) Benzodiazepine prescribing and withdrawal for 3234
patients in general practices. Fam Pract 11(4):358–362
Inciardi JA, Surratt HL, Kurtz SP, Cicero TJ (2007) Mechanisms of prescription drug diversion
among drug-involved club- and street-based populations. Pain Med 2(8):171–183
Iqbal MM, Sobhan T, Ryals T (2002) Effects of commonly used benzodiazepines on the fetus, the
neonate, and the nursing infant. Psychiatr Serv 53:39–49
Johnston LD, O’Malley PM, Bachman JG, Schulenberg JE (2009) Monitoring the future national
survey results on drug use, 1975–2008. volume I: secondary school students (NIH Publication
No. 09–7402). National Institute on Drug Abuse, Bethesda
Kan CC, Hilberink SR, Breteler MH (2004) Determination of the main risk factors for benzodi-
azepine dependence using a multivariate and multidimensional approach. Compr Psychiatry
45(2):88–94
Khoury B, Lecomte T, Fortin G, Masse M, Therien P, Bouchard V, Chapleau MA, Paquin K,
Hofmann SG (2013) Mindfulness-based therapy: a comprehensive meta-analysis. Clin Psychol
Rev 33(6):763–771
Lader M (2011) Benzodiazepines revisited –will we ever learn? Addiction 106:2086–2109
Lader M, Tylee A, Donoghue J (2009) Withdrawing benzodiazepines in primary care. CNS Drugs
23(1):19–34
Lang C, Brand S, Feldmeth AK, Holsboer-Trachsler E, P€ uhse U, Gerber M (2013) Increased self-
reported and objectively assessed physical activity predict sleep quality among adolescents.
Physiol Behav 120:46–53
Llorente MD, David D, Golden AG, Silverman MA (2000) Defining patterns of benzodiazepine
use in older adults. J Geriatr Psychiatry Neurol 13:150–160
Lund BC, Bernardy NC, Vaughan-Sarrazin M, Alexander B, Friedman MJ (2013) Patient and
facility characteristics associated with benzodiazepine prescribing for veterans with PTSD.
Psychiatr Serv 64(2):149–155
Manchikanti L (2006) Prescription drug abuse: what is being done to address this new drug
epidemic? Testimony before the subcommittee on criminal justice, drug policy and human
resources. Pain Physician 9:287–321
Mazurek Melnyk B, Kelly S, Lusk P (2013) Outcomes and feasibility of a manualized cognitive-
behavioral skills building intervention: Group COPE for depressed and anxious adolescents in
school settings. J Child Adolesc Psychiatr Nurs 27:1073–6077
McLarnon M, Monaghan T, Stewart S and Barrett SP (2011) Drugs misuse and diversion in adults
prescribed anxiolytics and sedatives. Pharmacotherapy 31(3):262–272. www.ncbi.nlm.nih.
gov/pubmed/21361736
Mohr C, Schneider S (2013) Anxiety disorders. Eur Child Adolesc Psychiatry 22(Suppl 1):
S17–S22
Montgomery P, Dennis J (2002) Physical exercise for sleep problems in adults aged 60+. Cochrane
Database Syst Rev 4:CD003404
Nubukpo P, Clement JP (2013) Medical drug abuse and aging. Geriatr Psychol Neuropsychiatr
Vieil 11(3):305–315
Opaleye ES, Noto AR, Sanchez ZM, Amato TC, Locatelli DP, Gossop M, Ferri CP
(2013) Nonprescribed use of tranquilizers or sedatives by adolescents: a Brazilian national
survey. BMC Public Health 24:13–499
21 Benzodiazepine Abuse and Addiction 365
Parr JM, Kavanagh DJ, Cahill L, Mitchell G, McD Young R (2009) Effectiveness of current
treatment approaches for benzodiazepine discontinuation: a meta-analysis. Addiction
104(1):13–24
Peturson H (1994) The benzodiazepine withdrawal syndrome. Addiction 89:1455–1459
Quaglio G, Pattaro C, Gerra G, Mathewson S, Verbanck P, Des Jarlais DC, Lugoboni F (2012)
High dose benzodiazepine dependence: description of 29 patients treated with flumazenil
infusion and stabilised with clonazepam. Psychiatry Res 198(3):457–462
Rickels K, Case WG, Schweizer E, Garcia-Espana F, Fridman R (1990) Benzodiazepine depen-
dence: management of discontinuation. Psychopharmacol Bull 26(1):63–68
Roberts RE, Roberts CR, Chen IG (2002) Impact of insomnia on future functioning of adolescents.
J Psychosom Res 53:561–569
Rubio G, López-Muñoz F, Ponce G, Pascual JM, Martı́nez-Gras I, Ferre F, Jiménez-Arriero MÁ,
Alamo C (2010) Zonisamide versus diazepam in the treatment of alcohol withdrawal
syndrome. Pharmacopsychiatry 43(7):257–262
Salzman C, Fisher J, Nobel K, Glassman R, Wolfson A, Kelley M (1992) Cognitive improvement
following benzodiazepine discontinuation in elderly nursing home residents. Int J Geriatric
Psychiatry 7:89–93
Sibinga EM, Perry-Parrish C, Chung SE, Johnson SB, Smith M, Ellen JM (2013) School-based
mindfulness instruction for urban male youth: a small randomized controlled trial. Prev Med
57:799–801
Substance Abuse and Mental Health Services Administration, Center for Behavioral Health
Statistics and Quality (2011) The TEDS report: substance abuse treatment admissions for
abuse of benzodiazepines. Rockville
Tan KR, Brown M, Labouèbe G, Yvon C, Creton C, Fritschy JM, Rudolph U, L€ uscher C (2010)
Neural bases for addictive properties of benzodiazepines. Nature 463(7282):769–774
Tan KR, Rudolph U, Luscher C (2011) Hooked on benzodiazepines: GABA-a receptor subtypes
and addiction. Trends Neurosci 34(4):188–197
Tan E, Healey D, Gray AR, Galland BC (2012) Sleep hygiene intervention for youth aged 10 to
18 years with problematic sleep: a before-after pilot study. BMC Pediatr 12:189
Thomas RE (1998) Benzodiazepines use and motor vehicle accidents. Systematic review of
reported association. Can Fam Physician 44:799–808
Voshaar RC, Couvée JE, van Balkom AJ, Mulder PG, Zitman FG (2006) Strategies for
discontinuing long-term benzodiazepine use: meta-analysis. Br J Psychiatry 189:213–220
Voyer P, Préville M, Roussel ME, Berbiche D, Beland SG (2009) Factors associated with
benzodiazepine dependence among community-dwelling seniors. J Community Health Nurs
26(3):101–113
Vozoris NT, Leung RS (2011) Sedative medication use: prevalence, risk factors and associations
with body mass index using population-level data. Sleep 34(7):869–874
Yu HE (2012) The prescription drug abuse epidemic. Clin Lab Med 32:361–377
Treatment of Cannabis Use Disorders
22
Divya Ramesh and Margaret Haney
Contents
22.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368
22.1.1 Cannabis Epidemiology and Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368
22.1.2 Cannabis Use Disorders in Humans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369
22.2 Treatment for Cannabis Use Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 370
22.2.1 Psychosocial Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 370
22.2.2 Pharmacotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
22.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 380
Abstract
Cannabis is being used by approximately 5 % of the world’s population, and
a subset of regular users develop a cannabis use disorder characterized by
tolerance, craving, and a withdrawal syndrome. Correspondingly, there is
a demand for cannabis treatment that has risen dramatically in recent years.
Yet, similar to other drug treatments, the vast majority of patients seeking
treatment for their cannabis use fail to achieve abstinence.
The objective of this chapter is to inform clinicians about characteristic
features of cannabis use disorders and update them on the current state of
treatment research. Psychosocial treatment remains the primary approach uti-
lized, but relatively poor response rates suggest that medications may be a useful
D. Ramesh
Departments of Pharmacology & Toxicology and Psychiatry, Institute for Drug & Alcohol
Studies, Virginia Commonwealth University, Richmond, VA, USA
e-mail: [email protected]
M. Haney (*)
New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and
Surgeons of Columbia University, New York, NY, USA
e-mail: [email protected]
22.1 Introduction
Cannabis, obtained from the hemp plant cannabis sativa, is the most-used illicit
drug worldwide, accounting for 75 % of all illicit drug use. Over the last decade,
2.5–5.0 % of the world’s population reported using cannabis, with an estimated
119–224 million users worldwide (UNODC 2012). The highest prevalence of
cannabis use is currently in Oceania (Australia and New Zealand) at 9.1–14.6 %,
followed by North America (10.8 %), Western and Central Europe (7.0 %), and
West and Central Africa (5.2–13.5 %). While the prevalence of cannabis use in Asia
(1.0–3.4 %) remains lower than the global average, Asia’s large population results
in the highest absolute number of users worldwide (approximately 26–92 million).
22 Treatment of Cannabis Use Disorders 369
Cannabis use disorders are defined as a problematic pattern of cannabis use leading to
clinically relevant impairment or distress occurring within a 12-month period as
manifested by cannabinoid tolerance and withdrawal; increasing amounts of cannabis
use over time; inability to control consumption; craving; and recurrent cannabis use
having negative implications on social, professional, and educational life (APA 2013).
Symptoms of cannabis withdrawal commonly appear after 24 h of abstinence,
reach their peak around 2–6 days, and remit within 2 weeks, although impaired
sleep patterns may persist for longer periods (Budney et al. 2004). According to
DSM-V, withdrawal is diagnosed if at least three of the following symptoms
develop within a week of abstinence: irritability, anger, or aggression; nervousness
or anxiety; sleep difficulty (insomnia, disturbing dreams); decreased appetite or
weight loss; restlessness; depressed mood; and at least one of the following physical
discomforts – abdominal pain, shakiness/tremors, fever, chills, or headache. Addi-
tionally, the following symptoms may be observed a week post abstinence: fatigue,
yawning, difficulty in concentration, and rebound periods of increased appetite and
hypersomnia following initial bouts of appetite loss and insomnia (APA 2013).
Cannabis withdrawal symptoms may cause significant distress and most likely
contribute to relapse among those seeking treatment for their cannabis use
(Haney et al. 2013a).
370 D. Ramesh and M. Haney
In recent years, the proportion of people seeking treating for their cannabis use has
been steadily increasing. Treatment admissions for cannabis have doubled in the
USA in the last decade and tripled in Europe and Australia. Worldwide, it is
currently estimated that 25 % of patients presenting for substance use treatment
are those with cannabis use disorders (UNODC 2012). The primary approach for
treatment is psychosocial, and to date, there is no approved pharmacological
treatment to facilitate psychosocial treatment approaches.
Research on psychosocial treatments for cannabis use disorders has been ongoing
for the last 25 years, and results from these studies have demonstrated that outpa-
tient treatment models can reduce cannabis use and promote abstinence compared
to control conditions. In both adults and adolescents, modest success rates have
been seen with cognitive behavioral therapy (CBT), motivational enhancement
therapy (MET), contingency management (CM), and family-based therapies.
CBT focuses on providing skills necessary to achieve abstinence and cope with
stressors and high-risk situations (Marlatt and George 1984; Monti et al. 2002).
MET is a non-confrontational approach that aims to build motivation to reduce drug
use, by addressing ambivalent feelings towards drug use, which may produce
a motivation to change behavior (Miller and Rollnick 2002). Evidence from
a series of controlled clinical trials for cannabis use disorders in adults suggests
that the combination of CBT and MET achieves greater rates of abstinence than
delayed treatment (Budney et al. 2007a). MET-CBT was associated with signifi-
cantly greater long-term abstinence and reduction in frequency of cannabis use than
control treatment, and typically achieved 19–29 % abstinence rates in the 12-month
follow-up.
In an effort to improve outcome, several studies have examined the efficacy of CM
for treating cannabis use disorders. CM, a process of systematically using positive
reinforcement to reinforce abstinent behavior, has been shown to significantly enhance
treatment retention and increase periods of abstinence for other drugs of abuse (Petry
and Simcic 2002). The results from trials examining the efficacy of CM alone or in
combination with MET-CBT for adult cannabis use disorders have shown that inclu-
sion of CM significantly increased rates of abstinence. Specifically, inclusion of CM
yielded enhanced abstinence rates to 35–37 % at the 12-month follow-up, whereas
MET alone had abstinence rates of 5–10 % (Budney et al. 2007a; Litt et al. 2013).
By contrast, CM was not quite as efficacious for adolescent or young adults
mandated to drug treatment. A study by Carroll and colleagues (2012) showed
that the combination of CM and CBT was ineffective in improving treatment
outcome for cannabis use disorders in young adults involved with the criminal
justice system compared to CBT alone. In adolescents (12–18 years) presenting
for publically funded treatment programs, a variety of treatment approaches,
22 Treatment of Cannabis Use Disorders 371
alone and in combination (e.g., CBT, MET, CM, family therapy), yielded about
25 % abstinence rates 1 year later regardless of treatment condition (Dennis
et al. 2004). These data suggest that maintaining cannabis abstinence may be
more difficult in this population relative to adults.
Taken together, psychosocial approaches improve outcomes for people with
cannabis use disorders relative to no treatment; however, relapse rates remain
high (about 70 %), consistent with abstinence rates for other drugs of abuse.
There is clearly a need to increase treatment outcomes by improving the efficacy
of currently available treatment options. The development of medications to sup-
plement psychosocial approaches may result in better treatment retention, allevia-
tion of withdrawal symptoms, and a reduction in cannabis use.
22.2.2 Pharmacotherapy
90-mg rimonabant reduced cannabis-induced heart rate increases but did not blunt
the positive subjective effects of cannabis, thereby failing to replicate the earlier
study. Unfortunately, rimonabant was found to increase the risk of adverse
psychiatric reactions (depression, suicidality) in a clinical trial for obesity, so
the medication has been removed from the market and further testing is not
possible.
An alternative approach to medications directly blocking the cannabinoid recep-
tor is to target neurotransmitter systems that have been implicated in the effects of
cannabis. For example, preclinical studies have demonstrated a functional interac-
tion between endogenous opioids and cannabinoids. Opioid antagonists such as
naloxone and naltrexone have been shown to attenuate the reinforcing and reward-
ing effects of cannabinoid agonists in rodents and nonhuman primates. Conversely,
in daily cannabis smokers, acute administration of a range of acute naltrexone doses
(12–100 mg) enhanced the subjective and cardiovascular effects of cannabis
(3.27 % THC) compared to placebo capsules (Cooper and Haney 2010). Yet,
repeated naltrexone administration (50 mg), for 2 weeks or longer, appears to
blunt positive subjective and reinforcing effects of smoked cannabis (Haney
et al. in preparation). Taken together, these results suggest that clinical studies
testing maintenance on naltrexone as an adjunct therapy in the management of
cannabis use disorders may be warranted.
In terms of clinical data, there are two case reports testing long-term cannabis
smokers with dronabinol in concert with other medications (Levin and Kleber
2008). One patient was medicated for 6 months with dronabinol (40 mg/day) and
divalproex (250 mg/day), a mood stabilizer that reduces irritability and mood
swings in bipolar disorder and during alcohol withdrawal. A second patient was
maintained on dronabinol (10–15 mg/day) while also receiving venlafaxine
(25 mg/day) for depression and modafinil (100 mg PRN) to counter the energy
decreases experienced with dronabinol. In both cases, patients achieved and
maintained abstinence.
A randomized, placebo-controlled, double-blind, 12-week trial was then
conducted (Levin et al. 2011). Participants (n ¼ 156) were randomized to either
dronabinol (40 mg/day) or placebo following a 1-week placebo lead-in phase; both
groups received weekly MET and CBT therapy. All participants reduced cannabis
use over time irrespective of treatment, and there was no significant difference
between treatment groups in the proportion of participants who achieved 2 weeks of
abstinence at the end of the medication phase. However, the dronabinol group had
higher treatment retention (77 %) compared to placebo (61 %), and consistent with
laboratory studies, withdrawal symptoms were significantly lower in the dronabinol
group than placebo.
Given that both the human laboratory and the clinic found that dronabinol
decreased withdrawal but did not alter cannabis use, the next study tested nabilone:
a cannabinoid agonist with better bioavailability, less individual variability in drug
response, and a more predictable dose–response function than dronabinol (Bedi
et al. 2012). Nabilone (6, 8 mg/day, for 8 days) significantly reversed withdrawal-
induced irritability and disruptions in sleep and food intake (Haney et al. 2013b).
Importantly, nabilone maintenance also decreased a laboratory measure of cannabis
relapse. These findings are the most promising human laboratory evidence to date,
where a single medication improved both cannabis withdrawal symptoms and
prevented relapse and suggest that nabilone is a promising candidate for investiga-
tion in a clinical trial for cannabis treatment.
In terms of other cannabinoids, a case report presented the effects of cannabidiol,
a non-psychoactive cannabinoid constituent of cannabis, on withdrawal symptoms
following abrupt cessation of cannabis use in a chronic, heavy cannabis smoker
(Crippa et al. 2013). Following maintenance on cannabidiol (300–600 mg/day) for
11 days, the patient demonstrated no self-reported abstinence symptoms.
Controlled testing of cannabidiol is needed.
Various non-cannabinoid medications have also been evaluated in controlled
inpatient studies for the treatment of cannabis withdrawal, largely with negative
results. For example, bupropion, an indirect noradrenergic and dopaminergic agent
used for tobacco cessation (150–300 mg/day for 28 days) was found to worsen
ratings of irritability, restlessness, depression, and troubled sleep during cannabis
withdrawal compared to placebo (Haney et al. 2001).
Since bupropion has stimulant properties that may have exacerbated abstinence-
associated agitation and insomnia, subsequent human laboratory studies assessed
the effects of medications with sedative properties on cannabis withdrawal and
374 D. Ramesh and M. Haney
relapse. Nefazodone and mirtazapine are both antidepressants that enhance norad-
renergic and serotonergic activity. During cannabis withdrawal, nefazodone main-
tenance (450 mg/day for 26 days) decreased certain cannabis withdrawal symptoms
(anxiety, muscle pain) but did not alleviate irritability, misery, or troubled sleep
(Haney et al. 2003). Mirtazapine (30 mg/day for 14 days), on the other hand,
robustly reversed sleep disruption and appetite loss during cannabis withdrawal,
but did not improve participants’ mood and did not decrease relapse (Haney
et al. 2010).
Consistent with the laboratory data, clinical trials with bupropion and
nefazodone were also negative. Bupropion (300 mg/day) and nefazodone
(600 mg/day) were each compared to placebo in treatment-seeking, cannabis-
dependent individuals (Carpenter et al. 2009). Patients (n ¼ 106) were randomized
to one of the study medications or placebo in this 13-week trial, with 1 week of
placebo lead-in, 10 weeks of study medication, and 2 weeks of lead-out. All patients
completed weekly sessions with a psychosocial intervention, and around half of the
patients completed the 10-week medication phase. Both cannabis use and with-
drawal symptoms decreased over time, and there was no effect of bupropion or
nefazodone relative to placebo. Results of this clinical trial are, therefore, consistent
with the conclusions of laboratory studies.
Venlafaxine and fluoxetine, both antidepressants, have been investigated for
their utility in treating cannabis use disorders in those with comorbid depression.
A randomized double-blind placebo-controlled trial with depressed cannabis-
dependent adolescents (n ¼ 70) found no advantage for fluoxetine (10–20 mg/day
for 12 weeks) over placebo on either depression or cannabis use outcomes
(Cornelius et al. 2010). A subsequent trial in adult patients (n ¼ 103) found that
extended-release venlafaxine (375 mg/day for 12 weeks) was not effective rela-
tive to placebo in reducing depression and could potentially increase cannabis use
in this population (Levin et al. 2013). Overall, neither laboratory nor clinical studies
provide compelling evidence for the utility of antidepressants to treat cannabis use
disorders.
Given that anxiety can be a symptom of cannabis withdrawal, the
non-benzodiazepine, antianxiety medication, buspirone, was tested in
a randomized, controlled clinical trial for cannabis use disorders (McRae-Clark
et al. 2009). Cannabis-dependent patients were randomized to buspirone
(60 mg/day) or placebo for 12 weeks in conjunction with a psychological interven-
tion (two or three sessions of motivational interviewing during the first 4 weeks).
The study reported a high dropout rate (50 %) and no direct effect of buspirone on
self-reported anxiety, withdrawal symptoms, or craving. However, exploratory
analyses suggested that decreased anxiety over the study predicted cannabis absti-
nence, indicating that anxiety symptoms may be a useful treatment target.
Divalproex has been investigated in the laboratory and the clinic for its mood-
stabilizing properties. Although divalproex (1,500 mg/day for 29 days) decreased
cannabis craving during abstinence, the medication worsened ratings of anxiety,
irritability, fatigue, and cognitive performance relative to placebo (Haney
et al. 2004). Similarly, a double-blind, placebo-controlled pilot study tested
22 Treatment of Cannabis Use Disorders 375
22.3 Conclusion
Prolonged cannabis use can lead to a clinically significant substance use disorder.
Over the past 20 years, there has been a steady increase in studies focusing on both
psychosocial approaches and medications development for cannabis use disorders.
Most psychosocial treatment studies are better than control conditions but none-
theless produce low rates of long-term abstinence. Thus, as with drugs such as
nicotine, alcohol, and opioids, adjunct pharmacotherapy is worth exploring to
maximize treatment outcome. Among the cannabinoid and non-cannabinoid agents
investigated, several appear to have therapeutic potential.
Cannabinoid agonists like dronabinol reduced withdrawal symptoms and
improved treatment retention but failed to alter cannabis use in either the laboratory
or the clinic. Yet another cannabinoid agonist, nabilone, reduced both laboratory
measures of withdrawal and relapse. The advantages of nabilone over dronabinol
include higher bioavailability as well as a longer duration of action, both of which
are essential features of a potential treatment medication. Thus, its efficacy needs to
be further explored in the clinic. Two medications shown to improve alcohol
treatment outcome, gabapentin and naltrexone, also show promise. Further clinical
studies confirming these promising findings are needed.
In terms of future directions, the inhibition of endocannabinoid catabolic
enzymes, fatty acid amide hydrolase (FAAH), and monoacylglycerol lipase reduces
cannabinoid withdrawal in animal models of cannabinoid dependence. Unlike
cannabinoid substitutes, FAAH inhibitors do not appear to possess abuse liability
(for a full review, see Panlilio et al. 2013). There is currently a study under way at
Yale University measuring the efficacy of FAAH inhibitors for reducing with-
drawal in cannabis-dependent individuals.
The impact of risk factors (both environmental and genetic) that lead to heavy
drug use and the factors that make achieving abstinence challenging need to be better
understood in order to optimize treatment approaches. Additionally, over 50 % of
patients with cannabis use disorders also abuse other drugs such as nicotine and
alcohol and have comorbid psychiatric disorders, but most treatment trials select for
psychiatrically healthy cannabis users without dependence on other substances.
Indeed, a recent laboratory study has shown that cigarette smoking is an important
predictor of cannabis relapse in the laboratory and can influence the efficacy of
medications used for treating cannabis use disorders (Haney et al. 2013a). In sum-
mary, with the growing treatment demand and increasing awareness about the risks of
378 D. Ramesh and M. Haney
References
Anthony JC, Warner LA, Kessler RC (1994) Comparative epidemiology of dependence on
tobacco, alcohol, controlled substances, and inhalants: basic findings from the national comor-
bidity survey. Exp Clin Psychopharmacol 2:244–268
APA (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric
Association, Arlington
Bedi G, Cooper ZD, Haney M (2012) Subjective, cognitive and cardiovascular dose-effect profile
of nabilone and dronabinol in marijuana smokers. Addict Biol
Bowen R, McIlwrick J, Baetz M, Zhang X (2005) Lithium and marijuana withdrawal. Can
J Psychiatry 50:240–241
Budney AJ, Hughes JR, Moore BA, Vandrey R (2004) Review of the validity and significance of
cannabis withdrawal syndrome. Am J Psychiatry 161:1967–1977
Budney AJ, Roffman R, Stephens RS, Walker D (2007a) Marijuana dependence and its treatment.
Addict Sci Clin Pract 4:4–16
Budney AJ, Vandrey RG, Hughes JR, Moore BA, Bahrenburg B (2007b) Oral delta-9-
tetrahydrocannabinol suppresses cannabis withdrawal symptoms. Drug Alcohol Depend
86:22–29
Carpenter KM, McDowell D, Brooks DJ, Cheng WY, Levin FR (2009) A preliminary trial:
double-blind comparison of nefazodone, bupropion-SR, and placebo in the treatment of
cannabis dependence. Am J Addict 18:53–64
Carroll KM, Nich C, Lapaglia DM, Peters EN, Easton CJ, Petry NM (2012) Combining cognitive
behavioral therapy and contingency management to enhance their effects in treating cannabis
dependence: less can be more, more or less. Addiction 107:1650–1659
Chait LD, Burke KA (1994) Preference for high- versus low-potency marijuana. Pharmacol
Biochem Behav 49:643–647
Compton D, Aceto M, Lowe J, Martin B (1996) In vivo characterization of a specific cannabinoid
receptor antagonist (SR141716A): inhibition of D9-tetrahdrocannabinol-induced responses and
apparent agonist activity. J Pharmacol Exp Ther 277:586–594
Cooper ZD, Haney M (2008) Cannabis reinforcement and dependence: role of the cannabinoid
CB1 receptor. Addict Biol 13:188–195
Cooper ZD, Haney M (2010) Opioid antagonism enhances marijuana’s effects in heavy marijuana
smokers. Psychopharmacology (Berl) 211:141–148
Cooper ZD, Foltin RW, Hart CL, Vosburg SK, Comer SD, Haney M (2012). A human laboratory
study investigating the effects of quetiapine on marijuana withdrawal and relapse in daily
marijuana smokers. Addict Biol
Cornelius JR, Bukstein OG, Douaihy AB, Clark DB, Chung TA, Daley DC et al (2010) Double-
blind fluoxetine trial in comorbid MDD-CUD youth and young adults. Drug Alcohol Depend
112:39–45
Crippa JA, Hallak JE, Machado-de-Sousa JP, Queiroz RH, Bergamaschi M, Chagas MH
et al (2013) Cannabidiol for the treatment of cannabis withdrawal syndrome: a case report.
J Clin Pharm Ther 38:162–164
Dennis M, Godley SH, Diamond G, Tims FM, Babor T, Donaldson J et al (2004) The Cannabis
Youth Treatment (CYT) study: main findings from two randomized trials. J Subst Abuse Treat
27:197–213
22 Treatment of Cannabis Use Disorders 379
Gray KM, Watson NL, Carpenter MJ, Larowe SD (2010) N-acetylcysteine (NAC) in young
marijuana users: an open-label pilot study. Am J Addict 19:187–189
Gray KM, Carpenter MJ, Baker NL, DeSantis SM, Kryway E, Hartwell KJ et al (2012) A double-
blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents. Am
J Psychiatry 169:805–812
Haney M, Ward AS, Comer SD, Hart CL, Foltin RW, Fischman MW (2001) Bupropion SR
worsens mood during marijuana withdrawal in humans. Psychopharmacology (Berl)
155:171–179
Haney M, Hart CL, Ward AS, Foltin RW (2003) Nefazodone decreases anxiety during marijuana
withdrawal in humans. Psychopharmacology (Berl) 165:157–165
Haney M, Hart CL, Vosburg SK, Nasser J, Bennett A, Zubaran C et al (2004) Marijuana
withdrawal in humans: effects of oral THC or divalproex. Neuropsychopharmacology
29:158–170
Haney M, Hart CL, Vosburg SK, Comer SD, Reed SC, Foltin RW (2008) Effects of THC and
lofexidine in a human laboratory model of marijuana withdrawal and relapse. Psychopharma-
cology (Berl) 197:157–168
Haney M, Hart CL, Vosburg SK, Comer SD, Reed SC, Cooper ZD et al (2010) Effects of baclofen
and mirtazapine on a laboratory model of marijuana withdrawal and relapse. Psychopharma-
cology (Berl) 211:233–244
Haney M, Bedi G, Cooper ZD, Glass A, Vosburg SK, Comer SD et al (2013a) Predictors of
marijuana relapse in the human laboratory: robust impact of tobacco cigarette smoking status.
Biol Psychiatry 73:242–248
Haney M, Cooper ZD, Bedi G, Vosburg SK, Comer SD, Foltin RW (2013b) Nabilone decreases
marijuana withdrawal and a laboratory measure of marijuana relapse.
Neuropsychopharmacology
Haney M, Bedi G, Cooper ZD (In preparation) Chronic naltrexone modulates marijuana’s
reinforcing, subjective and cardiovascular effects
Huestis MA, Gorelick DA, Heishman SJ, Preston KL, Nelson RA, Moolchan ET et al (2001)
Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist
SR141716. Arch Gen Psychiatry 58:322–328
Huestis MA, Boyd SJ, Heishman SJ, Preston KL, Bonnet D, Le Fur G et al (2007) Single and
multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis
users. Psychopharmacology (Berl) 194:505–515
Levin FR, Kleber HD (2008) Use of dronabinol for cannabis dependence: two case reports and
review. Am J Addict 17:161–164
Levin FR, McDowell D, Evans SM, Nunes E, Akerele E, Donovan S et al (2004) Pharmacotherapy
for marijuana dependence: a double-blind, placebo-controlled pilot study of divalproex
sodium. Am J Addict 13:21–32
Levin FR, Mariani JJ, Brooks DJ, Pavlicova M, Cheng W, Nunes EV (2011) Dronabinol for the
treatment of cannabis dependence: a randomized, double-blind, placebo-controlled trial. Drug
Alcohol Depend 116:142–150
Levin FR, Mariani J, Brooks DJ, Pavlicova M, Nunes EV, Agosti V et al (2013) A randomized
double-blind, placebo-controlled trial of venlafaxine-extended release for co-occurring canna-
bis dependence and depressive disorders. Addiction 108:1084–1094
Litt MD, Kadden RM, Petry NM (2013) Behavioral treatment for marijuana dependence: ran-
domized trial of contingency management and self-efficacy enhancement. Addict Behav
38:1764–1775
Marlatt GA, George WH (1984) Relapse prevention: introduction and overview of the model.
Br J Addict 79:261–273
Mason BJ, Crean R, Goodell V, Light JM, Quello S, Shadan F et al (2012) A proof-of-
concept randomized controlled study of gabapentin: effects on cannabis use, withdrawal and
executive function deficits in cannabis-dependent adults. Neuropsychopharmacology
37:1689–1698
380 D. Ramesh and M. Haney
McRae-Clark AL, Carter RE, Killeen TK, Carpenter MJ, Wahlquist AE, Simpson SA et al (2009)
A placebo-controlled trial of buspirone for the treatment of marijuana dependence. Drug
Alcohol Depend 105:132–138
McRae-Clark AL, Carter RE, Killeen TK, Carpenter MJ, White KG, Brady KT (2010) A placebo-
controlled trial of atomoxetine in marijuana-dependent individuals with attention deficit
hyperactivity disorder. Am J Addict 19:481–489
McRae-Clark AL, Baker NL, Maria MM, Brady KT (2013) Effect of oxytocin on craving and
stress response in marijuana-dependent individuals: a pilot study. Psychopharmacology (Berl)
Miller WR, Rollnick S (2002) Motivational interviewing: preparing people to change addictive
behavior, 2nd edn. Guilford Press, New York
Monti PM, Kadden RM, Rohsenow DJ, Cooney NL, Abrams DB (2002) Treating alcohol
dependence: a coping skills training guide, 2nd edn. Guilford Press, New York
Nanjayya SB, Shivappa M, Chand PK, Murthy P, Benegal V (2010) Baclofen in cannabis
dependence syndrome. Biol Psychiatry 68:e9–e10
Panlilio LV, Justinova Z, Goldberg SR (2013) Inhibition of FAAH and activation of PPAR: new
approaches to the treatment of cognitive dysfunction and drug addiction. Pharmacol Ther
138:84–102
Petry NM, Simcic F Jr (2002) Recent advances in the dissemination of contingency management
techniques: clinical and research perspectives. J Subst Abuse Treat 23:81–86
Potvin S, Stip E, Roy JY (2004) The effect of quetiapine on cannabis use in 8 psychosis patients
with drug dependency. Can J Psychiatry 49:711
Shafa R, Abdolmaleky HM, Yaqubi S, Smith C, Ghaemi SN (2009) COMT- inhibitors may be
a promising tool in treatment of marijuana addiction. Am J Addict 18:321–331, poster abstracts
from the AAAP 19th annual meeting and symposium
Tirado CF, Goldman M, Lynch K, Kampman KM, O’Brien CP (2008) Atomoxetine for treatment
of marijuana dependence: a report on the efficacy and high incidence of gastrointestinal
adverse events in a pilot study. Drug Alcohol Depend 94:254–257
United Nations Office on Drugs and Crime (UNODC) (2012) World drug report 2012. United
Nations publication, Sales No. E.12.XI.1: Vienna
Winstock AR, Lea T, Copeland J (2009) Lithium carbonate in the management of cannabis
withdrawal in humans: an open-label study. J Psychopharmacol 23:84–93
Further Reading
Budney AJ, Hughes JR (2006) The cannabis withdrawal syndrome. Curr Opin Psychiatry
19:233–238
Haney M, Bedi G, Cooper ZD, Glass A, Vosburg SK, Comer SD et al (2013) Predictors of
marijuana relapse in the human laboratory: robust impact of tobacco cigarette smoking status.
Biol Psychiatry 73:242–248
Levin FR, Mariani JJ, Brooks DJ, Pavlicova M, Cheng W, Nunes EV (2011) Dronabinol for the
treatment of cannabis dependence: a randomized, double-blind, placebo-controlled trial. Drug
Alcohol Depend 116:142–150
Vandrey R, Haney M (2009) Pharmacotherapy for cannabis dependence: how close are we? CNS
Drugs 23:543–553
Treatment of Cocaine Addiction
23
David A. Gorelick
Contents
23.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 382
23.2 Treatment Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383
23.2.1 Psychosocial Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383
23.2.2 Pharmacological Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386
23.2.3 Special Treatment Situations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393
23.2.4 International Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 396
23.2.5 Future Prospects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397
23.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 398
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399
Abstract
Cocaine use disorders represent a substantial clinical and public health burden in
many countries, yet there are no well-proven and broadly effective treatments
available, and no medication approved for this indication by any national
regulatory authority. Psychosocial treatments are the mainstay of care, guided
by the general principles of prompt engagement in treatment; minimum duration
of 3 months; strict monitoring of cocaine use with consistent consequences for
lapses; and engagement of the patient’s social network. Contingency manage-
ment (i.e., reinforcement for abstinence [cocaine-free urine samples] with
vouchers or prizes) and cognitive behavior therapy (CBT) have the strongest
evidence for efficacy in controlled clinical trials, often doubling the abstinence
rate over standard drug counseling. Other interventions with mixed evidence
include community reinforcement, motivational enhancement or interviewing,
and participation in Cocaine Anonymous. Medications with efficacy in more
D.A. Gorelick
Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
e-mail: [email protected]
than one controlled clinical trial include disulfiram, oral stimulants in sustained-
release formulation, and the anticonvulsant tiagabine. New treatments currently
undergoing clinical study include anti-cocaine vaccines and repetitive
transcranial magnetic stimulation (rTMS).
23.1 Introduction
Cocaine is a plant alkaloid found in leaves of the coca bush, Erythroxylon coca,
which grows in the Andes Mountains region of South America. Its psychoactive
properties make cocaine one of the most widely used and abused illicit drugs in the
world. There were an estimated 17 million cocaine users worldwide in 2011,
representing 0.4 % of the 15- to 64-year-old population (United Nations Office on
Drugs and Crime 2013). About one-quarter (27 %) were in North America
(4.6 million users, 1.5 % prevalence). While use in North America declined by
about one-third over the past 5 years, it is increasing in West and Central Europe
(4.0 million, 1.2 %); South America (3.3 million users, 1.3 %); Central America and
the Caribbean (0.36 million users, 0.7 %); West, Central, and Southern Africa (2.2
million users, 0.7 %); and Oceania (0.37 million users, 1.5 %). Cocaine use remains
relatively low in East and Southeast Europe (0.56 million, 0.2 %), North and
Eastern Africa (0.03 million, 0.02 %), and Asia (1.3 million, 0.05 %).
Cocaine use is associated with a variety of psychological and physical health
problems, resulting in a substantial clinical and public health burden in countries
where use is prevalent. About one in six (16 %) cocaine users (via the intravenous
or smoked routes of administration) develop addiction (psychological dependence)
to the drug, with subsequent psychological (e.g., depression, psychosis) and socio-
economic problems (Degenhardt and Hall 2012; Gorelick and Baumann 2014).
Physical health problems associated with cocaine use include infectious diseases
such as HIV and viral hepatitis (especially with injection use), trauma, cardiovas-
cular disease, and stroke (Degenhardt et al. 2011; Degenhardt and Hall 2012;
Gorelick and Baumann 2014). In 2010, cocaine use disorders were associated
globally with an estimated 1.09 million years lived with disability (rate of 16 per
100,000 persons) (Vos et al. 2012), 1.1 million disability-adjusted life years (16 per
100,000 persons) (Murray et al. 2012), and 500 deaths (<0.05 per 100,000 persons)
(Lozano et al. 2012). Data from longitudinal studies in five different countries
(Brazil, Canada, Denmark, France, Italy) suggest that addicted cocaine users have
death rates four- to eightfold higher than those of the same age and sex in the
general population (Degenhardt et al. 2011), with even higher death rates in the
presence of psychiatric comorbidity (Arendt et al. 2011).
Notwithstanding this substantial health burden, there are no widely used, broadly
effective treatments for cocaine addiction. No medication is approved for this
indication by any national regulatory authority because no medication has met
the scientifically rigorous standard of consistent, statistically significant efficacy in
adequately powered, replicated, controlled clinical trials. There are little or no
23 Treatment of Cocaine Addiction 383
treatment), nonjudgmental empathy with the patient (Darker et al. 2012), clear and
realistic orientation to treatment goals and behavioral expectations, strict monitor-
ing of cocaine (and other psychoactive substance) use (e.g., frequent urine drug
testing) with prompt feedback to the patient and consistent consequences for
cocaine use, involvement of the patient’s social network (to the extent possible),
and attention to any concurrent medical, psychiatric, vocational, legal, or social
problems (Friedmann et al. 2004). Involvement with peer self-help groups such as
Cocaine Anonymous (modeled after Alcoholics Anonymous) is also associated
with improved treatment outcome (Weiss et al. 2005).
use, whether emotional states (e.g., depression, anxiety, stress), cognitive states
(e.g., low self-efficacy), exposure to drug-associated cues, or acute withdrawal, is
sometimes termed relapse prevention or coping skills training (Hendershot
et al. 2011). A lapse (initial drug reuse) is not considered a treatment failure, but
an opportunity to implement the skills learned to prevent a lapse from becoming
a relapse.
CBT is more effective than drug counseling or psychotherapy in most, but not
all, comparative studies (Knapp et al. 2011; Penberthy et al. 2010). Focused relapse
prevention was no more effective than standard drug counseling in two of three
early controlled trials involving a total of 205 patients – the overall meta-analytic
effect size was 0.03 (95 % CI 0.17 to 0.11) (Irvin et al. 1999). The addition of
CBT to CM does not generally enhance the efficacy of the latter.
Cocaine’s positively reinforcing effects derive from its blockade of the dopa-
mine reuptake pump, causing presynaptically released dopamine to remain in the
synapse and enhancing dopaminergic neurotransmission (Howell and Kimmel
2008). Cocaine’s local anesthetic effects are believed to contribute to cocaine-
induced kindling, the phenomenon by which previous exposure to cocaine sensi-
tizes the individual so that later exposure to low doses produces an enhanced
response.
23.2.2.1 Antidepressants
Tricyclic and other heterocyclic antidepressants are the most studied class of
medications for cocaine dependence treatment. Their efficacy is presumed based
on both their pharmacological mechanism of increasing biogenic amine neurotrans-
mitter activity in synapses and their amelioration of the depressive symptoms
frequently observed among cocaine-dependent individuals seeking treatment (see
below for treatment of patients with comorbid depression).
Desipramine is the first and best studied medication for cocaine addiction
treatment and is typically dosed at 150–300 mg/day (about 2.5 mg/kg), similar to
doses used to treat depression. Meta-analysis suggests no significant efficacy
compared with placebo, but with substantial heterogeneity across studies
(Pani et al. 2011). Differences in patient characteristics, concomitant treatment,
and desipramine plasma concentrations may account for some of the variability in
desipramine efficacy. Patients dually dependent on cocaine and opiates may do
better on desipramine if their opioid dependence is treated with buprenorphine
rather than methadone (Kosten et al. 2005) or if they receive contingency manage-
ment treatment along with medication (Kosten et al. 2003). There is limited
evidence that patients with steady-state desipramine plasma concentrations above
200 ng/mL have poorer outcomes (Khalsa et al. 1993), with better outcomes at
concentrations around 125 ng/mL (Kosten et al. 2003).
Experience with other heterocyclic antidepressants provides only limited evi-
dence for efficacy (Pani et al. 2011). Reboxetine and maprotiline, which inhibit
norepinephrine reuptake, and mirtazapine, which increases brain serotonin and
norepinephrine activity by blocking the autoregulatory a2-adrenergic and 5-HT2
receptors, were effective in small open-label trials. Heterocyclic antidepressants not
showing efficacy include atomoxetine, which inhibits norepinephrine reuptake;
imipramine, the precursor of desipramine; and nefazodone and venlafaxine,
which block both serotonin and norepinephrine reuptake.
Heterocyclic antidepressants have not been associated with unexpected or med-
ically serious side effects. While theoretically possible, there is no evidence that
patients who relapse to cocaine use while still on medication are at increased risk of
cardiovascular side effects (Nelson et al. 1996).
Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, paroxetine,
and sertraline, have not been effective in controlled clinical trials, with one excep-
tion (Pani et al. 2011; Winstanley et al. 2011). One clinical trial found citalopram
(20 mg/day) significantly better than placebo (Moeller et al. 2007). That study,
unlike previous studies, used contingency management in addition to cognitive
388 D.A. Gorelick
23.2.2.3 Disulfiram
Disulfiram increases dopamine concentrations by blocking the conversion of dopa-
mine to norepinephrine by the enzyme dopamine-b-hydroxylase, so it can be
considered a functional dopamine agonist (Gaval-Cruz and Weinshenker 2009).
Five small controlled clinical trials in cocaine-dependent patients without alcohol
dependence (but with concurrent opioid dependence treated with methadone or
buprenorphine in four studies) found disulfiram (250 mg/day) significantly better
than placebo in promoting cocaine abstinence (Kosten et al. 2013; Pani et al. 2010).
However, two recent, larger controlled clinical trials (both in methadone-
maintained patients) found no efficacy for disulfiram (Carroll et al. 2012; Oliveto
et al. 2011). Some of the heterogeneity in treatment response may be due to genetic
factors. One of the recent positive clinical trials found no significant efficacy for
disulfiram in the subgroup of patients with the dopamine-b-hydroxylase gene allele
that results in low enzyme activity (Kosten et al. 2013). Two other recent small
controlled clinical trials in methadone-maintained patients that found no disulfiram
efficacy overall did find significant efficacy in subgroups with functional variants
in the ankyrin repeat and kinase domain containing 1 (ANKK1) and dopamine
D2 receptor (DRD2) genes (Spellicy et al. 2013) and a1A-adrenoreceptor
(ADRA1A) gene (Shorter et al. 2013b).
23 Treatment of Cocaine Addiction 389
Although disulfiram is well tolerated in clinical trials, where subjects are care-
fully screened for medical and psychiatric comorbidity and closely monitored for
adverse events, questions have been raised about its safety in routine clinical
practice (Malcolm et al. 2008). Several human laboratory studies give conflicting
results on the safety of the cocaine-disulfiram interaction (Baker et al. 2007),
although recent studies found no clinically significant adverse effects from the
triple interactions of cocaine-alcohol-disulfiram (Roache et al. 2011) or cocaine-
methadone-disulfiram (Atkinson et al. 2013). These findings suggest that disulfiram
may be a promising treatment for cocaine dependence in some subgroups of
patients, although raising a caution about potential adverse drug interactions should
patients use cocaine while on the medication.
23.2.2.4 Stimulants
Agonist maintenance treatment of cocaine-dependent patients with stimulant med-
ication might be clinically beneficial in reducing cocaine craving and use (Shearer
2008), by analogy with methadone maintenance treatment of opioid dependence or
nicotine replacement treatment of tobacco dependence. As with methadone, advan-
tages might include use of the less medically risky oral route of administration
(vs. injected or smoked cocaine), use of pure medication of known potency (thus
avoiding adulterant effects or inadvertent overdose), and use of a medication with
slower onset and longer duration of action (thus avoiding “rush”/“crash” cycling)
(Lile 2006).
Several orally active psychomotor stimulants marketed for the treatment of
attention deficit hyperactivity disorder (ADHD) or as appetite suppressants have
been used to test the substitution approach (Amato et al. 2011; Mariani and Levin
2012). Sustained-release d-amphetamine (30–60 mg daily) was effective in two
small controlled clinical trials, while immediate-release d-amphetamine (20–60 mg
daily) and methylphenidate (90 mg daily) were not. A controlled clinical trial of the
combination of sustained-release d-amphetamine with modafinil found poorer
efficacy than with amphetamine alone or placebo (Schmitz et al. 2012). Mazindol,
a stimulant approved for appetite suppression with less abuse potential than
amphetamines (classified as Schedule IV controlled substance), was ineffective in
three controlled clinical trials. None of these studies reported significant adverse
effects, suggesting that stimulant substitution treatment might be safe in cocaine-
using patients.
Modafinil, used for the treatment of excessive sleepiness in narcolepsy, obstruc-
tive sleep apnea, and shift work sleep disorder, is considered a weak stimulant
(Schedule IV). Its mechanisms of action are unclear but include some blockade of
presynaptic dopamine transporters as well as increases in brain glutamate release
and decreases in GABA release (Ballon and Feifel 2006). A small phase II clinical
trial found that 400 mg daily significantly reduced cocaine use (Mariani and Levin
2012). A later multisite clinical trial found no significant reduction in cocaine use in
the study sample as a whole. However, in the subgroup of subjects without alcohol
dependence, both 200 mg and 400 mg daily of modafinil significantly increased the
percentage of abstinent days. Modafinil was safe and well tolerated. It does not
390 D.A. Gorelick
23.2.2.5 Antipsychotics
The older (the so-called first-generation) antipsychotics, which are potent dopamine
receptor antagonists (chiefly D2 [postsynaptic] subtype), do not significantly alter
cocaine craving or use, as evidenced by clinical experience with patients with
schizophrenia who abuse cocaine while receiving chronic antipsychotic treatment
(Brady et al. 1990; Ohuoha et al. 1997). Greater efficacy was expected from the
newer “second-generation” antipsychotics, in part because of their broader spec-
trum of receptor binding (including dopamine D1 and serotonin receptors). How-
ever, this promise has not been confirmed in clinical trials of cocaine users without
comorbid psychiatric disorders (Amato et al. 2007). A small open-label trial of
olanzapine in 21 patients dually dependent on cocaine and opioids (being treated
with methadone) reported a decrease in cocaine use in 53.2 % of patients. However,
three more recent controlled clinical trials reported no significant advantage for
olanzapine over placebo (Amato et al. 2007; Hamilton et al. 2009). Two controlled
clinical trials using oral risperidone and one using long-acting injectable risperi-
done (Loebl et al. 2008) also found no advantage over placebo.
Any antipsychotic should be prescribed with caution to cocaine users because of
their potential vulnerability to the neuroleptic malignant syndrome, based on their
presumed cocaine-induced dopamine depletion (Akpaffiong and Ruiz 1991).
Cocaine users may also be at elevated risk of antipsychotic-induced movement
disorders (Duggal 2007; Henderson et al. 2007).
23.2.2.6 Anticonvulsants
Anticonvulsants might be effective in the treatment of cocaine dependence because
they increase inhibitory GABA activity and/or decrease excitatory glutamate activ-
ity in the brain, both actions that decrease the response to cocaine in the dopami-
nergic cortico-mesolimbic brain reward circuit (Brown et al. 2013).
23 Treatment of Cocaine Addiction 391
specific points on the body surface. The mechanism of action is unknown; specu-
lation has included stimulation of endogenous opioid systems. Acupuncture of the
outer ear (auricular) gained popularity as a treatment for drug withdrawal, espe-
cially using five standard locations recommended by the National Acupuncture
Detoxification Association (NADA): kidney, liver, lung, shen men, and
sympathetic. Meta-analyses of nine published studies (six using the NADA loca-
tions) did not find a significant benefit of active acupuncture over sham treatment
(Gates et al. 2006; Mills et al. 2005).
patients (Brown et al. 2012) and are more effective than lithium. Combining lithium
with an anticonvulsant may be helpful in treatment-resistant patients.
The second-generation antipsychotics show mixed results in cocaine-dependent
patients with comorbid bipolar disorder (Nejtek et al. 2008). Quetiapine reduced
cocaine use in one of two clinical trials; risperidone reduced cocaine use in one trial.
Switching treated patients to aripiprazole did not reduce their cocaine use.
Up to one-fourth of cocaine-dependent adults have either adult ADHD or
a history of childhood ADHD (Kollins 2008). Stimulant and dopaminergic medi-
cations are the mainstay of treatment for ADHD, suggesting that some of these
patients may be self-medicating their ADHD with cocaine. Case series and clinical
trials generally find that such medications successfully treat ADHD symptoms and
reduce cocaine use in adults: dextroamphetamine (up to 60 mg/day), methamphet-
amine (15 mg/day), bupropion (up to 100 mg three times a day), and sustained-
release methylphenidate (Gorelick 2014).
Although schizophrenia is not a common comorbid psychiatric disorder among
cocaine-dependent individuals, cocaine use and abuse are common among
treatment-seeking patients with schizophrenia (San et al. 2007). Clinical experience
indicates that first-generation antipsychotics, at doses that are effective in the
treatment of schizophrenia, do not significantly alter cocaine craving or use.
Several case series and open-label trials suggest that the second-generation
antipsychotics, including clozapine, olanzapine, quetiapine, risperidone, and
aripiprazole, may be more effective than older (first-generation) antipsychotics in
reducing cocaine and other drug use among patients with schizophrenia (San
et al. 2007). However, two head-to-head controlled clinical trials found no differ-
ence between olanzapine and haloperidol in reducing cocaine use, with each
medication reducing cocaine craving in one of the trials. A controlled clinical
trial comparing olanzapine and risperidone found a trend favoring greater reduction
in cocaine use by olanzapine.
The use of cocaine can exacerbate or provoke antipsychotic-induced movement
disorders (Duggal 2007; Henderson et al. 2007) and increase vulnerability to the
neuroleptic malignant syndrome (Akpaffiong and Ruiz 1991).
23.2.3.5 Age
Although adolescents make up a substantial minority of heavy cocaine users, they
have been largely excluded from clinical trials of cocaine pharmacotherapies
because of legal and informed consent considerations. On the basis of the scarcity
of published case reports, it is likely that medication is not often used in the
treatment of adolescent cocaine dependence.
intense the psychological effect and the greater the abuse liability (Nelson
et al. 2006). This is the so-called rate hypothesis of psychoactive drug effect. As
expected from this rate effect, routes of administration that produce rapid onset,
such as intravenous and smoked, are associated with greater abuse liability than
those with slower onset, such as intranasal and oral (Chen and Anthony 2004;
Gorelick 1992b). Thus, the Andean countries in which oral cocaine ingestion is
legal and common (e.g., by chewing the leaves, drinking coca tea) tend to have less
cocaine addiction than might be expected from their prevalence of cocaine use
(Montoya and Chilcoat 1996).
The treatment of cocaine addiction is generally comparable worldwide, with the
exception of the Andean countries. The legal availability of oral forms of cocaine in
those countries makes possible the agonist substitution approach using cocaine
itself (Hurtado-Gumucio 2000; Llosa 2009). However, such treatment has never
been evaluated in controlled clinical trials.
23.3 Conclusion
The absence of any medication that meets national regulatory standards for efficacy
and safety leaves physicians with little clear-cut guidance for pharmacological
treatment of stimulant dependence. Among existing medications marketed for
other indications, none has yet been proved broadly effective in replicated con-
trolled clinical trials. Disulfiram appears the most promising, especially for patients
with comorbid alcohol abuse. Tricyclic antidepressants such as desipramine and
imipramine (but not SSRIs such as fluoxetine) may be of use in patients with milder
dependence or with comorbid depression. Anticonvulsants such as topiramate,
tiagabine, and phenytoin (but not carbamazepine or gabapentin) show promise in
controlled clinical trials and warrant further evaluation. The stimulant maintenance
approach also warrants further evaluation using medications with low abuse poten-
tial (e.g., modafinil or sustained-release methylphenidate or amphetamine) or
perhaps even a slow-onset (e.g., oral or transdermal) form of cocaine itself.
More sophisticated patient-treatment matching could enhance the efficacy of
current medications by taking into account both patient characteristics that can
influence treatment response (e.g., severity of dependence, withdrawal status,
psychiatric comorbidity, or concomitant medications) and characteristics of the
psychosocial treatment accompanying the medication. For example, a few studies
suggest that some medications (e.g., L-DOPA, SSRIs) that are not effective when
used with drug abuse counseling or cognitive behavioral therapy may be effective
when combined with contingency management treatment (Moeller et al. 2007;
Schmitz et al. 2008).
23 Treatment of Cocaine Addiction 399
Acknowledgment Dr. Gorelick was supported by the Intramural Research Program, US National
Institutes of Health, National Institute on Drug Abuse. He has no conflicts of interest to report.
References
Akpaffiong MJ, Ruiz P (1991) Neuroleptic malignant syndrome: a complication of neuroleptics
and cocaine abuse. Psychiatr Q 62:299–309
Alessi SM, Rash C, Petry NM (2011) Contingency management is efficacious and improves
outcomes in cocaine patients with pretreatment marijuana use. Drug Alcohol Depend
118:62–67
Amato L, Minozzi S, Pani PP, Davoli M (2007) Antipsychotic medications for cocaine depen-
dence. Cochrane Database Syst Rev CD006306
Amato L, Minozzi S, Pani PP et al (2011) Dopamine agonists for the treatment of cocaine
dependence. Cochrane Database Syst Rev CD003352
Arendt M, Munk-Jørgensen P, Sher L, Jensen SOW (2011) Mortality among individuals with
cannabis, cocaine, amphetamine, MDMA, and opioid use disorders: a nationwide follow-up
study of Danish substance users in treatment. Drug Alcohol Depend 114:134–139
Atkinson TS, Sanders N, Mancino M, Oliveto A (2013) Effects of disulfiram on QTc interval in
non-opioid-dependent and methadone-treated cocaine-dependent patients. J Addict Med 7:243–248
Baker J, Jatlow P, Pade P, Ramakrishnan V, McCance-Katz EF (2007) Acute cocaine responses
following cocaethylene infusion. Am J Drug Alcohol Abuse 33:619–625
Ballon JS, Feifel D (2006) A systematic review of modafinil: potential clinical uses and mecha-
nisms of action. J Clin Psychiatry 67:554–566
Bellamoli E, Manganotti P, Schwartz RP et al (2013) rTMS in the treatment of drug addiction: an
update about human studies. Behav Neurol (in press)
Brady K, Anton R, Ballenger JC et al (1990) Cocaine abuse among schizophrenic patients. Am
J Psychiatry 147:1164–1167
Brown ES, Sunderajan P, Lu LT et al (2012) A randomized, double-blind, placebo-controlled trial
of lamotrigine therapy in bipolar disorder, depressed or mixed phase and cocaine dependence.
Neuropsychopharmacology 37:2347–2354
Brown RM, Kupchik YM, Kalivas PW (2013) The story of glutamate in drug addiction and of
N-acetylcysteine as a potential pharmacotherapy. JAMA Psychiatry 9:895–897
Carrieri MP, Vlahov D, Dellamonica P et al (2000) Use of buprenorphine in HIV-infected
injection drug users: negligible impact on virologic response to HAART. The Manif-2000
Study Group. Drug Alcohol Depend 60:51–54
Carroll KM, Rounsaville BJ (2007) A perfect platform: combining contingency management with
medications for drug abuse. Am J Drug Alcohol Abuse 33:343–365
400 D.A. Gorelick
Carroll KM, Kosten TR, Rounsaville BJ (2004) Choosing a behavioral therapy platform for
pharmacotherapy of substance users. Drug Alcohol Depend 75:123–134
Carroll KM, Nich C, Shi JM et al (2012) Efficacy of disulfiram and twelve step facilitation in
cocaine-dependent individuals maintained on methadone: a randomized placebo-controlled
trial. Drug Alcohol Depend 126:224–231
Chadwick MJ, Gregory DL (1990) A double-blind amino acids, L-tryptophan and L-tyrosine, and
placebo study with cocaine-dependent subjects in an inpatient chemical dependency treatment
center. Am J Drug Alcohol Abuse 16:275–286
Chen C-Y, Anthony JC (2004) Epidemiological estimates of risk n the process of becoming
dependent upon cocaine: cocaine hydrochloride powder versus crack cocaine. Psychopharma-
cology 172:78–86
Compton WM, Conway KP, Stinson FS, Colliver JD, Grant BF (2005) Prevalence, correlates, and
comorbidity of DSM-IV antisocial personality syndromes and alcohol and specific drug use
disorders in the United States: results from the National Epidemiologic Survey on Alcohol and
Related Conditions. J Clin Psychiatry 66:677–685
Conway KP, Compton W, Stinson FS, Grant BF (2006) Lifetime comorbidity of DSM-IV mood
and anxiety disorders and specific drug use disorders: results from the National Epidemiologic
Survey on Alcohol and Related Conditions. J Clin Psychiatry 67:247–257
Coviello DM, Alterman AI, Rutherford MJ et al (2001) The effectiveness of two intensities of
psychosocial treatment for cocaine dependence. Drug Alcohol Depend 61:145–154
Crits-Christoph P, Siqueland L, Blaine J et al (1999) Psychosocial treatments for cocaine depen-
dence National Institute on Drug Abuse collaborative cocaine treatment study. Arch Gen
Psychiatry 56:493–502
Dackis CA, Gold MS (1985) Pharmacological approaches to cocaine addiction. J Subst Abus Treat
2:139–145
Darker C, Sweeney B, El Hassan H et al (2012) Non-attendance at counseling therapy in cocaine-
using methadone-maintained patients: lessons learnt from an abandoned randomized con-
trolled trial. Ir J Med Sci 181:483–489
Degenhardt L, Hall WD (2012) Extent of illicit drug use and dependence, and their contribution to
the global burden of disease. Lancet 379:55–70
Degenhardt L, Singleton J, Calabria B, McLaren J, Kerr T, Mehta S, Kirk G, Hall WD (2011) Mor-
tality among cocaine users: a systematic review of cohort studies. Drug Alcohol Depend
113:88–95
Donovan JL, DeVane CL, Malcolm RJ et al (2005) Modafinil influences the pharmacokinetics
of intravenous cocaine in healthy cocaine-dependent volunteers. Clin Pharmacokinet
44:753–765
Duggal HS (2007) Cocaine use as a risk factor for ziprasidone-induced acute dystonia. Gen Hosp
Psychiatry 29:278–279
Dutra L, Stathopoulou G, Basden SL et al (2008) A meta-analytic review of psychosocial
interventions for substance use disorders. Am J Psychiatry 165:179–187
Friedmann PD, Hendrickson JC, Gerstein DR, Zhang Z (2004) The effect of matching compre-
hensive services to patients’ needs on drug use improvement in addiction treatment. Addict
99:962–972
Gates S, Smith LA, Foxcroft DR (2006) Auricular acupuncture for cocaine dependence. Cochrane
Database Syst Rev CD005192
Gaval-Cruz M, Weinshenker D (2009) Mechanisms of disulfiram-induced cocaine abstinence:
antabuse and cocaine relapse. Mol Interv 9:175–187
Gorelick DA (1992a) Alcohol and cocaine: clinical and pharmacological interactions. Recent Dev
Alcohol 11:37–56
Gorelick DA (1992b) Progression of dependence in male cocaine addicts. Am J Drug Alcohol
Abuse 18:13–19
Gorelick DA (1998) The rate hypothesis and agonist substitution approaches to cocaine abuse
treatment. Adv Pharmacol 42:995–997
23 Treatment of Cocaine Addiction 401
Nunes EV, Levin FR (2004) Treatment of depression in patients with alcohol or other drug
dependence: a meta-analysis. JAMA 291:1887–1896
Ohuoha DC, Maxwell JA, Thomson LE 3rd et al (1997) Effect of dopamine receptor antagonists
on cocaine subjective effects: a naturalistic case study. J Subst Abus Treat 14:249–258
Oliveto A, Poling J, Mancino MJ et al (2011) Randomized, double blind, placebo-controlled trials
of disulfiram for the treatment of cocaine dependence in methadone-stabilized patients. Drug
Alcohol Depend 113:184–191
Olmstead TA, Petry NM (2009) The cost-effectiveness of prize-based and voucher-based contin-
gency management in a population of cocaine- or opioid-dependent outpatients. Drug Alcohol
Depend 102:108–115
Pani PP, Trogu E, Vacca R et al. (2010) Disulfiram for the treatment of cocaine dependence.
Cochrane Database Syst Rev CD007024
Pani PP, Trogu E, Vecchi S, Amato L (2011) Antidepressants for cocaine dependence and
problematic cocaine use. Cochrane Database Syst Rev CD002950
Parolaro D, Rubino T (2008) The role of the endogenous cannabinoid system in drug addiction.
Drug News Perspect 21:149–157
Peles E, Kreek MJ, Kellogg S, Adelson M (2006) High methadone dose significantly reduces
cocaine use in methadone maintenance treatment (MMT) patients. J Addict Dis 25:43–50
Penberthy JK, Ait-Daoud N, Vaughan M, Fanning T (2010) Review of treatment for cocaine
dependence. Curr Drug Abus Rev 3:49–62
Pennings EJ, Leccese AP, Wolff FA (2002) Effects of concurrent use of alcohol and cocaine.
Addiction 97:773–783
Petry NM, Alessi SM, Ledgerwood DM (2012) A randomized trial of contingency management
delivered by community therapists. J Consult Clin Psychol 80:286–298
Petry NM, Alessi SM, Rash CJ (2013) A randomized study of contingency management in
cocaine-dependent patients with severe and persistent mental health disorders. Drug Alcohol
Depend 130:234–237
Pettinati HM, Kampman KM, Lynch KG et al (2008a) A double blind, placebo-controlled trial that
combines disulfiram and naltrexone for treating co-occurring cocaine and alcohol dependence.
Addict Behav 33:651–667
Pettinati HM, Kampman KM, Lynch KG et al (2008b) Gender differences with high-dose
naltrexone in patients with co-occurring cocaine and alcohol dependence. J Subst Abus Treat
34:378–390
Plebani JG, Lynch KG, Yu Q et al (2012) Results of an initial clinical trial of varenicline for the
treatment of cocaine dependence. Drug Alcohol Depend 121:163–166
Prendergast M, Podus D, Finney J, Geenwell L, Roll J (2006) Contingency management for
treatment of substance use disorders: a meta-analysis. Addiction 101:1546–1560
Roache JD, Kahn R, Newton TF et al (2011) A double-blind, placebo-controlled assessment of the
safety of potential interactions between intravenous cocaine, ethanol, and oral disulfiram. Drug
Alcohol Depend 119:37–45
Rothman RB, Blough BE, Baumann MH (2007) Dual dopamine/serotonin releasers as potential
medications for stimulant and alcohol addictions. AAPS J 9:E1–E10
Rothman RB, Baumann MH, Prisinzano TE, Newman AH (2008) Dopamine transport inhibitors
based on GBR12909 and benztropine as potential medications to treat cocaine addiction.
Biochem Pharmacol 75:2–16
Rounsaville BJ (2004) Treatment of cocaine dependence and depression. Biol Psychiatry 56:803–809
San L, Arranz B, Martinez-Raga J (2007) Antipsychotic drug treatment of schizophrenic patients
with substance abuse disorders. Eur Addict Res 13:230–243
Schaub M, Sullivan R, Stark L (2011) Snow control – an RCT protocol for web-based self-help
therapy to reduce cocaine consumption in problematic cocaine users. BMC Psychiatry 11:153
Schierenberg A, van Amsterdam J, van den Brink W, Goudriaan AE (2012) Efficacy of contin-
gency management for cocaine dependence treatment: a review of the evidence. Curr Drug
Abus Rev 5:320–331
404 D.A. Gorelick
Schmitz JM, Stotts AL, Rhoades HM et al (2001) Naltrexone and relapse prevention treatment for
cocaine-dependent patients. Addict Behav 26:167–180
Schmitz JM, Mooney ME, Moeller FG et al (2008) Levodopa pharmacotherapy for cocaine
dependence: choosing the optimal behavioral therapy platform. Drug Alcohol Depend
94:142–150
Schmitz JM, Rathnayaka N, Green CE et al (2012) Combination of modafinil and d-amphetamine
for the treatment of cocaine dependence: a preliminary investigation. Front Psychiatry 3:77
Schneider R, Mittelmeier C, Gadish D (1996) Day versus inpatient treatment for cocaine depen-
dence: an experimental comparison. J Mental Health Adm 23:234–245
Secades-Villa R, Garcia-Fernandez G, Pena-Suarez E et al (2013) Contingency management is
effective across cocaine-dependent outpatients with different socioeconomic status. J Subst
Abus Treat 44:349–354
Shearer J (2008) The principles of agonist pharmacotherapy for psychostimulant dependence.
Drug Alcohol Rev 27:301–308
Shoptaw S, Yang X, Rotheram-Fuller EJ et al (2003) Randomized placebo-controlled trial of
baclofen for cocaine dependence: preliminary effects for individuals with chronic patterns of
cocaine use. J Clin Psychiatry 64:1440–1448
Shorter D, Lindsay JA, Kosten TR (2013a) The alpha-1 adrenergic antagonist doxazosin for
treatment of cocaine dependence: a pilot study. Drug Alcohol Depend 131:66–70
Shorter D, Nielsen DA, Huang W et al (2013b) Pharmacogenetic randomized trial for cocaine
abuse: disulfiram and a1A-adrenoreceptor gene variation. Eur Neuropsychopharmacol
23:1401–1407
Simpson DD, Joe GW, Broome KM (2002) A national 5-year follow-up of treatment outcomes for
cocaine dependence. Arch Gen Psychiatry 59:538–544
Somoza EC, Winship D, Gorodetsky CW et al (2013) A multi-site, double-blind, placebo-
controlled clinical trial to evaluate the safety and efficacy of vigabatrin for treating cocaine
dependence. JAMA Psychiatry 70:630–637
Specio SE, Wee S, O’Dell LE et al (2008) CRF(1) receptor antagonists attenuate escalated cocaine
self-administration in rats. Psychopharmacology (Berl) 196:473–482
Spellicy CJ, Kosten TR, Hamon SC et al (2013) ANKK1 and DRD2 pharmacogenetics of
disulfiram treatment for cocaine abuse. Pharmacogenet Genomics 23:333–340
United Nations Office on Drugs and Crime (2013) World drug report 2013. United Nations
publication E.13.XI.6. United Nations Office on Drugs and Crime, Vienna
Vos T, Flaxman AD, Naghavi M et al (2012) Years lived with disability (YLDs) for 1160 sequelae
of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease
Study 2010. Lancet 380:2163–2196
Walsh SL, Haberny KA, Bigelow GE (2000) Modulation of intravenous cocaine effects by chronic
oral cocaine in humans. Psychopharmacology 150:361–373
Weiss L, Petry NM (2013) Older methadone patients achieve greater durations of cocaine
abstinence with contingency management than younger. Am J Addict 22:119–126
Weiss RD, Griffin ML, Gallop RJ et al (2005) The effect of 12-step self-help group attendance and
participation on drug use outcomes among cocaine-dependent patients. Drug Alcohol Depend
77:177–184
Winstanley EL et al (2011) A randomized controlled trial of fluoxetine in the treatment of cocaine
dependence among methadone-maintained patients. J Subst Abus Treat 40:255–264
Wiskerke J, Pattij T, Schoffelmeer ANM, De Vries TJ (2008) The role of CB1 receptors in
psychostimulant addiction. Addict Biol 13:225–238
Zhang Z, Friedmann PD, Gerstein DR (2003) Does retention matter? Treatment duration and
improvement in drug use. Addiction 98:673–684
Addiction to Amphetamines and
Methamphetamines 24
Ahmed Elkashef
Contents
24.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 406
24.2 ATS-Health-Related Problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 406
24.3 Treatment of ATS Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 407
24.3.1 Pharmacological Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408
24.3.2 Other Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409
24.4 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 412
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 412
Abstract
ATS addiction ranks second globally and contributes greatly to the total burden
of the disease of addiction. ATS addiction is associated with multiple health
problems like HIV and psychiatric diseases like psychosis. Early intervention
and treatment provided in an integrated setting promise better outcomes. Data
from controlled clinical trials show efficacy for cognitive behavioral therapy
(Matrix), motivational enhancement, and contingency management. Agonist
medications like d-amphetamine and methylphenidate may have a role in
treating ATS withdrawal symptoms and craving, particularly in patients with
comorbid ADHD/ADD. Other medications that may be helpful are bupropion
and modafinil for low to moderate users. Naltrexone and topiramate are also
promising especially for ATS addicts that are also addicted to other substances
like nicotine, alcohol, or opiates. Combination of psychotherapy particularly
contingency management and pharmacological treatment may offer synergistic
effects and have better outcome. The future is promising for better treatments
including monoclonal antibodies ad vaccines for the treatment ATS addiction.
A. Elkashef
Research and Clinical Studies Section, National Rehabilitation Center, Abu Dhabi,
United Arab Emirates
e-mail: [email protected]
24.1 Introduction
Amphetamine and methamphetamine are approved in the USA and other countries
worldwide for the treatment of attention-deficit/hyperactivity disorder, narcolepsy,
and obesity. The weak isomer L-methamphetamine is used in the over-the-counter
Vick’s inhaler.
ATS are powerful stimulants, with short-term effects that include increased
alertness, energy, and loss of appetite. Cardiovascular effects include irregular
heartbeat, increased heart rate, and blood pressure. Hyperthermia, convulsions,
and stroke have also been reported with ATS overdose and can result in death if
not treated.
24 Addiction to Amphetamines and Methamphetamines 407
Long-term ATS abuse can lead to addiction and psychosis almost indistinguish-
able from schizophrenia. Other psychiatric symptoms include chronic anxiety,
confusion, insomnia, mood disturbances, and violent behavior. PET studies have
shown significant changes in striatal dopamine in chronic methamphetamine users
in the form of downregulation or degeneration; these changes were associated with
cognitive impairment.
Some of the effects of chronic methamphetamine abuse appear to be, at least
partially, reversible. A recent neuroimaging PET study (Volkow et al. 2001)
showed recovery in striatal dopamine transporter following prolonged abstinence
(2 years, but not 6 months). This was associated with improved performance on
motor and verbal memory tests. However, function in other brain regions did not
display recovery even after 2 years of abstinence, indicating that some
methamphetamine-induced changes are very long-lasting.
Withdrawal symptoms have been reported in patients attempting to stop or entering
treatment, include depression, anxiety, fatigue, and an increased craving for the drug.
Injection drug use and risky sexual behavior among methamphetamine users
have been associated with increase HIV and hepatitis B and C infections, especially
among men who have sex with men. Methamphetamine abuse may also worsen the
progression of HIV and its consequences, including greater neuronal injury and
cognitive impairment compared with nondrug abusers.
Prenatal exposure to methamphetamine can lead to premature delivery, placental
abruption, fetal growth retardation, and heart and brain abnormalities. Ongoing
research is continuing to study developmental outcomes such as cognition, social
relationships, motor skills, and medical status of children exposed to methamphet-
amine before birth. However the use of other substances or alcohol and maternal
poor nutrition and health make the interpretation of these results difficult.
Dextroamphetamine
Another dopaminergic stimulant approved for weight loss, narcolepsy, and ADHD
was tried in two double-blind studies in meth-dependent patients. The first trial used
110 mg of sustained release d-amphetamine daily for 12 weeks with gradual
reduction over an additional 4 weeks. Medications were administered daily under
supervision. The primary outcome was meth concentration in hair samples at
baseline compared to follow-up using hair analysis. Although there was no signif-
icant effect for the primary outcomes, there was significantly greater reduction in
meth withdrawal symptoms and craving compared to placebo (Longo et al. 2010).
Another double-blind study (Galloway et al. 2011) used 60 mg sustained release
d-amphetamine for 8 weeks showed no effect for the primary outcome of reducing
meth use as evidenced by negative urines. Similar to the first study, this study also
reported significant effect on reduction of craving and improving meth withdrawal
symptoms for the d-amphetamine group.
Bupropion
The safety of coadministering bupropion and methamphetamine was assessed in
a clinical pharmacology study with no evidence of cardiovascular adverse events or
PK interaction (Newton et al. 2005). Two double-blind controlled outpatient studies
investigated the effects of bupropion SR 150 mg BID in methamphetamine-
dependent patients (Elkashef et al. 2008; Shoptow et al. 2008). Significantly,
a positive effect in reducing meth use was reported in light users defined as use
of 18 days or less/month. The effect was not seen in heavy users defined as
>18 days of use in a month or more than two positive urines samples per week
on screening. Confirmatory studies are underway.
Modafinil
Modafinil is a weak stimulant approved for the treatment of narcolepsy and
obstructive sleep apnea. It is proposed to exert its action on the glutamate and
hypocretin system; however, recent PET study suggests that it may also bind to the
dopamine transporter. 200 mg of modafinil was tested in a double-blind trial for
10 weeks in 80 methamphetamine-dependent patients. The trial outcomes were
negative except for a trend of reducing meth use in those who were medication
24 Addiction to Amphetamines and Methamphetamines 409
compliant and attended counseling sessions (Shearer et al. 2009). In another single
blind study, modafinil combined with cognitive behavioral therapy (CBT) for
treatment of 13 HIV + gay men with methamphetamine dependence. Six of the
ten patients who completed the study reduced their methamphetamine use by over
50 % (McElhiney 2009). Another double blind trial of 400mg Modafinil for 12
weeks, in methamphetamine dependant patients (Henizerling et al. 2010) did not
show effect on methamphetamine use.
A more recent multisite trial (Anderson et al. 2011) of 210 meth-dependent
patients randomized to placebo, 200 mg or 400 mg of daily modafinil for 12 weeks
was conducted. The primary outcome was methamphetamine negative urines per
week; patients provided three urine samples weekly. The trial was negative;
however, a post hoc analysis showed a significant effect for maximum duration
of abstinence (23 days vs. 10 days) favoring modafinil among compliant patients.
This study highlights the very important issue of measuring compliance in addic-
tion clinical trials as poor compliance could explain some of the negative outcome.
open-label study of 30 for 9 weeks. 18/30 subjects completed the study, and 16/18
tested negative for methamphetamine and cocaine during the last 6 weeks of the trial
(Brodie et al. 2005). A safety clinical pharmacology interaction study was conducted
in non-treatment-seeking methamphetamine-dependent patients given 15 and 30 mg
i.v. doses of methamphetamine and doses of GVG up to 5 mg (De La Garza
et al. 2009). There were no reports of cardiovascular interactions and no effects of
GVG on methamphetamine subjective effects. No published reports currently exist of
follow-up outpatient trials of GVG for the treatment of methamphetamine addiction.
Antidepressants
Mirtazapine was tried in a double-blind controlled study in 60 meth-dependent
patients for 12 weeks with significant effect in reducing meth-positive urines
(Colfax et al. 2011). The SSRIs, fluoxetine, paroxetine, and sertraline were each
tried in double-blind controlled studies (Batki et al. 1999, 2000; Piasecki
et al. 2002; Rawson et al. 2004; Shoptaw et al. 2006) with no effect on meth use.
Ondansetron
A serotonin 5-HT3 receptor antagonist was postulated to reduce dopaminergic
release in the striatum. A double-blind multisite, randomized trial of three doses
of ondansetron (0.25, 1, or 4 mg twice daily) for 8 weeks combined with CBT failed
to show an effect over placebo at decreasing methamphetamine use (Johnson
et al. 2008).
Naltrexone
In a human lab study of abstinent meth-dependent patients, naltrexone 50 mg
significantly reduced the subjective effects of d-amphetamine (Jayaram-Lindstrom
et al. 2007).
In a double-blind placebo-controlled outpatient study of 80 patients with
amphetamine dependence, naltrexone 50 mg + relapse prevention therapy was
effective in reducing amphetamine use (Jayaram-Lindstrom et al. 2008). Naltrex-
one plus N-acetyl cysteine were tried in adouble blind placebo controlled trail of 31
patients with methamphetamine dependence for 8 weeks. The primary outcome
was reduction in craving (Grant et al. 2010). No effect was reported.
Rivastigmine
Acetylcholinesterase inhibitors have been shown in animal studies to reduce
methamphetamine-seeking behavior. Rivastigmine was tried in a 2-week double-blind,
24 Addiction to Amphetamines and Methamphetamines 411
24.4 Summary
• ATS addiction ranks second globally and contributes greatly to the total burden
of the disease of addiction.
• ATS addiction is associated with multiple health problems like HIV and psy-
chiatric diseases like psychosis.
• ATS addiction treatment like other addiction treatment should be started early
and should be comprehensive, integrated, and long term.
• Psychotherapeutic interventions like CM, MI, CBT, Matrix, RP, and 12 steps are
equally effective for the treatment of ATS addiction and should be utilized as
appropriate.
• Agonist medications like d-amphetamine and methylphenidate may have a role
in treating ATS withdrawal symptoms and craving, particularly in patients with
comorbid ADHD/ADD.
• Other medications that may be helpful are bupropion and modafinil for low to
moderate users.
• Naltrexone and topiramate are also promising especially for ATS addicts that are
also addicted to other substances like nicotine, alcohol, or opiates.
• There are many trials that are currently in progress for ATS addiction; it is highly
recommended that clinicians search the literature periodically for updates prior
to initiating medication treatment for their patients.
References
Anderson Al, Li SH et al (2011) Modafinil for the treatment of methamphetamine dependence.
Drug Alcohol Depend, 11 Aug 2011
Anglin MD et al (2000) History of the methamphetamine problem. J Psychoactive Drugs
32(2):137–141
Batki SL, Moon J et al (1999) Methamphetamine dependence. A controlled trial: a preliminary
analysis. CPDD 61st annual scientific meeting, Acapulco, 235
Batki SL, Moon J et al (2000) Methamphetamine quantitative urine concentrations during
a controlled trial of fluoxetine treatment. Preliminary analysis. Ann N Y Acad Sci 909:260–263
Batki SL, Moon J et al (2001) Amlodipine treatment of methamphetamine dependence,
a controlled outpatient trial: preliminary analysis. Drug Alcohol Depend 63(Suppl 1):12
Batki SL, Bui L et al (2002) Methamphetamine-amlodipine interactions: preliminary analysis
(abstract). Drug Alcohol Depend 66:S12
Brodie JD, Figueroa E et al (2005) Safety and efficacy of gamma-vinyl GABA (GVG) for the
treatment of methamphetamine and/or cocaine addiction. Synapse 55(2):122–125
Cho AK, Segal DS (1994) Amphetamine and its analogs: psychopharmacology, toxicology, and
abuse, 1st edn. Academic Press, San Diego
Coffin PO, Santos GM et al (2012) Aripiprazole for the treatment of methamphetamine depen-
dence: a randomized, double-blind, placebo-controlled trial. Addiction. doi:10.1111/
add.12073
Colfax GN, Santos GM et al (2011) Mirtazapine to reduce methamphetamine use: a randomized
clinical trial. Arch Gen Psychiatry 68(11):1168–1175
De La Garza R, Maohoney JJ et al (2008) The acetylcholinesterase inhibitor rivastigmine does not
alter total choices for methamphetamine, but may reduce positive subjective effects, in
24 Addiction to Amphetamines and Methamphetamines 413
Contents
25.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 416
25.2 The Pathobiology, Clinical Manifestations, and Treatment of Nicotine
Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 417
25.2.1 Biology of Nicotinic Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 417
25.2.2 Clinical Effects of Nicotine and Tobacco . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 417
25.2.3 Psychosocial Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 419
25.2.4 Pharmacological Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421
25.2.5 Integration of Tobacco Dependence Treatment into
Mental Health-Care Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 429
25.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 430
25.3.1 Key Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431
Abstract
Although rates of tobacco use and dependence have been reduced substan-
tially over the past 40 years, one in five Americans continues to smoke. The
prevalence of smoking appears to be substantially higher in persons with
K.M. Mackowick
Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
e-mail: [email protected]
T.P. George (*)
Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Toronto,
ON, Canada
Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
e-mail: [email protected]; [email protected]
25.1 Introduction
The majority of tobacco users (>90 %) smoke cigarettes. Most of these individuals
smoke daily and have some degree of physiological dependence (Rigotti 2002).
418 K.M. Mackowick and T.P. George
psychiatric and substance use disorders has been observed for both individual
(Lancaster and Stead 2006) and group (Stead and Lancaster 2005) counseling
formats. Additionally, work by Brody and colleagues (2013) has shown that
reduced smoking with CBT (without pharmacotherapies) can reduce nAChR
densities to normal receptor levels.
Nicotine Gum
Nicotine ingested orally is extensively metabolized on first pass through the liver.
Nicotine polacrilex gum avoids this problem via buccal absorption. Because of the
ad-lib nature of the nicotine gum, smokers are able to respond immediately to any
stressors or cues that may be present in their environment (Piper et al. 2007).
Nicotine gum was approved as an OTC medication in the USA in 1996 and contains
2 or 4 mg of nicotine that can be released from a resin by chewing. Nicotine gum
should be administered by scheduled dosing (e.g., one piece of 2-mg gum/h). The
original recommended duration of treatment was 3 months, though many experts
believe longer treatment is more effective. Nicotine absorption from the gum
peaks 30 min after beginning to use the gum. Venous nicotine levels from 2- and
4-mg gum are about one third and two third, respectively, of the steady-state
(i.e., between cigarettes) levels of nicotine achieved with cigarette smoking. Nicotine
via cigarettes is absorbed directly into the arterial circulation; thus, arterial levels
from smoking are five to ten times higher than those from the 2- and 4-mg gums.
Absorption of nicotine in the buccal mucosa is decreased by an acidic environment,
and patients should not use beverages (e.g., coffee, soda, juice) immediately before,
during, or after nicotine gum use.
Several placebo-controlled trials established the safety and efficacy of nicotine
gum for smoking cessation [reviewed in (Silagy et al. 2004)]. There appears to be
some evidence to support using higher doses of nicotine gum (4-mg pieces) in more
highly dependent cigarette smokers (25 cpd), which supports the idea of matching
nicotine gum dose to dependence level of the smoker (Stead et al. 2012).
Side effects from nicotine gum are rare and are mostly limited to those of
mechanical origin (e.g., difficulty chewing, sore jaw) or of local pharmacological
origin (e.g., burning in the mouth, throat irritation). Tolerance develops to most side
effects over the first week, and education about how to properly use the gum
(e.g., do not chew too vigorously) decreases side effects.
Starting doses are 21–22 mg/24-h patch and 15 mg/16-h patch. Patches are applied
daily each morning. Nicotine via patches is slowly absorbed so that on the first day
venous nicotine levels peak 6–10 h after administration. Thereafter, nicotine levels
remain fairly steady with a decline from peak to trough of 25–40 % with 24-h
patches. Nicotine levels obtained with the use of patches are typically half of those
obtained by smoking. After 4–6 weeks on high-dose patch (21 or 22 mg/24 h and
15 mg/16 h), smokers are tapered to a middle dose (e.g., 14 mg/24 h or 10 mg/16 h)
and then to the lowest dose after 2–4 more weeks (7 mg/24 h or 5 mg/16 h). Most
studies suggest that abrupt cessation of the use of patches often causes no significant
withdrawal; thus, tapering does not appear to be necessary (Silagy et al. 2004). The
recommended total duration of treatment is usually 6–12 weeks.
The overall efficacy of the nicotine transdermal patch (NTP) for smoking
cessation has been well documented (Silagy et al. 2004). A meta-analysis of
17 RCTs in 1994 (Fiore et al. 1994) reported end of treatment abstinence rates
for NTP of 27 % versus 13 % for placebo patch (OR 2.6) and 22 % versus 9 % at
6-month follow-up (OR 3.0). The effects of active NTP were independent of patch
type, treatment duration, tapering procedures, and behavioral therapy format or
intensity, though it should be noted that behavioral treatment enhanced outcomes
with patch compared to patch alone. Additionally, combining the patch with
nicotine lozenge has been shown to produce the greatest benefit for smoking
cessation relative to placebo (above that of lozenge alone, patch alone, bupropion
SR, and bupropion + nicotine lozenge relative to placebo) (Piper et al. 2009).
Significant adverse events with nicotine patches have not been found, with the
most common minor side effects being skin reactions (50 %), insomnia and
increased or vivid dreams (15 % with 24-h patches), and nausea (5–10 %). Toler-
ance to these side effects usually develops within a week of use. Rotation of patch
sites helps to decrease skin irritation. Insomnia reported in the first week post-
cessation appears to be mostly due to nicotine withdrawal rather than the nicotine
patch itself. A 24-h patch can be removed before bedtime to determine if the
insomnia is due to the nicotine patch. Without treatment, insomnia usually abates
after 4–7 days. There appears to be little dependence liability associated with patch
use as only 2 % of patch users continue to use this product for an extended period
after a cessation trial (West et al. 2000), and this continued abstinence may be due
to the desire to maintain abstinence (Shiffman et al. 2003).
The target dose of this agent in nicotine dependence is 300 mg daily (150 mg
bid), and it is typically started 7 days prior to the target quit date (TQD) at 150 mg
daily, then increased to 150 mg bid after 3–4 days. Unlike the NRTs, there is no
absolute requirement that smokers completely cease smoking by the TQD, though
many smokers report a significant reduction in urges to smoke and craving, which
facilitates cessation at the time of the TQD when drug levels reach steady-state
plasma levels. Some smokers gradually reduce their cigarette smoking over several
weeks prior to quitting. Smokers who are faster metabolizers of nicotine
(as determined by genetic variation at the CYP2A6 allele) may benefit more from
bupropion therapy, as opposed to NRT or counseling (Ray et al. 2009b).
A pivotal multicenter study by Hurt and colleagues (1997) established the
efficacy and safety of sustained-release (SR) bupropion for treatment of nicotine
dependence which led to its FDA approval in the USA in 1998. In a 7-week double-
blind, placebo-controlled multicenter trial, three doses of bupropion SR (100, 150,
and 300 mg/day in bid dosing) in combination with weekly individual cessation
counseling were given to 615 cigarette smokers using at least 15 cigarettes per day.
The end of trial 7-day point prevalence cessation rates for each of the bupropion
doses, placebo, 100 mg/day, 150 mg/day, 300 mg/day, were 19.0 %, 28.8 %,
38.6 %, and 44.2 %, respectively. At 1-year follow-up, cessation rates were
12.4 %, 19.6 %, 22.9 %, and 23.1 %, respectively. Bupropion treatment also dose
dependently reduced weight gain associated with smoking cessation and signifi-
cantly reduced nicotine withdrawal symptoms at 150 and 300 mg/day doses.
The primary side effects reported with bupropion administration in cigarette
smokers are headache, nausea and vomiting, dry mouth, insomnia, and activation.
Many of these side effects are observed in the first week of treatment. The main
contraindication for the use of bupropion is a past history of seizures of any
etiology. The rates of de novo seizures are low with this agent (<0.5 %) at doses
of 300 mg daily or less but have been observed when daily dosing exceeds
450 mg/day.
The combination of bupropion SR with nicotine transdermal patch (NTP) was
evaluated in a double-blind, double placebo-controlled, randomized multicenter
trial (Jorenby et al. 1999). A total of 893 cigarette smokers, using at least 15 ciga-
rettes per day (cpd), were randomized to one of four experimental groups: (1) pla-
cebo bupropion (0 mg/day) + placebo patch; (2) bupropion (300 mg/day) + placebo
patch; (3) placebo bupropion + nicotine patch (21 mg/day for 4 weeks, with 2 weeks
of 14 mg/day and 2 weeks of 7 mg/day); and (4) bupropion + patch. Bupropion was
administered 1 week prior to the target quit date (Day 15) at which time patch
treatment was initiated for a total of 8 weeks. All subjects received weekly
individual smoking cessation counseling. Cessation rates at the 1-year follow-up
assessment were 15.6 % for placebo, 16.4 % for active NTP alone, 30.3 % for
bupropion alone, and 35.5 % for the combination of patch and bupropion. Both
bupropion + patch and bupropion-alone groups were significantly better than the
placebo and patch-alone conditions, but the combination was not significantly
better than bupropion alone. Weight suppression after cessation was most robust
in the combination therapy group. Side effects were consistent with the profiles of
426 K.M. Mackowick and T.P. George
patch and bupropion, and the combination was well tolerated. However, a higher
than expected rate of treatment-emergent hypertension (4–5 %) was noted with the
combination of bupropion and patch (Jorenby et al. 1999). Of note, patch-alone
treatment was significantly different from placebo at the end of the trial, but not at
the follow-up assessments.
Hays et al. (2001) examined the effects of bupropion versus placebo on the
prevention of smoking relapse in 784 cigarette smokers who achieved smoking
abstinence after a 7-week open-label trial of bupropion (300 mg/day). Abstinent
smokers were then randomized to bupropion (300 mg/day) or placebo for a total of
45 weeks. Fifty-nine percent of smokers enrolled in the open-label phase of the trial
quit smoking. Significantly more smokers were abstinent at the end of the 52-week
treatment period in bupropion versus placebo groups (55.1 vs. 42.3 %, p < 0.01),
but not at the 1-year follow-up assessment. In addition, days to smoking relapse
were higher in the bupropion versus placebo group (156 vs. 65 days, p < 0.05).
Weight gain was significantly less in the bupropion group at both the end of
treatment and 1-year follow-up. The results of this study suggest the efficacy
of bupropion in preventing smoking relapse. Data regarding the optimal duration of
bupropion therapy for maintenance treatment requires further study.
25.2.4.3 Varenicline
Varenicline tartrate (Chantix® in the USA, Champix® in Europe and Canada), an
a4b2 nAChR partial agonist and weak a7 agonist, was approved as a first-line
smoking cessation agent by the USFDA in 2006. The results of two independent
but identical 12-week Phase III trials comparing varenicline (1 mg bid) to bupropion
SR (150 mg bid) and placebo have recently been published (Gonzales et al. 2006;
Jorenby et al. 2006). The quit rate for both studies were similar for continuous
abstinence over the last 4 weeks (weeks 9–12) of the study: Study 1 (Jorenby
et al. 2006) varenicline, 43.9 %; bupropion SR, 29.8 %; and placebo, 17.6 %;
Study 2 (Gonzales et al. 2006) varenicline, 44.0 %; bupropion SR, 29.5 %; and
placebo, 17.7 %. Quit rates were significantly higher for participants taking
varenicline compared to bupropion SR (ps < 0.0001), and both drugs resulted in
significantly higher quit rates than placebo. Continuous abstinence over the follow-up
period (weeks 9–52) was lower, and participants taking varenicline continued to
show a higher rate of abstinence (Study 1, 22.1 %; Study 2, 23.0 %) than participants
taking bupropion (Study 1, 16.4 %, p < 0.001 compared to varenicline; Study
2, 15.0 %, p ¼ 0.064 compared to varenicline) and placebo (Study 1, 8.4 %; Study
2, 10.3 %). A third study examining the efficacy of the drug on smoking relapse-
prevention used a 12-week open-label varenicline phase followed by randomization
to 12 weeks of varenicline or placebo (Tonstad et al. 2006). These investigators found
that participants taking varenicline versus placebo were more likely to be continu-
ously abstinent during weeks 13–24 (70.5 % vs. 49.6 %, p < 0.001) and weeks 13–52
(43.6 % vs. 36.9 %, p ¼ 0.02). Varenicline was found to reduce cravings and smoking
satisfaction and to be safe and well tolerated. There were similar discontinuation rates
for varenicline and bupropion, and the most common adverse event reported by the
varenicline group was nausea (Study 1, 28.1 %; Study 2, 29.4 %).
25 Nicotine and Tobacco 427
Nortriptyline
Nortriptyline is a tricyclic antidepressant which has been shown in several double-
blind, placebo-controlled trials to be superior to placebo (Hall et al. 1998; Prochazka
et al. 1998) and to have comparable efficacy to bupropion (Hall et al. 2002). Higher
intensity behavioral therapies may help to improve its efficacy. The mechanism of
action is thought to relate to norepinephrine and serotonin reuptake blockade. Side
effects include dry mouth, blurred vision, constipation, and orthostatic hypotension. It
appears to have some utility in smokers with past histories of major depression, but its
potential for fatal overdose has likely limited its utilization in smokers. However,
nortriptyline can be recommended as a second-line agent after nicotine replacement
therapies and bupropion, though more study of this agent is necessary.
Clonidine
Clonidine is a presynaptic alpha-2 receptor agonist that dampens sympathetic activity
originating at the locus ceruleus. It appears to have efficacy for treating opioid
withdrawal and thus was tested with nicotine withdrawal during smoking cessation
trials. The most common side effects of clonidine are dry mouth, sedation, and
constipation. Postural hypotension, rebound hypertension, and depression are rare
with smoking cessation treatment. Several clinical trials tested oral or transdermal
clonidine in doses of 0.1–0.4 mg/day for 2–6 weeks with and without behavior
therapy and have suggested clonidine is more effective in women than in men. In
general, the effects of clonidine have not proven to be as robust as NRTs. An initial
study in n ¼ 71 heavy smokers by Glassman et al. (1988) showed that at doses up to
0.4 mg/day, cessation rates were doubled in comparison to placebo, and in a follow-
up study by this group in n ¼ 300 smokers, this initial finding was replicated
(Glassman et al. 1993). In fact, a meta-analysis by Covey and Glassman (1991) of
428 K.M. Mackowick and T.P. George
nine placebo-controlled studies and 813 patients found short-term quit rates of 39 %
on clonidine versus 21 % on placebo (OR 2.4, 1.7–32.8) and suggested that clonidine
was effective in the transdermal preparation and more helpful in female smokers.
A subsequent meta-analysis by Gourlay and Benowitz (1995) found long-term
follow-up quit rates in four subsequent studies of 31 % on clonidine and 17 % on
placebo (OR 2.0, 1.3–3.0). It appears to be useful in reducing nicotine withdrawal
symptoms acutely and may have a role in smokers who have high levels or anxiety
during early cessation (Niaura et al. 1996). This agent should be considered as
a second-line therapy for smokers failing initial treatment with NRTs or bupropion.
Mecamylamine
Mecamylamine (MEC) is a noncompetitive blocker at the ion channel site of both
high-affinity central nervous system and peripheral nAChRs. When MEC is given
to smokers who are not trying to stop smoking, they initially increase their smoking
in an attempt to overcome the blockade produced by this drug. MEC does not
precipitate withdrawal in humans perhaps because it is a noncompetitive nAChR
antagonist. Common side effects included abdominal cramps, constipation, dry
mouth, and headaches. Based on the idea that combined blockade and agonist
therapy at the nAChR might be beneficial (similar to the nAChR partial agonist
profile of varenicline), two randomized trials were conducted comparing MEC in
combination with nicotine patch to placebo and nicotine patch. The rationale of
these trials was that MEC would reduce the rewarding effects of nicotine, and the
patch would reduce nicotine withdrawal symptoms (Rose et al. 1994, 1998). In the
first trial (Rose et al. 1994), MEC (up to 10 mg/day, 5 mg bid for 5 weeks) or
placebo was given in combination with nicotine patch (21 mg/day) for up to
8 weeks, and cessation rates were significantly higher in the combination group
than the patch-alone group (12/24 [50.0 %] vs. 4/24 [16.7 %], p < 0.05). Meca-
mylamine was reported to reduce cigarette craving and negative affect and appetite
increases associated with tobacco withdrawal. In a subsequent study of 80 cigarette
smokers (Rose et al. 1998), MEC at doses of up to 10 mg/day was given as
a pretreatment for 4 weeks prior to nicotine patch initiation at the TQD, and
the combination of MEC and patch was continued for 6 weeks. Similar to the
first study, the combination of MEC with NTP increased continuous abstinence
rates after the TQD compared to NTP alone (19/40 [47.5 %] vs. 11/40 [27.5 %],
p < 0.05). These data suggest the efficacy of the combination of MEC with NTP,
and this combination should be considered a second-line therapy.
Naltrexone
Naltrexone is a long-acting congener of the m-opioid receptor antagonist naloxone.
The rationale for using naltrexone for smoking cessation is that the performance-
enhancing and other positive effects of nicotine may be opioid-mediated
(Pomerleau 1998; Krishnan-Sarin et al. 1999). Early studies observed that naltrex-
one monotherapy increases smoking, presumably an attempt to overcome blockade;
however, a study of naltrexone in heavy-smoking alcoholics found that cigarette
smoking was decreased modestly (Rosenhow et al. 2003). Adverse events include
25 Nicotine and Tobacco 429
elevated liver enzymes, nausea, and vomiting. A trial by Covey and colleagues
(1999) in 68 cigarette smokers using at least 20 cpd and highly motivated to quit
compared naltrexone (up to 75 mg/day) initiated 3 days prior to the TQD to placebo
for a total of 4 weeks. Cessation rates in the naltrexone group were nonsignificantly
higher than placebo (46.7 % vs. 26.3 %, p < 0.10), and at 6-month follow-up there
were no group differences. Recently, treatment with naltrexone has been shown to
reduce post-cessation weight gain among women, but not men (King et al. 2012).
Additional promising data with naltrexone was observed with the combination
of naltrexone and NRT. A preliminary study by Krishnan-Sarin et al. (2003)
suggested that the combination of naltrexone and NTP is superior to NTP alone
when NTP administration precedes that of naltrexone (presumably to decrease
naltrexone-related withdrawal). In a larger trial of the combination of nicotine
patch (21 mg/day) with four active doses of naltrexone (0, 25, 50, and
100 mg/day), it was shown that the highest dose of naltrexone with patch signifi-
cantly improves continuous smoking abstinence rates compared to placebo
(O’Malley et al. 2006), but these effects appeared to be confined to the first
weeks of treatment. Further studies of naltrexone either alone or in combination
with the patch are needed, including in patients with concurrent alcohol misuse.
Nicotine Vaccines
Nicotine vaccines (Hatsukami et al. 2005) are being developed by a number of
companies, but these are not currently available for public use. A systematic review
of smoking cessation trials conducted by pharmaceutical companies as part of the
drug development process showed that nicotine vaccines, while well tolerated, did
not enhance long-term cessation rates (Hartmann-Boyce et al. 2012), and recent
Phase III trials of one nicotine vaccine preparation (Nabi Biopharmaceuticals)
suggested that these agents did not increase rates of smoking cessation in
nicotine-dependent smokers. However, the nicotine vaccine may have promise
for the prevention of smoking relapse or initiation of smoking and could be
developed for these indications in the future. Side effects include soreness at the
injection site and hypersensitivity reactions to vaccine components.
As the high rates of tobacco use and dependence and low rates of smoking cessation
are becoming increasingly appreciated in psychiatric and addicted populations
(Lasser et al. 2000; Grant et al. 2004; Kalman et al. 2005), it is increasingly evident
that mental health and addiction clinics have done little to address the tobacco
culture that permeates these institutional environments. However, smoking bans are
becoming increasingly common in psychiatric hospitals and addiction treatment
programs and appear to be successfully implemented in the majority of reported
cases (Lawn and Pols 2005), but these developments have shown little uptake and
application in community settings (Mackowick et al. 2012).
430 K.M. Mackowick and T.P. George
25.3 Conclusion
References
Addington J, el-Guebaly N, Campbell W, Hodgins DC, Addington D (1998) Smoking cessation
treatment for patients with schizophrenia. Am J Psychiatry 155:974–976
Ascher JA, Cole JO, Colin JN, Feighner JP, Ferris RM, Fibiger HC, Golden RN, Martin P, Potter
WZ, Richelson E (1995) Bupropion: a review of its mechanism of antidepressant activity.
J Clin Psychiatry 56:395–401
Bedi G, Preston KL, Epstein DH, Heishman SJ, Marrone GF, Shaham Y, de Wit H (2011)
Incubation of cue-induced cigarette craving during abstinence in human smokers. Biol Psy-
chiatry 69:708–711
Brody AL, Mandelkern MA, London ED, Olmstead RE, Farahi J, Scheibal D, Jou J, Allen V,
Tiongson E, Chefer SI, Koren AO, Mukhin AG (2006) Cigarette smoking saturates brain
alpha-4, beta-2 nicotinic acetylcholine receptors. Arch Gen Psychiatry 63:907–915
Brody AL, Mukhin AG, Shulenberger S, Mamoun MS, Kozman M, Phoung J, Neary M, Luu T,
Mandelkern MA (2013) Treatment for tobacco dependence: effect on brain nicotinic acetyl-
choline receptor density. Neuropsychopharmacology. doi:10.1038/hpp.2013.53
Carpenter MJ, Hughes JR, Solomon LJ, Callas PW (2004) Both smoking reduction with nicotine
replacement therapy and motivation advice increase future cessation among smokers
unmotivated to quit. J Consult Clin Psychol 72:371–381
432 K.M. Mackowick and T.P. George
CDC (2008) Cigarette smoking among adults–United States, 2007. MMWR Morb Mortal Wkly
Rep 57(45): 1221–1226
CDC (2011) Vital signs: Current cigarette smoking among adults aged ≥ 18 years – United States,
2005–2010. MMWR Morb Mortal Wkly Rep 60(35): 1207–1212.
CDC (2013) Vital signs: current cigarette smoking among adults aged 18 years with mental
illness—United States, 2009–2011. MMWR Morb Mortal Wkly Rep 62:81–87
Chengappa KN, Kambhampati RK, Perkins K, Nigam R, Anderson T, Brar JS, Vemulapalli HK,
Atzert R, Key P, Kang JS, Levine J (2001) Bupropion sustained-release as a smoking cessation
treatment in remitted depressed patients maintained on treatment with selective serotonin
reuptake inhibitors. J Clin Psychiatry 62:503–508
Chou K-R, Chen R, Lee J-F, Ku C-H, Lu R-B (2004) The effectiveness of nicotine-patch therapy
for smoking cessation in patients with schizophrenia. Int J Nurs Stud 41:321–330
Covey LS, Glassman AH (1991) A meta-analysis of double-blind placebo-controlled trials of
clonidine for smoking cessation. Br J Addict 86:991–998
Covey LS, Glassman AH, Stetner F (1999) Naltrexone effects on short-term and long-term
smoking cessation. J Addict Dis 18:31–40
Dallery J, Houtsmuller EJ, Pickworth WB, Stitzer ML (2003) Effects of cigarette nicotine content
and smoking pace on subsequent craving and smoking. Psychopharmacology (Berl)
165:172–180
Dani JA, Jenson D, Broussard JI, De Biasi M (2011) Neurophysiology of nicotine addiction.
J Addict Res Ther 20(Suppl 1):001
Esterlis I, Cosgrove KP, Batis JC, Bois F, Stiklus SM, Perkins E, Seibyl JP, Carson RE, Staley JK
(2010) Quantification of smoking-induced occupancy of beta2-nicotinic acetylcholine recep-
tors: estimation of nondisplaceable binding. J Nucl Med 51:1226–1233
Evins AE, Mays VK, Rigotti NA, Tisdale T, Cather C, Goff DC (2001) A pilot trial of bupropion
added to cognitive behavioral therapy for smoking cessation in schizophrenia. Nicotine Tob
Res 3:397–403
Evins AE, Cather C, Deckerbach T, Freudenreich O, Culhane MA, Olm-Shipman CM, Henderson
DC, Schoenfeld DA, Goff DC, Rigotti NA (2005) A double-blind placebo-controlled trial of
bupropion sustained-release for smoking cessation in schizophrenia. J Clin Psychopharmacol
25:218–225
Fiore MC, Smith SS, Jorenby DE, Baker TB (1994) The effectiveness of the nicotine patch for
smoking cessation: a meta-analysis. JAMA 271:1940–1947
Fiore MC, Jaen CR, Baker TB et al (2008) Treating tobacco use and dependence: 2008 update US
public health service clinical practice guideline executive summary. Respir Care
53:1217–1222
George TP, O’Malley SS (2004) Current pharmacological treatments for nicotine dependence.
Trends Pharmacol Sci 25:42–48
George TP, Sernyak MJ, Ziedonis DM, Woods SW (1995) Effects of clozapine on smoking in
chronic schizophrenic outpatients. J Clin Psychiatry 56:344–346
George TP, Zeidonis DM, Feingold A, Pepper WT, Satterburg CA, Winkel J, Rounsaville BJ,
Kosten TR (2000) Nicotine transdermal patch and atypical antipsychotic medications for
smoking cessation in schizophrenia. Am J Psychiatry 157:1835–1842
George TP, Vessicchio JC, Termine A, Bregartner TA, Feingold A, Rounsaville BJ, Kosten TR
(2002) A placebo-controlled study of bupropion for smoking cessation in schizophrenia. Biol
Psychiatry 52:53–61
Giovino GA (2007) The tobacco epidemic in the United States. Am J Prev Med 33(6 Suppl):
S318–S326
Glassman AH, Stetner F, Walsh BT, Raizman PS, Fleiss JL, Cooper TB, Covey LS (1988) Heavy
smokers, smoking cessation, and clonidine. JAMA 259:2863–2866
Glassman AH, Covey LS, Dalack GW, Stetner F, Rivelli SK, Fleiss J, Cooper TB (1993) Smoking
cessation, clonidine, and vulnerability to nicotine among dependent smokers. Clin Pharmacol
Ther 54:670–679
25 Nicotine and Tobacco 433
Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, Watsky EJ, Gong J,
Williams KE, Reeves KR for the Varenicline Phase 3 Study Group (2006) Varenicline, an
alpha4 beta2 nicotinic acetylcholine receptor partial agonist, vs. sustained release bupropion
and placebo for smoking cessation. JAMA 296:47–55
Gourlay SG, Benowitz N (1995) Is clonidine an effective smoking cessation therapy? Drugs
50:197–207
Grant BF, Hasin DS, Chou P, Stinson FS, Dawson DA (2004) Nicotine dependence and psychiatric
disorders in the United States. Results from the National Epidemiologic survey on alcohol and
related conditions. Arch Gen Psychiatry 61:1107–1115
Hall SM, Reus VI, Munoz RF, Sees KL, Humfleet G, Hartz DT, Frederick S, Triffleman E (1998)
Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking. Arch Gen
Psychiatry 55:683–690
Hall SM, Humfleet GL, Reus VI, Munoz RF, Hartz DT, Maude-Griffin R (2002) Psychological
intervention and antidepressant treatment in smoking cessation. Arch Gen Psychiatry
59:930–936
Hartmann-Boyce J, Cahill K, Hatsukami D, Cornuz J (2012) Nicotine vaccines for smoking
cessation. Cochrane Database Syst Rev 8:CD007072
Hatsukami DK, Rennard S, Jorenby D (2005) Safety and immunogenicity of a nicotine conjugate
vaccine in current smokers. Clin Pharmacol Ther 78:456–467
Hayford KE, Patten CA, Rummans TA, Schroeder DR, Offord KP, Croghan IT, Glover ED, Sachs
DP, Hurt RD (1999) Efficacy of bupropion for smoking cessation in smokers with a former
history of major depression or alcoholism. Br J Psychiatry 174:173–178
Hays JT, Hurt RD, Rigotti NA, Niaura R, Gonzales D, Durcan MJ, Sachs DP, Wolter TD, Buist
AS, Johnston JA, White JD (2001) Sustained-release bupropion for pharmacologic relapse-
prevention after smoking cessation: a randomized, controlled trial. Ann Intern Med
135:423–433
Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO (1991) The Fagerstrom test for
nicotine dependence: a revision of the Fagerstrom tolerance questionnaire. Br J Addict
86:1119–1127
Heckman CJ, Egleston BL, Hofmann MT (2010) Efficacy of motivational interviewing for
smoking cessation: a systematic review and meta-analysis. Tob Control 19:410–416
Hertzberg MA, Moore SD, Feldman ME, Beckham JC (2001) A preliminary study of bupropion
sustained-release for smoking cessation in patients with chronic posttraumatic stress disorder.
J Clin Psychopharmacol 21:94–98
Hughes JR, Hatsukami DK (1986) Signs and symptoms of tobacco withdrawal. Arch Gen
Psychiatry 43:289–294
Hughes JR, Novy P, Hatsukami DK, Jensen J, Callas PW (2003) Efficacy of nicotine patch in
smokers with a history of alcoholism. Alcohol Clin Exp Res 27:946–954
Hughes JR, Keely J, Naud S (2004) Shape of the relapse curve and long-term abstinence among
untreated smokers. Addiction 99:29–38
Hurt RD, Dale LC, Offord KP, Croghan IT, Hays JT, Gomez-Dahl L (1995) Nicotine patch
therapy for smoking cessation in recovering alcoholics. Addiction 90:1541–1546
Hurt RD, Sachs DPL, Glover ED, Offord KP, Johnston JA, Dale LC, Khayrallah MA, Schroeder
DR, Glover PN, Sullivan CR, Croghan IT, Sullivan PM (1997) A comparison of sustained-
release bupropion and placebo for smoking cessation. N Engl J Med 337:1195–1202
Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, Smith SS, Muramato
ML, Daughton DM, Doan K, Fiore MC, Baker TB (1999) A controlled trial of
sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med
340:685–691
Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J,
Reeves KR for the Varenicline Phase 3 Study Group (2006) Efficacy of varenicline, an alpha4
beta2 nicotinic acetylcholine receptor partial agonist, vs. placebo or sustained release
bupropion for smoking cessation. JAMA 296:56–63
434 K.M. Mackowick and T.P. George
Kalman D, Kahler C, Tirch D, Penk W, Kaschib C, Monti PM (2004) Twelve-week outcomes from
an investigation of high dose nicotine patch therapy for heavy smokers with a past history of
alcohol dependence. Psychol Addict Behav 18:78–82
Kalman D, Morrisette SB, George TP (2005) Co-morbidity of smoking with psychiatric and
substance use disorders. Am J Addict 14:106–123
King AC, Cao D, Zhang L, O’Malley SS (2012) Naltrexone reduction of long-term smoking
cessation weight gain in women but not in men: a randomized controlled trial. Biol Psychiatry.
doi:10.1016/j.biopsych.2012.09.025
Kinnunen T, Doherty K, Militello FS, Garvey AJ (1996) Depression and smoking cessation:
characteristics of depressed smokers and effects of nicotine replacement. J Consult Clin
Psychol 64:791–798
Kleber HD, Weiss RD, Anton RF Jr, George TP, Greenfield SF, Kosten TR, O’Brien CP,
Rounsaville BJ, Strain EC, Ziedonis DM, Hennessey G, Connery H (2006) American Psychi-
atric Association. Clinical practice guidelines for the treatment of patients with substance use
disorders, 2nd edition. Am J Psychiatry 163:5–82
Krishnan-Sarin S, Rosen MI, O’Malley SS (1999) Naloxone challenge in smokers: evidence for an
opioid component in nicotine dependence. Arch Gen Psychiatry 56:663–668
Krishnan-Sarin S, Meandjiza B, O’Malley SS (2003) Nicotine patch and naltrexone for smoking
cessation: a preliminary study. Nicotine Tob Res 5:851–857
Lancaster T, Stead LF (2005) Individual behavioural counselling for smoking cessation. Cochrane
Database Syst Rev (2). doi: 10.1002/14651858.CD001292.pub2, Art no: CD001292
Lasser K, Boyd JW, Woolhander S, Himmelstein DU, McCormick D, Bor DH (2000) Smoking
and mental illness: a population-based prevalence study. JAMA 284:2606–2610
Lawn S, Pols R (2005) Smoking bans in psychiatric inpatient settings? A review of the research.
Aust NZ J Psychiatry 39:866–885
Mackowick KM, Lynch M-J, Weinberger AH, George TP (2012) Treatment of tobacco
dependence in people with mental health and addictive disorders. Curr Psychiatry Rep
14:478–485
McClure JB, Swan GE, Catz GL, Jack L, Javitz H, McAfee T, Deprey M, Richards J, Zbikowski
SM (2010) Smoking outcome by psychiatric history after behavioral and varenicline treatment.
J Subst Abuse Treat 38:394–402
McEvoy J, Freudenreich O, McGee M, VanderZwaag C, Levin E, Rose J (1995) Clozapine
decreases smoking in patients with chronic schizophrenia. Biol Psychiatry 37:550–552
McFall M, Saxon AJ, Thompson CE, Yoshimoto D, Malte C, Straits-Troster K, Kanter E, Zhou
X-HA, Dougherty CM, Steele B (2005) Improving the rates of quitting smoking for veterans
with posttraumatic stress disorder. Am J Psychiatry 162:1311–1319
McFall M, Atkins DC, Yoshimoto D, Thompson CE, Kanter E, Malte CA, Saxon AJ (2006) Inte-
grating tobacco cessation treatment into mental health care for patients with posttraumatic
stress disorder. Am J Addict 15:336–344
Montoya ID, Herbeck DM, Sviks DS, Pincus HA (2005) Identification and treatment of patients
with nicotine problems in routine clinical psychiatry practice. Am J Addict 14:441–454
Niaura R, Brown RA, Goldstein MG, Murphy JK, Abrams DB (1996) Transdermal clonidine for
smoking cessation: a double-blind randomized dose-response study. Exp Clin
Psychopharmacol 4:285–291
O’Malley SS, Cooney JL, Krishnan-Sarin S, Dubin JA, McKee SA, Cooney NL, Blakeslee A,
Meandzija B, Romano-Dahlgard D, Wu R, Makuch R, Jatlow P (2006) A controlled trial of
naltrexone augmentation of nicotine replacement therapy for smoking cessation. Arch Intern
Med 166:667–674
Pachas GN, Cather C, Pratt SA, Hoeppner B, Nino J, Carlini SV, Achtyes ED, Lando H,
Mueser KT, Rigotti NA, Goff DC, Evins AE (2012) Varenicline for smoking cessation
in schizophrenia: safety and effectiveness in a 12-week, open-label trial. J Dual Diagn
8:117–125
25 Nicotine and Tobacco 435
Patten CA, Brockman TA (2006) Combining medications with behavioral treatment. In: George
TP (ed) Medication treatments for nicotine dependence. Taylor Francis, Boca Raton,
pp 225–244
Piper ME, Federman EB, McCarthy DE, Bolt DM, Smith SS, Fiore MC, Baker TB (2007) Efficacy
of bupropion alone and in combination with nicotine gum. Nicotine Tob Res 9:947–954
Piper ME, Smith SS, Schlam TR, Fiore MC, Jorenby DE, Fraser D, Baker TB
(2009) A randomized placebo-controlled clinical trial of five smoking cessation pharmaco-
therapies. Arch Gen Psychiatry 66:1253–1262
Pomerleau OF (1998) Endogenous opioids and smoking: a review of progress and problems.
Psychoneuroendocrinology 23:115–130
Prochazka AV, Weaver MJ, Keller RT, Fryer GE, Licari PA, Lofaso D (1998) A randomized trial
of nortriptyline for smoking cessation. Arch Intern Med 158:2035–2039
Procyshyn RM, Tse G, Sin O, Flynn S (2002) Concomitant clozapine reduces smoking in patients
treated with risperidone. Eur Neuropsychopharmacol 12:77–80
Ray R, Schnoll RA, Lerman C (2009a) Nicotine dependence: biology, behavior, and treatment.
Annu Rev Med 60:247–260
Ray R, Tyndale RF, Lerman C (2009b) Nicotine dependence pharmacogenetics: roles of genetic
variation in nicotine-metabolizing enzymes. J Neurogenet 23:252–261
Rigotti NA (2002) Clinical practice: treatment of tobacco use and dependence. N Engl
J 346:506–512
Rollnick S, Butler CC, Stott N (1997) Helping smokers make decisions: the enhancement of brief
intervention for general medical practice. Patient Educ Couns 31:191–203
Rose JE, Behm FM, Westman EC, Levin ED, Stein RM, Ripka GV (1994) Mecamylamine
combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treat-
ment alone. Clin Pharmacol Ther 56:86–99
Rose JE, Behm FM, Westman EC (1998) Nicotine-mecamylamine treatment for smoking cessa-
tion: the role of pre-cessation therapy. Exp Clin Psychopharmacol 6:331–343
Rosenhow DJ, Monti PM, Colby SM, Guillver SB, Swift RM, Abrams DB (2003) Naltrexone
treatment fort alcoholics: effect on cigarette smoking rates. Nicotine Tob Res 5:231–236
SAMHSA (2009) Results from the National Survey on Drug Use and Health: national findings.
NSDUH series. Office of Applied Studies, Rockville
Shiffman S, Dresler CM, Hajek P, Bilburt SJ, Targett DA, Strahs KR (2002) Efficacy of a nicotine
lozenge for smoking cessation. Arch Intern Med 162:1267–1276
Shiffman S, Hughes JR, Di Marino ME, Sweeney CT (2003) Patterns of over-the-counter nicotine
gum use: persistent use and concurrent smoking. Addiction 98:1747–1753
Shoptaw S, Rotheram-Fuller E, Yang X, Frosch D, Nahom D, Jarvik ME, Rawson RA, Ling
W (2002) Smoking cessation in methadone maintenance. Addiction 97:1317–1328
Silagy C, Lancaster T, Stead L, Mant D, Fowler G (2004) Nicotine replacement therapies for
smoking cessation. Cochrane Database Syst Rev 3:CD000146
Sims TH, Fiore MC (2002) Pharmacotherapy for treating tobacco dependence: what is the ideal
duration of therapy? CNS Drugs 16:653–662
Slemmer JE, Martin BR, Damaj MI (2000) Bupropion is a nicotinic antagonist. J Pharmacol Exp
Ther 295:321–327
Sobell LC, Sobell MB, Leo GI, Cancilla A (1988) Reliability of a timeline method: assessing
normal drinkers’ reports of recent drinking and a comparative evaluation across several
populations. Br J Addict 83:393–402
Stead LF, Lancaster T (2005) Group behaviour therapy programmes for smoking cessation.
Cochrane Database Syst Rev (2). doi: 10.1002/14651858.CD001007.pub2. Art no: CD001007
Stead LF, Lancaster T (2012) Behavioural interventions as adjuncts to pharmacotherapy for
smoking cessation. Cochrane Database Syst Rev 12:CD009670
Stead LF, Perera R, Bullen C, Mant D, Hartmann-Boyce J, Cahill K, Lancaster T (2012) Nicotine
replacement therapy for smoking cessation. Cochrane Database Syst Rev 11:CD000146
436 K.M. Mackowick and T.P. George
Tiffany ST, Drobes DJ (1991) The development and initial validation of a questionnaire on
smoking urges. Addiction 86:1467–1476
Tindle HA, Shiffman S (2011) Smoking cessation behavior among intermittent smokers versus
daily smokers. Am J Public Health 101:e1–e3
Tonstad S, Tonnesen P, Hajek P, Williams KE, Billing CB, Reeves KR for the Varenicline Phase
3 Study Group (2006) Effect of maintenance therapy with varenicline on smoking cessation.
JAMA 296:64–71
Tverdal A, Bjartveit K (2006) Health consumption of reduced daily cigarette consumption. Tob
Control 15:472–480
Weinberger AH, Vessicchio JC, Sacco KC, Creeden CL, Chengappa KN, George TP
(2008) A preliminary study of sustained-release bupropion for smoking cessation in bipolar
disorder. J Clin Psychopharmacol 28:584–587
West R, Hajek P, Foulds J, Nilsson F, May S, Meadows A (2000) A comparison of the abuse
liability and dependence potential of nicotine patch, gum, spray, and inhaler. Psychopharma-
cology (Berl) 149:198–202
West R, Hajek P, Nilsson F, Foulds J, May S, Meadows A (2001) Individual differences in
preferences for and responses to four nicotine replacement products. Psychopharmacology
(Berl) 153:225–230
West R, Zatonski W, Cedzynska M, Lewandowska D, Pazik J, Aveyard P, Stapleton J (2011)
Placebo-controlled trial of cytosine for smoking cessation. N Engl J Med 365:1193–1200
Williams JM, Ziedonis DM, Foulds J (2004) A case series of nicotine nasal spray in the treatment
of tobacco dependence among patients with schizophrenia. Psychiatr Serv 55:1064–1066
Williams JM, Anthenelli RM, Morris C, Tredow J, Thompson JR, Yunis C, George TP (2012)
A double-blind, placebo-controlled study evaluating the safety and efficacy of varenicline
tartrate for smoking cessation in schizophrenia and schizoaffective disorder. J Clin Psychiatry
73:654–660
Wu BS, Weinberger AH, Mancuso E, Wing VC, Haji-Khamenh B, Levinson AJ, George TP
(2012) A preliminary feasibility study of varenicline for smoking cessation in bipolar disorder.
J Dual Diagn 8:131–132
Addiction to Caffeine and Other
Xanthines 26
Thierry Favrod-Coune and Barbara Broers
Contents
26.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 438
26.2 Caffeine and Methylxanthines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 438
26.3 Caffeine, Coffee, Tea, and Energy Drinks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 440
26.4 Main Effects of Caffeine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 441
26.5 Risks of Caffeine Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442
26.5.1 Acute Risks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442
26.6 Chronic Risks of Caffeine Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 444
26.6.1 Caffeine Dependence and Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 444
26.6.2 Other Chronic Risks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 444
26.7 Benefits of Methylxantine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445
26.7.1 Caffeine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445
26.7.2 Theophylline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 448
26.7.3 Theobromine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 448
26.7.4 Caffeine Abuse Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449
26.8 International Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449
26.9 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 450
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 452
Abstract
Xanthine (3,7-dihydro-purine-2,6-dione) is a purine base that can naturally be
found in human body tissues and fluids as well as in plants and other organisms.
Methylated xanthines (methylxanthines) are phosphodiesterase inhibitors and
adenosine receptor antagonists. Methylxanthines have thus different effects:
reduce inflammation and immunity, reduce sleepiness and increase alertness,
but also stimulate the heart rate and contraction and dilate the bronchi. The most
26.1 Introduction
For professionals in the addiction field, discussing the issue of caffeine, in a private
or professional context, is a pleasure. Finally there is a domain that allows us to
have a sort of positive message: “drink your coffee, it’s probably good for you, it’s
probably good for your patients.”
Our image of “controllers” telling in general frightening stories about the risks of
smoking, drinking, sniffing, or injecting different psychoactive substances can be
slightly improved if we can enchant the benefits of a few cups of espresso in the
morning. And it is even better if we can carefully formulate the recommendation
not to forget the daily bit of dark chocolate, full of theobromine, another member of
the methylxanthine group.
But is this really so? Are we sure there are no acute or long-term risks related to
caffeine use? Is there a safe level of use? Should we talk about coffee or caffeine
use? Are there subgroups of patients that should avoid xanthine use? And what
about caffeine addiction, is it a clinical entity or a popular but misused term?
In this chapter we will focus mostly on caffeine and marginally on other
methylxanthines. The objective of this chapter is to describe the effects, risks,
and benefits of use of caffeine; discuss “caffeinism and chocoholism”; and provide
some clinical recommendations.
O N
N
R2
Caffeine: R1 = R2 = R3 = CH3
Theobromine: R1 = H, R2 = R3 = CH3
Theophylline: R1 = R2 = CH3, R3 = H
kinase A, inhibiting the synthesis of tumor necrosis factor (TNF)-alpha and leuko-
triene) and adenosine receptor antagonists (inhibiting sleepiness-inducing adeno-
sine). Methylxanthines have thus different effects: reduce inflammation and
immunity, reduce sleepiness and increase alertness, but also stimulate the heart
rate and contraction and dilate the bronchi. The most well-known methylxanthines
are caffeine, methylbromine, and theophylline.
Caffeine can be found naturally in coffee beans but also in tea leaves, guarana,
and mate plants or kola nuts. Theobromine and theophylline are found in cacao
beans and mate plants; tea leaves contain some theophylline. Caffeine and other
methylxanthines can be manufactured. Theophylline is a well-known asthma
medication, currently used mostly as second line.
Caffeine is absorbed rapidly and completely through the gastrointestinal tract.
After oral consumption the plasma peak is after 30–45 min, and the half-time
elimination is around 3.5–6 h (Greden 1992) with high variability related to age,
hormones, use of nicotine or medications, etc. Metabolization takes essentially
place in the liver through the cytochrome P450 pathway, especially through the
cytochrome CYP1A2. The deficiency of CYP1A2 enzymes has been shown to
impair caffeine metabolism and prolong caffeine half-life (Cornelis et al. 2006), as
can certain medications, such as disulfiram (Beach et al. 1986) or quinolones,
through CYL1A2 inhibition. Also during pregnancy, the half-life of caffeine
increases, with one study suggesting that in the last month of pregnancy, half-life
increases to 10.5 h on average (Knutti et al. 1982). Smokers seem to metabolize
caffeine more quickly through acceleration of demethylation steps, with normali-
zation of the enzyme-inducing effects of nicotine occurring after 4 days of
abstinence (Brown et al. 1988).
440 T. Favrod-Coune and B. Broers
Caffeine has a low risk profile, but after intake of large quantities (over 250 mg),
especially in non-tolerant subjects, an overstimulation of the central nervous
and the cardiovascular system can occur, resulting in what is called a “caffeine
intoxication.” This clinical entity is mentioned in both the Diagnostic and
Statistical Manual of Mental Disorders (DSM) and International Classification of
Diseases (ICD).
In DSM-IV, the caffeine-related disorders are as follows:
292.89 – induced anxiety disorder
292.89 – induced sleep disorder
305.90 – intoxication
292.9 – related disorder NOS
For the ICD-10 criteria of caffeine intoxication, please see Table 26.2.
The incidence of caffeine intoxication seems to be increasing; it occurs
mainly in young patients, mainly due to the use of caffeine-containing medica-
tions or energy drinks (not due to coffee intake), and when hospitalization is
necessary, there is in general co-occurring use of other psychoactive substances
or pharmaceutical products (McCarthy et al. 2008). Death from caffeine over-
dose has been described (Holmgren et al. 2003), but it is not clear if in these
cases patients have taken medications or have genetic cytochrome abnormalities
26 Addiction to Caffeine and Other Xanthines 443
Table 26.2 ICD 10 criteria F15.0 Acute intoxication due to use of other stimulants, including
for intoxication and caffeine
withdrawal state of caffeine
A. The general criteria for acute intoxication (F1x.0) must be met
and other stimulants (other
than cocaine, F 14.0) B. There must be dysfunctional behaviour or perceptual
abnormalities, as evidenced by at least one of the following
(1) Euphoria and sensation of increased energy
(2) Hypervigilance
(3) Grandiose beliefs or actions
(4) Abusiveness or aggression
(5) Argumentativeness
(6) Lability of mood
(7) Repetitive stereotyped behaviours
(8) Auditory, visual, or tactile illusions
(9) Hallucinations, usually with intact orientation
(10) Paranoid ideation
(11) Interference with personal functioning
C. At least two of the following signs must be present
(1) Tachycardia (sometimes bradycardia)
(2) Cardiac arrhythmias
(3) Hypertension (sometimes hypotension)
(4) Sweating and chills
(5) Nausea and vomiting
(6) Evidence of weight loss
(7) Pupillary dilatation
(8) Psychomotor agitation (sometimes retardation)
(9) Muscular weakness
(10) Chest pain
(11) Convulsions
F15.3 Withdrawal state from other stimulants, including caffeine
A. The general criteria for withdrawal state (F1x.3) must be met
B. There is dysphoric mood (for instance, sadness or anhedonia)
C. Any two of the following signs must be present
(1) Lethargy and fatigue
(2) Psychomotor retardation or agitation
(3) Craving for stimulant drugs
(4) Increased appetite
(5) Insomnia or hypersomnia
(6) Bizarre or unpleasant dreams
From ICD-10 (2013)
inhibiting caffeine metabolism. Based on animal studies, the median lethal dose
was estimated to be 192 mg/kg; when extrapolating to humans, this should
correspond to an intake of around 10 g of caffeine, corresponding to 80–100
cups of coffee (Peters 1967), making the occurrence of overdose with regular
coffee not very probable.
444 T. Favrod-Coune and B. Broers
“Caffeine dependence” and “caffeine abuse” are not included in the DSM-IV, even
if these terms are frequently used in the lay and medical literature. In general there
are not sufficient criteria to establish the diagnosis of caffeine dependence, even if
50 % of regular caffeine users will present with withdrawal symptoms in case of
acute abstinence. As for caffeine intoxication, the caffeine withdrawal syndrome is
included in both DSM and ICD classifications. The ICD-10 criteria for the caffeine
withdrawal state (F15.3) are found in Table 26.2.
During the preparation of the new DSM5 classification discussions on the
inclusion of caffeine dependence and/or withdrawal syndrome have taken place,
but caffeine was not included as a DSM-5 substance abuse disorder (see www.
dsm5.org).
The caffeine withdrawal syndrome is probably largely underdiagnosed. It can
occur after sudden abstinence from regular caffeine even at rather low intake of
100 mg daily (Juliano and Griffiths 2004). The most frequent symptoms are
headache, fatigue, decreased energy/activeness, decreased alertness, drowsiness,
decreased contentedness, depressed mood, difficulty concentrating, irritability, and
being foggy/not clearheaded. Symptoms occur after 12–24 h of abstinence and last
for several days. The severity and duration of symptoms are related to the amount of
regular caffeine intake. Juliano and Griffiths (2004) suggest that expectancies are
not a prime determinant of caffeine withdrawal and that avoidance of withdrawal
symptoms plays a central role in habitual caffeine consumption.
Patients who are hospitalized and depending on their state or inpatient regulations
(decaffeinated coffee only in psychiatric settings) can find themselves in caffeine
withdrawal with symptoms that can be misinterpreted or unrecognized. For instance,
for a patient suffering from head trauma and not receiving his daily coffee, the
severity of the headache can very well be influenced by the lack of caffeine.
The same misinterpretation can occur during expeditions at high altitude. For
practical reasons or fear of increasing sleeplessness and risk of dehydration,
caffeine intake is often stopped in this context. Several symptoms of altitude
sickness and caffeine withdrawal are common, such as headache, fatigue, and
lassitude (Hackett 2010). Hackett suggests that during expeditions caffeine likely
will have more beneficial than negative effects, especially in regular coffee
drinkers.
Heavy caffeine use is often associated with increased risk for use, misuse, or
dependence on other substances or addictive behaviors. This correlation does
absolutely not mean causality, but different studies suggest a two- to threefold
increase of prevalence of tobacco dependence or problematic alcohol use for those
26 Addiction to Caffeine and Other Xanthines 445
consuming more than 6–7 cups of coffee per day compared to those taking 1–2 cups
(Greden 1992; Kabagambe 2013). The combined (and increasing) use of energy
drinks with alcohol in adolescents and young adults deserves specific attention.
Caffeine can induce panic attacks in some individuals, but seems not be corre-
lated to the occurrence of negative outcomes of chronic psychiatric problems.
A link between heavy caffeine use and schizophrenic relapse has been suggested
but not confirmed (Greden 1992).
Several studies suggest a correlation between high caffeine intake (>5 cups of
coffee daily) and risk of lower bone density and increased risk of fracture, espe-
cially in lean elderly women and/or those having low calcium intake, but with tea
intake correlated to higher bone density (Korpelainen 2003; Kagambe 2013).
The use of unfiltered coffee has been associated with increased level of choles-
terol, a major risk factor for cardiovascular disease (Rodrigues 2003). Still, the
effect of filtered and unfiltered coffee on other risk factors is not fully clear, and
even if caffeine can induce tachycardia and arrhythmia, the available literature
suggests that caffeine has more benefits than risks for cardiovascular disease.
The same seems to be true for the oncology field (see below).
26.7.1 Caffeine
As said before, when considering the benefits of caffeine, we remind that there is
a difference between the benefits of caffeine itself and the benefits of coffee or other
caffeine-containing drinks. Coffee contains hundreds of other compounds that are
antioxidants (polyphenols, flavonoids, catechins, melanoidins, etc.) that pass
through coffee filters.
Moreover, it is globally difficult to speak only of caffeine because only few
publications are about caffeine itself. Most scientific evidence is related to studies
on coffee and do not consider the biologic effect of caffeine. In energy drinks, the
consequences of caffeine are difficult to isolate from those due to the high content
of sugar and other components like vitamins or the amino acid taurine.
First of all, there are strong suggestions that taking caffeine from coffee is
associated with a diminution of the risk of total or specific mortality (Freedman
et al. 2012). This study is based on the follow-up of more than 229,000 men and
173,000 women for 13 years. At inclusion, participants’ age varied between 50 and
71 years. After adjustment for tobacco-smoking status and other possible biases, the
risk of death was inversely correlated to coffee consumption. The benefit became
significant at one cup of coffee per day for men (hazard ratio 0.94, 95 % confidence
interval 0.86–0.93) and at two or three cups of coffee for women (hazard ratio 0.87,
95 % confidence interval 0.83–0.92). The benefit tended to rise with the amount of
coffee taken, with a statistical inverse correlation between caffeine and mortality.
An inverse correlation was also observed for death from respiratory disease,
injuries, diabetes, and infection. No association was found between caffeine and
446 T. Favrod-Coune and B. Broers
(Freedman et al. 2012), other studies have detected no association concerning men and
a reduction in the cardiovascular mortality for women (relative risk of death 0.83,
confidence interval 0.73–0.95) (Lopez-Garcia et al. 2008). For stroke, a 20 % reduction
of relative risk has been found in a cohort study of women (Larsson et al. 2011); this
was consistent with the results of another study concerning men (Larsson et al. 2008).
The effect of caffeine on insulin resistance is controversial and probably depends
on the source of caffeine and the duration of exposition. At short term, caffeine has
been shown to diminish insulin sensitivity (Beaudoin and Graham 2011). In
a randomized controlled study, a dosage from 400 mg caffeine per day for
a week showed a diminution of 35 % (95 % confidence interval 7–62 %) of insulin
sensitivity (MacKenzie et al. 2007). In another study, sweet caffeinated beverages
tended to increase type 2 diabetes (Malik et al. 2010). Still, it was not possible to
separate the effect of sugar or caffeine. The long-term effect of pure caffeine from
other sources than tea or coffee seems to have the opposite effect in animal models,
ameliorating the insulin sensitivity and neutralizing the negative metabolic of
sucrose in rats (Park et al. 2007). The limitations of this study are that it was
conducted not in humans but in type I diabetic rats. In humans, the regular
consumption of coffee has been clearly linked to decrease incidence of type
2 diabetes (Huxley et al. 2009). In this study, the relative risk was diminished by
7 % for any additional cup of coffee or tea absorbed. This effect was not associated
with certainty to caffeine as it was also observed with decaffeinated coffee.
Caffeine also influences the metabolism of uric acid and occurrence of gout
(Choi et al. 2007). In this large observational study, more than 50,000 men without
former episode of gout were followed for 12 years. The relative risk of incidental
gout was reduced by almost 60 % (relative risk 0.41, 95 % confidence interval
0.19–0.88) for the group consuming a large amount of coffee (six cups a day or
more). The smallest efficient dose for gout protection was 4–5 cups of coffee a day
with a 40 % risk reduction (relative risk 0.60, 95 % confidence interval 0.41–0.87).
This was clearly linked to coffee and not caffeine, as this protective effect was not
observed with tea or other sources of caffeine.
Tea and coffee (at a dosage of 300 mg caffeine per day) have been shown to
protect against Parkinson disease, with a risk reduction of 25 % (relative risk 0.75,
95 % confidence interval 0.68–0.82) (Costa et al. 2010), excluding women taking
hormonal replacement after menopause.
A neuroprotective effect of coffee on Alzheimer disease seems to exist, but this
assumption is based on a small number of observational studies (Barranco Quintana
2007). The risk reduction could be 30 % (relative risk 0.7, 95 % confidence interval
0.55–0.9).
A recent case-control study in Australia confirmed the potential benefit of caffeine
to prevent road accidents (Sharwood et al. 2013). More than 500 professional drivers
involved in crash accidents were compared to controls. After adjustment for
confounding factors, drivers who consumed caffeine (from coffee, tea, energy drinks,
or tablets) had a risk reduction of 63 % of being involved in an accident (odds ratio
0.37, 95 % confidence interval 0.27–0.50). This is probably due to the psychostimulant
properties of caffeine (increase alertness, lessen fatigue, promote memory, prevent
448 T. Favrod-Coune and B. Broers
errors to people who are tired or working on night shift (Ker 2010). Also in light
drinkers, the accident reduction was found; this is an argument against that it was only
an effect of the reversal of withdrawal (Childs and de Wit 2006).
Another well-established positive effect from caffeine is the enhancement of
physical capacities (Burke 2008). The most effective dosage for this purpose seems
to be around 3 mg caffeine per kilogram of weight. Positive impact was found on
intermittent effort sports (e.g., soccer), continued effort sports lasting until 1 h (e.g.,
swimming), or endurance sports (e.g., running). The enhancing effect of caffeine is
so significant that for a long time, caffeine was considered a doping substance
controlled by the World Anti-doping Agency (WADA). In 2004 caffeine was
removed from the list (www.wada-ama.org).
The potential analgesic properties of caffeine are subject of debate. Caffeine is
successfully used in the treatment of headache or migraine (Goldstein et al. 2006)
and is a frequent component of combined analgesics or other medication (e.g.,
when mixed with paracetamol or salicylates or antihistamines). On the other hand,
it can be the cause of headache (Bigal et al. 2002). This phenomenon can take place
when people chronically consume caffeine or in withdrawal conditions.
Coffee and tea also seem to present benefit for mental health based on a data of
a large cohort from the Nurses’ Health Study. More than 50,000 women not suffering
from depression at baseline were followed for 10 years, between 1996 and 2006, and
stratified by their consumption of caffeine (Lucas et al. 2011). During the follow-up,
a 20 % risk reduction for depression was found for women consuming 550 mg of
caffeine or more when compared to the group consuming 100 mg or less
(multivariate relative risk 0.80, 95 % confidence interval 0.68–0.95). This effect is
quite clearly related to caffeine itself as it was not observed for women drinking
decaffeinated coffee. Such results are coherent with data from other studies showing
an inverse correlation between coffee, depression, and suicide (Kawachi et al. 1996).
26.7.2 Theophylline
26.7.3 Theobromine
confirm this. The appetite for chocolate would be more linked to other methylxan-
thine such as caffeine and taste or cultural influences. So up to know, there are no
proven benefits for theobromine (Smith 2011).
In case of acute intoxication (Yew and Laczek 2011), which necessitates more than
70 mg/kg (Bronstein et al. 2010), clinical management should be “supportive.” The
first action is to give standard protocols for cardiac life or other support (ABCs)
(Pohler 2010). Then give oxygen to the patient and check the blood glucose. In case
of extreme anxiety, agitation, or seizure and lack of effect of non-pharmacological
interventions, give short-acting benzodiazepines (e.g., lorazepam orally when pos-
sible or intravenously/intramuscularly).
Activated charcoal is effective in reducing the absorption of methylxanthine and
recommended early in the treatment. Then transfer the patient to an emergency unit
where the care will be supportive, depending on the symptoms. Cardiovascular or
neurologic toxicities are the most frequent. Sinus tachycardia occurs but does, in
general, not require any intervention, but arrhythmia does. In case of extremely
high caffeine levels, a dialysis or hemofiltration may be necessary.
Gastric lavage is rarely done because of aspiration risk. Caffeine is rapidly
absorbed, and gastric lavage should not be considered unless in the first hour
after intake.
In case of withdrawal, no specific treatment or intervention was found in
scientific publications. Anyway, caffeine withdrawal is not dangerous and self-
limited. Intervention would then not be crucial. A wait-and-see approach could be
used. Nevertheless, the main problems during caffeine withdrawal could be fatigue,
lack of concentration, or headache. We can recommend general interventions such
as rest, physical activity, and good fluid and electrolyte supply. In case of severe
headaches, simple analgesia (e.g., paracetamol) could be used. If the time to go
through withdrawal is really not adequate, for example, in case of professional or
familial obligations, caffeine (in a limited dose) could be taken in the form of
coffee, a caffeine-containing drink, or a tablet, and complete withdrawal conducted
later. For regular caffeine users who will be exposed to a period of caffeine
abstinence (e.g., planned medical intervention), a decrease of daily caffeine intake
days before is recommended (Favrod-Coune and Broers 2010).
Currently, coffee, tea, and other caffeine-containing drinks are legally available in
all countries and not subjected to regulation. Based on our review of benefits and
risks of methylxanthines, we believe that there is no rationale to change this. This
seems neither necessary nor useful in a public health or cultural perspective, as
prohibition certainly will have a number of unwanted side effects. Nevertheless,
450 T. Favrod-Coune and B. Broers
information and warning (on package of food or drinks) are probably warranted,
indicating the risk of high doses of caffeine and when mixed with alcohol and when
relevant the risk of sugar, calories, or other compounds.
The FDA has warned four companies about adding caffeine to alcoholic bever-
ages in 2010 (Herndon 2010) and stated that a further action, including the seizure
of products, is possible under federal law. The FDA stated that caffeine is an
“unsafe food additive” when mixed with alcohol.
Another international measure that we consider useful would be a limitation of
the amount of caffeine in energy drinks. It seems difficult to reach toxic levels of
caffeine when a drink contains 50–100 mg of caffeine. Nevertheless, content
of 500 mg caffeine in one drink can represent a real danger, especially for children
or teenagers, given their lower body weight and the propensity to like those drinks.
26.9 Conclusion
Safe caffeine use is possible and moderate caffeine use (200–300 mg per day)
probably has more benefits than risks. Relative contraindications for caffeine intake
are uncompensated heart disease, anxiety, and sleeping problems. Since most
studies on caffeine use are observational, we can of course not recommend the
use of caffeine or other methylxanthines for medical reasons to those who do not
drink. The studies are merely based on cohorts of individuals drinking coffee and
tea, so we should recommend the use of these beverages and not of energy drinks.
Energy drinks lack several compounds found in coffee or tea (antioxidants) and
contain others that possibly have a negative impact on health (sugar). In case of
liver disease, especially if related to alcohol and HCV, a daily intake of at least five
cups of coffee can be recommended to diminish the progression of the disease.
Coffee and caffeine withdrawal symptoms exist and are often not recognized,
especially in treatment settings, where caffeine withdrawal can be confounded with
other symptoms. Caffeine withdrawal occurs in half of regular coffee drinkers, even
at moderate caffeine intake. The most common symptoms are headache, fatigue,
and difficulty to concentrate. Health professionals and patients should be better
informed about these symptoms and the risk of occurrence of caffeine withdrawal.
Caffeine intoxication and withdrawal are recognized clinical entities, but caf-
feine dependence is currently not. Some individuals can meet difficulties in con-
trolling their caffeine intake and present withdrawal symptoms in case of
abstinence, but most often other criteria of dependence are lacking. In some cases
such behavior seems close to an obsessive-compulsive or eating disorder.
In psychiatric inpatient settings, often only decaffeinated coffee is available. We
recommend, for the reasons mentioned above, that both caffeinated and decaffein-
ated coffee be at the disposition of the patients, with restriction for those who suffer
from anxiety or insomnia. Caffeine taken from coffee seems to be without risk for
most psychiatric patients. Personalized recommendations (maximum daily quantity
of caffeine, time limit) are probably more appropriate than constraining all patients
to abstain from coffee consumption.
26 Addiction to Caffeine and Other Xanthines 451
References
Beach CA, Mays DC, Guiler RC, Jacober CH, Gerber N (1986) Clinical inhibition of elimination
of caffeine by disulfiram in normal subjects and recovering alcoholics. Pharmacol Ther
39:265–270
Bigal ME, Sheftell FD, Rapoport AM, Tepper SJ, Lipton RB (2002) Chronic daily headache:
identification of factors associated with induction and transformation. Headache 42:575–581
Brown CR, Jacob P 3rd, Wilson M, Benowitz NL (1988) Changes in rate and pattern of caffeine
metabolism after cigarette abstinence. Clin Pharmacol Ther 43(5):488–491
Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H (2006) Coffee, CYP1A2 genotype, and
risk of myocardial infarction. JAMA 295(10):1135–1141
Del Coso J, Muñoz-Fernández VE, Muñoz G, Fernández-Elı́as VE, Ortega JF, Hamouti N,
Barbero JC, Muñoz-Guerra J (2012) Effects of a caffeine-containing energy drink on simulated
soccer performance. PLoS One 7(2):e31380
Favrod-Coune F, Broers B (2010) The health effect of psychostimulants: a literature review.
Pharmaceuticals 3:2333–2361
Freedman ND, Park Y, Abnet CC, Hollenbeck AR, Sinha R (2012) Association of coffee drinking
with total and cause-specific mortality. N Engl J Med 366(20):1891–1904
Goldstein J, Silberstein SD, Saper JR, Ryan RE Jr, Lipton RB (2006) Acetaminophen, aspirin, and
caffeine in combination versus ibuprofen for acute migraine: results from a multicenter,
double-blind, randomized, parallel-group, single-dose, placebo-controlled study. Headache
46:444–453
Greden JF, Walters A (1992) Caffeine. In: Lowinson JH et al (eds) Substance abuse,
a comprehensive textbook, 2nd edn. Williams & Wilkins, Baltimore, pp 356–370
Hackett PH (2010) Caffeine at high altitude: Java at base-cAMP. High Alt Med Biol 11(1):13–17
Herndon M (2010) FDA warning letters issued to four makers of caffeinated alcoholic beverages.
This beverages present a public health concern. U.S. Food and Drugs Administration.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm234109.htm. Accessed
2 May 2013
ICD-10 classification of mental and behavioural disorders: diagnostic criteria for research. WHO
http://www.who.int/substance_abuse/terminology/icd_10/en/index.html. Accessed 30 Apr 2013
Kabagambe EK, Wellons MF, Lipman TO, Lin FH (2013) Benefits and risks of caffeine and
caffeinated beverages. UpToDate. http://www.uptodate.com. Accessed 2 May 2013
Kawachi I, Willett WC, Colditz GA, Stampfer MJ, Speizer FE (1996) A prospective study of
coffee drinking and suicide in women. Arch Intern Med 156(5):521–525
Ker K, Edwards PJ, Felix LM, Blackhall K, Roberts I (2010) Caffeine for the prevention of injuries
and errors in shift workers. Cochrane Database Syst Rev CD008508
Klastky AL, Morton C, Udaltsova N, Friedman GD (2006) Coffee, cirrhosis and transaminases
enzymes. Arch Int Med 166:1190–1195
Knutti R, Rothweiler H, Schlatter C (1982) The effect of pregnancy on the pharmacokinetics of
caffeine. Arch Toxicol 5:187–192
Lopez-Garcia E, van Dam RM, Li TY, Rodriguez-Artalejo F, Hu FB (2008) The relationship of
coffee consumption with mortality. Ann Intern Med 148:904–914
452 T. Favrod-Coune and B. Broers
Macı́as J, Palacios RB, Claro E, Vargas J, Vergara S, Mira JA, Merchante N, Corzo JE, Pineda JA
(2008) High prevalence of hepatitis C virus infection among noninjecting drug users: associ-
ation with sharing the inhalation implements of crack. Liver Int 28(6):781–786
MacKenzie T, Comi R, Sluss P, Keisari R, Manwar S, Kim J, Larson R, Baron JA (2007) Metabolic
and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial.
Metabolism 56:1694–1698
Park S, Jang JS, Hong SM (2007) Long-term consumption of caffeine improves glucose homeo-
stasis by enhancing insulinotropic action through islet insulin/insulin-like growth factor
1 signaling in diabetic rats. Metabolism 56(5):599–607
Reissig CJ, Strain EC, Griffiths RR (2009) Caffeinated energy drinks-a growing problem.
Drug Alcohol Depend 99:1–10
Smit HJ (2011) Theobromine and the pharmacology of cocoa. Handb Exp Pharmacol 200:201–234
Smit HJ, Gaffan EA, Rogers PJ (2004) Methylxanthines are the psycho-pharmacologically active
constituents of chocolate. Psychopharmacology (Berl) 76(3–4):412–419
Wolk BJ, Ganetsky M, Babu KM (2012) Toxicity of energy drinks. Curr Opin Pediatr
24(2):243–251
Further Reading
Barranco Quintana JL, Allam MF, Serrano Del Castillo A, Fernández-Crehuet Navajas R (2007)
Alzheimer’s disease and coffee: a quantitative review. Neurol Res 29(1):91–95
Beaudoin MS, Graham TE (2011) Methylxanthines and human health: epidemiological and
experimental evidence. Handb Exp Pharmacol 200:509–548
Berg JE, Høstmark AT (1996) Cardiovascular risk factors in young drug addicts. Addict Biol
1(3):297–302
Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Giffin SL (2010) 2009 annual
report of the American Association of Poison Control Centers’ National Poison Data System
(NPDS): 27th annual report. Clin Toxicol (Phila) 48(10):979–1178
Childs E, de Wit H (2006) Subjective, behavioral, and physiological effects of acute caffeine in
light, nondependent caffeine users. Psychopharmacology (Berl) 185(4):514–523
Cornish HH, Christman AA (1957) A study of the metabolism of theobromine, theophylline, and
caffeine in man. J Biol Chem 228(1):315–323
Costa J, Lunet N, Santos C, Santos J, Vaz-Carneiro A (2010) Caffeine exposure and the risk of
Parkinson’s disease: a systematic review and meta-analysis of observational studies.
J Alzheimers Dis 20(Suppl 1):S221–S238
Dai B, Liu Y, Fu L, Li Y, Zhang J, Mei C (2012) Effect of theophylline on prevention of contrast-
induced acute kidney injury: a meta-analysis of randomized controlled trials. Am J Kidney Dis
60(3):360–370
Freedman ND, Everhart JE, Lindsay KL, Ghany MG, Curto TM, Shiffman ML, Lee WM, Lok AS,
Di Bisceglie AM, Bonkovsky HL, Hoefs JC, Dienstag JL, Morishima C, Abnet CC, Sinha R,
HALT-C Trial Group (2009) Coffee intake is associated with lower rates of liver disease
progression in chronic HCV. Hepatology 50:1360–1369
Freedman ND, Curto TM, Lindsay KL, Wright EC, Sinha R, Everhart JE, HALT-C TRIAL
GROUP (2011) Coffee consumption is associated with response to peginterferon and ribavirin
therapy in patients with chronic hepatitis C. Gastroenterology 140(7):1961–1969
Huxley R, Lee CM, Barzi F, Timmermeister L, Czernichow S, Perkovic V, Grobbee DE, Batty D,
Woodward M (2009) Coffee, decaffeinated coffee, and tea consumption in relation to incident
type 2 diabetes mellitus: a systematic review with meta-analysis. Arch Intern Med
169(22):2053–2063
Larsson SC, Wolk A (2007) Coffee consumption and risk of liver cancer a meta-analysis.
Gastroenterology 132:1740–1745
26 Addiction to Caffeine and Other Xanthines 453
Larsson SC, Männistö S, Virtanen MJ, Kontto J, Albanes D, Virtamo J (2008) Coffee and tea
consumption and risk of stroke subtypes in male smokers. Stroke 39:1681–1687
Larsson SC, Virtamo J, Wolk A (2011) Coffee consumption and risk for stroke in women. Stroke
42:908–912
Lucas M, Mirzaei F, Pan A, Okereke OI, Willett WC, O’Reilly ÉJ, Koenen K, Ascherio A (2011)
Coffee, caffeine, and risk of depression among women. Arch Intern Med 171(17):1571–1578
Malik VS, Popkin BM, Bray GA, Després JP, Willett WC, Hu FB (2010) Sugar-sweetened
beverages and risk of metabolic syndrome and type 2 diabetes: a meta-analysis. Diabetes
Care 33(11):2477–2483
Sharwood LN, Elkington J, Meuleners L, Ivers R, Boufous S, Stevenson M (2013) Use of
caffeinated substances and risk of crashes in long distance drivers of commercial vehicles:
case-control study. BMJ 346:f1140
Yew D, Laczek JT (2011) Caffeine toxicity. Medscape. http://emedicine.medscape.com/article/
821863-overview. Accessed 2 May 2013
Khat Addiction
27
Michael Odenwald, Axel Klein, and Nasir Warfa
Contents
27.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 456
27.2 The Khat Controversy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457
27.3 The History of Khat Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457
27.4 From a Niche Crop to a Cash Crop . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458
27.5 The Development from Traditional to Binge Use Patterns . . . . . . . . . . . . . . . . . . . . . . . . . . . 458
27.6 What Is Known About Khat Addiction? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 459
27.7 Measurement and Diagnosis of Khat Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461
27.8 Khat-Associated Neurocognitive Deficits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 462
27.9 Treatment of Khat Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 462
27.10 Other Psychiatric Disorders and Somatic Problems Associated with
Khat Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463
27.11 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 464
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 464
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 466
Abstract
Khat refers to the young and tender leaves and shoots of the khat tree (Catha
edulis). It is an evergreen tree that can be found in the Abyssinian highlands, the
Horn of Africa, Eastern and Southern Africa, the Arab peninsula, and Afghanistan.
M. Odenwald (*)
Klinische Psychologie, Zentrum f€
ur Psychiatrie Reichenau, Universität Konstanz, Reichenau,
Germany
e-mail: [email protected]
A. Klein
Centre for Health Service Studies, University of Kent, Canterbury, Kent, UK
e-mail: [email protected]; [email protected]
N. Warfa
Barts and The London School of Medicine and Dentistry, Centre for Psychiatry, Wolfson Institute
of Preventive Medicine, Queen Mary University of London, London, UK
e-mail: [email protected]
27.1 Introduction
Khat refers to the young and tender leaves and shoots of the khat tree (Catha edulis). It
is an evergreen tree of the Celastraceae family, normally reaching 6 m in height, but
in an equatorial climate it might grow to 25 m. Catha edulis can be found in the
Abyssinian highlands, the Horn of Africa, Eastern and Southern Africa, the Arab
peninsula, and Afghanistan. Khat has many names including qat (Yemen), jad/chat
(Ethiopia, Somalia), miraa (Kenya), or marungi (Uganda, Rwanda).
The khat leaves have been consumed for centuries for their mildly stimulating
properties caused by several alkaloids contained in the leaves. Among more than
40 known compounds, the alkaloid cathinone (S-(-)-a-aminopropiophenone) is
considered to be the main psychoactive compound, but it is unstable and swiftly
decomposes after harvesting. Cathinone resembles amphetamine in chemical struc-
ture and affects the central and peripheral nervous system and behavior similarly
(Kalix 1990). Recently, synthetic cathinone derivates such as mephedrone have
been introduced to the drug market, often under the label “legal highs” (EMCDDA
2012). More stable compounds of the khat leaves are cathine (S,S-(+)-norpseudoe-
phedrine) and other alkaloids which are at the same time metabolites of cathinone
and less potent central and peripheral stimulants.
While chewing the fresh leaves has ever since been the preferred use form, in the
past it was often only available in dried form, powder or paste. Today, soon after
harvesting, the twigs and shoots are artfully rolled into bundles and wrapped into
banana leaves in order to retain moisture; today, deep frozen transports are more and
more common. In most instances, bundles are the traded units, but leaves of lower
quality might also be marketed in standardized plastic bags. The leaves and tender
stems are usually chewed and kept in a tight wad in the cheek pocket. Within about
15–30 min the user experiences physiological excitability, euphoria, talkativeness,
and flow of ideas known in Arabic as “mirquaan.” This is followed by a quieter,
more introvert phase, giving way to a gradual comedown, and among excessive
chewers often restlessness, irritability, and depressive reaction. Users often experience
sleep problems during the following night and a hangover the next morning.
These unpleasant aftereffects motivate some khat chewers to carry on chewing
without stopping.
27 Khat Addiction 457
The controversy around khat and especially the question whether it is a drug versus
a part of culture or tradition is probably as old as use itself (Krikorian 1984). It has
been condemned by the Ethiopian orthodox church and the more fundamentalist
Islamic schools of thought particularly in Saudi Arabia, who consider it “haram.”
Islamic scholars in Yemen, Somalia, and Ethiopia by contrast integrated khat use
into religious life, including the study of the Holy Koran or to enhance religious
experience as practiced by Sufi mystics. During the colonial era, arguments about
moral degeneration, falling economic productivity, and the association with
political unrest motivated official and largely unsuccessful bans on khat (Gatter
2012; Warfa et al. 2007). Strong pro-khat movements prevented in most countries
legal restrictions.
The scientific discourse on khat shows similar fissures, usually along the lines of
academic discipline (Odenwald et al. 2010a). Medical and pharmacological
research approached khat with the underlying assumption that it is analogous to
other psychoactive drugs; consequently, research focused on the discovery of the
addictive substance in the leaves and on the laboratory-based study of cathinone.
Today, cathinone is listed in Schedule I and cathine in Schedule III of the interna-
tional Convention on Psychotropic Substances of 1971, but the khat leaves are not
internationally controlled.
Anthropologists and social scientists, by contrast, stressed the cultural functions
and traditional values (Anderson et al. 2007). They often oppose the medical
position, e.g., arguing that the physical effects cannot explain the functions of its
use and that addiction is a western concept that does not fully grasp the case of khat.
Medieval writings and legends confirm its longstanding use but also ambivalent
attitudes towards its effects described as helpful and joyful as well as noxious
(Krikorian 1984). Before the eighteenth century, its use was confided to certain
ethnic groups and producing areas where khat was an integral part of the culture,
i.e., religious ceremonies and rites of passage, but there only the rich and the
farmers themselves were regular chewers. The former used khat to get inspiration
for artistic expression in poetry and songs, chewed communally, in dedicated rooms
within private households often called “mafrishes.” The latter as well as long-
distance travelers used khat to overcome tiredness and hunger. But it was also
chewed during Muslim prayers and ceremonies as well as by students to be able to
study all night. The traditionally moderating khat culture regulated its use and
prevented large-scale misuse by rules such as restriction to afternoon and evening
hours and weekends as well as rites of passage. Outside the few traditional
producing areas, it was very rare, e.g., for medicinal purposes, and not noticed by
European travelers before the Swedish botanist Peter Forsskål (1732–1763). Since
then, its use became more and more prevalent and by the year 1900 the “khat party”
458 M. Odenwald et al.
Since the end of the nineteenth century with successive transport innovations, the
railway network, road haulage, and air cargo, khat has made its way from a niche
crop to a cash crop. For commercial purposes, nowadays, it is grown in the
highlands around the Horn of Africa, Southern Arabia, and along the Eastern
African coast in altitudes of 1,500–2,500 m above sea level. Within centuries, an
amazing variety of khat types have developed out of regional climatic and envi-
ronmental conditions and local cultivation habits which has been the base for the
recent marketing of different khat brands. After decades of steeply increasing
production, now the khat sector has economic significance for Ethiopia and
Yemen and to a smaller extent for Kenya too, where it provides more than two
million jobs, for farmer, pickers, packers, and traders, i.e., the source of income for
up to 15 million (Anderson et al. 2007; Gatter 2012). Within a few decades, khat has
become a large regional and international market without the involvement of
multinationals. Today, production is rising in traditional khat countries, while at
the same time expanding to other African countries (e.g., Uganda, Rwanda). But the
production increase and the accompanying development have considerably con-
tributed to environmental and social problems, e.g., deforestation and food insecu-
rity in Ethiopia or groundwater decline due to massive increase of irrigation
farming in Yemen (Gatter 2012).
Estimating the prevalence of khat use is difficult, as the consumption in the different
countries still largely depends on socioeconomic, ethnic, and geographic factors.
The current literature is a patchwork of different studies produced with different
methods. The general trend suggests use is spreading across the general population,
including groups who have no tradition of khat consumption. This includes countries
where it was previously unknown altogether. It is estimated that more than ten
million people are using khat recreationally on any one day (Odenwald et al. 2010a).
In Yemen different prevalence estimates vary between 60 % and 90 % of adult
males and between 10 % and 50 % of adult women. Different Household Budget
Surveys indicated that Yemenite households spent on average 9–10 % of their
income on buying khat, but this proportion was up to 40 % in the lowest income
section (Gatter 2012).
27 Khat Addiction 459
The compulsive use of the khat leaves has been described since colonial times
(Halbach 1972). Compared to other substances with misuse potential, experts
consider the khat leaves, however, to have a low potential for addiction and
physical and social harms (Nutt et al. 2007), and they are not recommended to be
scheduled or controlled under the international conventions (World Health
Organization 2006). In some countries, however, they are illegal, in others the
status is not clear, while they are not controlled at all in the traditional khat
460 M. Odenwald et al.
countries (Griffiths et al. 2010). While the khat leaves are considered to produce
only mild psychological addiction, cathinone is believed to have a higher addiction
potential than amphetamine (Kalix 1991).
The current opinion on withdrawal symptoms upon discontinuation is that they
are expected to be mild, to be brief, and to occur only after prolonged use (World
Health Organization 2006) and include profound lassitude; anergia; difficulty in
initiating normal activity; slight trembling lasting for several days after cessation;
and nightmares, often paranoid in nature, for example, being attacked, strangled, or
followed (e.g., Kennedy et al. 1980). However, the existing empirical base is
meager and not related to current excessive use patterns.
In the same token, today it is generally believed that khat use does induce some
tolerance (World Health Organization 2006). It has been argued that the chewing
mode of ingestion limits the possible amount to consume in a certain time and, thus,
tolerance development is usually prevented. This view can be criticized based on
recent definitions of tolerance. Among stimulant users, tolerance development, the
upward shift in the set point for reward, and the subsequent dysphoria (“opponent
process”) are closely related to the development of “binge” consumption patterns:
Users need to increase the dose and the frequency of drug administration in order to
experience the desired psychological effects. Thus, khat tolerance development
might not only include increases in the amount of consumption per time unit but
rather the extension of the time spent for consuming it which leads to an increase of
the absolute amount ingested. Recent studies and personal observations indicate
that a growing group of binge users consume khat for more than 24 h in a row in
such large quantities a novice would never manage (Patel et al. 2005; Nabuzoka and
Badhadhe 2000; Widmann 2012). While the development of tolerance to physio-
logical effects was reported (Nencini et al. 1984), no study has ever directly
targeted the topic of tolerance to desired psychological effects, e.g., euphoria.
Researchers early on recognized the potential of khat to induce psychological
dependence (e.g., Kennedy et al. 1980). This is best illustrated in descriptions of
typical scenes of inner city khat markets at the Horn of Africa or in Eastern Africa at
the time just before a khat delivery arrives (Hansen 2010). At theses hours of day,
users speed to khat markets frequently causing traffic accidents; an aggressive and
nervous atmosphere prevails until the khat trucks arrive. In contrast, khat users who
visit foreign countries are said to abstain without any difficulties without
replacement.
Observational data confirm the existence of a specific Patois among Somali khat
users (Odenwald et al. 2010b): “xaraaro” means feelings of craving and nervous-
ness which are experienced by habitual chewers at the time of day before their usual
khat intake starts; “dubaab”, i.e. nightmares involving the sensation of being
suffocated, are usually experienced by heavy chewers in the first days after cessa-
tion. The phenomenon of “jibane” involves the use of khat in a group setting in
order to reduce aversive symptoms in the morning. The term “bac,” which literally
means “plastic bag,” refers to a transitory phenomenon involving paranoid anxiety
and illusions when khat users on their way home at night mistake litter on the street
for enemies or dangerous animals.
27 Khat Addiction 461
In recent years khat has increasingly been used in combination with other substances
like alcohol or benzodiazepines. Khat chewers usually smoke tobacco during khat
sessions and consume carbonated soft drinks; this goes so far that it is difficult to find
any khat chewer who doesn’t smoke. Inversely, there are many occasional smokers that
do only smoke during khat sessions (al’Absi and Grabowski 2012). In a recent study,
khat chewers used more tobacco, khat dependence correlated with tobacco depen-
dence, and there were signs of an enhancement effect (Kassim et al. 2011).
The UNODC’s annual World Drug Reports list khat in the statistics of “primary
substances of abuse”. According to these reports, khat-addicted individuals consti-
tute the largest group in Ethiopia and the second largest group in Kenya (United
Nations Office on Drugs and Crime 2012). However, the UNODC statistics have to
be treated with caution as they reflect the reporting of governmental statistics to the
UN and as the absolute numbers of provided treatments is very small in these
countries. But single research reports verify the existence of this group of patients
not just in the countries mentioned above but also in Uganda. Khat-dependent
individuals who seek treatment are usually admitted to psychiatric and general
substance treatment units. But the number of cases is small and the psychiatric and
addiction treatment facilities in this region of the world are few. Specialized khat
addiction programs or treatment facilities are nonexistent. Studies from these
countries describing the development or evaluation of khat addiction treatment
are lacking. But khat users in the traditional khat countries frequently report
motivation to and failed attempts to quit its use (Odenwald et al. 2012). We reported
before the observation that during the last 12 years, various local nongovernmental
organizations in Ethiopia, Somalia, Kenya, and Uganda have started to address
khat addiction as shown by many hand-painted billboards in Somali towns
promoting “khat counseling” together with other psychosocial services such as
“HIV counseling” (Odenwald et al. 2007). This reflects the demand for
khat-related treatment in the traditional khat countries. However, no studies exist
that addressed this counseling approach.
27 Khat Addiction 463
In western countries, khat addiction has been targeted by projects in the UK,
Denmark, and Sweden. While some of the projects included khat addicts into the
general addiction treatment settings, i.e., together with people dependent on other
types of substances, others developed programs specifically for homogeneous
ethnic subgroups, mostly Somalis. Observations from these projects confirm that
patients with khat addiction usually are immigrants from the traditional khat
countries, that utilization is poor, and that those who utilize these treatment
facilities have comorbid other substance-related and psychiatric problems.
Recently, khat addiction treatment has been included into web-based advertise-
ments of private substance treatment centers; among a range of different explana-
tions, this might suggest that there is a certain demand for this kind of treatment.
Scientific publications from western countries on khat addiction treatment are
missing. Systematic research on medication to treat khat addiction is equally
nonexistent. There are only a few reports that mentioned the use and effect of
certain psychopharmacological drugs in single cases.
Khat use has been associated to the presence of mental distress or disorders (Belew
et al. 2000). While there is no evidence for a simple causal relationship or a noxious
effect of khat use per se (Warfa et al. 2007), functional substance use to counteract
symptoms of depression, posttraumatic stress disorder, as well as medication side
effects have been described (Teferra et al. 2011). In these individuals, khat use may
be a risk factor for the development of suicidal thoughts (Bhui et al. 2003) and
psychotic symptoms (Odenwald et al. 2009). Today, more than 20 case descriptions
of khat-induced brief psychotic episodes are available in the medical literature.
Most reported excessive khat use before the onset of psychotic symptoms and
violent behavior in the course of the acute psychiatric development. Most of them
had completely remitted after 2–4 weeks, given abstinence is maintained even
without medication. But, most of these cases had repeated such episodes. Also
the exacerbation of psychotic symptoms in patients with preexisting psychotic
disorders has been reported (Bimerew et al. 2007; Teferra et al. 2011). A few and
weak studies found first support in favor of the hypothesis that early, chronic and
severe khat use might be a causal factor for the development of chronic psychotic
disorders (Odenwald et al. 2005).
Besides psychiatric sequelae, numerous somatic health problems have been
associated with khat use (Al-Motarreb et al. 2010; for detailed review see
Al-Habori 2005). As with mental health, moderate khat use seems not to be noxious
in most users and adverse effects are commonly linked with the currently growing
excessive use. There are many reports of severe physical harms among chronic
users, but other explanations have not been systematically ruled out, for example,
tobacco smoking which is frequently combined with khat use and pesticide content
in the leaves. Observed negative somatic consequences associated to khat use
464 M. Odenwald et al.
27.11 Conclusion
In sum, the topic of khat addiction urgently needs further empirical studies. Current
evidence supports the hypothesis that excessive and prolonged khat use can produce
a dependence and neurocognitive deficit syndrome qualitatively similar to that pro-
duced by amphetamine. But the question of khat-related withdrawal and tolerance
needs further studying, especially related to current binge use patterns. For the
application of diagnostic criteria to khat, conventions are needed as well as the
development of reliable and valid research instruments. The current knowledge on
khat addiction treatment is very poor especially as khat users seldom utilize addiction
treatment services. It is urgently needed to develop effective and adequate treatment
concepts to be applied in the traditional khat use countries and among immigrant
communities elsewhere in the world; there are millions of people who potentially
benefit from such knowledge. Like amphetamines khat can be associated to psychosis
and other psychological and somatic disorders. Therefore, strong research designs are
needed to rule out alternative explanations and develop public health strategies.
References
al’Absi M, Grabowski J (2012) Concurrent use of tobacco and khat: added burden on chronic
disease epidemic. Addiction 107(2):451–452
Alemseged F, Haileamlak A, Tegegn A, Tessema F, Woldemichael K, Asefa M, Mamo Y,
Tamiru S, Abebe G (2012) Risk factors for chronic non-communicable diseases at gilgel
gibe field research center, southwest Ethiopia: population based study. Ethiop J Health Sci
22(S):19–28
Al-Habori M (2005) The potential adverse effects of habitual use of Catha edulis (khat). Expert
Opin Drug Saf 4(6):1145–1154
Al-Motarreb A, Al-Habori M, Broadley KJ (2010) Khat chewing, cardiovascular diseases and
other internal medical problems: the current situation and directions for future research.
J Ethnopharmacol 132:540–548
Anderson D, Beckerleg S, Hailu D, Klein A (2007) The Khat controversy: stimulating the debate
on drugs. Berg, Oxford
Awas M, Kebede D, Alem A (1999) Major mental disorders in Butajira, southern Ethiopia. Acta
Psychiatr Scand Suppl 397:56–64
Belew M, Kebede D, Kassaye M, Enquoselassie F (2000) The magnitude of khat use and its
association with health, nutrition and socio-economic status. Ethiop Med J 38(1):11–26
Bhui K, Warfa N (2010) Trauma, khat and common psychotic symptoms among Somali
immigrants: a quantitative study. J Ethnopharmacol 132:549–553
Bhui K, Abdi A, Abdi M, Pereira S, Dualeh M, Robertson D, Sathyamoorthy G, Ismail H (2003)
Traumatic events, migration characteristics and psychiatric symptoms among Somali
refugees–preliminary communication. Soc Psychiatry Psychiatr Epidemiol 38(1):35–43
27 Khat Addiction 465
Bimerew MS, Sonn FCT, Korlenbout WP (2007) Substance abuse and the risk of readmission of
people with schizophrenia at Amanuel Psychiatric Hospital, Ethiopia. Curationis 30(2):74–81
Colzato LS, Ruiz M, Van den Wildenberg WP, Bajo M, Hommel B (2010) Long-term effects
of chronic khat use: impaired inhibitory control. Front Psychol 1:129
Colzato LS, Ruiz MJ, van den Wildenberg WP, Hommel B (2011) Khat use is associated with
impaired working memory and cognitive flexibility. PLoS One 6(6):e20602
Colzato LS, Ruiz MJ, van den Wildenberg WP, Hommel B (2012) Khat use is associated with
increased response conflict in humans. Hum Psychopharm 27(3):315–321
Elmi AS (1983) The chewing of khat in Somalia. J Ethnopharmacol 8(2):163–176
EMCDDA (2012) Annual report 2012: the state of the drugs problem in Europe. European
Monitoring Centre for Drugs and Drug Addiction, Lisbon
Gatter P (2012) Politics of Qat: the role of a drug in ruling Yemen. Jemen-Studien, vol Bd
20 1. Reichert, Wiesbaden
Griffiths P, Lopez D, Sedefov R, Gallegos A, Hughes B, Noor A, Royuela L (2010) Khat use and
monitoring drug use in Europe: the current situation and issues for the future.
J Ethnopharmacol 132(3):578–583
Halbach H (1972) Medical aspects of the chewing of khat leaves. Bull World Health Organ
47(1):21–29
Hansen P (2010) The ambiguity of khat in Somaliland. J Ethnopharmacol 132:590–599
Hoffman R, al’Absi M (2010) Khat use and neurobehavioral functions: suggestions for future
studies. J Ethnopharmacol 132(3):554–563
Hoffman R, al’Absi M (2012) Working memory and speed of information processing in chronic
khat users: preliminary findings. Eur Addict Res 19(1):1–6
Kalix P (1990) Pharmacological properties of the stimulant khat. Pharmacol Ther 48(3):397–416
Kalix P (1991) The pharmacology of psychoactive alkaloids from ephedra and catha.
J Ethnopharmacol 32(1–3):201–208
Kassim S, Croucher R (2006) Khat chewing amongst UK resident male Yemeni adults: an
exploratory study. Int Dent J 56(2):97–101
Kassim S, Islam S, Croucher R (2010) Validity and reliability of a severity of dependence Scale for
khat (SDS-khat). J Ethnopharmacol 132:570–577
Kassim S, Islam S, Croucher RE (2011) Correlates of nicotine dependence in U.K. resident
Yemeni khat chewers: a cross-sectional study. Nicotine Tob Res 13:1240
Kassim S, Hawash A, Johnston A, Croucher R (2012) Validation of self-reported khat chewing
amongst khat chewers: an exploratory study. J Ethnopharmacol 140(1):193–196
Kebede D, Alem A, Mitike G, Enquselassie F, Berhane F, Abebe Y, Ayele R, Lemma W, Assefa T,
Gebremichael T (2005) Khat and alcohol use and risky sex behaviour among in-school and
out-of-school youth in Ethiopia. BMC Public Health 5:109
Kennedy JG, Teague J, Fairbanks L (1980) Qat use in North Yemen and the problem of addiction:
a study in medical anthropology. Cult Med Psychiatry 4(4):311–344
Khattab NY, Amer G (1995) Undetected neuropsychophysiological sequelae of khat chewing in
standard aviation medical examination. Aviat Space Environ Med 66(8):739–744
Krikorian AD (1984) Kat and its use: an historical perspective. J Ethnopharmacol 12:115–178
Kroll J, Yusuf AI, Fujiwara K (2011) Psychoses, PTSD, and depression in Somali refugees in
Minnesota. Soc Psychiatry Psychiatr Epidemiol 46:481–493
Mikulica J (2012) Cambridge gambling task, spatial span and tower of Hanoi performance among
khat chewers. University of Konstant, Konstanz
Nabuzoka D, Badhadhe FA (2000) Use and perception of khat among young Somalis in a UK city.
Addict Res 8(1):5–26
Ndetei DM, Khasakhala LI, Ongecha-Owuor FA, Kuria MW, Mutiso V, Kokonya DA (2009)
Prevalence of substance abuse among patients in general medical facilities in Kenya. Subst
Abus 30(2):182–190
Nencini P, Ahmed AM, Amiconi G, Elmi AS (1984) Tolerance develops to sympathetic effects of
khat in humans. Pharmacology 28(3):150–154
466 M. Odenwald et al.
Nutt D, King LA, Saulsbury W, Blakemore C (2007) Development of a rational scale to assess the
harm of drugs of potential misuse. Lancet 369(9566):1047–1053
Odenwald M, Neuner F, Schauer M, Elbert TR, Catani C, Lingenfelder B, Hinkel H, Hafner H,
Rockstroh B (2005) Khat use as risk factor for psychotic disorders: a cross-sectional and case-
control study in Somalia. BMC Med 3(1):5
Odenwald M, Hinkel H, Schauer E, Neuner F, Schauer M, Elbert TR, Rockstroh B (2007)
The consumption of khat and other drugs in Somali combatants: a cross-sectional study.
PLoS Med 4(12):e341
Odenwald M, Hinkel H, Schauer E, Schauer M, Elbert T, Neuner F, Rockstroh B (2009) Use
of khat and posttraumatic stress disorder as risk factors for psychotic symptoms: a study of
Somali combatants. Soc Sci Med 69(7):1040–1048
Odenwald M, Klein A, Warfa N (2010a) Introduction to the special issue: the changing use and
misuse of khat (Catha edulis)–tradition, trade and tragedy. J Ethnopharmacol 132(3):537–539
Odenwald M, Warfa N, Bhui K, Elbert T (2010b) The stimulant khat–another door in the wall?
A call for overcoming the barriers. J Ethnopharmacol 132(3):615–619
Odenwald M, Lingenfelder B, Peschel W, Haibe FA, Warsame AM, Omer A, Stockel J, Maedl A,
Elbert T (2012) A pilot study on community-based outpatient treatment for patients with
chronic psychotic disorders in Somalia: change in symptoms, functioning and co-morbid
khat use. Int J Ment Heal Syst 6(1):8
Othieno CJ, Kathuku DM, Ndetei DM (2000) Substance abuse in outpatients attending rural and
urban health centres in Kenya. East Afr Med J 77(11):592–595
Patel SL, Wright S, Gammampila A (2005) Khat use among Somalis in four English cities.
vol Home Office Online Report 47/05. Home Office
Teferra S, Hanlon C, Alem A, Jacobsson L, Shibre T (2011) Khat chewing in persons with severe
mental illness in Ethiopia: a qualitative study exploring perspectives of patients and caregivers.
Transcult Psychiatry 48(4):455–472
Tulloch AD, Frayn E, Craig TK, Nicholson TR (2012) Khat use among Somali mental health
service users in South London. Soc Psych Psych Epid 47(10):1649–1656
United Nations Office on Drugs and Crime (2012) World drug report 2012. United Nations,
New York
Warfa N, Klein A, Bhui K, Leavey G, Craig T, Stansfeld SA (2007) Khat use and mental illness:
a critical review. Soc Sci Med 65:309–318
Weir S (1985) Qat in Yemen: consumption and social change. British Museum Publications
Limited, London
Widmann M (2012) Trauma and psychotic symptoms among khat users – a pilot study with Somali
refugees. University of Konstanz, Konstanz
World Health Organization (2006) WHO Expert Committee on Drug Dependence, Thirty-fourth
report. WHO Technical Report Series No. 942. WHO, Washington, DC
Further Reading
Al-Habori M (2005) The potential adverse effects of habitual use of Catha edulis (khat). Expert
Opin Drug Saf 4(6):1145–1154
Griffiths P, Lopez D, Sedefov R, Gallegos A, Hughes B, Noor A, Royuela L (2010) Khat use
and monitoring drug use in Europe: the current situation and issues for the future.
J Ethnopharmacol 132(3):578–583
Hoffman R, al’Absi M (2010) Khat use and neurobehavioral functions: suggestions for future
studies. J Ethnopharmacol 132(3):554–563
Kassim S, Hawash A, Johnston A, Croucher R (2012) Validation of self-reported khat chewing
amongst khat chewers: an exploratory study. J Ethnopharmacol 140(1):193–196
Odenwald M, Warfa N, Bhui K, Elbert T (2010) The stimulant khat–another door in the wall?
A call for overcoming the barriers. J Ethnopharmacol 132(3):615–619
Opioid Addiction: Short- and Long-Acting
Opioids 28
Marta Torrens, Francina Fonseca, Liliana Galindo, and Magi Farré
Contents
28.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 468
28.2 Opioids: Pharmacology and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 468
28.2.1 Pharmacology of Opioids and Endogenous Opioid System . . . . . . . . . . . . . . . . . . 468
28.2.2 Treatment of Opioid-Related Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485
28.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 494
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 494
Abstract
Opium is the natural product obtained from the juice of the opium poppy (Papaver
somniferum). Opiates include all natural plant alkaloids, such as morphine,
codeine, and thebaine, and many semisynthetic derivatives. An opioid is any
compound, regardless of the structure, which has the functional and pharmacolog-
ical properties of an opiate. Endogenous opioids are natural ligands for opioid
M. Torrens (*)
Addiction Unit Hospital del Mar Medical Research Institute (IMIM), Universidad Autònoma de
Barcelona, Barcelona, Spain
e-mail: [email protected]
F. Fonseca
Addiction Unit Hospital del Mar Medical Research Institute (IMIM), Instituto de Neuropsiquiatrı́a
y Adicciones, Parc de Salut Mar, Barcelona, Spain
e-mail: [email protected]
L. Galindo
Hospital del Mar Medical Research Institute (IMIM), Universidad Autònoma de Barcelona,
Barcelona, Spain
e-mail: [email protected]
M. Farré
Pharmacology Unit Hospital del Mar Medical Research Institute (IMIM), Universidad Autònoma
de Barcelona, Barcelona, Spain
e-mail: [email protected]
28.1 Introduction
Opium is the natural product obtained from the juice of the opium poppy (Papaver
somniferum). Opiates include all natural plant alkaloids, such as morphine, codeine,
and thebaine, and many semisynthetic derivatives. An opioid is any compound,
regardless of the structure, which has the functional and pharmacological properties
of an opiate. Endogenous opioids are natural ligands for opioid receptors found in
animals. Synthetic compounds include hydrocodone; oxycodone; hydromorphone;
heroin; antagonists such as naloxone, naltrexone, and nalmefene; and partial
agonists such as buprenorphine (Yaksh and Wallace 2011).
Opiates and opioids act on three opioid receptors (mu, kappa, and delta) which are
widely distributed in the brain and are associated with reward stimuli (Kristensen
et al. 1995). Endogenous opioids, called endorphins, are the ligands of these receptors
and play a central role in establishing habits and responses for survival and pain relief;
the opioid endogenous system plays an important role in opioid addiction (Mayer and
Hollt 2006), and also it has been implicated in the pathophysiology of dependence of
alcohol and cocaine (Kreek et al. 2009). The three opioid receptors belong to G protein
receptor family, and its structure has an extracellular N-terminus, seven transmem-
brane domains, three extra- and intracellular loops, and an intracellular C-terminus.
Agonist binding to these receptors results in conformational changes of the receptor
and the activation of the G protein cycle, affecting the intracellular effectors:
adenylate cyclases and Ca2+/K+ ion channels. The final effect in the cell is the
reduction of cAMP levels, the inhibition of the Ca2+ current, and the increase in the
28 Opioid Addiction: Short- and Long-Acting Opioids 469
Table 28.1 Classification of pharmacological opioid ligands based on its affinity for the opioid
receptors (m, d, k)
Mu Delta Kappa Others
Morphine Ag+++ Ag+ Ag+
Diacetylmorphine Ag+++ Ag+ Ag+
Methadone Ag+++ Ag+ Ag++ NMDA antagonist
Codeine Ag++
Buprenorphine PA An+++ An++
Oxycodone Ag+++
Hydromorphone Ag+++ Ag+
Hydrocodone Ag+++
Meperidine (pethidine) Ag+++ Ag+ Ag+ Serotonergic activity
Pentazocine An+ Ag+ Ag+
LAAM Ag+++
Tramadol Ag+ Norepinephric and
serotonergic activity
Tapentadol Ag+ Norepinephric activity
Naloxone An+++ An+ An++
Naltrexone An+++ An+ An+++
Nalmefene An+++ An+ An++
The number of symbols “+” is an indication of potency
Ag agonist, PA partial agonist, An antagonist
extracellular K+ current. These changes tend to decrease the excitation of the neuron
and inhibit the neurotransmission. Depending on the capacity to promote changes in
the G protein, ligands are classified into full opioid agonists, partial agonists, antag-
onists, and agonists–antagonists (Table 28.1) (Schäfer 2011).
• An agonist is a substance that is capable of binding to a receptor, producing their
activation and causing a biochemical or cellular response.
• An antagonist is the opposite of an agonist in the sense that as an antagonist it
also binds to a receptor, but does not activate the receptor and blocks its
activation by agonists.
• A partial agonist activates the receptor, but does not cause much effect as a full
agonist, and has a ceiling of maxim effect inferior than the agonist.
28.2.1.2 Morphine
Morphine is a natural product of the seeds of the poppy plant. Chemically, mor-
phine is an alkaloid that belongs to the class of phenanthrenes. Morphine is
prescribed primarily as a high-potency analgesic. Morphine is metabolized by
glucuronide conjugation to morphine-6-glucuronide (M6G) and morphine-3-
glucuronide. M6G has mu receptor agonist activity and is approximately twice as
potent as morphine in humans. In chronic administrations, M6G has a significant
portion of the analgesic actions of morphine, and its plasma concentration exceeds
those of morphine.
During the last years, slow-release oral morphine (SROM) has been proposed as
an alternative maintenance pharmacotherapy for treatment of opioid dependence
with retention rates similar to methadone (from 80.6 % to 95 %); also, uncontrolled
studies showed improvements in quality of life, withdrawal symptoms, craving, and
additional drug consumption (Jegu et al. 2011).
Pharmacodynamics
Morphine is the prototype for opioid agonist actions. Morphine is a selective
agonist at the mu-opioid receptor at lower doses. There are described central and
peripheral actions.
The main central actions are:
(a) Sedation: at higher doses, it could produce stupor, sleep, and coma. It worsens
the psychomotor performance. At very high doses, convulsions can appear.
(b) Euphoria: it produces euphoria, pleasure, and a well-being feeling and reduces
anxiety. The euphoria has been linked to the abuse potential of opioids.
(c) Analgesia: morphine can reduce the sensorial and affective components of
pain. It can relieve and suppress acute and chronic pain. This action is related
with the mu agonist action; mu receptors control the pain pathways in the
medulla. Also, it has actions in the limbic and cortical systems that reduce the
negative perception of pain.
(d) Respiratory depression: morphine can reduce the activity at the pontine
respiratory center. It reduces the sensitivity to CO2 and hypoxemia. It reduces
the number of breaths per minute and can end in an apnea. This effect is dose
dependent and directly relates with the mu agonism.
28 Opioid Addiction: Short- and Long-Acting Opioids 471
(e) Antitussive: it depresses the cough reflex at least in part by a direct effect on the
cough center in the medulla. This mechanism is not well known and has no
relation with analgesia or respiratory depression.
(f) Miosis: this effect is related with the disinhibition of the Edinger–Westphal
nucleus at the oculomotor nerve. This effect does not show tolerance and could
be adequate to detect recent use of opioids.
(g) Nausea and vomit: it is observed more frequently after the first administra-
tions. It is caused by direct stimulation of the chemoreceptor trigger zone for
emesis in the area postrema of the medulla.
(h) Neuroendocrine actions: morphine actions in the hypothalamus inhibit the
release of gonadotropin-releasing hormone and corticotrophin-releasing hor-
mone, producing a decrease in the luteinizing hormone, follicle-stimulating
hormone, adrenocorticotropic hormone (ACTH), and beta-endorphin. It also
stimulated the secretion of the antidiuretic hormone (ADH). By its effects in the
hypothalamus, also a central hypothermia is observed.
(i) Muscular tone: myoclonus is a rare side effect, ranging from mild twitching to
generalized spasm. In anesthetic use muscular rigidity can be observed.
The main peripheral actions are:
(a) Gastrointestinal: morphine can produce an increase in the tone of muscles of the
gastrointestinal tract, including the sphincters, and a reduction in the motility. As
a consequence, there is a reduction in the gastric emptying and in the peristaltism
and a contraction of sphincter. Clinically it is related with constipation.
(b) Cardiovascular: it could produce hypotension by its action in the vasomotor
center and by vasodilatation. Also a vagal bradycardia has been described.
Also, there is a potential to increase intracranial pressure.
(c) Histamine release: in the face, neck, and upper thorax, there is a feeling of
heat, flushing, and pruritus.
(d) Renal: morphine increases the tone of the detrusor muscle of bladder.
Pharmacokinetics
The pharmacokinetic properties of morphine and the rest of opioids described
in this chapter are summarized in Table 28.2. The pharmacokinetics of morphine
and its metabolites vary, depending on the route of administration. The oral bioavail-
ability ranges from 35 % to 75 %, with a plasma half-life ranging from 2 to 3.5 h.
The half-life is less than the time course of analgesia, which is 4–6 h, thus reducing the
accumulation. Morphine as other opioids presents a significant first-pass metabolism
in the liver with oral dosing. Morphine is biotransformed mainly by hepatic
glucuronidation to the major but inactive metabolite morphine-3-glucuronide (M3G)
and the biologically active morphine-6-glucuronide (M6G) compound in a lower
percentage (10 %). The M6G has a longer elimination half-life than morphine (4 h
vs. 2 h) and has a more powerful analgesic activity. This metabolite is related with both
the pharmacological effect and the toxicity of morphine. Thus, the equivalence between
parenteral and oral morphine varies depending on the frequency of the administration,
being 1:6 after a single administration and 1:2 or 1:3 after multiple doses; this is due to
the high concentrations of M6G that are reached after oral treatment.
472 M. Torrens et al.
(d) Black heroin or black tar heroin: as its name indicates, its aspect is similar to
tar; it is a black and sticky substance. It comes from America and its purity is
around 20 %. It is used for injection.
Pharmacodynamics
Heroin acts as a mu agonist through its metabolites 6-monoacetylmorphine
(6-MAM) and morphine. The effects of heroin are the same as other mu-opioid
agonists. With heroin use, thyroid hormone levels may be elevated because of
raised thyroid-binding globulin; thus, there are increased measures without
abnormal function (Kreek 1978). Heroin, as other short-acting opioids, reduces
rosettes formed by human T lymphocytes (Kreek 1978). The possible explanation
could be the increase of cortisol levels during opioid withdrawal and the consequent
suppression of immune function (Novick et al. 1989).
Pharmacokinetics
Heroin itself has no intrinsic opioid activity; but it is a very effective prodrug and
metabolized in humans to active opioid compounds first by deacetylation to the
active 6-monoacetylmorphine (6-MAM) and then by further deacetylation to mor-
phine, when administered by parenteral route (Inturrisi et al. 1984). The bioavail-
ability of diacetylmorphine, when measured by morphine concentrations, is 80 %
by intranasal route, 89 % by the smoked route, and 45 % in the chasing the dragon
type of use (Hendriks et al. 2001). Oral heroin has complete first-pass metabolism
(Inturrisi et al. 1984) with an oral bioavailability of 20–50 % and has very limited
systemic bioavailability (only 6-MAM and morphine can be found in the blood).
Compared to morphine, heroin given intramuscularly is about two times as potent
as morphine for pain relief with a faster onset of peak mood effect; however, it has
less sustained effect (Cone et al. 1993).
Heroin has an average half-life in blood of 3 min after intravenous administration;
the half-life of 6-monoacetylmorphine in humans appears to be 3–10 min (Inturrisi
et al. 1984). The blood clearance of heroin is greater than the upper range of hepatic
blood flow in humans, indicating that organs other than the liver are likely involved
in the metabolism of heroin, such as the gastrointestinal wall and the kidney (Inturrisi
et al. 1984), as well as hepatic carboxylesterases such as butyrylcholinesterase
(Kamendulis et al. 1996).
The use of intranasal, intramuscular, and subcutaneous heroin all produces peak
blood levels of heroin or 6-monoacetylmorphine within 5 min; however, intranasal
use has about half the relative potency (Cone et al. 1993).
28.2.1.4 Methadone
Pharmacodynamics
Methadone is a semisynthetic opioid agonist that is used in the chronic treatment of
pain and in the opioid dependence disorder. It was first synthesized by Bayer as an
analgesic in Germany in the late 1930s and first studied for human use in the 1950s
in the United States. It has been used as a maintenance treatment for heroin
addiction since the first years of the 1960s (Dole et al. 1966).
474 M. Torrens et al.
Pharmacokinetics
Methadone is rapidly absorbed after an oral dose, it can be detected in the blood at
15–45 min after oral administration, and peak plasma concentrations occur at 2–4 h
after dosing (Eap et al. 2002). The oral bioavailability of methadone was found to
be around 70–80 % in a range of doses of 10–60 mg with large intersubject
variations. Methadone is highly bound to plasma proteins, including albumin,
lipoproteins, and mainly to alpha-1-glycoprotein. Enantiomeric differences are
also relevant in protein binding (the unbound fraction for (S)-methadone is 10 %
while for the (R)-enantiomer is 14 %) and its metabolic disposition. Although
administered as a racemic mixture that contains the same amounts of (R)-metha-
done and (S)-methadone, the (R)-/(S)-methadone ratio varies significantly over
the 24-h administration interval in steady-state conditions; and also, large
interindividual differences can be seen in the (R)-/(S)-methadone ratio
(Eap et al. 1996). All these variables might contribute to interindividual response
differences to methadone treatment. Methadone is extensively metabolized in the
body, mainly by CYP3A4 in liver, and in the intestinal epithelium, and to a lesser
extent by CYP2B6 and CYP2D6. Its main metabolite (2-ethylidene-1,5-dimethyl-
3,3-diphenylpyrrolidine (EDDP)) is inactive: it is formed by N-demethylation
and spontaneous cyclization methadone half-life is about 28 h with a large
interindividual variability (between 4 and 91 h). (R)-methadone has a longer
half-life than (S)-methadone (38 vs. 29 h, respectively). After chronic administra-
tion, a reduction in half-life (from 55 to 22 h) has been detected because it
induces its own metabolism regulated by cytochrome P450 CYP3A4 (Wolff
et al. 2000).
The elimination of methadone is mostly due to metabolic clearance. The limited
amounts of circulating drug that undergo glomerular filtration are partially
reabsorbed by the kidney tubules, and this reabsorption is pH dependent. Metha-
done clearance varies from 23 to 210 ml/min, and there are significant differences
between both enantiomers (158 ml/min vs. 129 ml/min for (R)- and (S)-methadone,
respectively). Urinary pH has profound effects on methadone excretion and on the
volume of distribution of the drug. By keeping the urinary pH constant, the
interindividual differences of methadone elimination and plasma concentrations
are considerably reduced.
28.2.1.5 Codeine
Codeine is one of several naturally occurring alkaloids found in opium. It is
methylmorphine, with methyl substitution on the phenolic hydroxyl group of
morphine. It is more lipophilic than morphine and thus crosses the blood–brain
barrier faster. Its oral bioavailability is greater than that of morphine.
476 M. Torrens et al.
Pharmacodynamics
Codeine has very low affinity for opioid receptors; it is active because it is
metabolized in part to morphine. Codeine is commonly used to suppress cough at
doses lower than used for analgesia (starting with 10–20 mg given orally), which
can be increased to higher doses for chronic (lower airway) cough. Codeine reduces
cough via a central mechanism, with doses greater than 65 mg not indicated owing
to little increased effect with increasing side effects (Yaksh and Wallace 2011).
Pharmacokinetics
Codeine undergoes O-dealkylation to morphine. The conversion is catalyzed by
CYP2D6 (the same enzyme also converts dihydrocodeine, hydrocodone, and oxyco-
done). Other metabolites are mostly inactive and excreted in the urine; about 10 % are
demethylated to morphine via CYP2D6, which are mostly responsible for the
analgesic effect of codeine. Genetic variations in this enzyme system, complete or
partial lacking of CYP2D6 (poor metabolizers), may result in lower or no production
of morphine, and the subjects carrying this polymorphism would experience less
effects of codeine, but those with multiple duplications of CYP2D6 (ultra metabolizer,
ultrafast metabolizer) can transform abnormally large amounts of codeine into
morphine and have the risk of intoxication. Repeated doses of codeine may result in
the accumulation of the active metabolite M6G in patients with renal disease.
28.2.1.6 Buprenorphine
Buprenorphine is a semisynthetic opioid that, like oxycodone, is derived from
thebaine. The chemical structure of buprenorphine is that of an oripavine with a
C7 side chain, which contains a tert-butyl group. It is primarily mu-opioid receptor
partial agonist and a kappa antagonist with a ceiling effect. Buprenorphine alone
and in combination with naloxone was approved in 2002 by the FDA as an office-
based sublingual treatment for heroin and opioid addiction (Borg et al. 2009).
Norbuprenorphine is a major metabolite of buprenorphine in humans, with activity
at the mu-opioid receptor (Huang et al. 2001).
Pharmacodynamics
Initially developed as an analgesic, buprenorphine has been shown in most studies
to be as effective as morphine in many situations. It is 25–50 times more potent than
morphine. Buprenorphine has some modest kappa-opioid receptor activity, and it
has been shown that the kappa activity of buprenorphine is that of an antagonist
(Cowan 2007). Also, an agonistic effect on the opioid receptor-like (ORL1) recep-
tor has been described that has been also related to its characteristic ceiling effect
(Lutfy and Cowan 2004). Buprenorphine has high affinity for, but low intrinsic
activity at, mu receptors and displaces some full opioid agonists from receptors
(Strain et al. 2002). For this reason, and because of buprenorphine’s higher affinity
for the mu receptor, full agonists cannot displace it and therefore will not exert a
dose-related opioid effect on the receptors already occupied by buprenorphine, and
also it can induce a withdrawal syndrome in subjects using full opioid agonists
(Comer et al. 2001; Strain et al. 1995).
28 Opioid Addiction: Short- and Long-Acting Opioids 477
Pharmacokinetics
Buprenorphine has poor gastrointestinal bioavailability and fair sublingual bioavail-
ability (Brewster et al. 1981). FDA-approved formulations of the drug for the
treatment of opioid addiction are in the form of sublingual tablets that are held
under the tongue and absorbed through the sublingual mucosa; also, a sublingual
buprenorphine–naloxone film has been recently approved in some countries
(Lintzeris et al. 2013). Concentrations in blood peak within 5 min of intramuscular
injection and within 1–2 h of oral or sublingual administration. About 96 % of the
circulating drug is bound to protein. Both N-dealkylated and conjugated metabolites
are detected in the urine, but most of the drug is excreted unchanged in the feces.
Like morphine, the major metabolic pathway for buprenorphine is
glucuronidation, not the oxidation. Buprenorphine is metabolized to norbupre-
norphine, which occurs by dealkylation in the cytochrome P450-related enzyme
3A4 system, of which buprenorphine itself is a weak inhibitor (Yaksh and Wallace
2011). Buprenorphine undergoes extensive first pass in the liver; thus, it is admin-
istered sublingually with 50–60 % bioavailability.
A high percentage of buprenorphine is bound to plasma protein. The 3A4
metabolism involves some possible interactions with other drugs as antiretrovirals
being less than with methadone; however, buprenorphine has not been so exten-
sively studied (McCance-Katz and Mandell 2010).
The terminal elimination half-life of buprenorphine is long, and there is consider-
able variation in reported values (mean values ranging from 3 to 44 h). Most of a dose
of buprenorphine is eliminated in the feces, with approximately 10–30 % excreted in
urine (Elkader and Sproule 2005). Buprenorphine has a long duration of action
(24–48 h) when administered on a chronic basis, not because of its pharmacokinetic
profile but because of its very slow dissociation from mu-opioid receptors.
Despite the ceiling effect of buprenorphine as previously described, there have
been a number of reported cases of deaths in Europe with concurrent benzodiaze-
pine abuse (Lintzeris et al. 2007). After the report in many countries of the
buprenorphine diversion and the intravenous misuse, a new formulation was
developed in combination with naloxone (Yokell et al. 2011). In this formulation,
478 M. Torrens et al.
28.2.1.7 Oxycodone
Oxycodone is a semisynthetic compound derived from thebaine, with agonist
activity, primarily at mu receptors. Oxycodone has been used clinically since the
early 1900s. It is combined with aspirin or acetaminophen for moderate pain and is
available orally without coanalgesic for severe pain. It is a popular drug of abuse,
especially in the controlled-release formulation, which can be crushed for a
potentially toxic, rapid “high” comparable to the effects of the immediate-release
formulation (Webster et al. 2012).
Pharmacokinetics
The onset of action begins after 1 h, and in controlled-release form, it lasts for
approximately 12 h, with a plasma half-life of 3–4 h for the immediate release. Stable
plasma levels are achieved within 24 h. Oral bioavailability ranges from 60 % to 87 %,
with 45 % protein bound. Oxycodone is mostly metabolized in the liver, with the
remainder as well as the metabolites metabolized in the kidneys. It is O-demethylated
(CYP2D6) to oxymorphone and N-demethylated (CYP3A4 and CYP3A5 mediated)
to noroxycodone (more abundant) (Lugo and Kern 2004). Oxymorphone is also
a potent analgesic, and noroxycodone is a weaker analgesic (Lugo and Kern 2004).
In terms of protein binding and lipophilicity, oxycodone is similar to morphine,
with slightly longer half-life and greater bioavailability. Unlike morphine,
oxycodone is metabolized mostly by the cytochrome enzyme CYP2D6.
28.2.1.8 Hydromorphone
Hydromorphone is a semisynthetic opioid agonist and a hydrogenated ketone of
morphine. It was first synthesized in Germany in 1921 and was introduced into clinical
practice by 1926 (Murray and Hagen 2005). Hydromorphone has commonly been
viewed as a second-line drug in the treatment of pain, although being more potent
than morphine (five times more potent when given orally and 8.5 times as potent when
given intravenously) (Murray and Hagen 2005). It is used for the treatment of acute
pain, chronic cancer pain, and, to a lesser extent, chronic nonmalignant pain (Murray
and Hagen 2005). It is excreted along with its metabolites by the kidney. It can be given
intravenously, by infusion, orally, and per rectum, with low oral bioavailability.
Recently, an osmotic controlled-release oral delivery system (OROS)
hydromorphone extended release has been designed, which allows once-daily
dosing. Some clinical trials have been performed to evaluate the convertibility of
other opioids in chronic pain. The side effects are comparable to other opioids.
28 Opioid Addiction: Short- and Long-Acting Opioids 479
Pharmacokinetics
Hydromorphone is shorter acting than morphine. It is derived from morphine,
although it may also be produced in the body in small amounts by N-demethylation
of hydrocodone. It has an oral bioavailability of 30–40 %, with an analgesic onset
after 10–20 min, which peaks at about 30–60 min and persists for about 3–5 h. The
oral–parenteral ratio is about 5:1, with an equivalency of 1.5 mg of hydrocodone to
10 mg morphine (Murray and Hagen 2005).
28.2.1.9 Hydrocodone
Hydrocodone is a prescription drug frequently used for relatively minor (such as
dental) pain. It is often used in combination with acetaminophen; thus, there can
be hepatotoxicity associated with its abuse. Hydrocodone has the same potency as
morphine on a milligram-for-milligram basis.
Pharmacokinetics
Hydrocodone is well absorbed from the gastrointestinal tract. The peak plasma
concentration appears after 1.3 h of its administration and has a half-life of 2–4 h,
with a peak effect at 0.5–1 h (McEvoy 2007). Its duration of action is 3–4 h. It is
metabolized by CYP3A4 and CYP2D6, and its main metabolites are
norhydrocodone and hydromorphone. Codeine may show up as trace quantities of
hydrocodone in urine testing as up to 11 % of codeine is metabolized to
hydrocodone (Oyler et al. 2000), which could be misinterpreted as hydrocodone
abuse.
28.2.1.10 Meperidine
Meperidine or pethidine is a phenylpiperidine. It was first developed as an anticho-
linergic agent. It is mostly effective in the CNS and bowel; however, it is no longer
used for treatment of chronic pain owing to concerns regarding toxicity of its
metabolite and should not be used for more than 48 h or at doses above
600 mg/day. It has serotonergic activity when combined with monoamine oxidase
inhibitors (MAOIs), which can produce serotonin toxicity (clonus, hyperreflexia,
hyperthermia, and agitation); besides, the analgesic effects of meperidine are not
pronounced (Latta et al. 2002).
Pharmacodynamics
Meperidine is a potent mu agonist yielding strong analgesic actions. Peak respira-
tory depression is observed within 1 h of intramuscular administration, and there is
a return toward normal starting at 2 h, approximately. Like other opioids, meper-
idine causes pupillary constriction, increases the sensitivity of the labyrinthine
apparatus, and has effects on the secretion of pituitary hormones similar to those
of morphine. Meperidine sometimes causes CNS excitation, characterized by
tremors, muscle twitches, and seizures; these effects are due largely to the accu-
mulation of a metabolite, normeperidine. Meperidine has well-known local anes-
thetic properties, particularly noted after epidural administration. As with
morphine, respiratory depression is responsible for an accumulation of CO2.
480 M. Torrens et al.
Pharmacokinetics
Meperidine is absorbed by all routes of administration, but the rate of absorption may
be erratic after intramuscular injection. By the oral route, the onset of analgesia
begins after 15 min, with peak in 1–2 h, which is close to the peak level in plasma,
with duration of about 1.5–3 h (Yaksh and Wallace 2011). It is absorbed by all
routes, but intramuscular administration results in a less reliable peak plasma level
after 45 min, with a wide range of plasma concentrations. After oral administration,
about 50 % of the drug enters the circulation without first-pass metabolism, with
peak at 1–2 h. Sixty percent of meperidine is protein bound, and little is excreted
unmetabolized (Latta et al. 2002). Meperidine is mostly metabolized in the liver,
with half-life of about 3 h. In humans, meperidine is hydrolyzed to meperidinic acid,
which in turn is partially conjugated. Meperidine also is N-demethylated to
normeperidine, which then may be hydrolyzed to normeperidinic acid and subse-
quently conjugated. Normeperidine has modest analgesic properties, but it is
a potent CNS stimulant and can cause seizures (Yaksh and Wallace 2011).
28.2.1.11 Pentazocine
Pentazocine was approved in the late 1960s, both the oral and the parental formu-
lations. It is a partial agonist or antagonist at mu receptor and also a kappa receptor
partial agonist. For analgesia, it has been manufactured also with acetaminophen.
Later, it was manufactured in combination with naloxone to diminish its intrave-
nous use. Its abuse declined after this change in the formulation according to
DAWN emergency room register (Fudala and Johnson 2006).
Pharmacodynamics
The pattern of CNS effects produced by pentazocine generally is similar to that of
the morphine-like opioids, including analgesia, sedation, and respiratory depres-
sion. The analgesic effects of pentazocine are due to agonistic actions at opioid
receptors but present a ceiling effect. The cardiovascular responses to pentazocine
differ from those seen with typical receptor agonists, in that high doses cause an
increase in blood pressure and heart rate. Pentazocine does not antagonize the
respiratory depression produced by morphine. However, when given to patients
dependent on morphine or other mu agonists, pentazocine may precipitate with-
drawal due to its partial agonist–antagonist actions at the mu receptor. At high doses
(60–90 mg), pentazocine elicits dysphoric and psychotomimetic effects, probably
due to its kappa agonist properties.
Pharmacokinetics
Pentazocine is a mixed agonist–antagonist that can be given intramuscularly or
orally but is not currently available in the oral formulation. Because it can cause
psychotomimetic effects, it has a very limited role in the treatment of chronic pain.
28 Opioid Addiction: Short- and Long-Acting Opioids 481
Its duration of action is 3–6 h. Its peak effect is at 0.5–1 h when given intramus-
cularly and 1–2 h when given orally. Sixty percent of the drug is bound to protein.
Pentazocine is metabolized by the liver via oxidative and glucuronide conjugation
with an extensive first-pass effect. When administered orally, the bioavailability of
pentazocine is about 10 %, except in patients with cirrhosis, which increases
bioavailability to 60–70 %. The drug half-life is 2–3 h. Small amounts of
unchanged pentazocine are excreted with urine (Yaksh and Wallace 2011).
28.2.1.12 LAAM
Levacetylmethadol or levomethadyl acetate or levo-a-acetylmethadol (LAAM) is
a synthetic, longer-acting (48-h) congener of methadone that also is orally effective.
LAAM was first studied in the 1970s for the treatment of heroin addiction
and approved in 1993 by the FDA after a large multicenter safety trial (Kreek
and Vocci 2002). Postmarketing, after reports of prolonged QTc intervals on
electrocardiogram leading to torsade de pointes that may have been caused by
LAAM, a black-box warning was added to the product label and marketing contin-
ued in the United States until 2003. LAAM was withdrawn from the European
countries at 2001. This effect may have been the result of preexisting cardiac disease
or undefined drug interactions (Kreek and Vocci 2002). At this moment, LAAM is
not marketed by any pharmaceutical company.
LAAM acts as a pure opioid agonist, active mostly at the mu-opioid receptor
(Yaksh and Wallace 2011; Kreek and Vocci 2002).
Pharmacokinetics
LAAM shares with methadone the properties of long duration of effect (48 h
vs. 24 h for methadone), in part owing to its active metabolites nor-LAAM and
dinor-LAAM, as well as its steady-state perfusion of mu-opioid receptors. LAAM
was previously considered a prodrug, but this was refused in a study (Walsh
et al. 1998) showing that intravenous LAAM produced significant subjective and
physiological effects that appeared within 5 min, whereas the effects of oral LAAM
appeared more slowly within 1–2 h after drug administration; the pharmacokinetic
data indicate that the immediate effects of intravenous LAAM could be attributable
to the parent drug rather than the active metabolites.
Oral LAAM undergoes extensive first-pass metabolism to the active
demethylated metabolite nor-LAAM, which is further demethylated to a second
active metabolite, dinor-LAAM. These metabolites are more potent than the parent
drug. Oral bioavailability is less than 50 %. Nor-LAAM and dinor-LAAM accu-
mulate with chronic administration. In addition, LAAM and its metabolites bind to
tissue proteins. The clearance of nor-LAAM and LAAM is similar, whereas the
clearance of dinor-LAAM is more prolonged than that of its parent compound. The
peak pharmacological effect of LAAM as measured by the amount of pupillary
constriction occurred at 8 h and then diminished at a rate most like that of
nor-LAAM metabolism (Borg et al. 2009).
LAAM is metabolized in the gut wall and liver to active metabolites, nor-LAAM
and dinor-LAAM, through sequential demethylation (Walsh et al. 1998).
482 M. Torrens et al.
28.2.1.13 Tramadol
Tramadol is a synthetic codeine and morphine analog that is a weak mu agonist.
It also exerts some capacity to inhibit the uptake of norepinephrine and serotonin. It is
more effective in the treatment of the mild and moderate pain than in the treatment of
severe and chronic pain (Yaksh and Wallace 2011). Misuse, diversion, physical
dependence, abuse, addiction, and withdrawal have been reported in conjunction
with the use of tramadol. Tramadol has been shown to reinitiate physical dependence
in some patients who have previously been dependent on other opioids; thus, it should
be avoided in patients with a history of addiction (Mayor 2013).
Pharmacodynamics
Tramadol is a chiral molecule, administered as a racemic mixture; the
(R)-enantiomer and the metabolite (R)-O-desmethyltramadol (M1) are agonists of
the m-opioid receptor, and they inhibit serotonin reuptake. The (S)-enantiomer
inhibits norepinephrine reuptake and stimulates two adrenergic receptors (Lewis
and Han 1997). As a consequence, the (S) form enhances the inhibitory effects on
pain transmission in the spinal cord.
The pharmacological effects are similar to those of morphine, and the main
adverse effects include nausea, vomiting, dizziness, dry mouth, sedation, and
headache. Respiratory depression and constipation are mild compared to morphine.
Tramadol can cause seizures and possibly exacerbate seizures in patients with
predisposing factors. Some effects of tramadol can be reversed by naloxone as
respiratory depression, but not the analgesia. There is an increased risk of seizures
with the combined use of tramadol and naloxone.
Pharmacokinetics
Tramadol has a bioavailability of 100 % after an intramuscular dose and 68 % after
an oral dose. Its affinity for the mu-opioid receptor is weaker than morphine, but the
O-demethylated metabolite M1 is two to four times as potent as the parent drug and
may account for part of the analgesic effect.
Tramadol is metabolized in the liver, mainly by CYP2D6 and CYP3A4, thus
explaining some reported cases of interactions with methadone (Leavitt 2005), and
also undergoes conjugation and renal excretion. Poor metabolizers of CYP2D6
have less analgesic effects due to lower levels of O-desmethyltramadol (M1). The
elimination half-life is 6 h for tramadol and 7.5 h for its active metabolite.
Analgesia begins within an hour of oral dosing and peaks within 2–3 h. The duration
28 Opioid Addiction: Short- and Long-Acting Opioids 483
28.2.1.14 Tapentadol
Tapentadol is a centrally acting synthetic analgesic, indicated for the management
of moderate to severe acute pain in adults. The recommended doses are 50 mg,
75 mg, or 100 mg every 4–6 h depending upon pain intensity. Daily doses greater
600 mg are not recommended. In the case of the extended-release preparation, usual
doses are 100–250 mg twice daily. Tapentadol immediate release was originally
approved by the FDA in November 2008, and in 2011, the extended-release
formulation (Hartrick and Rozek 2011; Hoy 2012).
Pharmacodynamics
Tapentadol exact mechanism of action is unknown. Preclinical studies have shown
that tapentadol is a mu-opioid receptor agonist and a norepinephrine reuptake
inhibitor. It is 18 times less potent than morphine in binding to the human
mu-opioid receptor and is two to three times less potent in producing analgesia in
animal models. Tapentadol has been shown to inhibit norepinephrine reuptake
resulting in increased norepinephrine concentrations. The principal therapeutic
action of tapentadol is analgesia. As other opioids, tapentadol causes respiratory
depression, tolerance, and dependence (Hartrick and Rozek 2011; Hoy 2012).
Pharmacokinetics
Absolute bioavailability is approximately 32 % due to extensive first-pass metab-
olism. Maximum serum concentrations of tapentadol are observed at around 1.25 h
after dosing. In extended-release formulations, maximum serum concentrations are
observed between 3 and 6 h after administration.
The major pathway of tapentadol metabolism is conjugation with glucuronic
acid. After oral administration approximately 70 % of the dose is excreted in the
urine in the conjugated form (55 % O-glucuronide and 15 % sulfate of tapentadol).
Only 3 % of drug was excreted in the urine as unchanged drug. In addition,
tapentadol is metabolized to N-desmethyl tapentadol (13 %) by CYP2C9 and
CYP2C19 and to hydroxyl tapentadol (2 %) by CYP2D6, which are further
metabolized by conjugation. None of the metabolites contribute to the analgesic
activity. Tapentadol and its metabolites are excreted almost exclusively (99 %) via
the kidneys. The terminal half-life is on average 4–5 h after oral administration
(Hartrick and Rozek 2011; Hoy 2012).
28.2.1.15 Naloxone
Naloxone is a pure opioid antagonist for parenteral use. It is an N-allyl derivative of
oxymorphone. Naloxone is competitive antagonist at all opioid receptors, but it has
greatest affinity for mu receptors. Naloxone is usually administered in the emer-
gency department to revert heroin overdoses and also as an aid to distinguish causes
of coma (if patient does not respond to naloxone, nonopioid causes should be
considered) (Boyer 2012).
484 M. Torrens et al.
Pharmacodynamics
Small doses of naloxone reliably reverse or prevent the effects of pure opioid agonists
and most mixed agonists–antagonists (Schäfer 2011; Mitchell et al. 2003). However,
given alone, naloxone is nearly devoid of clinically demonstrable effects. In humans,
extremely large doses (4 mg/kg) cause a mild increase in heart rate and systolic blood
pressure, as well as slowing of EEG alpha-wave activity.
Pharmacokinetics
Naloxone is widely distributed and rapidly achieves effective concentrations in
the CNS after parenteral administration. Plasma and brain concentrations fall
precipitously because of rapid redistribution. The drug is rapidly cleared by hepatic
biotransformation, mainly to the 3-glucuronide. The clearance is very high
(approximately 30 ml kg 1 min 1), which suggests that extrahepatic elimination
may be occurring. The terminal half-life is 1–2 h. The onset of antagonist effect is
extremely rapid, but the duration of action is quite brief. The duration of naloxone is
nearly always shorter than that of the opioids whose effects it is intended to
antagonize. It has to be taken into account that opioid reversal can sometimes
have important hemodynamic consequences. Increases in systemic pressure, heart
rate, and plasma levels of catecholamines can occur. Oral or sublingual adminis-
tration of naloxone has very low systemic bioavailability due to marked hepatic
first-pass metabolism. Enteral naloxone can block opioid action at the intestinal
receptor level but has no general effects.
28.2.1.16 Naltrexone
Naltrexone is an opioid antagonist, chemically related to naloxone. Compared to
naloxone, it has higher oral bioavailability and a longer duration of action. Naltrex-
one has been used for relapse prevention in opioid dependence because of its ability
to antagonize all the actions of opioids. Also, there is evidence that naltrexone blocks
activation by alcohol of dopaminergic pathways in the brain that are thought to be
critical to reward, so it is used also in the treatment of alcohol dependence, as relapse
prevention substance.
A depot formulation of naltrexone that provides 30 days of medication after
a single injection has been approved for the treatment of alcoholism and heroin
dependence in detoxified patients (Lobmaier et al. 2011). This formulation elimi-
nates the necessity of daily pill-taking and prevent relapse when the recently
detoxified patient leaves a protected environment (Krupitsky et al. 2011).
Pharmacodynamics
If administered at doses of 25 mg/day, it blocks completely the mu-opioid receptor,
impeding the effects of the opioid agonists. If administered in alcohol-dependent
subjects (doses of 50 mg/day), patients experience less craving for alcohol and less
feelings of reward if they drink alcohol. A pharmacogenomic-related response to
naltrexone in opioid-dependent subjects at mu receptor gene (OPRM1) has been
described: those patients carrying the Asp40 allele had an increased percentage of
days abstinent and a decreased percentage of heavy drinking days if treated with
28 Opioid Addiction: Short- and Long-Acting Opioids 485
naltrexone versus placebo, while those with the Asn40/Asn40 genotype showed no
medication differences (Anton et al. 2008).
The most common side effect of naltrexone is nausea. An increase of trans-
aminases could be observed, and if the dose is excessive, it can cause liver damage
(Rosow and Dershwitz 2011).
Pharmacokinetics
Naltrexone is rapidly absorbed and undergoes 95 % first-pass metabolism to
6-b-naltrexol. This is an active metabolite that probably accounts for most of the
naltrexone activity. The metabolite accumulates during chronic treatment and has
a terminal half-life of 12.9 h, so significant antagonist effects may persist for
2–3 days after naltrexone is stopped.
28.2.1.17 Nalmefene
Nalmefene is another long-lasting opioid antagonist. It is the 6-methylene deriva-
tive of naltrexone. It is an antagonist at the mu- and delta-opioid receptors and
a partial agonist at the kappa receptors (Soyka and Rosner 2010); there is no
evidence of activity in any other receptor. Some advantages over naltrexone have
been described, including greater oral bioavailability (Gal et al. 1986), longer
duration of action (Gal et al. 1986; Ingman et al. 2005), and lack of dose-dependent
liver toxicity (Mason et al. 1999).
As said previously, nalmefene also exerts a kappa partial agonism; the kappa-
opioid system has been associated with motivational aspects in alcohol dependence,
and nalmefene has been associated with a decreased alcohol self-administration in
preclinical studies (Walker and Koob 2008).
Pharmacokinetics
Nalmefene is rapidly absorbed; the mean half-life was 13.4 h after single and
repeated dosing, meaning that it has linear pharmacokinetics (Soyka and Rosner
2010). A slow dissociation of the drug from the mu-opioid receptor has been
described. A clearance half-life of 28.7 5.9 h has been reported for central opioid
receptors and a plasma elimination half-life of 8.30 0.34 h. Oral nalmefene may
block receptors for longer and have a longer half-life over 24 h than naltrexone
(Soyka and Rosner 2010). There is no evidence of any serious adverse drug
reactions in hepatic or other body systems.
Opioid addiction is a chronic and relapsing disorder with high costs to indi-
viduals, families, and society. Opiates, including the increasing abuse of pre-
scription opioids, continue to be the main problem drug worldwide. The total
number of opiate users at the global level is now estimated around 16.5 million
people or 0.4 % of the population aged 15–64. A high prevalence for opiate
use has been reported from Southwest and Central Asia, Eastern and
486 M. Torrens et al.
Southeastern Europe, and North America (United Nations Office on Drugs and
Crime 2013).
The text revision of the fifth edition of Diagnostic and Statistical Manual
of Mental Disorders (DSM-5) divides opioid-related disorders into opioid addic-
tion, opioid intoxication, opioid withdrawal, and other opioid-induced disorders
(i.e., induced depression, induced anxiety, etc.)
Opioid addiction includes physiological, behavioral, and cognitive symptoms,
ending in a repeated use of opioid drugs, despite significant problems related to
such use, and is characterized by compulsion to seek and take the drug; as in
other drug dependence, there is a loss of control in limiting the intake and
emergence of a negative emotional state (i.e., dysphoria, anxiety, irritability)
reflecting a motivational withdrawal syndrome when access to the drug is prevented
(Koob and Volkow 2010). Opioid addiction can be mild, moderate, or severe
depending on the number of criteria fulfilled.
In this section we present the main therapeutic strategies used in the treatment of
opiate overdose, withdrawal, and addiction (Table 28.3).
If the patient has no response to 10 mg, then an opioid likely is not responsible for
the respiratory depression.
Finally, once the consciousness level is reverted, it is important to investigate
a possible suicide intention risk of the patient and to perform a psychiatric
assessment.
Detoxification
Detoxification involves the substitution of the abused opioid by other long half-life
opioid agonist or partial agonist (methadone or buprenorphine, usually) or an
alpha2-adrenergic agonist (clonidine or lofexidine) and a progressive reduction in
order to reduce the intensity of the withdrawal syndrome (Amato et al. 2005a;
Gowing et al. 2009a, b).
When comparing detoxification treatments, methadone versus alpha2-adrenergic
agonist treatments, studies showed similar results by means of withdrawal intensity
and treatment completion (Gowing et al. 2009b). However, participants stayed in
treatment for longer and experienced fewer adverse side effects on methadone and
buprenorphine (Ziedonis et al. 2009). Also, clonidine, the most frequently tested
488 M. Torrens et al.
alpha2-adrenergic agonist, has been associated with potentially hazardous side effects
as sedation and hypotension (Gowing et al. 2009b).
Methadone detoxification guidelines recommend to start with an initial dose of
10–45 mg/day, orally, depending on the severity of opioid withdrawal symptoms.
Every 2 h it is necessary to assess the intensity of withdrawal and ensure that the dose
will not exceed 60 mg/day. The same dose of the first day should be administered for
2–3 days and then reduced to 5–10 mg/day until total suppression. The detoxification
usually lasts 10–20 days.
When buprenorphine (or buprenorphine–naloxone) is used in the detoxification
treatment, initial doses of 4–6 mg of buprenorphine are recommended, and then
increase the dose until 8–10 mg/day. After 2–3 days, the recommendation is to
reduce the dose to 2 mg every 1–2 days until complete suppression. It is important
to administer the first dose 24 h after the last heroin use, when the first withdrawal
symptoms appear, in order to avoid a precipitated withdrawal.
In general, the use of long-acting opioids (such as methadone) is recommended
in opioid detoxification, with a long and slow tapering, medical supervision,
ancillary medications, and psychosocial treatment to improve the outcomes and
reduce the risk of relapse (Amato et al. 2005a). However, there is a low rate of
success in detoxification treatments with high prevalence of relapse in heroin use.
Rapid and ultrarapid protocols for detoxification are described. These inpatient
protocols involve a rapid clonidine taper combined with a transition to narcotic
antagonist treatment with naltrexone. Ultrarapid detoxification protocols require
the use of general anesthesia or heavy sedation. A review of the evidence on rapid
and ultrarapid detoxification concluded that the studies were inadequate because
of the small number of subjects included, variations in protocols utilized, lack of
randomized design and/or control groups, and lack of long-term follow-up
(O’Connor and Kosten 1998). In addition, deaths and psychotic syndromes have
been reported during the 16–40 h following ultrarapid detoxification (Kaye
et al. 2003; Shreeram et al. 2001); for this reason alone, ultrarapid detoxification
procedures cannot be recommended.
however, most of the studies were not controlled with other maintenance treatments.
Its main advantage over methadone treatments is the lower risk to induce prolonga-
tion of the QTc interval (Fredheim et al. 2006), allowing an easy switch from
methadone to SROM in case of detection of a QTc interval above 500 ms.
The major concerns with SROM treatments are the risk of misuse and diversion
and the severe adverse events, such as overdose (Beer et al. 2010), described in
countries such as Austria.
designed to help patients find and retain employment; housing services that
can vary from group accommodation for the homeless to more stable, affordable,
long-term accommodation; the referral to participate in activities, such as enjoying
leisure activities of their choice; and self-help groups, which, in the context
of opioid dependence, are voluntary, small-group structures formed by peers to
assist each other in their struggle with opioid dependence. Usually abstinence
oriented, they often provide both material assistance and emotional support and
promulgate an ideology or values through which members may attain a greater
sense of personal identity. Social skills training refers to methods that use
the principles of learning theory to promote the acquisition, generalization, and
durability of skills needed in social and interpersonal situations. Training
should take place in the context of real everyday life experiences, not in closed,
unrealistic settings.
In opioid dependence, the efficacy of psychosocial interventions has little
evidence due to the difficulty in the design of controlled trials. Also, there is scarce
knowledge about the effectiveness of psychosocial interventions alone or in com-
bination with pharmacological strategies and which intervention is the most effec-
tive. There are studies recommending counseling (Grönbladh and Gunne 1989),
relapse prevention, and motivational interview techniques (Pollack et al. 2002).
Also, family therapy (Stanton and Shadish 1997) and psychoanalytic psychotherapy
have been shown to have some benefits in the treatment of opioid dependence
disorder (Woody et al. 1987).
A Cochrane collaboration study (Mayet et al. 2010) addressed the issue of the
efficacy and acceptability of psychosocial interventions alone for treating opiate use
disorders. Only randomized controlled trials comparing psychosocial interventions
alone versus pharmacological intervention, placebo, or no intervention were
selected. The psychosocial interventions evaluated included the following: contin-
gency management, brief reinforcement-based intensive outpatient therapy coupled
with contingency management, cue exposure therapy, alternative program for
methadone maintenance treatment program (MMTP) dropouts, and enhanced out-
reach counseling program. The main findings were that both enhanced outreach
counseling and brief reinforcement-based intensive outpatient therapy coupled with
contingency management had significantly better outcomes than standard therapy
regarding relapse to opioid use, re-enrolment in treatment, and retention in treat-
ment. At 1-month and 3-month follow-up, the effects of reinforcement-based
intensive outpatient therapy were not sustained.
A parallel review (Amato et al. 2011) was performed to evaluate the effective-
ness of any psychosocial plus any agonist maintenance treatment versus standard
agonist treatment for opiate dependence. In this review, 35 studies and 4,319
participants were included, evaluating 13 different psychosocial interventions.
Comparing any psychosocial plus any maintenance pharmacological treatment to
standard maintenance treatment, results do not show benefit for retention in treat-
ment and outcomes. Surprisingly, there were no differences also for contingency
management approaches; the authors stated that the short duration of the trials
could interfere in the results.
494 M. Torrens et al.
28.3 Conclusion
In this chapter the authors have presented the main pharmacological characteristics
of the most common opioids involved in drug addiction and addiction treatment
(both opioid addiction and alcohol addiction) and the present alternatives for the
treatment of the opioid dependence disorder. The majority of research until few
years ago has been focused on the effects mediated by mu-opioid receptors.
However, in recent years most interest has been shifted to the effects on the
kappa-opioid receptors. The kappa system including its natural ligand
(dynorphin) interacts with dopaminergic pathways and modulates the reward,
mood, and stress processes by its effects on the hypothalamic–pituitary–adrenal
(HPA) axis. Kappa agonism usually produces aversion and dysphoria; in rats,
depressant-like effects after the administration of kappa agonists have been described;
on the other hand, the anhedonic symptoms that appear after stress exposure or
cocaine withdrawal are ameliorated with kappa antagonists (Shirayama et al. 2004;
Chartoff et al. 2012). Researchers postulate that increased endogenous kappa/
dynorphin activation could result in neuropsychiatric adverse events (Butelman
et al. 2012), explaining in part the high rates of psychiatric comorbidity in the addicted
patients (Tejeda et al. 2012). From a therapeutic point of view, the use of kappa partial
agonists could provide a stable counter-modulatory tone to dopaminergic urges and
cause a relative blockade of excessive or fluctuating kappa/dynorphin tone; both
effects may mitigate against relapse and reescalation (Butelman et al. 2012).
Acknowledgment The authors Torrens M, Fonseca F, Galindo L, and Farré M appreciate the
support of the network of addictive disorders “Red de Trastornos Adictivos” (RTA) Fondo de
investigación sanitaria ISCIII- Programa RETICS RD12/0028/0009.
References
Amato L, Davoli M, Minozzi S, Ali R, Ferri M (2005a) Methadone at tapered doses for the
management of opioid withdrawal. Cochrane Database Syst Rev 3:CD003409
Amato L, Davoli M, Perucci CA, Ferri M, Faggiano F, Mattick RP (2005b) An overview of
systematic reviews of the effectiveness of opiate maintenance therapies: available evidence to
inform clinical practice and research. J Subst Abuse Treat 28(4):321–329
Amato L, Minozzi S, Davoli M, Vecchi S (2011) Psychosocial combined with agonist mainte-
nance treatments versus agonist maintenance treatments alone for treatment of opioid depen-
dence. Cochrane Database Syst Rev 10:CD004147
Andrews CM, Krantz MJ, Wedam EF, Marcuson MJ, Capacchione JF, Haigney MC (2009)
Methadone-induced mortality in the treatment of chronic pain: role of QT prolongation.
Cardiol J 16(3):210–217
Ansermot N, Albayrak O, Schläpfer J, Crettol S, Croquette-Krokar M, Bourquin M, Déglon JJ,
Faouzi M, Scherbaum N, Eap CB (2010) Substitution of (R, S)-methadone by (R)-methadone:
impact on QTc interval. Arch Intern Med 170(6):529–536
Anton RF, Oroszi G, O’Malley S, Couper D, Swift R, Pettinati H, Goldman D (2008) An
evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the
treatment of alcohol dependence: results from the Combined Pharmacotherapies and
28 Opioid Addiction: Short- and Long-Acting Opioids 495
Behavioral Interventions for Alcohol Dependence (COMBINE) study. Arch Gen Psychiatry
65(2):135–144
Beer B, Rabl W, Libiseller K, Giacomuzzi S, Riemer Y, Pavlic M (2010) Impact of slow-release
oral morphine on drug abusing habits in Austria. Neuropsychiatry 24(2):108–117
Bell J, Burrell T, Indig D, Gilmour S (2006) Cycling in and out of treatment; participation in
methadone treatment in NSW, 1990–2002. Drug Alcohol Depend 81(1):55–61
Borg L, Kravets I, Kreek MJ (2009) The pharmacology of long-acting as contrasted with short-
acting opioids. In: Ries RK, Fiellin DA, Miller SC, Saitz R (eds) Principles of addiction
medicine, 4th edn. Lippincott, Williams & Wilkins, Philadelphia, pp 117–131
Boyer EW (2012) Management of opioid analgesic overdose. N Engl J Med 367(2):146–155
Brewster D, Humphrey MJ, Mcleavy MA (1981) The systemic bioavailability of buprenorphine by
various routes of administration. J Pharm Pharmacol 33(8):500–506
Brugal MT, Domingo-Salvany A, Puig R, Barrio G, Garcia de Olalla P, de la Fuente L (2005)
Evaluating the impact of methadone maintenance programmes on mortality due to overdose
and aids in a cohort of heroin users in Spain. Addiction 100(7):981–989
Butelman ER, Yuferov V, Kreek MJ (2012) Kappa-opioid receptor/dynorphin system: genetic and
pharmacotherapeutic implications for addiction. Trends Neurosci 35(10):587–596
Calsyn DA, Malcy JA, Saxon AJ (2006) Slow tapering from methadone maintenance in a program
encouraging indefinite maintenance. J Subst Abuse Treat 30(2):159–163
Chartoff E, Sawyer A, Rachlin A, Potter D, Pliakas A, Carlezon WA (2012) Blockade of kappa
opioid receptors attenuates the development of depressive-like behaviors induced by cocaine
withdrawal in rats. Neuropharmacology 62(1):167–176
Chugh SS, Socoteanu C, Reinier K, Waltz J, Jui J, Gunson K (2008) A community-based evaluation
of sudden death associated with therapeutic levels of methadone. Am J Med 121(1):66–71
Clark N, Lintzeris N, Gijsbers A, Whelan G, Dunlop A, Ritter A, Ling W (2002) LAAM maintenance
vs methadone maintenance for heroin dependence. Cochrane Database Syst Rev 2:CD002210
Comer SD, Collins ED, Fischman MW (2001) Buprenorphine sublingual tablets: effects on IV
heroin self-administration by humans. Psychopharmacology 154(1):28–37
Cone EJ, Holicky BA, Grant TM, Darwin WD, Goldberger BA (1993) Pharmacokinetics and
pharmacodynamics of intranasal “snorted” heroin. J Anal Toxicol 17(6):327–337
Cowan A (2007) Buprenorphine: the basic pharmacology revisited. J Addict Med 1(2):68–72
Davis AM, Inturrisi CE (1999) D-Methadone blocks morphine tolerance and N-methyl-
D-aspartate-induced hyperalgesia. J Pharmacol Exp Ther 289(2):1048–1053
de Vos JW, Ufkes JG, Kaplan CD, Tursch M, Krause JK, van Wilgenburg H, Woodcock BG,
Staib AH (1998) L-Methadone and D, L-methadone in methadone maintenance treatment: a
comparison of therapeutic effectiveness and plasma concentrations. Eur Addict Res 4(3):134–141
Dolan KA, Shearer J, White B, Zhou J, Kaldor J, Wodak AD (2005) Four-year follow-up of
imprisoned male heroin users and methadone treatment: mortality, re-incarceration and hep-
atitis C infection. Addiction 100(6):820–828
Dole VP, Nyswander ME, Kreek MJ (1966) Narcotic blockade. Arch Intern Med 118(4):304–309
Eap CB, Finkbeiner T, Gastpar M, Scherbaum N, Powell K, Baumann P (1996) Replacement of
(R)-methadone by a double dose of (R, S)-methadone in addicts: interindividual variability of
the (R)/(S) ratios and evidence of adaptive changes in methadone pharmacokinetics. Eur J Clin
Pharmacol 50(5):385–389
Eap CB, Buclin T, Baumann P (2002) Interindividual variability of the clinical pharmacokinetics
of methadone: implications for the treatment of opioid dependence. Clin Pharmacokinet
41(14):1153–1193
Elkader A, Sproule B (2005) Buprenorphine: clinical pharmacokinetics in the treatment of opioid
dependence. Clin Pharmacokinet 44(7):661–680
Farre M, Mas A, Torrens M, Moreno V, Cami J (2002) Retention rate and illicit opioid use during
methadone maintenance interventions: a meta-analysis. Drug Alcohol Depend 65(3):283–290
Ferri M, Davoli M, Perucci CA (2011) Heroin maintenance for chronic heroin-dependent indi-
viduals. Cochrane Database Syst Rev 12:CD003410
496 M. Torrens et al.
Ferri M, Minozzi S, Bo A, Amato L (2013) Slow-release oral morphine as maintenance therapy for
opioid dependence. Cochrane Database Syst Rev 6:CD009879
Fiellin DA, Friedland GH, Gourevitch MN (2006) Opioid dependence: rationale for and efficacy
of existing and new treatments. Clin Infect Dis 43(Suppl 4):S173–S177
Fonseca F, Marti-Almor J, Pastor A, Cladellas M, Farre M, de la Torre R, Torrens M (2009)
Prevalence of long QTc interval in methadone maintenance patients. Drug Alcohol Depend
99(1–3):327–332
Fredheim OM, Borchgrevink PC, Hegrenaes L, Kaasa S, Dale O, Klepstad P (2006) Opioid
switching from morphine to methadone causes a minor but not clinically significant increase in
QTc time: a prospective 9-month follow-up study. J Pain Symptom Manage 32(2):180–185
Fudala PJ, Johnson RE (2006) Development of opioid formulations with limited diversion and
abuse potential. Drug Alcohol Depend 83(Suppl 1):S40–S47
Gal TJ, DiFazio CA, Dixon R (1986) Prolonged blockade of opioid effect with oral nalmefene.
Clin Pharmacol Ther 40(5):537–542
Gowing L, Ali R, White JM (2009a) Buprenorphine for the management of opioid withdrawal.
Cochrane Database Syst Rev 3:CD002025
Gowing L, Farrell M, Ali R, White JM (2009b) Alpha2-adrenergic agonists for the management of
opioid withdrawal. Cochrane Database Syst Rev 2:CD002024
Grönbladh L, Gunne L (1989) Methadone-assisted rehabilitation of Swedish heroin addicts. Drug
Alcohol Depend 24(1):31–37
Hartrick CT, Rozek RJ (2011) Tapentadol in pain management: a m-opioid receptor agonist and
noradrenaline reuptake inhibitor. CNS Drugs 25(5):359–370
Hendriks VM, van den Brink W, Blanken P, Bosman IJ, van Ree JM (2001) Heroin self-
administration by means of ‘chasing the dragon’: pharmacodynamics and bioavailability of
inhaled heroin. Eur Neuropsychopharmacol 11(3):241–252
Hoy SM (2012) Tapentadol extended release: in adults with chronic pain. Drugs 72(3):375–393
Hser YI, Saxon AJ, Huang D, Hasson A, Thomas C, Hillhouse M, Jacobs P, Teruya C,
McLaughlin P, Wiest K, Cohen A, Ling W (2013) Treatment retention among patients
randomized to buprenorphine/naloxone compared to methadone in a multi-site trial. Addiction
2014 Jan;109(1):79–87
Huang P, Kehner GB, Cowan A, Liu-Chen LY (2001) Comparison of pharmacological activities
of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist.
J Pharmacol Exp Ther 297(2):688–695
Ingman K, Hagelberg N, Aalto S, Nagren K, Juhakoski A, Karhuvaara S, Kallio A, Oikonen V,
Hietala J, Scheinin H (2005) Prolonged central mu-opioid receptor occupancy after single and
repeated nalmefene dosing. Neuropsychopharmacology 30(12):2245–2253
Inturrisi CE, Max MB, Foley KM, Schultz M, Shin SU, Houde RW (1984) The pharmacokinetics
of heroin in patients with chronic pain. N Engl J Med 310(19):1213–1217
Jegu J, Gallini A, Soler P, Montastruc JL, Lapeyre-Mestre M (2011) Slow-release oral
morphine for opioid maintenance treatment: a systematic review. Br J Clin Pharmacol
71(6):832–843
Judson BA, Horns WH, Goldstein A (1976) Side effects of levomethadone and racemic methadone
in a maintenance program. Clin Pharmacol Ther 20(4):445–449
Kamendulis LM, Brzezinski MR, Pindel EV, Bosron WF, Dean RA (1996) Metabolism of cocaine
and heroin is catalyzed by the same human liver carboxylesterases. J Pharmacol Exp Ther
279(2):713–717
Kaye AD, Gevirtz C, Bosscher HA, Duke JB, Frost EA, Richards TA, Fields AM (2003) Ultrarapid
opiate detoxification: a review. Can J Anaesthesiol 50(7):663–671
Koob GF, Volkow ND (2010) Neurocircuitry of addiction. Neuropsychopharmacology 35(1):217–238
Krantz MJ, Martin J, Stimmel B, Mehta D, Haigney MC (2009) QTc interval screening in
methadone treatment. Ann Intern Med 150(6):387–395
Kreek MJ (1973) Medical safety and side effects of methadone in tolerant individuals. JAMA
223(6):665–668
28 Opioid Addiction: Short- and Long-Acting Opioids 497
Kreek MJ (1978) Medical complications in methadone patients. Ann N Y Acad Sci 311:110–134
Kreek MJ, Vocci FJ (2002) History and current status of opioid maintenance treatments: blending
conference session. J Subst Abuse Treat 23(2):93–105
Kreek MJ, Wardlaw SL, Hartman N, Raghunath J, Friedman J, Schneider B, Frantz AG (1983)
Circadian rhythms and levels of beta-endorphin, ACTH, and cortisol during chronic metha-
done maintenance treatment in humans. Life Sci 33(Suppl 1):409–411
Kreek MJ, Zhou Y, Butelman ER, Levran O (2009) Opiate and cocaine addiction: from bench to
clinic and back to the bench. Curr Opin Pharmacol 9(1):74–80
Kristensen K, Christensen CB, Christrup LL (1995) The mu1, mu2, delta, kappa opioid
receptor binding profiles of methadone stereoisomers and morphine. Life Sci 56(2):
PL45–PL50
Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL (2011) Injectable
extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled,
multicentre randomised trial. Lancet 377(9776):1506–1513
Latta KS, Ginsberg B, Barkin RL (2002) Meperidine: a critical review. Am J Ther 9(1):53–68
Leavitt SB (2005) Addiction treatment forum: methadone-drug interactions. http://www.atforum.
com/SiteRoot/pages/addiction_resources/Drug_Interactions.pdf. Accessed 5 April 2013
Lewis KS, Han NH (1997) Tramadol: a new centrally acting analgesic. Am J Health Syst Pharm
54(6):643–652
Lintzeris N, Mitchell TB, Bond AJ, Nestor L, Strang J (2007) Pharmacodynamics of diazepam
co-administered with methadone or buprenorphine under high dose conditions in opioid
dependent patients. Drug Alcohol Depend 91(2–3):187–194
Lintzeris N, Leung SY, Dunlop AJ, Larance B, White N, Rivas GR, Holland RM, Degenhardt L,
Muhleisen P, Hurley M, Ali R (2013) A randomised controlled trial of sublingual
buprenorphine-naloxone film versus tablets in the management of opioid dependence. Drug
Alcohol Depend 131(1–2):119–126
Lobmaier P, Kornør H, Kunøe N, Bjørndal A (2008) Sustained-release naltrexone for opioid
dependence. Cochrane Database Syst Rev (2)
Lobmaier PP, Kunøe N, Gossop M, Katevoll T, Waal H (2010) Naltrexone implants compared to
methadone: outcomes six months after prison release. Eur Addict Res 16(3):139–145
Lobmaier PP, Kunoe N, Gossop M, Waal H (2011) Naltrexone depot formulations for opioid and
alcohol dependence: a systematic review. CNS Neurosci Ther 17(6):629–636
Lugo RA, Kern SE (2004) The pharmacokinetics of oxycodone. J Pain Palliat Care Pharmacother
18(4):17–30
Lutfy K, Cowan A (2004) Buprenorphine: a unique drug with complex pharmacology. Curr
Neuropharmacol 2(4):395–402
Marsch LA (1998) The efficacy of methadone maintenance interventions in reducing illicit opiate
use, HIV risk behavior and criminality: a meta-analysis. Addiction (Abingdon, England)
93(4):515–532
Mason BJ, Salvato FR, Williams LD, Ritvo EC, Cutler RB (1999) A double-blind, placebo-
controlled study of oral nalmefene for alcohol dependence. Arch Gen Psychiatry 56(8):719–724
Mattick RP, Kimber J, Breen C, Davoli M (2008) Buprenorphine maintenance versus placebo or
methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2:CD002207
Mayer P, Hollt V (2006) Pharmacogenetics of opioid receptors and addiction. Pharmacogenet
Genomics 16(1):1–7
Mayet S, Farrell M, Ferri M, Amato L, Davoli M (2010) Psychosocial treatment for opiate abuse
and dependence. Cochrane Database Syst Rev 1:CD004330
Mayor S (2013) Drug experts call for stronger regulation of tramadol to reduce misuse. BMJ (Clin
Res Ed) 346:f1264
McCance-Katz EF, Mandell TW (2010) Drug interactions of clinical importance with methadone
and buprenorphine. Am J Addict 19(1):2–3
McEvoy GK (2007) American hospital formulary service. AHFS Drug Information. American
Society of Health-System Pharmacists, Bethesda, MD
498 M. Torrens et al.
McLellan AT, Hagan TA, Meyers K, Randall M, Durell J (1997) “Intensive” outpatient substance
abuse treatment: comparisons with “traditional” outpatient treatment. J Addict Dis
16(2):57–84
Megarbane B, Buisine A, Jacobs F, Resiere D, Chevillard L, Vicaut E, Baud FJ (2010) Prospective
comparative assessment of buprenorphine overdose with heroin and methadone: clinical
characteristics and response to antidotal treatment. J Subst Abuse Treat 38(4):403–407
Mendelson J, Jones RT (2003) Clinical and pharmacological evaluation of buprenorphine and
naloxone combinations: why the 4:1 ratio for treatment? Drug Alcohol Depend 70(2 Suppl):
S29–S37
Minozzi S, Amato L, Vecchi S, Davoli M, Kirchmayer U, Verster A (2011) Oral naltrexone
maintenance treatment for opioid dependence. Cochrane Database Syst Rev 4:CD001333
Mitchell TB, White JM, Somogyi AA, Bochner F (2003) Comparative pharmacodynamics and
pharmacokinetics of methadone and slow-release oral morphine for maintenance treatment of
opioid dependence. Drug Alcohol Depend 72(1):85–94
Mitchell TB, Dyer KR, Newcombe D, Salter A, Somogyi AA, Bochner F, White JM (2004) Sub-
jective and physiological responses among racemic-methadone maintenance patients in rela-
tion to relative (S)- vs. (R)-methadone exposure. Br J Clin Pharmacol 58(6):609–617
Murray A, Hagen NA (2005) Hydromorphone. J Pain Symptom Manage 29(5 Suppl):S57–S66
Novick DM, Poretsky L, Kalin MF (1989) Methadone and thyroid-function tests. Clin Chem
35(8):1807–1808
O’Connor PG, Kosten TR (1998) Rapid and ultrarapid opioid detoxification techniques. JAMA
279(3):229–234
Oyler JM, Cone EJ, Joseph RE Jr, Huestis MA (2000) Identification of hydrocodone in human
urine following controlled codeine administration. J Anal Toxicol 24(7):530–535
Pollack MH, Penava SA, Bolton E, Worthington JJ, Allen GL, Farach FJ, Otto MW
(2002) A novel cognitive-behavioral approach for treatment-resistant drug dependence.
J Subst Abuse Treat 23(4):335–342
Rosow CE, Dershwitz M (2011) Essential drugs in anesthetic practice. Clinical pharmacology of
opioids. In: Evers AS, Maze M, Kharasch ED (eds) Null, 2nd edn. Cambridge University Press,
New York, pp 531–547
San L, Camı́ J, Fernández T, Ollé JM, Peri JM, Torrens M (1992) Assessment and management of
opioid withdrawal symptoms in buprenorphine-dependent subjects. British Journal Addiction
87(1):55–62
Schäfer M (2011) Essential drugs in anesthetic practice. Mechanism of action of opioids. In: Evers
AS, Maze M, Kharasch ED (eds) Anesthetic pharmacology, 2nd edn. Cambridge University
Press, New York, pp 493–508
Schottenfeld RS, Chawarski MC, Mazlan M (2008) Maintenance treatment with buprenorphine
and naltrexone for heroin dependence in Malaysia: a randomised, double-blind, placebo-
controlled trial. Lancet 371(9631):2192–2200
Schwartz PJ, Moss AJ, Vincent GM, Crampton RS (1993) Diagnostic criteria for the long QT
syndrome. An update. Circulation 88(2):782–784
Sellman D (2010) The 10 most important things known about addiction. Addiction 105(1):6–13
Shirayama Y, Ishida H, Iwata M, Hazama GI, Kawahara R, Duman RS (2004) Stress increases
dynorphin immunoreactivity in limbic brain regions and dynorphin antagonism produces
antidepressant-like effects. J Neurochem 90(5):1258–1268
Shreeram SS, McDonald T, Dennison S (2001) Psychosis after ultrarapid opiate detoxification.
Am J Psychiatry 158(6):970
Soyka M (2012) Buprenorphine and buprenorphine/naloxone soluble-film for treatment of opioid
dependence. Exp Opin Drug Deliv 9(11):1409–1417
Soyka M, Rosner S (2010) Nalmefene for treatment of alcohol dependence. Exp Opin Investig
Drugs 19(11):1451–1459
28 Opioid Addiction: Short- and Long-Acting Opioids 499
Stanton MD, Shadish WR (1997) Outcome, attrition, and family couples treatment for drug abuse:
a meta-analysis and review of the controlled, comparative studies. Psychol Bull
2(122):170–179
Strain EC, Preston KL, Liebson IA, Bigelow GE (1995) Buprenorphine effects in methadone-
maintained volunteers: effects at two hours after methadone. J Pharmacol Exp Ther
272(2):628–638
Strain EC, Walsh SL, Bigelow GE (2002) Blockade of hydromorphone effects by buprenorphine/
naloxone and buprenorphine. Psychopharmacology 159(2):161–166
Strang J, Metrebian N, Lintzeris N, Potts L, Carnwath T, Mayet S, Williams H, Zador D, Evers R,
Groshkova T, Charles V, Martin A, Forzisi L (2010) Supervised injectable heroin or injectable
methadone versus optimised oral methadone as treatment for chronic heroin addicts in England
after persistent failure in orthodox treatment (RIOTT): a randomised trial. Lancet
375(9729):1885–1895
Sullivan MA, Rothenberg JL, Vosburg SK, Church SH, Feldman SJ, Epstein EM, Kleber HD,
Nunes EV (2006) Predictors of retention in naltrexone maintenance for opioid dependence:
analysis of a stage I trial. Am J Addict 15(2):150–159
Tejeda HA, Shippenberg TS, Henriksson R (2012) The dynorphin/kappa-opioid receptor system
and its role in psychiatric disorders. Cell Mol Life Sci 69(6):857–896
Torrens M, Domingo-Salvany A, Alonso J, Castillo C, San L (1999) Methadone and quality of life.
Lancet 353(9158):1101
Uchtenhagen AA (2011) Heroin maintenance treatment: from idea to research to practice. Drug
Alcohol Rev 30(2):130–137
United Nations Office on Drugs and Crime (2013) World drug report 2013, Vienna
United States General Accounting Office (1990) Methadone maintenance: some treatment pro-
grams are not effective; greater federal oversight needed. In: U.S. General Accounting Office
(ed) Report to the chairman, select committee on narcotics abuse and control, house of
representatives. Washington, DC
Veilleux JC, Colvin PJ, Anderson J, York C, Heinz AJ (2010) A review of opioid dependence
treatment: pharmacological and psychosocial interventions to treat opioid addiction. Clin
Psychol Rev 30(2):155–166
Walker BM, Koob GF (2008) Pharmacological evidence for a motivational role of kappa-opioid
systems in ethanol dependence. Neuropsychopharmacology 33(3):643–652
Walsh SL, Johnson RE, Cone EJ, Bigelow GE (1998) Intravenous and oral l-alpha-
acetylmethadol: pharmacodynamics and pharmacokinetics in humans. J Pharmacol Exp Ther
285(1):71–82
Ward J, Mattick RP, Hall W (1998) Methadone maintenance treatment and other opioid replace-
ment therapies. Harwood Academic Publishers, Amsterdam
Webster LR, Bath B, Medve RA, Marmon T, Stoddard GJ (2012) Randomized, double-blind,
placebo-controlled study of the abuse potential of different formulations of oral oxycodone.
Pain Med 13(6):790–801
Wedam EF, Bigelow GE, Johnson RE, Nuzzo PA, Haigney MC (2007) QT-interval effects of
methadone, levomethadyl, and buprenorphine in a randomized trial. Arch Intern Med
167(22):2469–2475
Wolff K, Rostami-Hodjegan A, Hay AW, Raistrick D, Tucker G (2000) Population-based phar-
macokinetic approach for methadone monitoring of opiate addicts: potential clinical utility.
Addiction 95(12):1771–1783
Woody GE, McLellan AT, Luborsky L, O’Brien CP (1987) Twelve month follow-up of psycho-
therapy for opiate dependence. Am J Psychiatry 5(144):590–596
World Health Organization (2009) Guidelines for the psychosocially assisted pharmacological
treatment of opioid dependence. http://www.who.int/substance_abuse/publications/opioid_
dependence_guidelines.pdf
500 M. Torrens et al.
Yaksh TL, Wallace MS (2011) Opioids, analgesia and pain management. In: Brunton LL, Chabner
BA, Knollmann BC (eds) Goodman and Gilman’s the pharmacological basis of therapeutics,
12th edn. McGraw Hill, New York
Yokell MA, Zaller ND, Green TC, Rich JD (2011) Buprenorphine and buprenorphine/naloxone
diversion, misuse, and illicit use: an international review. Curr Drug Abuse Rev 4(1):28–41
Ziedonis DM, Amass L, Steinberg M, Woody G, Krejci J, Annon JJ, Cohen AJ, Waite-O’Brien N,
Stine SM, McCarty D, Reid MS, Brown LS Jr, Maslansky R, Winhusen T, Babcock D,
Brigham G, Muir J, Orr D, Buchan BJ, Horton T, Ling W (2009) Predictors of outcome for
short-term medically supervised opioid withdrawal during a randomized, multicenter trial of
buprenorphine-naloxone and clonidine in the NIDA clinical trials network drug and alcohol
dependence. Drug Alcohol Depend 99(1–3):28–36
Buprenorphine in the Treatment of Opioid
Addiction: The French Experience 29
Melina Fatseas, Jacques Dubernet, Jean-Pierre Daoulouède,
and Marc Auriacombe
Contents
29.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 502
29.2 The French Experience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 503
29.2.1 “Buprenorphine Treatment” in the French Context . . . . . . . . . . . . . . . . . . . . . . . . . . . 503
29.2.2 Main Outcomes of Buprenorphine Treatment in France . . . . . . . . . . . . . . . . . . . . . 504
29.2.3 Problems Related to Buprenorphine Treatment in France . . . . . . . . . . . . . . . . . . . . 505
29.2.4 What Is Next? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 507
29.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 508
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 509
M. Fatseas
Département (Pôle) d’Addictologie, CH Charles Perrens et CHU de Bordeaux, Bordeaux, France
Faculté de Médecine, Université de Bordeaux (Segalen), Bordeaux, France
Addiction Psychiatry Sanpsy CNRS USR 3413, Université de Bordeaux CH Charles Perrens
(Pôle Addictologie), Bordeaux, France
J. Dubernet
Département (Pôle) d’Addictologie, CH Charles Perrens et CHU de Bordeaux, Bordeaux, France
Faculté de Médecine, Université de Bordeaux (Segalen), Bordeaux, France
Bizia, CH Côte Basques, Bayonne, France
J.-P. Daoulouède
Département (Pôle) d’Addictologie, CH Charles Perrens et CHU de Bordeaux, Bordeaux, France
Bizia, CH Côte Basques, Bayonne, France
M. Auriacombe (*)
Département (Pôle) d’Addictologie, CH Charles Perrens et CHU de Bordeaux, Bordeaux, France
Faculté de Médecine, Université de Bordeaux (Segalen), Bordeaux, France
Addiction Psychiatry Sanpsy CNRS USR 3413, Université de Bordeaux CH Charles Perrens
(Pôle Addictologie), Bordeaux, France
Bizia, CH Côte Basques, Bayonne, France
e-mail: [email protected]
Abstract
Buprenorphine provides a number of benefits and was registered as a medication
for opiate addiction treatment by the French health authorities as early as 1995.
All registered medical doctors may prescribe this treatment without requiring
any supplementary educational program or special licensing. The French health
organizations enable a substantial care within primary care settings through
medical and social support and through the possibility of supervised dispensing
through pharmacy services. Overall, 26 % of French physicians prescribe
buprenorphine to 75 % of overall patients in buprenorphine maintenance treat-
ment. Buprenorphine maintenance treatment for problem heroin users has been
associated in France to consistent public health, social, individual and economic
benefits; might be contingent upon characteristics of the French health and social
services system; and may not necessarily be generalizable as is to other areas of
the world.
29.1 Introduction
Buprenorphine maintenance treatment for problem heroin users has been associated
in France to consistent public health, social, individual, and economic benefits
(Fédération française d’addictologie 2004).
Studies have reported a significant decrease of heroin use and injection practice
and an improvement in the social conditions of those in treatment (Duburcq
et al. 2000; Bilal et al. 2003). Data also suggest among those that inject a decrease
of risk-taking behavior related to injection, such as needle and paraphernalia
sharing (Cadet-Taı̈rou and Chollet 2004). Similarly, in both retrospective and
prospective studies (De Ducla et al. 2000; Duburcq et al. 2000; Fhima
et al. 2001) carried out among drug-dependent outpatients treated by general
practitioners, results indicate a significant decrease of both heroin and benzodiaz-
epine use over time in treatment and that persistent benzodiazepine use among
buprenorphine-treated individuals was related to less supervised dispensing and
lower buprenorphine dosage. A study documented particularly the positive impact
of buprenorphine on the social conditions of patients (Bilal et al. 2003), indicating
that all markers of social vulnerability assessed through standardized questionnaires
(employment, housing, social insurance, days of in-patient treatment related to drug
consumption, and number of convictions) were improved after a 6-month period
with buprenorphine.
Another consistent impact is the dramatic decrease of the reported overdose
deaths since the development of buprenorphine treatment. In France, overdose
deaths are registered by the police (Office Central pour la Répression du Trafic
Illicite des Stupéfiants 1999). The causes of such deaths are determined on the basis
of on-site evidence. This source of information is, as in most countries, considered to
be an underrepresentation of true overdoses. Since country-specific methodological,
legal, and political issues affect this reporting, the data cannot be compared between
different countries. But since the monitoring system has been unchanged for many
years, it is appropriate to compare the development of overdoses from year to
year within France (Auriacombe et al. 2001). In this regard, the French overdose
mortality monitoring system shows a consistent decrease in overdose deaths since
the introduction of buprenorphine. The number of overdose deaths declined by 79 %,
while the overall number of opiate-abusing individuals in either buprenorphine (80 %)
29 Buprenorphine in the Treatment of Opioid Addiction: The French Experience 505
or methadone (20 %) treatment increased by over 95 % (from less than 2,000 per year
to over 60,000 per year) within the 5 years following the introduction of buprenorphine
and the involvement of general practitioners. Some authors have suggested that the
increase in buprenorphine-treated individuals is the major cause for the decline in
overdose deaths (Lepere et al. 2001). However, it should be acknowledged that
during this same time, there was a development of syringe exchange programs, an
increased availability of center-based methadone treatment, and a possible overall
change in attitude toward intravenous drug users by health providers (Emmanuelli and
Desenclos 2005).
The majority of patients were out-of-treatment, and they injected primarily heroin
and cocaine as well as buprenorphine. A significant minority was in buprenorphine
treatment and only injected buprenorphine. On all variables, this latter group had
better adjustment: more employment, less needle sharing, and less polydrug use.
Thus, the simple prevalence of intravenous diversion may not be the best indication of
the overall effectiveness of buprenorphine treatment. This study only documents the
existence of buprenorphine abuse, but even this population of regular buprenorphine
intravenous abusers appears to be doing better than those that use less or no
buprenorphine. Similar results with similarly limited information were found in
a study focusing only on syringe exchange programs (Valenciano et al. 2001). Two
studies (Fontaa and Bronner 2001; Franques et al. 2003) have compared the use of
the intravenous route in both methadone- and buprenorphine-treated individuals.
Interestingly, the prevalence of use of the intravenous route was similar in both
populations, about 20 %. However, the buprenorphine patients were more likely to
inject their own prescribed buprenorphine, whereas those methadone patients who
injected were more likely to inject heroin and cocaine but not methadone, which is
only available as a difficult-to-inject syrup at the time.
Finally, cases of buprenorphine use as first drug of abuse or dependence have
been reported in France (Escot and Fahet 2004) in low-threshold programs. In these
settings, buprenorphine as the first opiate used concerned 6 % of the subjects, and
buprenorphine as the first opiate used with a diagnosis of dependence, 12 % of the
subjects. These buprenorphine-dependent subjects were more likely to have
a problematic associated use of alcohol or benzodiazepines and reported more
often to use buprenorphine for its anxiolytic or psychotropic effect, in order to
relieve social or psychological difficulties than just as a recreational alternative.
buprenorphine to the black market and possible clinically inappropriate use. Under-
standing some of the determinants of these individual behaviors, such as patient
motivation for use, can give insight as to how to do better (Fatseas et al. 2009).
Within the French treatment system, an important variable that may influence
office-based treatment efficacy could be the frequency with which supervised – as
opposed to take-home – doses of buprenorphine are administered. In a study,
202 patients were assigned quasi-randomly to daily supervised dosing for either
2 weeks, 3 months, or 6 months, after which dosing was on a weekly schedule
(Auriacombe et al. 2002). Results from this study showed that retention in treatment
at the 6-month follow-up was highest for those patients in the 6-month daily
supervised dosing group (80 %) and lowest for those patients in the 2-week daily
supervised dosing group (46 %). Rates of opiate-positive urine samples were
lowest for the 6-month daily supervised dosing group, compared to the 3-month
daily supervised and 2-week daily supervised groups. Finally, average daily
buprenorphine doses at the 6-month assessment were similar for the three groups.
These results suggest that initial efficacy for office-based buprenorphine treatment
may be enhanced by a more closely supervised dispensing of medication and that
this may be acceptable to patients.
Finally, data strongly suggest that prescription practices (single daily and indi-
vidually titrated dosing) and prescribers’ attitudes and beliefs about drug-dependent
patients are closely associated to general treatment outcomes and patient
compliance and behavior (De Ducla et al. 2000; Feroni et al. 2005).
29.3 Conclusion
References
Auriacombe MD, Grabot JP, Daulouède et al (1992) Alternatives to methadone maintenance:
laudanum, buprenorphine. In: Harris H (ed) 54th annual scientific meeting, College on
Problems of Drug Dependence. National Institute on Drug Abuse Research monograph
vol 132, p 308, Keystone
Auriacombe M, Grabot D, Daulouede JP et al (1994) A naturalistic follow-up study of French-
speaking opiate-maintained heroin-addicted patients: effect on biopsychosocial status. J Subst
Abuse Treat 11(6):565–568
Auriacombe M, Franques P, Tignol J (2001) Deaths attributable to methadone vs buprenorphine in
France. JAMA 285(1):45
Auriacombe M, Franques P, Daulouède J et al (2002) Traitements de substitution : le médicament
est. . . celui qui le donne. Les modalités de mise à disposition d’un traitement de substitution par
buprénorphine influencent-elles la réponse générale au traitement ? Courrier des Addict 4:104–106
Auriacombe M, Fatseas M, Dubernet J et al (2004) French field experience with buprenorphine.
Am J Addict 13(Suppl 1):S17–S28
Bell JR, Butler B, Lawrance A et al (2009) Comparing overdose mortality associated with
methadone and buprenorphine treatment. Drug Alcohol Depend 104(1–2):73–77
Bilal S, Menares J, De La Selle P et al (2003) Impact des traitements de substitution aux opiacés
sur la vie sociale. Une etude en medecine de ville. Ann Med Interne (Paris) 154(Spec No 2):
S6–S14
Blanchon T, Boissonnas A, Vareseon I et al (2003) Homelessness and high-dosage buprenorphine
misuse. Subst Use Misuse 38(3–6):429–442
Cadet-Taı̈rou A, Chollet D (2004) La substitution à travers 13 sites français, 1999–2002, Pratiques
et disparités régionales. CNAMTS/OFDT, Paris
Cadet-Taı̈rou A, Gandilhon M, Lahaie E et al (2010) Drogues et usages de drogues en France. État
des lieux et tendances récentes 2007–2009 (9e rapport TREND). OFDR, Paris
Carrieri MP, Amass L, Lucas GM et al (2006) Buprenorphine use: the international experience.
Clin Infect Dis 43(Suppl 4):S197–S215
Cowan A, Lewis JW (1995) Buprenorphine. Wiley-Liss, New York
Damon M, Claroux-Bellocq D, Degré A (2001) Substitution par la buprénorphine en médecine de
ville, en Aquitaine. Revue médicale de l’assurance maladie 32(4):311–318
De Ducla M, Gagnon A, Mucchielli A et al (2000a) Comparison of high dose buprenorphine
treatments of opiate dependent outpatients in four healthcare networks. Ann Med Interne
(Paris) 151(Suppl B):B9–B15
De Ducla M, Gagnon A, Mucchielli A et al (2000b) Suivi de patients pharmacodependants aux opiaces
traites par buprenorphine haut dosage a partir de reseaux de soins. Etude retrospective nationale.
Experience de medecins generalistes francais. Ann Med Interne (Paris) 151(Suppl A):A27–A32
Duburcq A, Charpak Y, Blin P et al (2000) Suivi a 2 ans d’une cohorte de patients sous
buprenorphine haut dosage. Resultats de l’etude SPESUB (suivi pharmaco-epidemiologique
du Subutex en medecine de ville). Rev Epidemiol Sante Publique 48(4):363–373
EMCDDA (2005) Annual report 2005: the state of the drug problem in the European Union and
Norway issue 3: buprenorphine-treatment, misuse and prescription practices. European Mon-
itoring Centre for Drugs and Drug Addiction, Lisbon
Emmanuelli J, Desenclos JC (2005) Harm reduction interventions, behaviours and associated
health outcomes in France, 1996–2003. Addiction 100(11):1690–1700
Escot S, Fahet G (2004) Usages non substitutifs de la buprénorphine haut dosage menée en France,
en 2002–2003. Trend Août
Fatseas M, Auriacombe M (2007) Why buprenorphine is so successful in treating opiate addiction
in France. Curr Psychiatry Rep 9(5):358–364
Fatseas M, Lavie E, Denis C et al (2009) Self-perceived motivation for benzodiazepine use and
behavior related to benzodiazepine use among opiate-dependent patients. J Subst Abuse Treat
37(4):407–411
510 M. Fatseas et al.
Contents
30.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 512
30.2 Clinical Studies of Buprenorphine Implants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 513
30.2.1 Buprenorphine Implants Formulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 513
30.2.2 Buprenorphine Implants Clinical Program . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 513
30.2.3 Buprenorphine Implants Pharmacokinetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 513
30.2.4 Clinical Safety of Buprenorphine Implants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 515
30.2.5 Clinical Efficacy of Buprenorphine Implants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 515
30.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 519
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 519
Abstract
To address shortcomings that opioid dependence treatment with daily sublingual
buprenorphine doses has, such as medication adherence, buprenorphine abuse
and diversion, and accidental exposure to children, Buprenorphine Implants
(BI) have been developed as a subdermally implantable formulation of
buprenorphine with 6-month duration of action. A New Drug Application has
been submitted for this novel medication and is currently under review by the
FDA. This chapter provides a summary of the clinical studies of BI to describe
the formulation and its pharmacokinetics, efficacy, and safety. The data showed
superiority of BI to Placebo Implants (PI) and non-inferiority to sublingual
M.S. Mumenthaler
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
K.L. Beebe (*)
Titan Pharmaceuticals, Inc., South San Francisco, CA, USA
e-mail: [email protected]
30.1 Introduction
To test the clinical efficacy of BI, two multicenter, double-blind, Placebo Implant-
controlled studies (PRO-805 and PRO-806) with one containing an exploratory
open-label active comparator arm (PRO-806) and two open-label extension studies
(PRO-807, PRO-811) were conducted. Study 806 was partially funded by a grant
from NIDA. Two pharmacokinetic studies also provided supportive efficacy and
safety information (studies TTP- 400-02-01 and PRO-810). The six studies are
summarized in Table 30.1.
During all six clinical studies, plasma samples were collected for measurement of
buprenorphine concentrations. Figure 30.1 shows the six individual mean plasma
concentration-time curves of these studies. The buprenorphine plasma concentra-
tion profile after subdermal implantation of BI shows an expected initial peak on the
first day followed by a gradual concentration decrease over 4 weeks to a more
constant, low plasma level (“steady state”) that is then maintained within an
efficacious range for the duration of the 6-month treatment. In a 24-week, open-
label, sequential dose group study (TTP-400-02-01), steady-state plasma
buprenorphine concentrations in the 2- and 4-implant groups were approximately
dose linear, and the within-patient variability during the plateau phase was low,
with coefficients of variation (CVs) ranging from 11 % to 20 % for patients who
received two implants and 9–20 % for patients who received four implants.
In the single crossover, open-label, relative bioavailability PK study (PRO-810),
comparing the reference drug Suboxone ® SL tablets (16 mg/day) to four 80 mg BI,
514 M.S. Mumenthaler and K.L. Beebe
6
6
Plasma BPN (ng/mL)
4
3 PRO-807 (4 or 5 implants, n=62)
4 PRO-810 (4 implants, n=9)
2
1 PRO-811 (4 or 5 implants, n=85)
3 TTP-400 (4 implants, n=6)
0
0 4 8 12 16 20 24 28 32 36 40 44 48
Hours Post-Implantation mean ± SD
2
0
0 2 4 6 8 10 12 14 16 18 20 22 24
Weeks Post-Implantation
The safety evaluation of BI, which included analysis of adverse events (AEs),
clinical laboratory assessments, ECG evaluations, and vital signs, showed that BI
were well tolerated and posed minimal safety risks through two 24-week periods in
adults with opioid dependence. The safety observations in all phase 3 studies were
consistent with the known profiles of marketed buprenorphine forms and with the
safety of EVA subdermal implants that are in wide clinical use. Further, the
non-implant site safety profile observed with BI was unremarkable and fundamen-
tally similar in the BI, Placebo Implant (PI), and SL buprenorphine groups, with
discrete events occurring more frequently in one group or another with no system-
atic pattern. No unexpected systemic AEs occurred, and implant site AEs were
generally minor, easily managed, and rarely leading to study discontinuation. The
most common non-implant site adverse events (in >5 % of patients) that occurred
at a higher incidence in the BI group than in the PI group were headache,
nasopharyngitis, nausea, constipation, URI, back pain, toothache, anxiety, upper
abdominal pain, vomiting, oropharyngeal pain, fatigue, and cough. The most
common implant site adverse events (in >5 % of patients) in the first double-
blind study (PRO-805) were pruritus, pain, erythema, hemorrhage, edema, hema-
toma, and scar. With modified procedures introduced in study PRO-806, the
implant site adverse events decreased substantially and only pain and hematoma
were reported in more than 5 % of patients. Collectively, the data from the safety
program indicate that BI are safe and well tolerated for maintenance treatment of
opioid dependence.
All clinical studies evaluated similar patient populations. This chapter will focus on
the two multicenter, placebo-controlled 24-week pivotal trials (PRO-805,
PRO-806) and will provide only brief descriptions of efficacy measures in the
open-label extension. The primary efficacy objective was to determine whether
BI reduced illicit opioid use relative to PI, and the primary efficacy measure was the
proportion of urine samples negative for opioids collected from weeks 1 to 24 (with
missing urines imputed as positive), incorporating patient self-reported opioid use,
and examined as a cumulative distribution function (CDF). Additional efficacy
measures included study completion, Clinical Opiate Withdrawal Scale (COWS),
Subjective Opiate Withdrawal Scale (SOWS), Visual Analog Scale (VAS) for
opioid cravings, Clinical Global Impressions scores for self and observer
(CGI-self, CGI-observer), and supplemental SL buprenorphine use.
In studies PRO-805 and PRO-806, patients underwent an outpatient induction
period with SL buprenorphine or buprenorphine/naloxone tablets (12–16 mg/day)
and were then randomized to either receive four BI or four Placebo Implants. All
patients could receive supplemental rescue medication (SL buprenorphine/nalox-
one) if they met one or more of the following pre-specified criteria: (a) withdrawal
516 M.S. Mumenthaler and K.L. Beebe
symptoms with a score of >12 on the COWS, (b) cravings with a score of >20 mm
on the opioid cravings VAS, and (c) patient request for rescue medication deemed
appropriate by the investigator. Patients who required supplemental SL
buprenorphine/naloxone 3 days per week for two consecutive weeks or 8 days
of supplemental SL buprenorphine/naloxone over four consecutive weeks received
one additional implant. Patients returned to the clinic thrice weekly for urine
toxicology screening and other data collection and attended twice-weekly
manual-guided drug counseling during study weeks 1–12 and weekly counseling
during weeks 13–24. A more detailed description of the study methodology can be
found in (Ling et al. 2010).
PRO-805 PRO-806
50 50
% Opioid-Negative Urines
0 0
Mean (sem) Median Mean (sem) Median
BPN Implant Placebo Implant BPN Implant Placebo Implant
Fig. 30.2 Mean, median percentage of opioid-negative urine samples, weeks 1–24
Fig. 30.3 CDF of the percentage of opioid-negative urine samples, weeks 1–24
symptoms and cravings as assessed by these measures were similar in the BI and PI
groups at baseline (immediately following SL buprenorphine induction) but were
significantly higher (reflecting more withdrawal symptoms and craving) in the PI
groups compared to the BI groups (P < .0001 for all scores) across 24 weeks of
treatment. These results support that opioid withdrawal symptoms and cravings
(both self- and observer-assessed) were better controlled, in a clinically and nom-
inally statistically significant sense, in the BI group than in the PI group.
Clinician-rated Clinical Global Impressions-Severity (CGI-S) (of opioid
dependence) and Improvement scales (CGI-I) (Guy 1976) were obtained at weeks
16 and 24. At week 16 the proportion of “responder” patients was higher in the BI
groups than in the PI groups for both the CGI-self and CGI-observer scores,
although the differences were not nominally statistically significant. At week
24, the differences between the two treatment groups had increased and were
nominally statistically significant on both scores in study PRO-805 and for
518 M.S. Mumenthaler and K.L. Beebe
30.3 Conclusion
Collectively, the data of six clinical studies indicate that Buprenorphine Implants are
a safe and efficacious maintenance treatment for opioid dependence. BI was superior
to PI in both double-blind studies for the primary outcome measure, the proportion
of urine samples negative for opioids. Secondary and exploratory endpoints
supported the conclusion that BI was more efficacious than PI. These included
analyses of opioid-negative urines during various segments of the treatment period,
the proportion of patients completing each study, measures of opioid withdrawal
symptoms and cravings, patient- and observer-rated improvement in opioid
dependence, and use of supplemental buprenorphine. In secondary and exploratory
comparisons, BI and open-label SL buprenorphine resulted in similar proportions of
opioid-negative urine samples over 24 weeks, documenting the overall comparability
of 4–5 Buprenorphine Implants to sublingual buprenorphine (12–16 mg/day) in a
6-month treatment for opioid dependence. The Buprenorphine Implants clinical
program demonstrated safety and efficacy of Buprenorphine Implants for the
maintenance treatment of opioid dependence.
References
Chandler RK, Fletcher BW, Volkow ND (2009) Treating drug abuse and addiction in the criminal
justice system: improving public health and safety. JAMA 301:183–190
Dijkstra BA, Krabbe PF, Riezebos TG, van der Staak CP, De Jong CA (2007) Psychometric
evaluation of the Dutch version of the Subjective Opiate Withdrawal Scale (SOWS). Eur
Addict Res 13:81–88
Guy W (1976) ECDEU assessment manual for psychopharmacology. National Institute of Mental
Health, US Dept of Health, Education, and Welfare, Washington, DC, pp 76–338
Ling W, Casadone P, Bigelow G, Kampman KM, Patkar A, Bailey GL et al (2010) Buprenorphine
implants for treatment of opioid dependence: a randomized controlled trial. JAMA
304:1576–1583
Luty J, O’Gara C, Sessay M (2005) Is methadone too dangerous for opiate addiction? BMI
331(7529):1352–1353
Marsh LA (1998) The efficacy of methadone maintenance interventions in reducing illicit opiate
use, HIV risk behavior and criminality: a meta-analysis. Addiction 93(4):515–532
Tompkins DA, Bigelow GE, Harrison JA, Johnson RE, Fudala PJ, Strain EC (2009) Concurrent
validation of the Clinical Opiate Withdrawal Scale (COWS) and single-item indices against the
Clinical Institute Narcotic Assessment (CINA) opioid withdrawal instrument. Drug Alcohol
Depend 105:154–159
Winstock AR, Lea T, Sheridan J (2008) Prevalence of diversion and injection of methadone and
buprenorphine among clients receiving opioid treatment at community pharmacies in New
South Wales Australia. Int J Drug Policy 19:450–458
Use of Different Drug Formulations of
Opioid Antagonist (Naltrexone) to Treat 31
Opioid Dependence in Russia
Contents
31.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 522
31.2 Naltrexone Studies - Russian Context . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 523
31.2.1 Studies of Oral Naltrexone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 523
31.2.2 Studies with Long-Acting, Sustained-Release Formulations . . . . . . . . . . . . . . . . . 526
31.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 528
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 529
Abstract
Opioid addiction is one of the most severe drug problems due to its high level of
morbidity, mortality, and psychosocial consequences. Naltrexone completely
blocks the effects of opioids and, when administered to detoxified opioid addicts
and taken as directed, prevents relapse and reduces the chances for a wide range
of adverse effects associated with untreated addiction. It has been available as
a 50 mg tablet since the mid-1970s, and early studies showed very limited
efficacy due to lack of interest by patients, high dropout rates, and
a preference for methadone maintenance. In addition, patients must be detoxified
and free of physiologic opioid dependence prior to starting naltrexone because it
E. Krupitsky (*)
Department of Addictions, St. Petersburg Bekhterev Psychoneurological Research Institute,
St. Petersburg, Russia
e-mail: [email protected]; [email protected]
E. Zvartau
Department of Pharmacology, St. Petersburg State Pavlov Medical University, St. Petersburg,
Russia
e-mail: [email protected]
G. Woody
Treatment Research Institute, Philadelphia, PA, USA
e-mail: [email protected]
31.1 Introduction
Naltrexone, an opioid antagonist, was approved by the US Food and Drug Admin-
istration to treat opioid dependence in 1984. Approval was based primarily on its
pharmacologic profile, as it blocks opioid effects by antagonism at the m-opioid
receptors (Kleber 2007). Naltrexone is a perfect antagonist for treating heroin
dependence, as 50 mg (one tablet) blocks the effects of heroin for 24-36 h; it is
easy to administer (one tablet per day or two tablets every other day), safe
(no common serious adverse events if used in recommended doses), and well
tolerated (a relatively small number of side effects) and does not have addictive
potential; and tolerance does not develop to the opioid antagonism.
However, one problem markedly reduces naltrexone’s efficacy and has limited
its use for treating heroin and other forms of opioid dependence worldwide: patients
often do not like it and do not take it on a daily basis. The dropout rate with oral
naltrexone has been better in the limited number of patients in whom there is
substantial external motivation to remain abstinent, such as physicians who are in
monitoring programs and could lose their license if they relapse, those involved in
the criminal justice system who could go to prison if they relapse, and those facing
loss of employment (O’Brien and Cornish 2006; Kleber 2007).
Recent World Health Organization guidelines for the pharmacologic treatment
of opioid dependence suggest that the limited evidence available demonstrates that
in dependent opioid users who have withdrawn from opioids, those treated with
naltrexone are less likely to use heroin or engage in criminal activity than those who
do not take naltrexone, but the proportion who continue taking naltrexone has been
very low (World Health Organization 2009). However, our recent studies of
naltrexone for treating opioid dependence in St. Petersburg, Russia, have shown
that in some cultural settings, naltrexone may be much more effective. In particular,
31 Use of Different Drug Formulations of Opioid Antagonist (Naltrexone) 523
Russian law forbids substitution therapy for opioid dependence with methadone or
buprenorphine, and the national health-care system supports over 25,000 inpatient
detoxification and rehabilitation treatment beds, thus making it easy to start patients
on naltrexone. Naltrexone is the only specific pharmacotherapy that is currently
approved for use in the Russian Federation and is available as an oral tablet and two
extended-release formulations: implantable and injectable. The results of studies
using these formulations are summarized below.
Fluoxetine (NP + F) did not differ significantly from NP plus FP, and N plus F did
not differ from naltrexone alone (N + FP; P ¼ 0.2). However, women in the N plus
F group showed a trend toward an advantage when compared with women receiv-
ing naltrexone and fluoxetine placebo (N + FP; P ¼ 0.08), probably due to a higher
level of depression, anxiety, and anhedonia in women at study intake compared
with men. Thus, it was confirmed in this larger study that naltrexone was more
effective than placebo for relapse prevention in opioid addicts in Russia. In addi-
tion, naltrexone and fluoxetine, or naltrexone alone, were both more effective than
fluoxetine alone, although the combination of naltrexone and fluoxetine had
a tendency to be more effective than naltrexone alone in women (Krupitsky
et al. 2006). Overall, the antidepressant did not dramatically improve the naltrexone
treatment outcome. It should be added that oral naltrexone was generally well
tolerated, the number of side effects was limited, and neither serious adverse events
nor lethal overdose occurred.
Using the number of visits as the denominator, nonlocal site AEs were reported by
8/886 (1 %) in the NI+OP group, 4/522 (1 %) in the PI+ON group, and 3/394 (1 %)
in the PI+ON group; none were serious and all resolved without medication.
There was no evidence of increased overdose death after naltrexone treatment
ended. Thus, the implant was more effective than ON or placebo. More patients
in NI+OP than in the other groups developed wound infections or local irritation at
the implant site, but none were serious and all resolved with treatment (Krupitsky
et al. 2012).
No significant differences were detected between groups in physical and social
anhedonia, thus implying that the long-acting naltrexone did not interfere with
normal pleasurable stimuli. Similar to our studies with oral naltrexone, psychiatric
symptoms (anxiety, depression, opioid craving) were markedly reduced in patients
who remained in treatment and did not relapse, and no differences were noted
between groups for those who remained in treatment and did not relapse. The
efficacy of oral naltrexone was lower in this implant study compared with our
previous oral naltrexone studies (Krupitsky et al. 2004, 2006), which may be related
to the age of opioid addicts and the degree to which family members could
supervise compliance. For example, the mean age of patients in the implant study
was 28-29 years, significantly higher than previous studies, in which the average
was 21-23 years. These older patients were less likely to be living with relatives,
which made it more difficult for the relatives to supervise compliance.
Results of two recent randomized trials of another naltrexone implant developed
in Australia also demonstrated its advantages over oral naltrexone (Hulse
et al. 2009) and usual-treatment aftercare (Kunoe et al. 2009); however, these
studies did not have a placebo control group. Other long-acting, slow-release
naltrexone formulations (implantable and injectable) for opioid dependence are
being developed and tested (Krupitsky and Blokhina 2010).
Implantable naltrexone formulations have several limitations. First, they require
a minor surgical procedure that carries with it the risk of wound infections and
cosmetic defects. Second, it is possible for the patient to remove the implant within
the first few weeks, as Prodetoxone slowly dissolves and can be removed reason-
ably intact within the first few weeks. Third, in some patients (<10 %), the implant
appeared to block opioids for less than 2 months. Therefore, a long-acting, slow-
release formulation that is injectable and simple to use and does not require surgery
might have some advantages over an implant formulation.
multicenter trial (Krupitsky et al. 2011). The study, conducted at 13 sites in Russia,
recruited males and females (18 years) meeting DSM-IV criteria for opioid
dependence disorder, who had completed inpatient opioid detoxification
(30 days) and who were off opioids for 7 days. Patients were voluntarily seeking
treatment and were excluded if they were under justice system coercion, i.e., parole
or probation, or pending legal proceedings with potential for incarceration. Patients
were randomized to either injectable naltrexone 380 mg (Vivitrol ®) or placebo in
a 1:1 ratio, stratifying by site and gender in a centralized, permuted-block method.
Vivitrol ® was injected within 1 week following detoxification and then every
4 weeks, for a total of six injections over 24 weeks. Participants were also offered
12 biweekly sessions of manualized individual drug counseling (IDC), adapted for
opioid dependence. The primary outcome was the response profile for confirmed
abstinence, based on opioid-negative urine drug tests and self-report of nonuse
during weeks 5–24. Patients were predominantly young, male, white, and addicted
to heroin for 10 years and had high rates of HIV and hepatitis C infection. In the
30 days prior to the first injection, heroin was used by 221 (88.4 %) of participants,
methadone by 29 (11.6 %), and other opioids/analgesics by 33 (13.2 %). Baseline
characteristics showed no significant intergroup differences. Vivitrol ® yielded
a median of 90 % confirmed abstinent weeks vs. 35 % for placebo (p ¼ 0.0002);
total abstinence occurred in 36 % of Vivitrol ® patients vs. 23 % (p ¼ 0.0224). An
anti-craving effect was observed; at baseline (scale 0–100), there was no group
difference (21.8 vs. 18.2); however, during treatment Vivitrol ® showed a mean
reduction of 10.1 (vs. +0.7 for placebo; p < 0.0001). Median retention was
>168 days with Vivitrol ® vs. 96 days with placebo (p ¼ 0.0042). Naloxone
challenge confirmed relapse to physiologic opioid dependence in 17 placebo
patients vs. one Vivitrol ® patient, a 94 % difference (p < 0.0001). Reduced HIV
risk behavior and improved mental health function were observed with Vivitrol ®
vs. placebo. Adverse events were reported by 50 % on Vivitrol ® vs. 32.3 % on
placebo. Mean increases, for Vivitrol ® vs. placebo, were similar for ALT (6.9
vs. 5.6 IU/L) and AST (3.8 vs. 6.7 IU/L), but hepatic enzyme abnormalities were
more common with Vivitrol ®. All nonserious adverse events were rated mild or
moderate and included nasopharyngitis, insomnia, injection site pain, and tooth-
ache. No patients died or overdosed. Thus, in opioid-dependent patients, Vivitrol ®
with counseling demonstrated efficacy vs. placebo across multiple recovery goals
including prevention of relapse, showing that it represents a new approach that is
distinct from opioid maintenance treatment through once-monthly, injectable,
opioid blockade.
31.3 Conclusion
Studies conducted in St. Petersburg, Russia, for more than a decade have demon-
strated the efficacy and safety of different naltrexone formulations (oral, implant-
able, injectable) for relapse prevention and maintenance of abstinence in detoxified
opioid addicts. The positive results from different formulations seem related to two
31 Use of Different Drug Formulations of Opioid Antagonist (Naltrexone) 529
cultural factors. One is that detoxification is widely available and relatives can be
recruited to supervise daily dosing of the oral formulation; however, this advantage
appears to decrease as the population ages. The second is that substitution therapy is
not available; thus, naltrexone is the only effective medication, which makes it
easier to motivate patients to use it. Findings from studies of long-acting, extended-
release formulations (implantable and injectable) show that they are more effective
than oral formulations and likely to be important additions to current treatment
options not only in Russia but also for patients in other settings who do not want or
do not have ready access to agonist or long-term residential treatment. How
extended-release naltrexone formulations compare with maintenance treatment
using methadone or buprenorphine in settings in which all three treatment options
are available is a topic for future studies.
Acknowledgment The studies of oral naltrexone with or without fluoxetine were supported by
NIDA grants P60-DA05186l (Dr. O’Brien) and DA017317 and K05-DA 17009 (Dr. Woody) and
the Department of Veterans Affairs. Alkermes (USA) supported the study of injectable naltrexone
(Vivitrol ®) in Russia.
Disclosure DuPont Pharmaceutical provided naltrexone, and Gideon Richter provided fluoxetine
for the studies of oral naltrexone with or without fluoxetine. Fidelity Capital (Russia) provided
Prodetoxone at reduced cost.
Dr. Krupitsky had been serving a consultant for Alkermes in 2007–2010. No other potential
conflicts of interest relevant to this article were reported.
References
Dunbar JL, Turncliff RZ, Hayes SC, Farrell CB (2007) Population pharmacokinetics of extended-
release injectable naltrexone (XR-NTX) in patients with alcohol dependence. J Stud Alcohol
Drugs 68:862–870
Hulse GK, Morris N, Arnold-Reed D, Tait RJ (2009) Improving clinical outcomes in treating
heroin dependence. Arch Gen Psychiatry 66:1108–1115
Kleber H (2007) Pharmacologic treatments for opioid dependence: detoxification and maintenance
options. Dialogues Clin Neurosci 9:455–470
Krupitsky EM, Blokhina EA (2010) Long acting sustained release formulations of naltrexone for
heroin dependence: a review. Curr Opin Psychiatry 23:210–214
Krupitsky EM, Burakov AM, Didenko TY, Romanova TN, Grinenko NI, Slavina TY,
Grinenko AY, Tcheremissine OV (2002) Effects of citalopram treatment of protracted with-
drawal (syndrome of anhedonia) in patients with heroin addiction. Addict Disord Their Treat
1:29–33
Krupitsky EM, Zvartau EE, Masalov DV, Tsoi MV, Burakov AM, Egorova VY, Didenko TY,
Romanova TN, Ivanova EB, Bespalov AY, Verbitskaya EV, Neznanov NG, Grinenko AY,
O’Brien CP, Woody GE (2004) Naltrexone for heroin dependence treatment in St. Petersburg,
Russia. J Subst Abuse Treat 26:285–294
Krupitsky EM, Zwartau EE, Masalov DV, Tsoy MV, Burakov AM, Egorova VY, Didenko TY,
Romanova TN, Ivanova EB, Bespalov AY, Verbitskaya EV, Neznanov NG, Grinenko AY,
O’Brien CP, Woody GE (2006) Naltrexone with or without fluoxetine for preventing relapse to
heroin addiction in St. Petersburg, Russia. J Subst Abuse Treat 31:319–328
Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL (2011) Injectable
extended-release naltrexone for opioid dependence: a double-blind placebo-controlled multi-
center randomized trial. Lancet 377:1506–1513
530 E. Krupitsky et al.
Min Zhao
Contents
32.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 532
32.2 The Epidemic of Drug Use and HIV/AIDS in China . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 532
32.3 The Development of Methadone Maintenance Treatment Program . . . . . . . . . . . . . . . . . . . 533
32.3.1 Preparation Phase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 534
32.3.2 The Pilot Phase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 534
32.3.3 The Scale-Up Stage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535
32.3.4 The Quality Improving Phase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535
32.3.5 MMT Mobile Service . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 536
32.3.6 Extension MMT Service Site . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 536
32.4 The Governance and Technical Support for MMT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537
32.5 The Outcomes of MMT Programs in China . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 538
32.6 Challenges and Future Direction in MMT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 539
32.6.1 The Service Coverage and Utilization Needs to Be Increased . . . . . . . . . . . . . . . 539
32.6.2 The Retention of the Clients Need to Be Increased . . . . . . . . . . . . . . . . . . . . . . . . . . 539
32.6.3 MMT Programs Should Serve as a Comprehensive Service Platform . . . . . . . 540
32.6.4 Collaboration Among Multi-sectors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 541
32.6.5 Capacity Building for Staffs in MMT Clinics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 541
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 542
Abstract
China has a long history of opium abuse problems and currently faces the
challenge of a dual epidemic of drug use and HIV/AIDS. China has adopted
methadone maintenance therapy (MMT) as a primary strategy to combat this
dual epidemic. The results from the studies have shown that most of the
interventions MMT programs were successful and had positive effects in reduc-
ing drug-related risk behaviors among drug users. It is expected that the
M. Zhao
Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine,
Shanghai, Peoples’ Republic of China
e-mail: [email protected]; [email protected]
coverage and quality of the MMT programs will improve and they will fully
achieve their goals in the near future.
32.1 Introduction
China is the largest populated country in the world and suffered from a long history
of opium abuse problems. As for economic development and modern socialization,
like other Western countries, China faces the challenge of dual epidemics of drug
use and HIV/AIDS. The former has fuelled the latter and in the last 30 years, both
the number of drug users and cases of HIV/AIDS have increased dramatically. This
has prompted the government to consider employing harm reduction strategies to
control the spread of HIV/AIDS among drug users. Following the success of the
proven “substitution” pharmacotherapy approach that has been tested extensively
in the Western nations, China has adopted methadone maintenance therapy (MMT)
as a primary strategy to combat the combination threat of drug use and HIV/AIDS.
MMT program has been implemented in China for nearly 10 years and achieved
remarkable progress with the support of central government.
China has had a long history of drug use, especially opium abuse. The country
enjoyed a relatively drug-free period between the 1950s and 1980s due to
a successful antidrug campaign. Shortly after the new Chinese government
established in 1949, under Mao’s leadership, the government launched a national
level antidrug campaign, which included compulsory detoxification of drug
abusers, severe punishment for drug dealers, and the replacement of opium with
other crops, and was greatly assisted by closing the borders (McCoy et al. 2001).
However, in the late 1970s, China introduced its “open door” and economic
development policy. China is close to the “Golden Triangle” and “Golden Cres-
cent,” two of the three biggest opiate suppler areas in the world. Concurrent with
increased trade of licit goods, the trade in illicit goods, including narcotics,
reemerged (Zhao et al. 2004). When drug use reemerged in the late 1970s, it was
concentrated in Yunnan and Guangxi provinces which border with Myanmar and
Vietnam. At that time, Chinese authorities were under the impression that China
only served as a trafficking route for drug smugglers to traffic drugs to other
countries and that there was no or little drug consumption. Efforts were exclusively
focused on seizures of smuggled drugs, with little attention given to prevention and
treatment of drug use among the Chinese. Along drug traffic routes, more and more
youths and young adults became drug users, and later, drug use spread very quickly
from border areas to inner regions of the country (Zhao et al. 2004). It was not until
the mid-1990s that Chinese officials and scholars recognized that drug use was
a severe social problem. China’s Public Security Bureaus (PSB) started to register
drug users in 1990. The registered number of drug users in 1990 was 70,000 and this
32 Implementation of Methadone Maintenance Treatment in China 533
figure rose to 1.79 million in 2011 (National Narcotic Control Commission 2012),
representing a rapid epidemic of drug use problems in China.
With the drug use problem increasing rapidly, the drug use-related family,
social, and public health problems become more and more oblivious. One of the
severe public health consequences is HIV/AIDS transmission among drug users.
Needle sharing to inject heroin is believed to have been the principal entry route of
HIV into China. Indeed, first HIV outbreak was identified among 146 injecting
drug users in Yunnan province in 1989 (Wang 2007). Since then, China has
observed an ever-growing HIV/AIDS epidemic. In 2001, up to 66.5 % of newly
diagnosed HIV infections were related to drug use. The prevalence of HIV is
highest in those provinces located closest to the borders of Myanmar (Yunnan
Province), Vietnam (Guangxi Autonomous Region), and Central Asia (Xinjiang
Uygur Autonomous Region). The HIV/AIDS has spread rapidly through the
injecting drug user (IDU) population and had reached IDUs in all 31 provinces
by 2002. By the end of 2005, HIV was estimated to have infected 288,000 drug
users, accounting for 44.3 % of China’s 650,000 HIV infections (Bao and Liu
2009). The prevalence of HIV in China is roughly 0.05 %, but among drug users it
is much higher and surveys among drug users have found the prevalence to be
12.5 % among drug users (Bao and Liu 2009). Facing the threats of HIV/AIDS
epidemics among drug users, harm reduction efforts began in 2003 and have
slowed the pace of HIV infection among drug users has stabilized and reduced,
particularly since 2005, with the overall growth rate of newly reported cases
having decreased from 9.0 % in 2006 to 5.8 % in 2009. By the end of Oct.
2012, 492,000 HIV-infected cases were reported and 25.8 % of the cases were
injecting drug users (IDUs). It was thought that IDU is no longer the major
HIV/AIDS transmission mode in China. Among the harm reduction strategies,
methadone maintenance treatment was the most successfully implemented pro-
gram in China.
In the early 1990s, government officials began the lengthy process of understanding
how best to constrain the dual epidemic of HIV and drug use. This included
learning from other countries, developing policies and plans suitable to China,
piloting harm reduction strategies, and ultimately implementing a multifaceted
program to slow the HIV epidemic among drug users. When first introduced,
harm reduction was controversial because it conflicted with laws and regulations
on narcotics control. Thus, despite a large body of evidence supporting the
effectiveness of MMT, it was initially difficult to convince government officials,
especially those in law enforcement, to try this strategy (Yin et al. 2010). But finally
the National Center of AIDS/STD Control and Prevention (NCAIDS) make great
effort to develop MMT program as a strategy to control HIV transmission by
several phases.
534 M. Zhao
the clinics were based on need and the local government agencies’ willingness to
participate. A total of 1,029 clients were enrolled during the first calendar year of
the pilot. To estimate the effectiveness of these first eight clinics, the national
secretariat established a monitoring and evaluation system.
In 2004, the first national meeting on piloting MMT was convened among experts
and government officials from Ministry of Health and National Narcotics Bureau.
The meeting served to share the experiences and to promote rapid scale-up
throughout the country. With growing political and technical support, the MMT
program began to steadily expand. By the end of 2005, there were 58 MMT clinics
opened in 11 provinces. Thus, the pilot period ended and the MMT program moved
to national scale. In 2006, the adjoining Five-Year Action Plan to Control
HIV/AIDS (2006–2010) set specific targets for scaling up MMT; by the end of
2007 and 2010, MMT would be made available for no fewer than 40 % and 70 % of
opiate users, respectively, in counties and districts with more than 500 registered
drug users (State Council of P. R. China 2006). Also, in July 2006, the National
Working Group revised the temporary scheme to improve MMT services. Several
crucial improvements were made to benefit and cover more target groups. Notably,
the enrolment and exclusion criteria were relaxed. For example, (1) clients are no
longer required to have a history of detoxification or several failed attempts to quit
using drugs to enter the program, (2) clients are no longer required to be registered
as local residents and a transfer system has been set up to meet the needs of those
who are relocating either permanently or temporarily, and (3) relapse is no longer
a strong reason for expulsion. Furthermore, a detailed clinical guideline for meth-
adone treatment was added to the protocol to support clinical practice, and com-
prehensive interventions are highlighted in the new protocol that suggests clinics
offer ancillary services. These include counseling, psychosocial support, testing for
HIV, syphilis, hepatitis C and tuberculosis, referrals for antiretroviral treatment,
peer education, health education, group activities, and skills training for employ-
ment. The treatment fee for MMT services was not specified, as in some areas
where heroin is easily obtained at low cost, the fee is reduced or even waived. In
2007, central government funding was also allocated to the program, enabling those
places with less than 500 registered drug users to establish MMT clinics. Another
target of 500 MMT clinics was set and 503 MMT clinics were cumulatively
accomplished by the end of 2007, in 23 provinces serving 97,554 clients.
There were 680 clinics by the end of 2009, in 27 provinces with some 242,000
clients ever enrolled, roughly half of whom remain in treatment. Areas of greatest
need have MMT clinics and the expansion has thus slowed down and then the focus
536 M. Zhao
08/2002 02/2003 03-06/2004 10/2004-12/2005 07-09/2006 2008 2009 2010 2011 11/2012
Preparation Pilot phase Scale up phase Quality
phase improving
phase
of the National Working Group is focused on improving the service quality. It was
emphasized to improve the retention rates and a series of intensive training was
carried out to improve the service quality. Clinic services have been extended to
offer clients a range of ancillary services, including HIV, syphilis, and hepatitis
C testing; information, education, and communication; psychosocial support ser-
vices; and referrals for treatment of HIV, tuberculosis, and sexually transmitted
diseases. Regular evaluation and professional supervise were organized to identify
problems and provide technical support. By the end of Nov. 2012, there were
755 clinics in 28 provinces with 381,900 clients ever enrolled, roughly 78.2 % of
whom remain in treatment within 1 year. The development process of MMT
program in China is illustrated in Fig. 32.1.
China is a vast country with many rural areas where the density of population is
varied largely. In order to provide MMT services to drug users in remote, rural areas
to access to methadone, the first MMT mobile service vehicle was established in
Nov. 2006 in Yunnan province. The mobile MMT service vehicle serves as a small
MMT clinic, equipped with necessary medical equipment, medicine, and qualified
professionals and securities. Every day the mobile MMT service vehicle travels
decades of miles with several fix stops where the patients are concentrated. Fol-
lowing the success experiences in Yunnan, the mobile services were available later
in other provinces, with a total of 30 MMT vehicles by the end of Nov. 2012.
clinics are responsible for the technique support such as staff training and clinical
supervision for the extension sites. The fixed MMT clinics are also in charge of the
everyday clinical management such as patients recruit, data collection, laboratory
test, and methadone delivery in the extension MMT service sites. There are
308 extension MMT service sites available by the end of November 2012 since it
was first opened in Yunnan province.
The National Working Group was given an overall responsibility for managing the
MMT program, supervising the operation, and overseeing its expansion. At the
provincial and county level, working groups have also been established to take on
these duties locally. The National Working Group members meet regularly to
identify potential gaps, resolve emerging issues, and refine the management of
the program. The NCAIDS serves as the secretariat for the National Working
Group, which is tasked with executing the national plan, coordinating the imple-
mentation, providing technical support to the clinics, and conducting routine
monitoring and evaluation. The national training center was established in the
Yunnan Institute of Drug Abuse to provide clinical and administrative training
for key staff working in MMT clinics. Two specific training programs are provided
to trainees. The first is a 10-day intensive training course covering addiction theory,
clinical practice, and administrative skills for delivery of MMT services. The
second is on-site training provided by clinical addiction experts to assist local
staff for the first 7 days after a clinic has opened, to guide them in the practice of
addiction treatment and data management. The MMT clinics in China are nonprofit
medical facilities assigned by local public security and public health departments to
be established and operated by local Centers for Disease Control and Prevention
(CDC), primary health hospitals, mental health hospitals, or voluntary detoxifica-
tion centers in areas with a concentration of drug users. Typically, an MMT clinic is
required to have eight to ten staff members including qualified doctors, pharmacist,
security personnel, etc. Doctors are primarily responsible for prescribing metha-
done, providing physical examination, and psychological counseling, and they are
required to be certified physicians authorized to prescribe analgesic and psychotro-
pic drugs. Nurses are responsible for dispensing methadone to the clients and
observing them taking the methadone. Other clinic staff members are responsible
for data entry, management, report, and other logistical issues. One or two security
personnel are required for each of the MMT clinic. Patients meet with the doctor
every day and pay not more than 10 Yuan (or US $1.25) for the daily dosage. Urine
testing is routinely required. The services offered at methadone clinics have been
broadened and provide access to other services, including HIV and hepatitis testing,
antiretroviral therapy for eligible AIDS patients, group activities, peer education,
and skills training for employment. Regular monitoring and evaluation need to be
carried out to quality control. A national MMT program database was developed in
2004 to monitor the pilot and was later upgraded to a web-based management
538 M. Zhao
The results of the empirical studies in China revealed that most of the interventions
of MMT program were successful and had positive effects in reducing drug-related
risk behaviors among drug users. A 2007 evaluation survey conducted in the first
phase of eight MMT clinics found a positive change in the self-reported rate of
injecting drug use, drug-related illegal offenses, employment opportunities, and
family relations. Only eight HIV seroconversions were found among 1,153 sero-
negative clients during the 12-month follow-up (Pang et al. 2007). Another two
MMT intervention studies showed that the use of MMT decreased the frequency of
IDU and criminal behaviors. The sentinel surveillance data showed that HIV
infection prevalence among drug users has been leveled off and has a tendency to
decrease after the MMT program was implemented in China (Yin et al. 2010,
Fig. 32.2).
These positive results are consistent with the large body of empirical evidence
on effectiveness of harm reduction programs in other countries. One study in
Yunnan province analyzed the cost and cost-effectiveness of methadone mainte-
nance treatment (MMT) program, and it demonstrates that MMT is a cost-effective
9.0
8.0
7.0
HIV Prevalence
6.0
5.0
4.0
3.0
2.0
1.0
0.0
95
96
97
98
99
00
01
02
03
04
05
06
07
08
09
19
19
19
19
19
20
20
20
20
20
20
20
20
20
20
Year
Fig. 32.2 HIV sentinel surveillance data for drug users, 1995–2009
32 Implementation of Methadone Maintenance Treatment in China 539
intervention for reducing HIV transmission among injecting drug users (Xing
et al. 2012). In summary, the MMT program not only decreased the drug use and
HIV transmission; it was also a cost-effective intervention.
First, despite a high number of registered opiate addicts in the country, the number
of clients in the MMT program is very limited, with low coverage of the total drug-
using population (Li et al. 2007). There is great variation in the numbers of clients
in each MMT clinic, some with more than 200, whereas others have fewer than 20.
According to the newest data from the National Working Group’s report recently,
there are 755 MMT clinics, and only 209,400 clients (less than 20 % of the
registered number of drug users) are currently in the treatment. The majority
(63.8 %) of the MMT clinics only had less than 200 clients. Clearly the program
does not reach the majority of opiate addicts, although there is adequate capacity to
handle more clients.
Given human resources constraints and the size of the country, it is not feasible
to offer MMT services in all areas with drug use. It is pragmatic to provide the
service in the worst affected areas first, and only areas with more than 500 drug
addicts had MMT clinics. The denominator used to calculate the targeted clients is
currently registered drug users, which may be significantly less than the actual
number. Although mobile MMT service vehicles and extension MMT service site
have been implemented to increase the service coverage in some areas, it may be
a long time before services are more widely accessible. The existing MMT clinics
can serve much more clients than the actual number of clients in MMT programs
now; therefore, a very important strategy should focus on how to increase the
service utilization. In-depth research are needed to find out the barriers for service
utilization, and related adjustment on policy and operation of the MMT programs
should be taken to address these barriers.
Second, the client dropout rate is high in most sites (Qian et al. 2006) and a consider-
able proportion of clients continue illicit drug use while participating in MMT.
540 M. Zhao
The MMT program has suffered from a high relapse rate, especially in its initial phases.
In 2009, the overall retention of MMT in China was about 50 % and most of the clients
who dropped out relapsed to drug use.
Previous studies have documented that both treatment and individual level
characteristics are associated with treatment retention. Treatment characteristics
are crucial predictors of retention and drug use. For example, methadone dosage is
strongly positively associated with retention and other favorable treatment out-
comes. MMT clients in China receive lower dosages of methadone compared with
patients treated in other countries. The average daily dosage of methadone given to
Chinese clients in eight pilot MMT clinics was 44.9 21.9 mg (Pang et al. 2007).
One qualitative study showed that the average dosage prescribed in the 28 clinics
was 35 mg per day (Lin and Detels 2011). Therefore, it is necessary to formulate
clear guidelines concerning individualized dosage management and to improve
training among service providers in MMT clinics in China. The National Working
Group has realized the abovementioned problems and challenges and is making
a great effort to solve these problems. The scale-up pace of MMT program has been
slowed down and the focus of the National Working Group has been shifted to
improve service quality to increase the retention and drug use.
Drug addiction behavior is defined as illegal and can be sent to compulsory drug
rehabilitation institution by public security system. The conflicting approach
between “zero tolerance” policies toward drug use and harm reduction programs
including MMT and a lack of cooperation among related departments may make it
difficult for the effective implementation of MMT programs. Entry into the MMT
program requires registration as a drug user with the public security system, and this
may be a big barrier for patients since they do not want to be marked as “drug
addicts” which is highly stigmatized in China. MMT clinics are required to report to
the police patients who are drug positive for the third time. Clinics operated by law
enforcement are likely to be stricter and less able to deviate from official guidelines
than facilities that are operated by the public health system. Some patients who
relapse in the MMT clinics were sent to compulsory drug rehabilitation center;
therefore, many patients are scared to go to MMT clinics.
Significant progress has recently been made in this area and the public security
system are being ever more supportive, especially of MMT, paving the way for
faster scale-up of MMT programs. Health workers cannot expect law enforcers to
ignore illegal behaviors, but they can work with them to find mutually agreeable
strategies for achieving their respective goals. Synchronized drug use control
approach, open communication, and strong cooperation among involved govern-
mental departments are needed to ensure the effective implementation of MMT
program in China. As a substantial number of drug users are incarcerated and
a proportion of them are HIV positive, MMT program should be considered in
incarceration centers to prevent further spread of HIV and drug use in the future.
Evidence-based treatment approaches for addiction are effective only when properly
implemented and conducted. Compared with Western nations, MMT programs in
China are still at an early stage of development. Staffs working in MMT have different
backgrounds with different levels of professional capacity. The majority of MMT
clinicians only received minimum professional trainings and lack sufficient expertise
in managing pharmacotherapy treatment or in delivering psychosocial interventions.
Drug addiction is a very complicated condition with multidrug use and complex
comorbid physical or mental health problems, and well-trained treatment staffs are
needed to deal with these problems. Studies have consistently indicated that metha-
done maintenance combined with psychosocial services is more effective in retaining
patients, decreasing relapse rates, and reducing costs than maintenance treatment
alone. But no standardized comprehensive psychosocial service or counseling is
available for patients due to the shortage of professional capacity in China. Therefore,
sustained and intensive professional trainings are needed to enhance the capacity of
staffs in MMT programs. Institutional capacity building to deliver sustainable and
standardized services will ultimately improve retention rates in China.
542 M. Zhao
References
Bao PY, Liu MZ (2009) Systematic review of HIV and HCV infection among users in China.
Int J STD AIDS 20:339–405
Li MQ, Lee SS, Gan ZG, Y-i T, Meng JH, He ML (2007) Achieving a high coverage – the
challenge of controlling HIV spread in heroin users. Harm Reduct J 4:8
Li JH, Ha TH, Zhang CM, Liu HJ (2010) The Chinese government’s response to drug use and
HIV/AIDS: a review of policies and programs. Harm Reduct J 7:1–6
Lin C, Detels R (2011) A qualitative study exploring the reason for low dosage of methadone
prescribed in the MMT clinics in China. Drug Alcohol Depend 117(1):45–49
Lin C, Wu Z, Rou K, Pang L, Cao X, Shoptaw S, Detels R (2010) Challenges in providing services
in methadone maintenance therapy clinics in China: service providers’ perceptions. Int J Drug
Policy 21:173–178
McCoy CB, McCoy HV, Lai SH, Wang X, Meng J (2001) Reawakening the dragon: changing
patterns of opiate use in Asia, with particular emphasis on China’s Yunnan province. Subst Use
Misuse 36:49–69
National Narcotic Control Commission (2012) Annual national narcotic control report 2012.
Ministry of Public Security, Beijing
Pang L, Hao Y, Mi G, Wang C, Luo W, Rou K, Li J, Wu Z (2007) Effectiveness of first eight
methadone maintenance treatment clinics in China. AIDS 21(Suppl 8):S103–S107
Qian HZ, Schumacher JE, Chen HT, Ruan YH (2006) Injection drug use and HIV/AIDS in China:
review of current situation, prevention and policy implications. Harm Reduct J 1:3–4
State Council of P. R. China (2006) China’s action plan for reducing and preventing the spread of
HIV/AIDS (2006–2010). State Council of P.R. of China, Beijing
Wang L (2007) Overview of the HIV/AIDS epidemic, scientific research and government
responses in China. AIDS 21(S8):S3–S7
Wu Z, Sullivan GS, Wang Y, Rotheram-Borus JM, Detels R (2007) Evolution of China’s response
to HIV/AIDS. Lancet 369:679–690
Xing Y, Sun J, Cao W, Lee L, Guo H, Li H, Duan S (2012) Economic evaluation of methadone
maintenance treatment in HIV/AIDS control among injecting drug users in Dehong, China.
AIDS Care 24(6):756–762
Yin W, Hao Y, Sun X, Gong X, Li F, Li J, Rou K, Sullivan SG, Wang C, Cao X, Luo W, Wu Z
(2010) Scaling up the national methadone maintenance treatment program in China: achieve-
ments and challenges. Int J Epidemiol 39:ii29–ii37. doi:10.1093/ije/dyq210
Zhao C, Liu Z, Zhao D, Liu Y, Liang J, Tang Y, Liu Z, Zheng J (2004) Drug abuse in China.
Ann N Y Acad Sci 1025:439–445
An Overview of Iran Drug Treatment and
Harm Reduction Programs 33
Saeed Momtazi, Alireza Noroozi, and Richard A. Rawson
Contents
33.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 544
33.2 Drug policy and Drug Treatment in Iran . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 545
33.2.1 From Over-Criminalization to Harm Reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 545
33.2.2 First National Epidemiological Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 546
33.2.3 Methadone Maintenance Treatment (MMT) Programs . . . . . . . . . . . . . . . . . . . . . . . 547
33.2.4 Methadone Maintenance Treatment Program in Prisons . . . . . . . . . . . . . . . . . . . . . 550
33.2.5 Buprenorphine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551
33.2.6 Tincture of Opium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 552
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 552
Abstract
The opioid addiction rate in Iran is among the highest in the world. One
contributing factor is Iran’s long border with the world’s main opium producer,
Afghanistan, with consequent extensive availability of opium and heroin. Fol-
lowing the 1979 Islamic revolution, drug policy employed in Iran was primarily
based on a supply reduction rationale, with an aggressive criminal justice/
S. Momtazi (*)
Psychiatry, Zanjan University of Medical Sciences, Zanjan, Iran
UCLA Integrated Substance Abuse Programs, Semel Institute, Geffen School of Medicine,
University of California, Los Angeles, CA, USA
e-mail: [email protected]
A. Noroozi
Iranian National Center for Addiction Studies (INCAS), Tehran, Iran
R.A. Rawson
Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, USA
Integrated Substance Abuse Programs, Semel Institute for Neuroscience and Human Behavior,
David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
e-mail: [email protected]
33.1 Introduction
Since centuries ago until the present time, psychoactive substances have influ-
ences on personal, sociocultural, religious, and even political aspects of Iranians’
life. Wine, according to mythical stories and archeological excavations from
5400 BC, may have originated in Iran (McGovern 2003). It was a drink of choice
for the upper class patricians in premodern times. Its use diminished temporarily
after the introduction of Islam in the seventh century, but after a short period of
time, people started drinking wine and its use continued to be popular but hidden
until the present-day Islamic Republic (Matthee 2005). In ancient Iran (Persia),
Mei (the Persian word wine) has been a central theme of poetry more than
a thousand years, although alcohol is strictly forbidden in Islam. Shiraz, a very
old city in Iran (1 h far from Persepolis), continued to be a center of wine
production in Islamic era, and today, its name is on a very famous dry red
table wine (Robinson 2006). Safavid dynasty permitted producing and exporting
wine and also drinking it but not in public. It is interesting that Safavid kings
were the most religious Iranian kings after Islam, but some of them died from
alcoholism (Matthee 2005) (Fig. 33.1).
The eleventh century Persian poet Farrokhi has said: Although wine is forbid-
den, I believe that it becomes licit for lovers when spring arrives, God gives us his
blessing as we drink. Come and don’t regret it.
Opium was also a popular drug since Safavid dynasty (1502–1736) and became
more popular during Qajar period (1785–1925).
Dr. Jacob Eduard Polak (1818–1891) – a Jewish Austrian physician who worked
in Iran between 1851 and 1860 as a teacher of the first Iranian medical school – has
33 An Overview of Iran Drug Treatment and Harm Reduction Programs 545
written in his book with the original title “Persien, das land und seine bewohner”:
“opium use is a very popular habit and it has no negative social stigma or shame for
users. It is not forbidden and every Iranian who can afford its cost uses it daily. . .
most people only took up the habit only in old age and stick to the same amount, so
that effects tended to be minimal.” Iranians began to develop a noticeable addiction
to opium in the mid-ninetieth century. Although opium has existed in Iran in some
form or another for centuries, widespread addiction was not known in the country
until about 1860 (McLaughlin 1976).
The first treatment centers specialized for addiction and first outpatient methadone
program in Iran initiated in the early 1970s. The first program was launched in 1974
in Shiraz city which used opioid agonist medication for assisted withdrawal of
opioid-dependent clients. Before that there are reports of methadone use for
546 S. Momtazi et al.
In order to have a real picture of substance abuse in the nation, the Iranian Welfare
Organization in collaboration with the United Nation’s International Drug Con-
trol Program (UNDCP) office performed a rapid situation assessment in a study
from 1998 to 1999. According to the data of this study and other studies,
authorities in Iran Drug Control Headquarters (DCHQ) and other officials believe
that around 1,200,000–2,000,000 individuals living in Iran would have
a diagnosis of drug abuse or drug dependence according to the DSM-IV criteria.
The average Iranian addict is very likely male, married, and employed. Data from
various provinces and within different groups show that more than 90 % of the
drug-abusing population is male. In fact, the RSA study claimed that on average,
93 % of drug abusers in the nation are male, whether imprisoned, in treatment, or
on the streets. The lowest preponderance of males belonged to Tehran, with 87 %.
Around two-thirds of the addict population is married. This figure is lowest in
Tehran, where only half seem to be married. Even in the incarcerated group, the
majority (51 %) was married. In fact, less than 10 % of the addicts live alone;
a spouse, parent, or sibling is usually present. Employment is also the rule in this
group. Unemployed drug abusers comprise only a fifth of the population.
According to study, a quarter of Iranian narcotic abusers have a history of
intravenous (IV) injection of opioids, mainly heroin. Appearance of heroin injec-
tion dates back to 1960s. A study performed on 318 narcotic abusers with
a lifetime history of IV drug abuse has shown that the average Iranian IV drug
user (IDU) is 31.4 (8.7) years of age, significantly 2 years younger than
non-IDU; has started drug use around 3.5 years before non-IDUs (19.6 year vs
23.1 year); and has started injecting while 26.2 (6.7) years old. Thus, injection
of illicit drugs begins on average 7 years after its non-IV consumption. While the
male-to-female ratio for non-IDU is 12:1, it is 31.3:1 for IDUs. More than half of
the IDUs are single (Mokri 2002).
33 An Overview of Iran Drug Treatment and Harm Reduction Programs 547
With the aim of adopting more effective strategies to address opioid use and
HIV-related drug-using behavior among opioid-dependent population, the first
methadone maintenance treatment (MMT) pilot project was conducted in Roozbeh
psychiatric hospital, in August 2002 (UNODC 2005). It was a double-blind
randomized, controlled trial comparing fixed doses of 40 and 70 mg daily oral
methadone to treat opioid dependency. The result of the study indicated that MMT
effectively reduced illicit opioid use and criminal and violent behavior and helps
patient save a reasonable sum of money formerly spent on drug consumption.
Three-month treatment retention among 40 mg, 70 mg, and total sample were
44, 74, and 54 %, respectively. Another multicenter, open-label study of individ-
ualized dose of methadone maintenance treatment showed dramatic improvement
of illegal opioid use, injection, and mood and social and personal functioning
indicators of opioid-dependent clients seeking help from Roozbeh hospital
(Iranian National Center for Addiction Studies, since October 2003), West Trian-
gular Clinic, and Persepolis drop-in center measuring by Opioid Treatment Index
(Razzaghi et al. 2005).
The finding of abovementioned studies supporting feasibility, acceptability, and
effectiveness of MMT led to adoption of MMT as a building block of drug
treatment and HIV prevention programs for people who inject opioids by Ministry
of Health (MoH) and DCHQ. By 2004, Substance Abuse Prevention and Treatment
Office (SAPTO) of MoH developed the first protocol for MMT which included
clinical guideline to provide the treatment, as well as regulations for establishment
of opioid agonist treatment program referred as “agonist units” within substance
abuse treatment centers. Certified drug treatment programs affiliated to public-
owned, private, or nongovernmental organizations (NGOs) were allowed to estab-
lish MMT programs for 50 clients providing one multidisciplinary treatment team
consisted of one trained general physician, one clinical psychologist, and two
nurses. The opioid agonist treatment units could increase their MMT slots to
100 after 1 year of activity without any violation of regulations and providing
548 S. Momtazi et al.
two multidisciplinary treatment teams. They also allowed increasing their MMT
treatment slots to 200 after another year of activity and providing four multidis-
ciplinary treatment teams and one social worker. For each 100,000 general popu-
lation, one opioid agonist unit was allowed to establish, and they must have at least
1 km distance with each other.
Addiction treatment practitioners in Iran have had many decades of experiences
with short-term assisted withdrawal of opioid dependents with clonidine or opioid
medications before introduction of MMT at 2002. Initially some practitioner,
clients, and their families preferred short-term withdrawal with methadone over
long-term maintenance programs; however, gradually both practitioner and the
clients realized that the methadone treatment should be long term to be successful.
Newly established agonist units’ slots were filled very soon, and waiting lists for
entering to methadone maintenance programs were developed. At the end of 2004,
93 public-owned and 201 private agonist units were reported in 4,091 and 3,701
clients on MMT, respectively (Razzaghi et al. 2009).
To increase accessibility of methadone maintenance treatment, requirements
for establishment of opioid agonist treatment were eased by second edition
of the protocol which released in 2006 (SAPTO 2006) and other regulations issued
by MoH in 2007. Currently certified outpatient drug treatment programs
could establish an agonist unit for 100 MMT clients providing one multidis-
ciplinary treatment team consisted of one trained general physician, one trained
bachelor level psychologist or counselor, and one nurse as well as enough
physical environments to deliver the program including one prescribing room,
one counseling room, one distribution unit, and one waiting room. Agonist
units could increase their MMT slots, if they provide enough staff and physical.
The limitation of establishment of new agonist units in terms of the
area population and distance from other agonist units has been removed for
private sector.
The first methadone protocol devised the following inclusion criteria for MMT
program: (1) diagnosis of opioid dependence according to DSM-IV-TR criteria,
(2) using drugs through injection, (3) above 18 years old, and (4) written informed
consent for treatment. Non-IV drug users were allowed to enter MMT only after
psychiatrist visit verifying existence of at least one of following conditions:
(1) chronic psychiatric comorbidity, (2) history of three documented failed treat-
ment attempt in a client above 30 years old and at least 10 years of drug use history,
(3) diagnosis of cluster B personality disorder, (4) female gender, or (5) history of
imprisonment (SAPTO 2004). These criteria were aimed to increase availability of
MMT for people who inject opioids who needed it more, but limited access to
psychiatrist in some setting led to revision of them in the second methadone
protocol (SAPTO 2006) as follows: (1) diagnosis of opioid dependence according
to DSM-IV-TR criteria, (2) above 18 years old, (3) written informed consent for
treatment, and (4) one of the conditions – (a) IV drug use, (b) heroin or crack heroin
use, (c) opium users with history of three previous failed treatment attempt in
a client with at least 10 years of drug use history, (d) HIV positive, (e) history of
imprisonment, or (f) female gender.
33 An Overview of Iran Drug Treatment and Harm Reduction Programs 549
Table 33.1 No. of MMT Year No. of clients on MMT in the community
clients in community
programs 2002 160
2003 1,133
2004 1,551
2005 7,792
2006 35,139
2007 66,126
2008 111,699
2009 158,975
2010 237,688
2011 283,019
The criteria for MMT programs aimed to increase treatment access for people
who inject drugs or use heavier opioids such as heroin or crack heroin, but there
has been a high demand for this program from people who use opium through
swallowing or smoking. This shows that on one hand, MMT has been an accept-
able intervention for Iranian opium users, but on the other hand, it has been
a challenge for opioid treatment system in the country because opium users
compete with heroin or injecting drug users to fill MMT slots which mainly
provide by private sector without any insurance coverage (Mokri and
Schottenfeld 2008). To address this issue, DCHQ supported MoH and Social
Welfare Organization (SWO) to scale up public-funded, low-cost MMT programs
provided for socially disadvantaged and homeless opioid users across the country
in 2007. At the end of 2007, 173 public-owned and 587 private agonist units were
reported in 15,983 and 50,191 clients on MMT, respectively (Noroozi et al. 2011).
Table 33.1 presented number of MMT clients in community programs at the end
of each year from 2002 to 2011.
There is no limitation on methadone dose or length of treatment in Iranian
national protocol. MMT programs delivered through outpatient clinics must pro-
vide regular assessments and psychosocial interventions, although low-threshold
MMT programs delivering through drop-in centers do not need to provide intensive
psychosocial services and drug testing. Drop-in centers initially established to
provide harm reduction services including needle, syringe programs (NSPs),
wound care, HIV prevention, psycho-education, and support services including
bath and warm meals for hard-to-reach homeless injecting drug users in suburb
areas of Tehran and few large metropolitan areas in 2003. Treatment team in
low-threshold MMT programs consisted of one trained general practitioner and
one nurse which could provide services to 100 MMT clients. The low-threshold
MMT clients do not benefit from privilege of take-home methadone doses. The
number of MoH-funded drop-in centers and outreach teams established by NGOs
increased from 12 and 12 in 2004 to 79 and 126 in 2007, respectively. The number
of clients who received MMT in MoH-funded DICs during this time period
increased from 886 to 4,114 (Razzaghi et al. 2009). Effectiveness of MMT provided
550 S. Momtazi et al.
Although the frequency of drug use might decrease after imprisonment, the high-
risk drug-using behavior including injecting drug use and shared injection will
increase (Center for Education and Research of Prison Organization 2002). Meth-
adone maintenance program has showed its efficacy in a randomized controlled
33 An Overview of Iran Drug Treatment and Harm Reduction Programs 551
Table 33.2 No. of MMT Year No. of clients on MMT in correctional settings
clients in Prisons
2002 100
2003 300
2004 1,423
2005 2,814
2006 8,048
2007 19,500
2008 25,400
2009 25,000
2010 28,826
2011 38,256
33.2.5 Buprenorphine
Ahmadi and his colleagues were the first who compared efficacy of different doses
of sublingual buprenorphine for maintenance treatment of opioid dependence in
Shiraz, Iran. They showed sublingual buprenorphine is safe and effective for
maintenance treatment of opioid dependence in outpatient settings, and the treat-
ment group which received higher daily buprenorphine dose (8 mg) had signifi-
cantly higher retention rate as compared to lower doses groups (Ahmadi and
Bahrami 2002; Ahmadi et al. 2004).
Buprenorphine has been approved to use for assisted withdrawal or maintenance
treatment of opioid dependence since summer 2006. The previously certified
“agonist units” were allowed to use buprenorphine without limitation for treatment
slots. Although there is no insurance coverage or governmental support for
buprenorphine program, there is a demand for it particularly from opioid users
with less severe opioid dependence.
552 S. Momtazi et al.
References
Ahmadi J, Bahrami N (2002) Buprenorphine treatment of opium-dependent outpatients seeking
treatment in Iran. J Subst Abus Treat 23(4):415–417
Ahmadi J, Babaee-Beigi M, Alishahi M, Maany I, Hidari T (2004) Twelve-month maintenance
treatment of opium-dependent patients. J Subst Abus Treat 26(1):363–366
Bayanzadeh SA, Bolhari J, Noori R, Lavasani F, Karimi E (2007) The role of pharmacotherapeutic
and psychosocial interventions in reducing drug related harm among addict prisoners. J Iran
Univ Med Sci 14(55):47–55 (in Farsi)
Center for Education and Research of Prison Organization (2002) Assessment of drug abuse in
Iranian prisons. Drug Control Headquarter Publications, Tehran (in Farsi)
Farnia M, Ebrahimi B, Shams A, Zamani S (2010) Scaling up methadone maintenance treatment
for opioid-dependent prisoners in Iran. Int J Drug Policy 21(5):422–424. doi:10.1016/j.
drugpo.2010.03.008
Haghdoost AA, Mostafavi E, Mirzazadeh A, Navadeh S, Feizzadeh A, Fahimfar N, Kamali K
(2011) Modelling of HIV/AIDS in Iran up to 2014. J AIDS HIV Res 3(12):231–239
International Narcotics Control Board (INCB) (2009) China hosts centennial commemoration.
Focus on international drug control. Newsletter 2
Lawrinson P, Ali R, Buavirat A, Chiamwongpaet S, Dvoryak S, Habrat B, Jie S, Mardiati R,
Mokri A, Moskalewicz J, Newcombe D, Poznyak V, Subata E, Uchtenhagen A, Utami DS,
Vial R, Zhao C (2008) Key findings from the WHO collaborative study on substitution therapy
for opioid dependence and HIV/AIDS. Addiction 103(9):1484–1492. doi:10.1111/j.1360-
0443.2008.02249.x
33 An Overview of Iran Drug Treatment and Harm Reduction Programs 553
Matthee R (2005) The pursuit of pleasure: drugs and stimulants in Iranian history. Princeton
University Press, Princeton
McGovern PE (2003) Ancient wine: the search for the origins of viniculture. Princeton University
Press, Princeton
McLaughlin GT (1976) The poppy is not an ordinary flower: a survey of drug policy in Iran,
vol 44. Fordham L. Rev, New York, 701
Ministry of Health and Medical Education (2010) Islamic Republic of Iran country report on
monitoring of the United Nations General Assembly Special Session on HIV and AIDS
(UNGASS report), MOH, Health Deputy, CDC, February 2010. http://data.unaids.org/pub/
Report/2010/iran_2010_country_progress_report_en.pdf. Accessed 8 Feb 2013
Ministry of Health and Medical Education (2012) Islamic Republic of Iran progress report- on
monitoring of the United Nations General Assembly Special Session on HIV and AIDS. National
AIDS Committee Secretariat, Ministry of Health and Medical Education. http://www.unaids.org/
en/dataanalysis/knowyourresponse/countryprogressreports/2012countries/IRIran%20AIDS
%20Progress%20Report%202012%20English%20final1_1.pdf. Accessed 8 Feb 2013
Mokri A (2002) Brief overview of the status of drug abuse in Iran. Arch Iran Med 5:184–190
Mokri A, Schottenfeld R (2008) Drug abuse and HIV transmission in Iran- responding to public
health challenges. In: Celentano D, Beyrer C (eds) Public health aspects of HIV/AIDS in low
and middle income countries- epidemiology, prevention and care, 1st edn. Springer, New
York, pp 581–599
Mokri A, Shahraki MA, Yaghouni M (2007) Substitution treatment with tincture of opium:
preliminary results of an open label clinical trial in Iran. Abstract book of International
Harm Reduction Association (IHRA) conference. Warsaw, pp 115–116
Momtazi S, Rawson R (2010) Substance abuse among Iranian high school students. Curr Opin
Psychiatry 23:221–226
Noroozi A, Shamshiri A, Gilanipour M, Ahmadzad-Asl M, Saberi-Zafarghandi MB,
Naserbakht N et al (2011) The geographical distribution of psychosocial disorders and
addiction- resources and services in Iran: 2007. Issue of substance use disorders.
Bureau of Psychosocial Health and Addiction. Ministry of Health and Medical Education
Publications, Tehran
Noroozi A, Radfar SR, Alam Mehrjerdi Z, Motevalian SA, Haghdoost A, Nematollahi P (2012)
Bio- behavioral survey of injecting drug users and their sexual partners in three provinces in
Iran. Final report. Iranian National Center for Addiction Studies (INCAS) & Iran Office of
United Nation Office on Drug and Crime, Tehran
Razzaghi EM, Mokri A, Vazirian M (2005) Effectiveness of methadone maintenance program in
reducing illicit drug use and HIV related high-risk behavior: a multi-center study. Report to
UNODC. http://www.unodc.org/pdf/iran/publications/. Accessed 8 Feb 2013
Razzaghi EM, Rahimi-Movaghar A, Haghdoost AA, Bashti SH, Safarcherati A, Noroozi
A et al (2009) The spatial distribution of psychosocial disorders and health facilities in Iran,
2005. Bureau of Psychosocial Health & Applied Research Office. Ministry of Health and
Medical Education Publications, Tehran
Shekarchizadeh H, Ekhtiari H, Khami MR, Virtanen JI (2012) Patterns of pre-treatment drug
abuse, drug treatment history and characteristics of addicts in methadone maintenance treat-
ment in Iran. Harm Reduct J 9(1):18. doi:10.1186/1477-7517-9-18
Substance Abuse Prevention and Treatment Office (SAPTO) (2004) Treatment protocol of opioid
dependence with opioid agonist medications, 1st edn. Ministry of Health and Medical Educa-
tion Publication, Tehran (in Farsi)
Substance Abuse Prevention and Treatment Office (SAPTO) (2006) Treatment protocol of opioid
dependence with opioid agonist medications, 2nd edn. Ministry of Health and Medical
Education Publication, Tehran (in Farsi)
United Nations Office on Drugs and Crimes (UNODC) (2005) Effectiveness of methadone
maintenance program in reducing illicit drug use and HIV related high-risk behavior:
554 S. Momtazi et al.
Contents
34.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 556
34.2 Features of Diversion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 557
34.2.1 Consequences of Diversion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 557
34.2.2 Indicators of Diversion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 557
34.2.3 Strategies to Limit Diversion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 557
34.2.4 “A Better Approach”, Defining Treatment Outcomes in Opioid
Dependence (OD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 558
34.2.5 Patterns and Prevalence of Diversion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559
34.2.6 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 561
34.2.7 Key Messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 563
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 564
Abstract
Diversion is defined in this publication as unauthorized rerouting or use of
a substance, and abuse is defined as any use of a prescription drug that deviates
from medical practice. This refers to the manner in which medication is used
such as snorting, injecting, taking excessive quantities, or combining it with
other substances for intoxicative purposes.
Diversion and abuse of pharmacotherapy used in opioid-dependence treat-
ment can have a serious negative impact on public health at the individual and
societal level. Diversion can lower the credits of treatment services through
increased morbidity and mortality and economic burden through lost productiv-
ity and unemployment. Diversion is a global problem, but most studies and
concerns arise from the USA, Australia, and Northern Europe. While existing
H. Alho
Institute of Clinical Medicine, Department of Medicine, University of Helsinki, Helsinki, Finland
e-mail: [email protected]
34.1 Introduction
Though strong evidence indicates that diversion and abuse is occurring, a global
understanding of the consequences is missing or the issue is varied. The impact of
consequences on public health can be used to raise awareness of this issue, identify
regional epidemiological trends across globe, and drive management strategies in
opiate maintenance area. The most well-known consequences include:
• Increased patient morbidity and mortality (Centers for Disease Control and
Prevention 2010) through an increased risk of:
– Overdose/fatal respiratory depression (Laberke and Bartsch 2010; Perret
et al. 2000)
– Nonfatal overdose and related emergency admissions (Centers for Disease
Control and Prevention 2010)
– Contracting blood-borne viruses such as HIV and hepatitis C (HCV) (Center
for Disease Control and Prevention 2011; Berson et al. 2001)
– Complications associated with injection drug use including limb ischemia,
tissue necrosis, and endocarditis (Ho et al. 2009a)
• A negative impact on prescribers’ practice (Noroozi and Mianji 2008)
• Threatened reputation of treatment services and compromised public acceptance
of long-term treatment of opioid-dependent individuals (Noroozi and Mianji
2008).
Despite evidence demonstrating that abuse and diversion does happen, there is
increasing consensus that considers diversion to be noncompliance and a sign of
suboptimal treatment. The majority of studies related to diversion relate to patterns
and rates of injection drug use and injection drug use-associated mortality. Meth-
adone has been the most researched opioid pharmacotherapy for both lead impact
measures, followed by buprenorphine, hydrocodone, and oxycodone. However,
despite association with potential hepatic complications in clinical studies, few
studies can be identified suggesting a role for methadone or buprenorphine in
hepatic complications. The majority of diversion studies per product derived from
the USA, followed by Australia. Data from the USA largely focused on the
diversion and abuse of prescription opioid analgesics, in addition to opioid-
dependence pharmacotherapy. In regions demonstrating a paucity of research/
publications such as southern Europe, Asia (excluding Singapore), and Pacific
countries, those identified focused on the diversion and abuse of methadone and
buprenorphine. Reports from South Asia indicate that prescribing for pain is
inadequate. There is a paucity of data across South Asia regarding the extent of
diversion and abuse, although the problem is widely acknowledged. There is also
a significant lack of treatment facilities across the region, as well as HIV awareness
and needle-syringe programs (Larance et al. 2011).
In general, studies have shown that around 70 % of those injecting medication
are self-treating, either due to inability to access treatment or suboptimal thera-
peutic dosing (Alho et al. 2007; Courty 2009). A post marketing surveillance
study (2003–2007) from the USA indicated that there were steady increases in the
rates of abuse, misuse, and diversion of both methadone and buprenorphine. Rate
ratios (per 100,000 population quarter) of abuse, misuse, and diversion were
consistently higher for methadone than buprenorphine (Dasgupta et al. 2010).
A global literature review (Degenhardt et al. 2011) on mortality among dependent
or regular opioid users across regions, according to specific causes, and related to
a number of demographic and clinical variables demonstrated that overdose was
the most common cause of death, with a crude overdose mortality rate 1.71 times
higher in men than women. Out-of-treatment periods had 2.38 times higher
mortality risk than in-treatment periods (p < 0.0005). Higher prevalence of opioid
injection was associated with higher mortality rates. Retrospective data analysis
(Laberke and Bartsch 2010) of methadone-associated deaths in Zurich, Switzer-
land, showed that most of the detected deaths occurred during illicit intake of
methadone and high percentage of cases involved polydrug intoxication (76 %).
An epidemiological review from the USA indicates that deaths from unintentional
drug overdoses in the USA have risen steeply since the early 1990s and are
the second leading cause of accidental death, with 27,658 such deaths recorded
in 2007. The increase has been propelled by a rising number of overdoses of
opioids, which caused more deaths than heroin and cocaine combined in 2007
alone (Okie 2010).
560 H. Alho
34.2.6 Discussion
studies which were conducted in the USA and Australia. This could be due to that in
the USA, the Drug Abuse Warning Network (DAWN) (Drug Abuse Warning
Network 2011) monitors drug-related visits to hospital emergency departments
and drug-related deaths investigated by medical examiners and coroners. Emer-
gency department data is published biannually. Mortality data is published annu-
ally, and additional analyses are available during the year. DAWN collects detailed
drug data including that for illicit substances, prescription medication, and over-
the-counter remedies. The Australian Illicit Drug Reporting System (2009) and the
Ecstasy and Related Drugs Reporting System have operated in all jurisdictions
since 2000 and publish annual reports of trends associated with illicit drug use
(including heroin, amphetamines, cocaine, and cannabis). Trends are extrapolated
from three data sources: interviews with injecting drug users, interviews with key
experts who regularly encounter illicit drug users, and existing indicator data
sources relating to illicit drug use.
Large proportion of publications per impact area is related to methadone-
associated mortality (Perret et al. 2000). Evidence shows that methadone diversion
is associated with a high risk of mortality due (Reynaud et al. 1998) to its full opioid
agonist profile, effect on respiratory depression, and multiple drug interactions
leading to increased plasma levels of methadone and toxicity. In addition, a long
elimination half-life (24–36 h) may increase the risk of fatal overdose due to
excessive intake and dose accumulation in the body. The high mortality risk
attributed to methadone is supported by the high numbers of emergency calls for
overdose or accidental exposure of children to methadone and the numbers of
deaths in which methadone has been implicated, either alone or in combination
with other substances (Rainey 1986; Gibson and Degenhardt 2007). It has been
thought that the increase in methadone mortality may result from inappropriate
prescribing to patients who have risk factors or indicators for abuse and increasing
use of methadone as a low-cost analgesic by inexperienced prescribers. Even when
buprenorphine may be more widely diverted than methadone (Ho et al. 2009b;
Reynaud et al. 1998), buprenorphine-based treatment seems to be associated with
fewer fatalities than methadone (Rainey 1986; Kim et al. 2012; Winstock
et al. 2008).
However, there is clear and increasing evidence of harm associated with the
diversion of prescription opioid analgesia. This phenomenon appears to be some-
what specific to the USA as the greatest number of publications relating to oxyco-
done, and hydrocodone in particular, originate from this region and are second only
to methadone. In addition, the prevalence of prescription opioid analgesic abuse
reported by publications from this region ranged from 72 % to 75 % (Gibson and
Degenhardt 2007). In accordance with the trends in prescription opioid mortality,
data shows an increasing prevalence of opioid analgesic abuse in rural and urban-
ized regions in the USA (Gibson and Degenhardt 2007).
Although buprenorphine maintenance therapy is associated with significant
benefits including decreased HIV risk behavior and lower risk of fatal overdose
(Rainey 1986) compared with methadone (Kim et al. 2012), injection of
buprenorphine is associated with potentially fatal harms, as cutaneous
34 Opioid Agonist Diversion in Opioid-Dependence Treatment 563
complications (Ho et al. 2009a), infective endocarditis (Jenkinson et al. 2005), and
by mixing buprenorphine with other drugs including alcohol and benzodiazepines
can be dangerous and may lead to fatal overdose (Bell et al. 2009). The injection of
the combined buprenorphine-naloxone product was designed to cause precipitated
withdrawal in opioid-dependent individuals, thereby acting as a deterrent to abuse.
Although data suggest that injection rates of buprenorphine-naloxone are signifi-
cantly lower than rates of mono-buprenorphine injection (Ho et al. 2009b), and the
street value of the combination product is significantly less than corresponding
mono-product (Montesano et al. 2010), further epidemiological studies are needed
to determine whether the combination product is effective in deterring diversion
and abuse. Buprenorphine has been considered being less fatal in overdosing
because of its ceiling effect; however, recent studies show that buprenorphine’s
metabolite, norbuprenorphine, is assessed as being a potent respiratory depressor in
rodents. Recently, norbuprenorphine, in contrast to buprenorphine, was shown in
mice and in vitro to be a substrate of human P-glycoprotein, a drug-transporter
involved in all steps of pharmacokinetics including transport at the blood-brain
barrier (Havens et al. 2007). Even a major role for drug-drug interactions that can
lead to P-glycoprotein inhibition in buprenorphine-associated fatalities and respi-
ratory depression, there is no proof that buprenorphine can cause fatal poisoning
except on children (Alhaddad and Cisternino 2013).
References
Aitken CK, Higgs PG, Hellard ME (2008) Buprenorphine injection in Melbourne, Australia – an
update. Drug Alcohol Rev 27:197–199
Alhaddad H, Cisternino S, Declèves X et al (2013) Respiratory toxicity of buprenorphine results
from the blockage of P-glycoprotein-mediated efflux of norbuprenorphine at the blood-brain
barrier in mice. Br J Anaesth 110(5):842. doi:10.1093/bja/aet082
Alho H, Sinclair D, Vuori E, Holopainen A (2007) Abuse liability of buprenorphine-naloxone
tablets in untreated IV drug users. Drug Alcohol Depend 88:75–78
Altice FL, Bruce RD, Lucas GM et al (2011) HIV treatment outcomes among HIV-infected, opioid-
dependent patients receiving buprenorphine/naloxone treatment within HIV clinical care
settings: results from a multisite study. J Acquir Immune Defic Syndr 56(Suppl 1):S22–S32
American psychiatric Association (2001) Diagnostic and statistical manual of mental disorders,
4th Edition, Text Revision (DSM-IV-TR). American Psychiatric Publishing, Arlington, USA
American Psychiatric Association (2004) Diagnostic and statistical manual of mental disorders
(DSM-IV)
Auriacombe M, Franques P, Tignol J (2001) Deaths attributable to methadone vs buprenorphine in
France. JAMA: J Am Med Assoc 285:45
Australian drug trends: findings of the illicit drug reporting system and the ecstasy and related
drugs reporting system. Last updated on 13/07/2009. http://www.aic.gov.au/crime_types/
drugs_alcohol/illicit_drugs/ndarc_adt.aspx
Bacha J, Reast S, Pearlstone A (2010) Treatment practices and perceived challenges for European
physicians treating opioid dependence. Heroin Addict Relat Clin Probl 12:9–19
Beer B, Rabl W, Libiseller K et al (2010) Impact of slow-release oral morphine on drug abusing
habits in Austria. Neuropsychiatry 24:108–117
Bell J (2010) The global diversion of pharmaceutical drugs: opiate treatment and the diversion of
pharmaceutical opiates: a clinician’s perspective. Addiction 105:1531–1537
Bell JR, Butler B, Lawrance A et al (2009) Comparing overdose mortality associated with
methadone and buprenorphine treatment. Drug Alcohol Depend 104:73–77
Berson A, Gervais A, Cazals D et al (2001) Hepatitis after intravenous buprenorphine abuse in
heroin addicts. J Hepatol 34:346–350
Cami J, Farre M (2003) Drug addiction. N Engl J Med 349:975–986
Center for Disease Control and Prevention (2011) HIV Strategic Plan 2011 through 2015 (Division
of HIV/AIDS Prevention). www.cdc.gov/hiv/pdf/policies_DHAP-strategic-plan.pdf
34 Opioid Agonist Diversion in Opioid-Dependence Treatment 565
Center for Disease Control and Prevention (2004) HIV prevention strategic plan through 2005.
CDC. www.cdc.giv/hiv/resources/reports/psp/pdf/prev-strat-plan.pdf
Center for Disease Control and Prevention (2010) Emergency department visits involving
nonmedical use of selected prescription drugs – United States, 2004–2008. Morb Mortal
Wkly Rep 59:705–735
Chong E, Poh KK, Shen L et al (2009) Infective endocarditis secondary to intravenous subutex
abuse. Singap Med J 50:34–42
Courty P (2009) Use and abuse of high-dose buprenorphine (HDB) obtained without
a prescription: a French survey. Heroin Addict Relat Clin Probl 11:23–30
Dasgupta N, Bailey EJ, Cicero T et al (2010) Post-marketing surveillance of methadone and
buprenorphine in the United States. Pain Med 11:1078–1091
De Maeyer J, Vanderplasschen W, Broekaert E (2010) Quality of life among opiate-dependent
individuals: a review of the literature. Int J Drug Policy 21:364–380
Degenhardt L, Larance BK, Bell JR et al (2009) Injection of medications used in opioid substi-
tution treatment in Australia after the introduction of a mixed partial agonist-antagonist
formulation. Med J Aust 191:161–165
Degenhardt L, Bucello C, Mathers B et al (2011) Mortality among regular or dependent users of
heroin and other opioids: a systematic review and meta-analysis of cohort studies. Addiction
106:32–51
Drug Abuse Warning Network (2011) Last updated on 14/09/2011. http://www.samhsa.gov/data/
DAWN.aspx
Fiellin DA, O’Connor PG (2002) New federal initiatives to enhance the medical treatment of
opioid dependence. Ann Intern Med 137:688–692
Gibson AE, Degenhardt LJ (2007) Mortality related to pharmacotherapies for opioid dependence:
a comparative analysis of coronial records. Drug Alcohol Rev 26:405–410
Goldstein A, Herrera J (1995) Heroin addicts and methadone treatment in Albuquerque: a 22-year
follow-up. Drug Alcohol Depend 40:139–150
Hansen RN, Oster G, Edelsberg J et al (2011) Economic costs of nonmedical use of prescription
opioids. Clin J Pain 27:194–202
Havens JR, Walker R, Leukefeld CG (2007) Prevalence of opioid analgesic injection among rural
nonmedical opioid analgesic users. Drug Alcohol Depend 87:98–102
Ho RC, Ho EC, Mak A (2009a) Cutaneous complications among i.v. buprenorphine users.
J Dermatol 36:22–29
Ho RC, Ho EC, Tan CH, Mak A (2009b) Pulmonary hypertension in first episode infective
endocarditis among intravenous buprenorphine users: case report. Am J Drug Alcohol Abuse
35:199–202
International Narcotics Control Board (2011) Annual report. https://www.incb.org/documents/
Publications/AnnualReports/AR2011/AR_2011_English.pdf
Jenkinson RA, Clark NC, Fry CL, Dobbin M (2005) Buprenorphine diversion and injection in
Melbourne, Australia: an emerging issue? Addiction 100:197–205
Kim HK, Smiddy M, Hoffman RS et al (2012) Buprenorphine may not be as safe as you think:
a pediatric fatality from unintentional exposure. Pediatrics 130(6):e1700–e1703
Kimber J, Copeland L, Hickman M et al (2010) Survival and cessation in injecting drug users:
prospective observational study of outcomes and effect of opiate substitution treatment. BMJ
341:c3172
Laberke PJ, Bartsch C (2010) Trends in methadone-related deaths in Zurich. Int J Legal Med
124:381–385
Larance B, Ambekar A, Azim T et al (2011) The availability, diversion and injection of pharma-
ceutical opioids in South Asia. Drug Alcohol Rev 30:246–254
Merriam–Webster’s Dictionary of Law (1996) Merriam–Webster, Inc.
Montesano F, Zaccone D, Battaglia E et al (2010) Therapeutic switch to buprenorphine/naloxone
from buprenorphine alone: clinical experience in an Italian addiction centre. Clin Drug Investig
30(Suppl 1):13–19
566 H. Alho
Contents
35.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 568
35.2 Hallucinogens, Dissociatives and New Psychoactive Substances . . . . . . . . . . . . . . . . . . . . . 568
35.2.1 Classical Hallucinogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 568
35.2.2 Dissociatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 578
35.2.3 Designer Drugs and “Legal Highs”: MDMA and New Psychoactive
Substances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 581
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 593
Abstract
Hallucinogenic drugs have as their primary effect the production of disturbances
of perception. Hallucinogens can be classified according their chemical structure
as: indoleamines (similar to serotonin), phenethylamines (similar to catechol-
amines), dissociatives (phencyclidines) and others (including salvinorin, dextro-
methorphan, muscarinic antagonists and cannabinoids). The hallucinogenic
effects appear to be related to the agonistic action on 5-HT2A receptors in the
cortex. Ketanserin, a 5-HT2 antagonist, blocks some of the specific effects of
LSD and other hallucinogens. It also activates the dopaminergic receptors and
M. Farré (*)
Pharmacology Unit Hospital del Mar Medical Research Institute (IMIM), Universidad Autònoma
de Barcelona, Barcelona, Spain
e-mail: [email protected]
L. Galindo
Hospital del Mar Medical Research Institute (IMIM), Universidad Autònoma de Barcelona,
Barcelona, Spain
e-mail: [email protected]
M. Torrens
Addiction Unit Hospital del Mar Medical Research Institute (IMIM), Universidad Autònoma de
Barcelona, Barcelona, Spain, Barcelona, Spain
e-mail: [email protected]
35.1 Introduction
popularity of LSD in the 1960s associated with the hippie movement resulted in its
ban in the United States in 1967. In recent years, there has been new interest in the
investigation of the therapeutic use of hallucinogens (Hill and Thomas 2011).
Intoxication
Patients come to have symptoms of sympathetic activation, perceptual changes and
psychiatric symptoms (agitation, anxiety, panic, psychosis). There are also frequent
“bad trips” that present with psychiatric symptoms (anxiety or significant panic
reaction). Intoxications are occasionally accompanied by delirium (a separate
diagnostic category). The elimination of the substance gradually improves the
symptoms. There are no documented fatalities from LSD use, but fatal accidents
and suicides have occurred during intoxication.
any of the senses. It is not known what causes flashbacks. Theories include
persisting damage to visual processing systems, dysfunction of inhibitory cortical
interneurons, reverse tolerance, and that they comprise an atypical dissociative state
(Garratt et al. 1993). Flashbacks may occur several days to several years after the
antecedent use of lysergic acid diethylamide and have been reported with mescaline,
phencyclidine and marijuana. Some users find these episodes pleasant and even refer
to them as “free trips”. For others they can be terrifying and recur frequently
(hallucinogen persisting perception disorder). An antecedent good trip does not
predict a good flashback. It is unclear what determines who will experience flash-
backs and whether or not the experience will be pleasant (McGee 1984).
Flashbacks have reportedly been induced by a myriad of situations, including
stress, exercise, pregnancy, sexual intercourse, dark environments, flashing lights,
monotony, and use of other psychoactive drugs. It is estimated that anywhere from
15 % to 60 % of LSD users experience flashbacks. The flashback experience is often
precipitated by psychiatric illness, as with the use of other drugs (Lerner
et al. 2002). It is possible that the success of the medications listed above is related
to the treatment of concurrent illness. Regardless of treatment, the frequency of
flashbacks tends to decrease with time.
Affective Disorders
While feelings of being overwhelmed, scared and afraid of losing control occur
in a panic attack, lysergic acid diethylamide intoxication is further characterised
by dramatic and persistent perceptual distortions. As with any altered mental
state, the clinician should have a low threshold for suspecting delirium. Unlike
delirium, there is no fluctuation level of consciousness with LSD intoxication. There
is no specific pharmacological treatment for this disorder. When the patients stop
consumption anxious-depressive syndrome may occur, requiring symptomatic treat-
ment (Passie et al. 2008; Jones 2009; O’Brian 2011).
Somatic Complications
Although LSD is considered relatively safe compared with other drugs of abuse,
there are case reports of respiratory failure, hyperthermia and coagulopathies
35 Addiction to Hallucinogens, Dissociatives, Designer Drugs and “Legal Highs” 575
associated with massive doses. Early on, a relationship between lysergic acid
diethylamide and chromosomal damage was suspected, but this has been consistently
refuted and lysergic acid diethylamide does not appear to be teratogenic. LSD,
however, does induce uterine contractions, which could disrupt pregnancy.
Mescaline
Mescaline, or 3,4,5-trimethoxyphenylethylamine is a phenethylamine hallucinogen
found in several species of North and South American cacti, including
Peyote (Lophophora williamsii) and San Pedro. Mescaline was first isolated from
peyote cacti in 1896 and was synthesised approximately 20 years later.
Natural peyote has a bitter taste. It is dried and chewed, soaked in water and
drank or injected. The hallucinogenic dose is approximately 5 mg/kg (0.3–0.5 g). Each
button contains about 50–100 mg of mescaline, and users typically ingest 3–8 buttons.
Within the first 30 min, before the onset of psychological symptoms, users
may experience nausea, vomiting, restlessness and headaches. By 1–2 h, however,
these unpleasant physiological symptoms dissipate and the psychic phase,
characterised by euphoria, sensory distortions, and feelings of confidence, begins.
The entire experience lasts up to 14 h. As is the case with LSD and the other
serotonergic hallucinogens, tolerance develops rapidly and physical dependence
does not occur. Treatment of acute intoxication and adverse consequences, as with
LSD and psilocybin, involves reassurance and use of benzodiazepines if necessary
(Jones 2009).
576 M. Farré et al.
Tryptamines
There are a number of non-controlled tryptamines that are used for their psyche-
delic properties. They have effects similar to the tryptamines already controlled
such as psilocybin (found in Psylocybes mushrooms or “magic mushrooms”) or
dimethyltryptamine (DMT). Tryptamines can be synthesised, although they also
exist in plants, fungi and animals.
Albert Hoffman isolated and then synthesised psilocybin. It was marketed by
Sandoz laboratories under the trade name Indocybin® as a potential tool for psycho-
therapy in the 1960s. The mushrooms can be eaten fresh, dried, or brewed. They are
usually ingested orally. Psilocybin is a prodrug that is converted in the body into
the pharmacologically active compound psilocin by a dephosphorylation reaction.
Typical doses of psilocybin range from 4 to 20 mg (40 mg/kg) corresponding to 1–2 g
of dried mushrooms. Sympathomimetic symptoms occur at lower doses (3–5 mg),
and psychological effects are elicited by doses above 8 mg. Psychological effects
begin within 30 min of ingestion, peak at 2–3 h, and dissipate by 12 h (Passie
et al. 2002). Psilocybin occasioned sustained experiences similar to spontaneously
occurring mystical experiences. Only one third of “magic mushrooms” bought on the
street actually contain psilocybin (many are simply store-bought mushrooms laced
with phencyclidine) and there are many wild poisonous mushrooms. Adulteration
and misidentification are the most common causes of serious adverse outcomes. As
with the other serotonergic hallucinogens, tolerance develops quickly, but physical
dependence does not occur (Griffiths et al. 2006, 2011).
Dextromethorphan
Dextromethorphan is the dextro isomer of levorphanol, a codeine derivative. It
is a substance commonly used as a cough suppressant at doses between 15 and 30 mg
orally every 6–8 h. It is marketed in single or in multicomponent medicines
for the treatment of symptoms associated with the common cold or flu. In some
countries dextromethorphan is used as an adjunct to morphine in the treatment
of pain. It is a hallucinogen when administered orally at doses of 240–480 mg.
The hallucinogenic effects of dextromethorphan are due to its antagonistic
action on NMDA glutamate receptors. It has no opioid activity.
Readily absorbed orally, it is metabolised to dextrorphan, which is the active
ingredient in cough medicine, by cytochrome P-4502D6. Up to 5–10 % of Cauca-
sians have a deficiency of this isoenzyme and therefore cannot metabolise dextro-
methorphan to dextrorphan (poor metabolisers). This drug is commonly used to
determine the phenotype of said cytochrome. The elimination half-life is 1.5–4 h
for dextromethorphan and somewhat higher for its major metabolite, dextrorphan,
in extensive metabolisers. It is a minority use substance, commonly used as
ketamine to provoke feelings of mind–body separation and pictures of so-called
near-death experiences. Poisoning presents with light-headedness, fatigue, nausea
and vomiting, and ataxia. Also described are euphoria, nystagmus, mydriasis or
even coma and death, plus cases of psychosis, dystonia and serotonin syndrome. In
the event of poisoning, supportive measures and symptomatic treatment are
recommended (Abanades et al. 2004, 2007a, b).
35 Addiction to Hallucinogens, Dissociatives, Designer Drugs and “Legal Highs” 577
Salvia divinorum
Salvinorin A is the psychoactive substance in the plant Salvia divinorum. It can
induce dissociative effects and is a potent producer of visual and other hallucinatory
experiences. Salvinorin A, appears to be the most potent naturally occurring
hallucinogen. Its native habitat is the cloud forests in Mexico. It has been consumed
for hundreds of years by local Mazatec shamans, who use it to facilitate visionary
states of consciousness during spiritual healing sessions. It is also used in traditional
medicine at lower doses as a diuretic to treat ailments including diarrhoea, anaemia,
headaches and rheumatism.
In Canada, a national school survey in 2011 reported the widespread use of novel
psychoactive substances (NPS) among tenth-grade students (aged 15–16), includ-
ing Salvia divinorum (lifetime prevalence of 5.8 %), jimson weed, or Datura
(2.6 %), a hallucinogenic plant. The general household survey for 2011 lists only
Salvia divinorum (lifetime prevalence of 1.6 %) among NPS. According to the 2011
Eurobarometer survey (Gallup Organization 2011), Latvia is the country with the
highest lifetime prevalence the use of Salvia divinorum in the European Union. In
the USA the use of Salvia divinorum in youths (aged 17–18) has an annual
prevalence of 5.9 % (United Nations Office on Drug and Crime Drug 2013).
Salvinorin A is present in the dried plant (about 0.18 %). It is a potent and
selective kappa-opioid receptor agonist; in addition, it is a potent D2 receptor
partial agonist, and it is likely that this action plays a significant role in its effects
as well. Salvia divinorum is usually smoked and produces rapid and intense effects
with a short action (15–30 min). Its effects include various psychedelic experiences,
including past memories (such as revisiting places from childhood memory),
merging objects and overlapping realities (such as the perception of being in several
locations at the same time). In contrast to other drugs, its use often prompts
dysphoria, i.e. feelings of sadness and depression, as well as fear. In addition, it
may prompt a decreased heart rate, slurred speech, lack of coordination and
possibly loss of consciousness.
Differing studies suggest no overall consensus so far with regard to the long-
term effects of Salvia on mood. It is well-established that some kappa-opioid
agonists can cause dysphoria in humans, and research using rats in forced-swim
tests has been used to suggest that Salvia might have “depressive-like” effects.
Ayahuasca
Ayahuasca, also commonly called yagé, is a hallucinogenic brew of various
psychoactive infusions or decoctions prepared with the Banisteriopsis caapi vine
(which contains the beta-carboline alkaloids harmaline and harmine). It is mixed
with the leaves from the genus Psychotria (Psychotria viridis) that contain dimeth-
yltryptamine (DMT). DMT itself is not active orally because it is normally
destroyed by deamination enzymes in the gut, but when the two plants are ingested
together the beta-carboline alkaloids inhibit the deamination enzymes that ordinar-
ily destroy DMT (monoamine oxidase, MAO). Ayahuasca is used largely as
a religious sacrament. The psychedelic effects of ayahuasca include visual and
auditory stimulation, the mixing of sensory modalities, and psychological
578 M. Farré et al.
introspection that may lead to great elation, fear, or illumination. Its purgative
properties are important, producing intense vomiting and occasional diarrhoea. In
native or religious communities using ayahuasca, there is no evidence of psycho-
logical maladjustment, mental health deterioration or cognitive impairment (Bouso
et al. 2012).
Ibogaine
Ibogaine is an indole alkaloid found in plants such as Tabernanthe iboga. The plant
originates in Africa and is traditionally used in sacramental initiation ceremonies.
Ibogaine is a hallucinogen at the 400-mg dose range. Ibogaine is a tryptamine that
acts as an agonist (for the 5-HT2A receptor). In addition, it acts as an antagonist of
the NMDA receptor set and an agonist for the kappa-opioid receptor. Ibogaine is
metabolised in the human body by cytochrome P4502D6, and the major metabolite
is noribogaine (12-hydroxyibogamine). Noribogaine is most potent as a serotonin
reuptake inhibitor and acts as a moderate kappa-opioid receptor antagonist and
weak mu-opioid receptor full agonist. In recent years, ibogaine has been studied,
and even patented as a pharmacotherapy for opiate and other addictions, involving
doses that range as high as 1,500 mg orally. There are no well controlled studies in
humans assessing its efficacy at opiate detoxification. The ingested material is taken
from the plant or pure powder (Brown 2013). Ibogaine can produce a QT interval
prolongation and induce ventricular tachycardia after initial use. Fatalities follow-
ing ibogaine ingestion are documented in the medical literature (Alper et al. 2012).
35.2.2 Dissociatives
35.2.2.1 Phencyclidine
Phencyclidine is rarely consumed in Europe, but is very common in the
USA. Approximately 2.5 % of the US population reports having ever used phency-
clidine. The proportion of users increases with age, from 0.3 % of 12- to 17-year-olds,
to 1.3 % of 18- to 25-year-olds, to 2.9 % of those aged 26 years and older reporting
ever having used phencyclidine. There appears to have been an increase among 12th
graders in ever used (1.6–2.3 % over the past 3 years) (Johnston et al. 2013a).
35 Addiction to Hallucinogens, Dissociatives, Designer Drugs and “Legal Highs” 579
35.2.2.2 Ketamine
Ketamine exists as two optical isomers, S and R-., the S-(+) isomer is more
potent that the R( ) isomer. The S-isomer, or esketamine, has been
recently marketed in some countries. Ketamine is used via an intramuscular or
intravenous route as an analgesic and anaesthetic. Recently, ketamine has been used
experimentally for the therapy of treatment-resistant depression (Aan Het Rot
et al. 2012).
In the case of ketamine, in the UK, 1.8 % of 16- to 24-year-olds reported last-
year ketamine use, with levels remaining stable between 2008 and 2012, although
they increased from 0.8 % in 2006. Targeted surveys in nightlife settings report
higher levels of lifetime prevalence, for example, in Danish clubbers 10 % had tried
ketamine. Among UK respondents to an Internet survey who were identified as
regular clubbers, 40 % reported last-year use of ketamine and 2 % last-year use of
GHB (European Monitoring Centre for Drugs and Drug Addiction 2013a). In the
United States the past-year use of ketamine appears to be relatively stable among
12th graders (1.5–1.7 % over the past 3 years) (Johnston et al. 2013a). In Canada,
among tenth-grade students (aged 15–16) lifetime prevalence of ketamine use was
1.6 %. Given the strong decline in ketamine use in the United States since the
beginning of the millennium, its use among tenth-grade students in Canada is now
slightly higher than in the United States (1.2 % in 2011). In Australia, a small
580 M. Farré et al.
decline occurred in the annual prevalence of ketamine use among the population
aged 14 and above, from 0.3 % in 2004 to 0.2 % in 2010 (United Nations Office on
Drug and Crime 2013).
Although the pharmaceutical presentation is injectable solution, it is transformed
and crystallised in powder to consume. The illegal use of ketamine (Special K,
Super K, kit-kat, K) has been increasing in recent years and is one of the so-called
club drugs, drugs used at electronic music parties. Another type of consumption is
related to the search for new sensations. Consumers also use ecstasy and gamma
hydroxybutyrate (GHB). Like PCP, ketamine is an antagonist of the NMDA
glutamate receptors. It is administered by injection intramuscular or intravenous),
orally, by smoking and by inhalation. The elimination half-life of ketamine is
2–3 h. The effects are fast, short-lasting and dose-dependent, and can cause
perceptual changes (from dissociation body sensation to near-death experiences)
and psychopathological reactions similar to those of phencyclidine (Morgan and
Curran 2012).
Appealing effects described by users include visual hallucinations and out-of-
body experiences; undesirable effects include memory loss and decreased sociabil-
ity. General central nervous system depressant effects include poor concentration
and poor recollection similar to alcohol intoxication, which is not unexpected for an
anaesthetic drug. Effects of ketamine include profound changes in consciousness
and psychotomimetic effects, such as changes in body image (feeling that the body
is made of wood, plastic, or rubber) and possible feelings of spiritual separation
from the body, including out-of-body experiences. At low doses, users describe
mild dissociative effects, distortion of time and space, and hallucinations. At large
doses, users experience severe dissociation with intense detachment such that their
perceptions seem to be located deep within their consciousness and reality is far off
in the distance; this is called the “K-hole”. The analgesic and dissociative effects
may result in injury or even death.
Tolerance to the desired effects develops rapidly, resulting in reduced length of
the subjective experience and requiring an increase in dose to maintain the expected
effects. Users escalate the amount used to achieve the full hallucinogenic experi-
ence, up to seven times the original amount. Use of higher recreational doses
can result in more adverse effects, especially physiological side effects. Use of
very high doses can result in the onset of full anaesthetic effects, which may result
in an overdose situation for a recreational user. Continued use of ketamine
or phencyclidine, despite experiencing these consequences, constitutes addiction
(using the phencyclidine use disorder criteria). Some people develop
compulsive consumption, which is more reminiscent of the use of cocaine or
psychostimulants.
The clinical symptoms of intoxication from ketamine are tachycardia, altered
consciousness, disorganised speech and nystagmus. Treatment consists of support-
ive measures. Some ketamine users suffer urinary symptoms such as urinary
frequency, urgency, dysuria and haematuria, which improve or disappear after
cessation of use (Abanades et al. 2004, 2007a, b; O’Brian 2011).
35 Addiction to Hallucinogens, Dissociatives, Designer Drugs and “Legal Highs” 581
35.2.3.1 Definitions
The emergence of new psychoactive substances that are not controlled under
existing drug laws is not a new phenomenon. Over the last 20 years, a variety of
terms and definitions have been used for new psychoactive substances that emerge
on the market and are not under international control. The use of different terms to
define the same substance can create confusion, because it can be found in different
categories. Currently, the preferred term is new/novel psychoactive substances
(NPS).
The emergence started in the 1970s with the so-called “designer drugs”. They
were defined as psychoactive substances produced from chemical precursors in
a clandestine laboratory, which, by slight modification of the chemical structure,
have been intentionally designed to mimic the properties of known psychoactive
substances, and which are not under international control (Buchanan and Brown
1988). Over the past few years, the globalisation and the widespread use of the
internet have allowed the unprecedented growth in both the number and availability
of these substances. In the European Union (EU), 24 novel psychoactive substances
were identified for the first time in 2009, 41 in 2010, 49 in 2011 and 73 in 2012
(European Monitoring Centre for Drugs and Drug Addiction 2013b).
”Designer drugs” have been defined by the International Narcotics Control
Board as follows: “Substances that have been developed especially to avoid
existing drug control measures and are manufactured by making a minor modifi-
cation to the molecular structure of controlled substances, resulting in new sub-
stances with pharmacological effects similar to those of the controlled substances”
(United Nations Office on Drug and Crime 2013). According to the European
Monitoring Centre for Drugs and Drug Addiction (EMCDDA) and the European
Police Office (Europol), designer drugs can be best defined as substances designed
to mimic the effects of known drugs by slightly altering their chemical structure in
order to circumvent existing controls.
More recently, “legal highs” has been used as an umbrella term for unregulated
novel psychoactive substances, or products claiming to contain them, which are
intended to mimic the effects of controlled drugs. The term includes a wide range of
synthetic and/or plant-derived substances and products. These may be marketed as
“legal highs” (emphasising “legality”), “herbal highs” (stressing the natural/plant
origin), as well as “research chemicals” and “party pills”.” Legal highs” are usually
sold via the internet or in bricks and “head shops” or” smart shops”. In most cases
they are intentionally mislabelled with regard to their intended use (e.g. labelled as
“not for human consumption”, “plant food”, “bath salts”, “room odourisers”,
“incenses”) and the active substances that they contain. This “legal highs” market
can be distinguished from other drug markets by the speed at which suppliers
circumvent drug controls by offering new alternatives to restricted products
(Deluca et al. 2012).
582 M. Farré et al.
Drugs and Drug Addiction 2013b). As the internet is an important marketplace for
NPS, the EMCDDA undertakes a regular snapshot exercise to monitor the number
of online shops offering products to European consumers. This number of shops
continues to grow, with 693 online shops identified in January 2012.
The use of NPS has grown rapidly over the past decade, in contrast to the
prevalence of the use of internationally controlled drugs, which generally seems
to have stabilised in the same time period. Producing and marketing such sub-
stances holds the promise of high profits without penalty. When brought under
control in one country, production and/or the distribution centres of these sub-
stances are shifted to another country so that the sales, often conducted via the
internet, can continue.
In other cases, the substances are modified slightly so that they are not covered
by the respective country’s legislation. The number of NPS reported by Member
States to the United Nations Office on Drugs and Crime (UNODC) rose from 166 at
the end of 2009 to 251 by mid-2012. This exceeds the total number of psychoactive
substances currently controlled by the international drug conventions (234 sub-
stances) (United Nations Office on Drug and Crime 2013).
Well-known examples of NPS include substances such as synthetic cannabi-
noids contained in various herbal mixtures, piperazines, products sold as “bath
salts” (i.e. cathinone-type substances, such as mephedrone and methylenedioxypyr-
ovalerone [MDPV]) and various phenethylamines. Ketamine was among the
first NPS to appear. Its abuse was first recognised in North America at the beginning
of the 1980s. It became a noticeable phenomenon in Europe in the 1990s, before
spreading extensively throughout Asia and, to a lesser extent, throughout South
America and Southern Africa. NPS belonging to the phenethylamine family
appeared on the market in the 1990s and substances belonging to the piperazine
family at the beginning of the 2000s. From 2004 onwards, synthetic cannabinoids,
such as Spice, appeared on the market, followed by synthetic cathinones and other
emerging groups of NPS.
According to the Eurobarometer, 5 % of young people reported having used
these NPS in the past (Gallup Organization 2011). The national survey on drug use
in students aged 14–18 years in 2010, conducted by the Spanish Drug Observatory
(OED), assessed the use of ketamine, Spice drugs, piperazines, mephedrone, nexus
(2-CB), methamphetamine, magic mushrooms, “research chemicals” and other
LH. Reported prevalence of use was 3.5 %, 2.5 % and 0.5 % for lifetime, last
year and last month respectively for any of these substances (Clinical Committee
Report 2011).
The lifetime prevalence of legal substances that imitate the effects of illicit drugs
rises with age, from 3.6 % among the European Union population aged 15–18 to
5.6 % among those aged 19–21 and 22–24. The lifetime prevalence for the use of legal
substances that imitate the effects of illicit drugs in individual European Union countries
ranged from 0.3 % in Malta to more than 16 % in Ireland. Levels above the European
Union average (4.8 %) have been reported—in descending order—from Ireland,
Poland, Latvia and the UK, followed by Luxembourg, Slovenia, Estonia, Portugal,
Lithuania, France and Spain (United Nations Office on Drug and Crime 2013).
586 M. Farré et al.
Cathinones
There are signs that synthetic cathinones, including mephedrone, may have carved
a space in the illicit stimulants market in some countries. At present, however, only
the UK has repeat surveys that include these drugs. In the most recent data, 1.1 % of
adults (16–59) in England and Wales reported using mephedrone in the last year,
making it the fourth most commonly used illicit drug. Among 16- to 24-year-olds,
last-year prevalence was the same as that of ecstasy (3.3 %), the third most
prevalent drug among this age group. A decrease in levels of use, however, was
noted for all groups compared with the 2010/2011 survey.
More generally, mephedrone-related mortality and morbidity continue to be
reported in Europe, although at relatively low levels. Some countries also report
the injection of mephedrone, MDPV and other synthetic cathinones among groups
of problem drug users and drug treatment clients (Hungary, Austria, Romania, UK)
(European Monitoring Centre for Drugs and Drug Addiction 2013b).
In the USA data on changes in the prevalence of the use of MDPV are not
available. However, data show that the number of calls to poison control centres
concerning “bath salts” (often linked to MDPV) rose from 304 in 2010 to
6,134 in 2011, a 20-fold increase in 1 year (United Nations Office on Drug and
Crime 2013).
Piperazines
The British Crime Survey found in 2011 that the annual prevalence of BZP was
0.1 %. The Mixmag Global Drug Survey, in 2011, reported a lifetime prevalence of
17.2 % and last-year prevalence of 5 % and a prevalence in the last month of 0.5 %
(United Nations Office on Drug and Crime 2013). In New Zealand, the market for
NPS has been associated with piperazines. The national household survey there
revealed that 5.6 % of the population aged 15–64 had used BZP in the past year
(United Nations Office on Drug and Crime 2013).
35 Addiction to Hallucinogens, Dissociatives, Designer Drugs and “Legal Highs” 587
Heat stroke is a severe complication that can cause death; it includes hyperthermia,
rhabdomyolysis, myoglobinuria, disseminated intravascular coagulation and
renal failure. Fulminant hepatitis and hepatic necrosis have been reported.
Hyponatraemia is an uncommon complication associated with inappropriate
antidiuretic hormone (SIADH) secretion and excessive water intake. Its chronic
use is linked to a progressive neurodegeneration of the serotonergic neurotransmis-
sion system (de la Torre et al. 2013; Cuyas et al. 2011).
Two main pathways are involved in MDMA metabolic clearance:
1. O-demethylation partially regulated by CYP2D6 followed by catechol-
O-methyltransferase (COMT)-catalysed methylation (HMMA) and/or glucuro-
nide/sulphate conjugation; and
2. N-dealkylation leading to 3,4-methylenedioxyamphetanmine (MDA), further
subject to similar metabolic reactions to MDMA (O-demethylenation and
O-methylation). MDMA metabolic clearance accounts for about 75 % of plasma
clearance and 30 % of its metabolism is regulated by CYP2D6 (de la Torre
et al. 2005; Segura et al. 2005). In addition, MDMA is a competitive inhibitor of
CYP2D6; after a single dose most hepatic CYP2D6 are inactivated within 2 h,
returning to a basal level of CYP2D6 activity after at least 10 days. Other
isoenzymes of cytochrome P450 and a relevant contribution of renal excretion
play part in their clearance.
Globally, the clinical relevance of the CYP2D6 polymorphism (de la Torre et al.
2004, 2005) is lower than that predicted by in vitro studies (de la Torre et al. 2012;
Yubero-Lahoz et al. 2011, 2012).
In addition, there is some evidence that MDMA produces in the mid- to
long-term selective long-lasting serotonergic neurotoxicity in animal models
when administered at relatively high doses and/or after repeated administration.
Unique low doses or repeated low doses separated by large intervals did not
seem neurotoxic. It has been proposed that MDMA induces a number of serotonin
neuroadaptations and anatomical alterations (e.g. axotomy of serotonergic neu-
rons). Complementary or alternative to this view of MDMA-induced neurotoxicity,
there is new evidence showing that MDMA causes substantial regulatory changes
in the expression of serotonergic markers, including the serotonin transporter. The
direct extrapolation of these results from animal to human is difficult (de la Torre
and Farré 2004; Green et al. 2012).
In humans, ligand-binding imaging studies have reported decreased 5-HTT
binding throughout the cerebral cortices and the hippocampus in Ecstasy
users compared with healthy controls. Furthermore, these studies have shown
that decreased 5-HTT binding is associated with lower memory performance in
Ecstasy users. Although some studies have observed MDMA abstinence-related
recovery of 5-HTT availability in the mid-brain and thalamus there are no data on
5-HTT recovery in the cortex, and post-mortem evidence indicates that cortical
5-HTT protein reductions can be more robust and durable than indicated by
neuroimaging studies. Overall, these findings are suggestive of MDMA-induced
neurotoxicity, which primarily affects the serotonin system and is linked to
cognitive alterations (e.g. memory dysfunction) and a higher prevalence of
35 Addiction to Hallucinogens, Dissociatives, Designer Drugs and “Legal Highs” 589
psychopathology (e.g. mood disorders) among Ecstasy users (de la Torre and Farré
2004; de la Torre et al. 2013; De Sola Llopis et al. 2008; Pardo-Lozano et al. 2012).
The therapeutic use of MDMA is under investigation. Few recent randomised,
controlled trials of MDMA-assisted psychotherapy for post-traumatic stress
disorder have been published showing some therapeutic efficacy (Mithoefer
et al. 2013). MDMA can induce abuse, but it is not clear and in some cases drug
dependence occurs, but not drug withdrawal. Users reported tolerance to its desired
effects, and tend to cease consumption spontaneously. MDMA can cause intoxica-
tion, in this case the DSM-V diagnostic criteria for stimulants can be applied
(American Psychiatric 2013). There are no specific drugs for treating disorders
caused by MDMA. Psychotropic drugs will be used according to the patient’s
symptoms (benzodiazepines, hypnotics, antipsychotics, antidepressants). As in the
other drug addiction programmes, psychiatric and psychological support are used.
Tryptamines
Some tryptamines have been associated with the emergence of NPS. Their main
properties can be found in the hallucinogenics part of this chapter.
Phenethylamines
Phenethylamines include a large series of compounds that range from amphet-
amines or entactogens, such as MDMA to hallucinogens (see the part of this chapter
on hallucinogens). A large number of non-controlled phenethylamines also fall into
the category of NPS. However, the main phenethylamines on the illicit markets are
already under international control, including amphetamine, methamphetamine
and methylphenidate, as well as MDMA (“ecstasy”) and mescaline. NPS
phenethylamines appeared on the market after a shortage of ecstasy that occurs
between 2009 and 2010; major substitutes were other amphetamines, mCPP and,
above all, mephedrone.
They are presented in the form of pills, capsules or a powder, which users can
swallow, snort or inject, producing similar effects to MDMA, amphetamines and
hallucinogens. Amphetamines are chemically phenylethylamine derivatives, and
590 M. Farré et al.
Cathinones
Currently, the most problematic group of NPS from the perspective of public health
and safety seems to be the synthetic cathinones, such as mephedrone
(4-(methylmethcathinone, 4-MMC, 4-methylephedrone) or methylenedioxypyro-
valerone (MDPV). Cathinones are derivatives of cathinone, which is found in the
khat plant (Catha edulis), although most are synthetically manufactured.
Mephedrone and other cathinones can come in the form of capsules, tablets or
white powder that users may swallow, snort, inject, smoke or use rectally, produc-
ing similar effects to MDMA, amphetamines and cocaine.
A number of cathinones are already under international control, including
cathine, cathinone and methcathinone, as well as amfepramone and pyrovalerone.
The most widely used, non-controlled cathinones at the international level include
mephedrone (often known in the market as “m-cat”, “meph”, “drone” or “meow”),
methylone (“explosion” or “top cat”) and MDPV.
35 Addiction to Hallucinogens, Dissociatives, Designer Drugs and “Legal Highs” 591
Mephedrone and the cathinones are expected to act as a central nervous system
stimulant by promoting the release of monoamine neurotransmitters and likely
inhibiting their reuptake. Both amphetamines and cathinones bind to norepineph-
rine, dopamine and serotonin transporters, each of them differing from each other
by its relative binding potency. In particular, the presence of the ring substituent on
the phenethylamine core modifies the pharmacological properties by giving the
compound some MDMA-like effects, whereas amphetamines and cathinone deriv-
atives without ring substituents exert mostly stimulant effects (European Monitor-
ing Centre for Drugs and Drug Addiction 2012). The human pharmacology,
including pharmacokinetics of the majority of new cathinones are unknown
(Schifano et al. 2011).
The most common routes for recreational use include insufflation (snorting) and
oral ingestion. Because of its solubility in water, mephedrone is reportedly used for
rectal administration (dissolved in an enema or within gelatine capsules) as well as
injecting intravenously. Insufflation is likely to be the most common modality.
When snorted, mephedrone elicits its effects within a few minutes, with the peak
being reached in <30 min followed by a rapid comedown. According to online
users’ advice, mephedrone dosage for snorting may range between 25 and 75 mg,
with the lower threshold being at 5–15 mg, and with a level in excess of 90 mg to be
considered a high dosage.
Mephedrone effects have been variously compared by users with those of
cocaine, amphetamine and MDMA. Self-reported subjective effects may include:
intense stimulation and alertness, euphoria, empathy/feelings of closeness, socia-
bility and talkativeness, intensification of sensory experiences, moderate sexual
arousal and perceptual distortions (reported with higher dosages only). Some
56 % of those who had used mephedrone may complain of at least one unwanted
effect associated with its use. These may include: loss of appetite, dry mouth,
nausea, vomiting, tremors, tense jaws, trismus, bruxism, mild muscle clenching,
stiff neck/shoulders, headache (very common), dizziness/light headedness, tinni-
tus, seizures, nystagmus, pupil dilation, blurred vision, numbness of tactile sen-
sitivity; anxiety, agitation, confusion, dysphoria, irritability, aggression,
depression, lack of motivation and anhedonia; time distortions, long-lasting
hallucinations, paranoid delusions, short-term psychosis, short-term mania,
insomnia and nightmares; impaired short-term memory, poor concentration and
mental fatigue; tachycardia, elevated blood pressure, respiratory difficulties,
chest pain and vasoconstriction (Schifano et al. 2011; Hill and Thomas 2011;
Wood et al. 2011).
The use of ephedrone (methylcathinone) has recently been associated with
symptoms similar to those seen in patients with Parkinson’s disease (manganism)
owing to the compound manganese dioxide, which is a by-product of synthesis with
permanganate (De Bie et al. 2007).
The use of MDPV was, in a number of cases, associated with highly bizarre
behaviour, including a number of suicides, deaths associated with MDPV delirium
and highly violent homicides (Murray et al. 2012).
592 M. Farré et al.
Piperazines
The basic piperazine was first introduced into medicine in 1953, for its anthelmintic
properties. The piperazines can be classified into two groups:
• Benzylpiperazines including 1-benzylpiperazine (BZP), and its analogue 1- (3,4-
metilenodioxibenzil) piperazine (MDBP).
• The phenylpiperazines, such as 1-(3-chlorophenyl) piperazine (MCCP),
1-(3-trifluoromethylphenyl) piperazine (TFMPP), 1-(4-methoxyphenyl) pipera-
zine (MeOPP), 1-(4-chlorophenyl) piperazine (pCPP) and 1-(o-methoxyphenyl)
piperazine (WOFP).
BZP has been studied as an anthelmintic, but was never commercialised, unlike
piperazine. The mCPP is an active metabolite of trazodone and nefazodone, both with
antidepressant properties. It is used in psychopharmacological research as central
serotonergic system challenge. Generically, they are known as “herbal highs”,
“herbal tonics”, “herbal ecstasy” or “party pills”. They are generally taken orally
and are presented in the form of tablets or capsules. The BZP capsules contain 50 to
200 mg. The mCPP was introduced onto the market as a legal alternative to ecstasy in
times of shortages. Often, the mCPP is sold as ecstasy or, in some tablets, mixed with
MDMA. In fact, users are often unable to distinguish the effects of BZP from those of
D-amphetamine; they report alertness, mood escalation, euphoria and a general feel-
ing of well-being. BZP was initially legally marketed in some countries (notably New
Zealand) as an alternative to methamphetamine. If combined with TFMPP, effects
similar to those of MDMA (“ecstasy”) are produced. Thus, BZP/TFMPP combina-
tions have been widely used on the club and rave scene in many countries. These
substances have been shown to have a mixed mechanism of action, acting on both the
serotonin and the dopamine receptor systems, much like MDMA, thus showing
entactogenic properties. In contrast to BZP, TFMPP is rarely used on its own. Street
names of BZP include “Jax” and “Flying Angel”. Tablets often contain various types
of piperazines (MCCP mixtures, TFMMP, OMPP and/or pCPP). They can be found
for sale on the internet, as essentially unrestricted derivatives.
Adverse effects of BZP include repetitive thought patterns, increased heart rate,
hypertension, dilation of pupils, nausea, flushing, slight urinary incontinence, chest
pain, hallucinations, confusion, acute psychosis, respiratory failure, renal toxicity
and seizures. BZP produces toxic effects similar to those of amphetamines and
other sympathomimetics. Fatal intoxications have been described (Hill and Thomas
2011; Schep et al. 2011).
Phencyclidine Derivatives
Some new phencyclidine and ketamine derivatives are considered NPS. Their main
characteristics are explained in other parts of this chapter.
References
Aan Het Rot M, Zarate CA Jr, Charney DS, Mathew SJ (2012) Ketamine for depression: where do
we go from here? Biol Psychiatry 72(7):537–547
Abanades S, Peiro AM, Farre M (2004) Club drugs: old medicines as new party drugs. Med Clin
(Barc) 123(8):305–311
594 M. Farré et al.
European Monitoring Centre for Drugs and Drug Addiction and European Police Office (2012) 2011
annual report on the implementation of council decision 2005/387/JHA. Lisbon
European Monitoring Centre for Drugs and Drug Addiction and Europol (2013a) New drugs in
Europe, 2012. Publications Office of the European Union, Luxembourg
European Monitoring Centre for Drugs and Drug Addiction (2013b) European drug Report 2013.
Publications Office of the European Union, Luxembourg
Farré M, de la Torre R, Mathuna BO, Roset PN, Peiro AM, Torrens M et al (2004) Repeated doses
administration of MDMA in humans: Pharmacological effects and pharmacokinetics. Psycho-
pharmacology (Berl) 173(3–4):364–375
Farré M, Abanades S, Roset PN, Peiro AM, Torrens M, O’Mathuna B et al (2007) Pharmacological
interaction between 3,4-methylenedioxymethamphetamine (ecstasy) and paroxetine: Pharmaco-
logical effects and pharmacokinetics. J Pharmacol Exp Ther 323(3):954–962
Gallup Organization (2011) Young attitudes on drugs: analytical report. Flash Eurobarometer
series no. 330, 2011. European Commission. July 2011
Garratt JC, Alreja M, Aghajanian GK (1993) LSD has high efficacy relative to serotonin in enhancing
the cationic current Ih: intracellular studies in rat facial motoneurons. Synapse 13(2):123–134
Green AR, King MV, Shortall SE, Fone KC (2012) Lost in translation: preclinical studies on
3,4-methylenedioxymethamphetamine provide information on mechanisms of action, but
do not allow accurate prediction of adverse events in humans. Br J Pharmacol 166(5):1523–1536
Griffiths RR, Richards WA, McCann U, Jesse R (2006) Psilocybin can occasion mystical-type
experiences having substantial and sustained personal meaning and spiritual significance.
Psychopharmacology (Berl) 187(3):268–283, discussion 284–92
Griffiths RR, Johnson MW, Richards WA, Richards BD, McCann U, Jesse R (2011) Psilocybin
occasioned mystical-type experiences: Immediate and persisting dose-related effects. Psycho-
pharmacology (Berl) 218(4):649–665
Hill SL, Thomas SH (2011) Clinical toxicology of newer recreational drugs. Clin Toxicol (Phila)
49(8):705–719
Johnston LOP et al (2008) Monitoring the future national results on adolescent drug use: overview
of key findings, 2007. National Institute on Drug Abuse. United States: NIH publication; 2008.
Report no. 08–6418
Johnston LOP et al (2013a) Monitoring the future national survey results on drug use
1975–2012: Vol. 1. United States: Institute for Social Research, The University of Michigan,
Ann Arbor
Johnston LOP et al (2013b) Monitoring the future national survey results on drug use 1975–2012:
vol 2. college students and adults ages 19–50. United States: Institute for Social Research, The
University of Michigan, Ann Arbor
Jones RT (2009) Hallucinogen-related disorders. In: Sadock BJ, Sadock VA, Ruiz P (eds) Kaplan
an Sadock’s comprehensive textbook of psychiatry, 9th edn. Lippincott Williams & Wilkins,
Philadelphia, pp 1331–1440
Krebs TS, Johansen PO (2013) Psychedelics and mental health: a population study. PLoS One
8(8):e63972
Lerner AG, Gelkopf M, Skladman I, Oyffe I, Finkel B, Sigal M et al (2002) Flashback and
hallucinogen persisting perception disorder: clinical aspects and pharmacological treatment
approach. Isr J Psychiatry Relat Sci 39(2):92–99
McGee R (1984) Flashbacks and memory phenomena. A comment on “flashback phenomena–clinical
and diagnostic dilemmas”. J Nerv Ment Dis 172(5):273–278
Meyerhoefer M (2011) Serotonergic hallucinogens. In: Johnson B, editor. Addiction Medicine.
Springer, New York, pp 585–602
Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Martin SF, Yazar-Klosinski B, Michel Y,
Brewerton TD, Doblin R (2013) Durability of improvement in post-traumatic stress
disorder symptoms and absence of harmful effects or drug dependency after
3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term
follow-up study. J Psychopharmacol 27(1):28–39
596 M. Farré et al.
Morgan CJ, Curran HV (2012) Independent Scientific Committee on Drugs. Ketamine use:
a review. Addiction 107(1):27–38
Murray BL, Murphy CM, Beuhler MC (2012) Death following recreational use of designer drug
“bath salts” containing 3,4-methylenedioxypyrovalerone (MDPV). J Med Toxicol 8(1):69–75
Mustata C, Torrens M, Pardo R, Perez C, Psychonaut Web Mapping Group, Farre M (2009) Spice
drugs: cannabinoids as a new designer drugs. Adicciones 21(3):181–186
O’Brian C (2011) Drug addiction. In: Brunton LL, Chabner BA, Knollman BA, Knollman BC
(eds) Goodman and Gilman’s the pharmacological basis of therapeutics, 12th edn. McGraw-
Hill, New York, pp 649–667
Pardo-Lozano R, Farre M, Yubero-Lahoz S, O’Mathuna B, Torrens M, Mustata C et al (2012)
Clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”): the
influence of gender and genetics (CYP2D6, COMT, 5-HTT). PLoS One 7(10):e47599
Passie T, Seifert J, Schneider U, Emrich HM (2002) The pharmacology of psilocybin. Addict Biol
7(4):357–364
Passie T, Halpern JH, Stichtenoth DO, Emrich HM, Hintzen A (2008) The pharmacology of
lysergic acid diethylamide: a review. CNS Neurosci Ther 14(4):295–314
Prozialeck WC, Jivan JK, Andurkar SV (2012) Pharmacology of kratom: an emerging botanical
agent with stimulant, analgesic and opioid-like effects. J Am Osteopath Assoc 112(12):792–799
Sanders-Bush E, Hazelwood L (2011) 5-hydroxitryptamine (serotonin) and dopamine. In: Brunton
LL, Chabner BA, Knollman BC (eds) Goodman and Gilman’s the pharmacological basis of
therapeutics, 12th edn. McGraw-Hill, New York, pp 335–362
Schep LJ, Slaughter RJ, Vale JA, Beasley DM, Gee P (2011) The clinical toxicology of the
designer “party pills” benzylpiperazine and trifluoromethylphenylpiperazine. Clin Toxicol
(Phila) 49(3):131–141
Schifano F, Albanese A, Fergus S, Stair JL, Deluca P, Corazza O et al (2011) Mephedrone
(4-methylmethcathinone; ‘meow meow’): chemical, pharmacological and clinical issues.
Psychopharmacology (Berl) 214(3):593–602
Schiff PL (2006) Ergot and its alkaloids. Am J Pharm Educ 70(5):98
Sedefov R, Gallegos A, Mounteney J, Kenny P (2013) Monitoring novel psychoactive substances.
A global perspective. In: Dargan P, Wood DM (eds) Novel psychoactive substances.
Academic, London, pp 29–54
Segura M, Farré M, Pichini S, Peiró AM, Roset PN, Ramı́rez A, Ortuño J, Pacifici R, Zuccaro PG,
Segura J, de la Torre R (2005) Contribution of CYP2D6 to 3,4-methylenedioxymetham-
phetamine (MDMA) disposition in humans: use of paroxetine as a metabolic inhibitor probe.
Clin Pharmacokinet 44:649–60
Sharp T, Boothman L, Raley J, Queree P (2007) Important messages in the ‘post’: Recent
discoveries in 5-HT neurone feedback control. Trends Pharmacol Sci 28(12):629–636
United Nations Office on Drug and Crime (2013) United Nations Office on Drug and Crime 2013.
June 2013. Report no. No.E.13.XI.6. New York
Vollenweider FX, Kometer M (2010) The neurobiology of psychedelic drugs: Implications for the
treatment of mood disorders. Nat Rev Neurosci 11(9):642–651
Winter JC (1971) Tolerance to a behavioral effect of lysergic acid diethylamide and cross-
tolerance to mescaline in the rat: Absence of a metabolic component. J Pharmacol Exp Ther
178(3):625–630
Wood DM, Greene SL, Dargan PI (2011) Clinical pattern of toxicity associated with the novel
synthetic cathinonemephedrone. Emerg Med J 28(4):280–282
Yubero-Lahoz S, Pardo R, Farre M, O’ B, Torrens M, Mustata C et al (2011) Sex differences in
3,4-methylenedioxymethamphetamine (MDMA; ecstasy)-induced cytochrome P450 2D6 inhi-
bition in humans. Clin Pharmacokinet 50(5):319–329
Yubero-Lahoz S, Pardo R, Farre M, Mathuna BO, Torrens M, Mustata C et al (2012) Changes in
CYP1A2 activity in humans after 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)
administration using caffeine as a probe drug. Drug Metab Pharmacokinet 27(6):605–613
Inhalant Addiction
36
Tania Real, Silvia L. Cruz, and Marı́a Elena Medina-Mora
Contents
36.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 598
36.2 Definition and Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 598
36.2.1 Epidemiology: How Widespread Is Its Use? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 602
36.2.2 Use Among Special Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 604
36.2.3 Patterns of Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605
36.3 Health Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 607
36.3.1 Acute Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 607
36.3.2 Chronic Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 608
36.3.3 Prenatal Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 609
36.3.4 Molecular Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 609
36.3.5 Morbidity and Mortality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 610
36.4 Correlates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 611
36.5 Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 611
36.6 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 612
36.6.1 Recovery Potential and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 612
36.6.2 Policy Options . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 613
36.7 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615
Abstract
Inhalants are a special class of drugs that require particular attention from health
and social welfare experts and policy makers. They are substances of abuse not
included in the International Regulations. They are also less frequently targets
for health and social interventions as well as for research funding. Inhalants are
the only drugs of abuse defined by the route of administration rather than by
their attributes, specifically by similar mechanisms of action or common phar-
macological effects. They include a broad group of substances with different
uses, short and long-term negative effects, and consequences. These products
have legal uses in industry and households and are therefore readily available.
Inhalants are used by young students and populations with special needs,
mainly children and adolescents from poor sectors of society, workers who
use solvents for their everyday work (such as varnishers, house painters, and
anesthetists), and heavy drug users, especially when they lack access to other
substances. The short-term effects of inhalants are similar to alcohol and other
central nervous system depressants and can produce impaired motor coordina-
tion, emotional liability, and speaking difficulties. Chronic effects include
neurotoxicity, cognitive impairment, headaches, diminished sensorial abilities
(loss of vision, audition, and coordination), and an increase in mental disorders
and sleep disturbances. Inhalant use prevention involves different strategies,
including education, skill building, environmental changes, and policy devel-
opment. There is little research on evidence-based treatment for inhalant addic-
tion. However, treatment should include supportive psychotherapy, family and
psychosocial interventions, general health care proper nutrition, and vitamins
or nutritional supplements. The long-term outcome of inhalant addiction
is usually progressive neurocognitive deterioration with multiple medical
complications.
36.1 Introduction
Inhalants are a special group of substances with varied effects, differences in use
patterns and populations affected, and with special needs for prevention, treatment
and policy formulations. This chapter focuses on this issue; it is divided in 6 sections,
beginning with a general overview of the substances and definitions. This is
followed by a description of prevalence, the groups of affected population and use
patterns in different regions of the world. Particular attention is paid to use among
groups with special needs, to their effects and consequences; the social determinants
that underlie the problem and opportunities for solution are also addressed. These
sections are followed by a brief overview of the evidence for prevention and
treatment. The chapter ends with a discussion on policies to address the problem.
NIDA’s definition (2012) includes the main issues that characterize this varied
group of substances and their effects: the intentionality of their use, due to the
chemicals’ mind-altering effects; the nature of the short-term effects (most of them
produce a rapid high that resembles in some aspects alcohol intoxication); the
effects when sufficient amounts are inhaled, as nearly all solvents and gases
produce a loss of sensation and even unconsciousness; the long-term irreversible
effects that can include hearing loss, limb spasms, and bone marrow and brain
damage; and lastly, the risk of death when sniffing high concentrations of inhalants,
which may result in death from heart failure hypothermia or suffocation.
A wide range of substances are grouped together into this class, which by its very
nature challenges definitions and classifications. Inhalants include (1) solvents
(liquids or semisolid substances that evaporate and include glue, shoe polish,
toluene, and gasoline, among others); (2) aerosol sprays (volatile substances or
gases such as spray paints, hair sprays, cleaners for computers, etc.); (3) gases
(anesthetics for medical use such as ether, chloroform, butane, and refrigeration
products); and (4) nitrites that include products containing butyl nitrite and amyl
nitrite, known as “poppers,” locker room deodorizers, or “rush,” and nitrous oxide
known as “whippets.”
The physicochemical classification is: (a) gases or can easily become vapors at
room temperature (without heating); (b) nonpolar molecules with high affinity for
lipids and can therefore cross all biological membranes; (c) flammable; (d) usually
lighter than water in their liquid form, but as vapors are heavier than air, meaning
that they are not easily dispersed from rooms where they have been inhaled
(Cruz 2011).
Since many substances meet these criteria, they can be classified on the basis of
chemical structure (hydrocarbons, ethers, ketones, etc.), commercial use (solvents,
anesthetics, propellants, etc.), physical state (gases, liquids, aerosols), or effects on
the central nervous system (depressants, vasodilators, etc.). Each classification has
its own limitations, and some substances may fit into several categories. For
example, butane is a hydrocarbon gas used both as a fuel and a propellant; nitrous
oxide is a propellant and also an anesthetic gas used in dentistry. Moreover, a single
substance can have different names such as toluene, methylbenzene,
phenylmethane, or toluol. This compounds the difficulties associated with inhalant
research. Table 36.1 shows some commonly misused compounds and their syno-
nyms and chemical structure, examples of commercial products, threshold limit
values (TLV: maximum average concentration to which workers can be exposed
8 h/day, 5 days/week, without experiencing significant adverse health effects), and
vapor concentrations in air that are dangerous to life and health (IDHL). This table
also includes CAS#, a unique chemical abstract service number that may be used to
obtain key information on individual compounds. A detailed table of the physico-
chemical properties of main inhalants can be found elsewhere (Bowen and Cruz
2014).
Although there is insufficient evidence to establish a scientifically based phar-
macological classification of inhalants, it is possible to distinguish at least three
different categories with various mechanisms of actions: (a) solvents, fuels, and
600
Hydrocarbons, Benzene Benzol, phenyl hydride, cyclohexatriene 71-43-2 Gasoline 0.5 500
aromatic
Toluene CH3 Toluol, methyl-benzene, phenylmethane 108-88-3 Solvents, paints, thinners, glues, lacquers, 50 500
gasoline, inks, cigarette smoke
Xylene Xylol, dimethyl-benzene, methyl 1330-20-7 Cleaning agents, thinner. Used in printing, 100 900
toluene rubber and leather industries
Ethyl-benzene Phenyl ethane, ethyl benzol 100-41-4 Gasoline, paints, inks. Used as styrene 100 800
precursor
Propyl-benzene Phenyl propane, isocumeme 103-65-1 Gasoline. Used in textile dyeing and printing N.E. N.E.
Hydrocarbons, 1,1,1-TCE Cl Trichloroethane, TCE, 71-55-6 Cleaning products, paints, correction fluids, 350 700
Cl
Diethyl-ether O
Ethyl ether, octapentane, ethoxy ethane 60-29-7 Anesthetic, solvents, fuels 400 1,900
Inorganic Nitrous oxide O− Dinitrogen monoxide 10024-97-2 Anesthetic, laughing gas, propellant (hair 50 N.E.
+
N
N
sprays, whipped cream, cooking spray),
engine combustion enhancer
Hydrocarbons, Propane Dimethyl methane, LP gas 74-98-6 Industrial fuel, refrigerant, aerosol propellant 1,000 2,100
acyclic
Butane Methylethyl ethane, Freon 600 106-97-8 Lighter fuel, gas tanks for cooking, 800 N.E.
LP gas refrigerant, aerosol propellant (deodorant
sprays)
Hydrocarbons, 1,1- F F Ethylene fluoride, Freon 152 a, R152a, 75-37-6 Propellant (PC duster), refrigerant (air 1,000 N.E.
Halogenated difluoroethane HCF152a, Dymel conditioning)
1,1,1,2- F Freon 134 811-97-2 Propellant (PC duster), refrigerant (car air N.E. N.E.
F
F
Tetrafluoroethane F conditioning systems)
R134
Sources: PubChem, NIOSH ICSC (International Chemical Safety Cards), ATSDR (Agency for Toxic Substances and Disease Registry), Household Products
Database, and Haz Map.
CAS# chemical abstract service number, TLV threshold limit value, IDLH immediately dangerous to life and health
601
602 T. Real et al.
anesthetics; (b) nitrous oxide; and (c) volatile alkyl nitrites. The first is the most
extensive group and includes inhalants misused throughout the world in the form of
gasoline, industrial solvents, adhesives, paints, sprays, inks, pen markers, and many
other commercial products. Among solvents, toluene is the most frequently misused
and the best-studied inhalant compound. It is the main component of paint thinners
(mixed with xylene, ethylbenzene, and other solvents in different proportions), inks,
adhesives, and degreasing agents. Commercial xylene (a mixture of the three iso-
mers: ortho-, metha-, and para-xylene) is used in the leather and rubber industries
and histology laboratories. The solvent known as 1,1,1-TCE or trichloroethylene is
also present in correction fluids, but no longer produced in most developed countries
because it is harmful to the ozone layer. Gasoline is a mixture of several solvents,
which may or may not contain lead. Several anesthetic gases such as halothane,
ether, and chloroform are included in the same group with solvents because they
share some of the effects and mechanisms of action of misused solvents.
Nitrous oxide is in a class of its own because of its unique pharmacological
profile and affinity for specific receptors. It is used as a propellant in whipped cream
products and as an anesthetic gas for dental procedures. As for nitrites, they are
smooth muscle relaxant and vasodilator drugs rather than depressant substances and
are inhaled from small bottles, some of which “pop” when opened (hence the name
“poppers”) (Cruz and Bowen 2008).
Worldwide inhalant misuse has mainly spread among young people. Although there
are variations in the age of onset, the trend in most countries is toward an increas-
ingly early start. Age at first use is generally 6–8 years, while peak age for abuse is
14–15 years (O’Malley 2012). The period of risk for drug use initiation among
special populations such as youth from Indian communities has been reported as
between the ages of 10 and 13 years, with the onset among some individuals being
as young as 5–6 years of age (Hillabrant 2001).
In the Americas, there are countries like Canada and the United States that have
seen a decrease in consumption. However, in Latin America and the Caribbean, it is
a growing problem and has gone from being a drug consumed by street children to
one that is consumed by children and young students and even university students
(OEA 2011).
According to a study on young Americans (Johnston et al. 2014), inhalant
consumption increased from the late 1970s to the mid-1990s, especially in 8th,
10th, and 12th grade. Trends have changed and in 2001, consumption began to
decrease. The last measurement in 2013 shows that annual prevalence was 5.2 % in
8th grade, 3.5 % in 10th grade, and 2.5 % in 12th grade. Despite the variations, the
trend is for consumption to decline, a trend that is believed to be associated with
information campaigns.
In Canada, the Report on Alcohol and Drug Use by Students (Young 2011)
indicated that among 7th and 12th grade students, inhalants are the fourth most ever
36 Inhalant Addiction 603
consumed drug (2.2 % and 3.8 %), respectively, preceded by alcohol, cannabis, and
ecstasy, and prevalence in the last year reached 2.6 % and 4.4 %.
In Mexico, this practice has experienced periods of increase and decrease among
students in various regions. For instance, in Mexico City, annual prevalence
increased from 4.4 % in 2006 to 7.5 % in 2009, to decrease again in 2012 to
5.9% among high school students, with use remaining stable after 2009 (Villatoro
et al. 2012). More recent surveys show that inhalation rates have remained
unchanged. According to the National Household Survey 2011 conducted among
the population ages 12–65, annual prevalence of use in the previous year was low,
0.1 % with no significant modifications from 2008 (SSA et al. 2012). This same
trend is reported by the Epidemiological Surveillance System that gathers infor-
mation on cases seeking treatment in nongovernmental organizations. Inhalants
were the drug of “impact” defined as the one which, according to patients, consti-
tuted their main problem of abuse in 7.6 % of patients in 2009 and 7.2 % in 2011
(SSA 2013).
In most Latin American and Caribbean countries, apart from tobacco and
alcohol, inhalants are the most commonly used substance after cannabis, especially
among high school students, although there are countries where it is the first drug of
choice (OEA 2011).
The lowest prevalence of ever use has been reported in Venezuela (0.7 %),
Dominican Republic (1.1 %), Honduras (1.6 %), Guatemala (2.1 %), and Nicaragua
(2 %) in surveys conducted among high school students between 2003 and 2009.
The lowest prevalence in the past year in this same population was reported in the
same countries, together with Uruguay (1.4 %). And the lowest use last month was
also reported in the same countries: with less than 0.4 % reporting use.
The highest prevalences in the three measurements ever use, in the past year and last
month, were found in Brazil (15.6 %, 14.3 %, 9.9 %), Barbados (19.6 %, 9.9 %, 6.4 %),
Guyana (21.7 %, 10.5 %, 6.9 %), Trinidad and Tobago (26.3 %, 13.2 %, 7.4 %), and
Jamaica (28.1 %, 13.9 %, 9.4 %) in surveys conducted between 2004 and 2007.
College students also report use of these substances. In countries in the Andean
Region, a study showed that during the past year, the highest prevalence was
reported in Bolivia (1.8 %) followed by Colombia and Peru (1.4 % and 1.7 %)
and Ecuador with 0.77 %.
There are also differences by sex: in Argentina, Bolivia, Colombia, Costa Rica,
Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, Panama,
Suriname, and Uruguay, men have higher rates. In countries such as Antigua,
Barbados, Granada, and Trinidad and Tobago, rates are higher among women,
especially in Jamaica where the proportion is over twice that of men. In the United
States, girls in 8th and 10th grade have slightly higher consumption (OEA 2011).
In Mexico, household surveys show that more males than females use solvents
(ENA 2011), but among high school students, gender differences have vanished
(Villatoro et al. 2012). A similar situation is observed in Ontario, Canada, among
high school students, with no difference in rates last year by sex, 5.3 % and 5.9 %
among males and females, respectively (CAMH 2011). In Chile in secondary
students (13–17 years), last year prevalence was 3.7 % and 3.1 % for males and
604 T. Real et al.
females, respectively, and in Ecuador 3.1 % males and 2.2 % females reported
having used in the last 12 months (UNODC 2010).
In Europe, rates for students between the age of 15 and 16 varied between 17 %
in the Isle of Man and 15 % in Ireland to 3 % in Bulgaria, Ukraine, and Lithuania
(ESPAD 2007). In Africa, solvents and inhalants were the seventh drug of choice
with a prevalence of 3.2 % in 2009.
In 2008, in Central Asia, UNODC (2008) reported that inhalant consumption
among young people had increased and in some cases exceeded that of cannabis.
For example, Tajikistan has a prevalence over the past 12 months of 8.4 % for boys
and of 4.2 % for girls. In the past month, the figure was 2.1 % for boys and 3.6 % for
girls. In Kazakhstan, the prevalence for boys was 2.4 % as opposed to 2 % for girls
in the past year and 1.3 % and 1.1 % in the past month. Kyrgyzstan reported 2.4 %
of boys and 1.7 % in girls in the past year, and for the last month, the figures are
1.6 % and 1.1 %. An earlier survey in this country (2006) reported inhalants as the
first drug of use, with 5.4 % ever use. Lastly, in Uzbekistan, figures for the past year
are 0.4 % for boys and 0.3 % for girls and 0.3 % versus 0.2 % in the past month.
A final word of caution, the rates reported in this section of the chapter are drawn
mainly from surveys, that not always use the same definitions, and furthermore,
these sources might underestimate prevalence of use rates among difficult-to-reach
populations, not included in survey approaches, such as street children and pris-
oners, described in the following section. Rates of use among these groups are
considerably higher.
Studies conducted in different parts of the world show that young people from
low-income, chaotic, broken, or abusive homes appear to have the highest rates of
use (Oetting et al. 1988). According to O’Malley (2012), in the United States and
Canada, long-term use of inhalants is more common in inner-city and remote rural
community residency; it is also associated with lower socioeconomic class, Latin
American immigration, and family dysfunction.
Villatoro et al. (2012), analyzed data from national household surveys in Mexico
and, found that those drug users that reported having ever inhaled, as compared to
cannabis users that had not experimented with these substances, came from more
disorganized and violent communities and also reported having being involved in
fights, selling drugs, and other problem behaviors more frequently. Storr
et al. (2004) using data from a nationally representative population sample ages
12 and older in the United States (n ¼ 25,500) examined whether living in
disadvantaged communities increased the likelihood of coming into contact with
drug dealers as compared with persons living in more advantaged areas, and found
that the physical and social characteristics of a neighborhood determined the
likelihood of becoming involved with drugs.
High inhalant abuse rates have also been documented among street
children living in South America, Eastern Europe, and Asia (Forster et al. 1996;
36 Inhalant Addiction 605
Pagare et al. 2004). For instance, in a study conducted in Mexico in 100 cities, rates
of use varied from 3 % among adolescents working on the streets to 72 % among
those living in the streets; the substance of choice being toluene (Medina-Mora
et al. 1999).
This practice has also been reported across indigenous communities in Australia
and North America (Beauvais and Oetting 1988; Chalmers 1991). In these com-
munities, lifetime prevalence rates of petrol sniffing among adolescents reach
50–60 % and appear to be associated with the isolation (both geographical and
social), poverty, and unemployment prominent among these marginalized groups
(Cairney et al. 2002). According to Remington and Hoffman (1984), inhalation of
gasoline tends to occur in poor, isolated communities and on Indian reservations
where unemployment is widespread and few organized social activities are avail-
able to youth.
The National Inhalant Prevention Coalition (NIPC) reported that 20 % of the
Kickapoo Tribe is “addicted to spray paint,” this group’s drug of choice. According
to this Coalition, it alleviates hunger, and the periods of intoxication last longer than
those produced by alcohol. Users also report that paint-induced hallucinations are
easily incorporated into tribal traditions (News Briefs, NIPC 1997). A survey of
Navajo 8th graders found that almost 25 % have tried inhalants, with 12 % having
used inhalants in the previous month. This survey reinforces the findings of other
studies that report that the majority of inhalant abusers are young. Leal et al.
(1977) also found that toluene abusers in Mexico City declared that solvent sniffing
alleviated hunger and that they enjoyed the altered perceptions it produced.
As is the case with other drugs, inhalers can be classified as experimenters, regular
users, heavy users, and persons with dependence. Among students, especially those
in early adolescence, the most common pattern involves experimentation with
a low proportion of regular users and an even smaller proportion of students that
have developed dependence. For instance, among American and Australian stu-
dents, experimental inhalant use rates during early adolescence are high (26 % of
12-year-old students), whereas the proportion that reports inhaling on a regular
basis is over six times smaller (4 %) (Johnston et al. 2003; White and Hayman
2004). In Mexico City and Jalisco, experimentation rates (using one to five times)
among young students (7–9 years of school) are also considerably higher (66 % and
76 %, respectively) than rates for use on over five occasions (44 % and 24 %) of all
persons that have ever used (Villatoro et al. 2012; Chávez et al. 2013). This pattern
differs from the one observed among adolescents living on the streets who are
heavily involved in inhalation, with daily heavy use being the most common pattern
combined with periods of complete abstinence (Medina-Mora and Berenzon 1997).
Few studies report dependence rates among them. Perron and colleagues (2011),
using data from the National Epidemiologic Survey on Alcohol and Related
Conditions (NESARC) household sample of persons ages 18 and older in the
606 T. Real et al.
United States, documented that 19.5 % of lifetime inhalant users met the criteria for
DSM-IV inhalant use disorder (abuse 17.2 % or dependence 2.3 %).
Inhalants are usually “sniffed” directly from the container to the nose, but
inhaling fumes through the mouth (“huffing”) is also common. The open tube of
glue or nail polish is usually placed close to the nose and the fumes are inhaled.
Sometimes users heat substances to speed up the vaporization process which
increases the risk of gas explosions. Other forms of use include inhaling from
damp rags or shirt sleeves or from plastic or paper bags (“bagging”). Fatal accidents
may occur when the inhaler places the whole bag over his head; balloons filled with
substances such as nitrous oxide have also been reported (NIPC 1997). Some
authors have reported that the route of administration is related to environmental
factors such as the presence of police and the need to disguise use (Medina-Mora
and Berenzon 1995). A case study in India reports petrol inhalation by a 10-year-old
boy who began to inhale it accidentally by putting his face to the keyhole of the
petrol tank on his father’s motorbike (Basu et al. 2004).
Preference for specific substances varies according to the characteristics of the
groups that use them and their effects; Takagi et al. (2010), for example, when
assessing preferences for types of paint among inhalers in Australia, found that
compared to non-chrome users, chrome-using groups was more likely to report
deliberately inhaling to experience altered perceptions (such as visual and auditory
hallucinations). A greater proportion of chrome users reported that the perceptual
alterations they experienced after sniffing paint differed between paint colors, with
more vivid hallucinations being produced by chrome colors. Similarly, Leal et al.
(1977) reported that children living on the streets in downtown Mexico City
preferred pure toluene for its psychotropic effects and lower level of toxicity.
Cruz and Domı́nguez (2011) have also documented hallucinations among heavy
inhalers in Mexico who use toluene or a mixture of solvents.
Common choices for solvents among American Indian youth and Alaskan
Natives are gasoline (28 %), glue (23 %), paint removers and nail polish remover
(18 %), and paint sprays (17 %). In this group, as is often the case with street
children (Medina-Mora et al. 1997), most of the substances inhaled contain mix-
tures of chemicals, making it almost impossible to determine which compounds are
responsible for the effects experienced by the abuser and observed by therapists
(Oetting et al. 1988).
Trotter et al. (1977) reported that inhalant abuse was sometimes combined with
drinking the liquid residue left in aerosol cans after sniffing the propellant (Trotter
1997). Hillabrant (2001) published interviews with Navajo adolescents who
reported the fad of drinking hair spray, users of which faint after five bottles
an hour.
Some groups in Mexico use “compressed air” at special gatherings known as
“perreos” or “grinding, booty dancing, bumping, or housing” in the Caribbean.
Inhalants and alcohol are the substances consumed; attendees may buy a piece of
rag soaked in toluene that has been flavored. Risky sexual behavior and fights are
common (Gutiérrez et al. 2007). Having sex under the effects of poppers has been
documented among gays and; use of these substances has been associated with
36 Inhalant Addiction 607
Inhalants: Short-term effects are similar to alcohol and other central nervous system
inhibitors as regards initial stimulation and persistence. They act as anxiolytics,
antidepressants, and anticonvulsants and are associated with impaired motor coor-
dination, emotional lability, and difficulty speaking. Chronic effects include neu-
rotoxicity, cognitive impairment, headaches, diminished sensorial abilities (loss of
vision, audition, and coordination), and an increase in mental disorders and sleep
disturbances.
There is evidence that the more widely used inhalants share cellular mechanisms
and have similar effects to other drugs, particularly depressors of the central
nervous system (Cruz 2011) although the use of these substances has also been
associated with illusions and hallucinations (Cruz and Dominguez 2011). When
used by pregnant rats, they affect development, and irregular heartbeat during
intoxication has also been described (Cruz et al. 2003). Unfortunately,
a significant shortage of information remains, despite the increase in research
projects addressing the neurobiology of inhalants; the majority are still conducted
on toluene. Little is known of abstinence, and researchers do not know the extent to
which cognitive or other effects may be reversible, although some laboratory
experiments with enriched environments have provided evidence of reversibility
(Lubman et al. 2008; Páez-Martı́nez et al. 2013).
Inhalants vary in their chemical composition and consequently in how and where
they act. In fact, it is rather surprising that such a dissimilar group of substances
should have the same effects, although this is partly due to their common admin-
istration route. Misusing inhalants implies introducing gases other than air into the
body causing poor brain oxygenation (hypoxia) and the attendant deleterious
consequences. This happens with all inhalants regardless of their pharmacological
profile and constitutes a significant health hazard in itself.
Once in the body, inhaled vapors rapidly achieve various specific molecular
targets to induce a state of intoxication similar to that produced by other central
nervous system depressant drugs such as alcohol and barbiturates. The pulmonary
route is highly efficient because the lungs are profusely irrigated and have extensive
absorption surface. This results in rapid intoxication, which is, however, short-lived
due to inhalants’ high volatility. In order to maintain the effects, users repeat the
experience every few minutes to maintain the desired level of active substance in
the brain.
608 T. Real et al.
Repeated inhalant use produces chronic irritation of the respiratory airways with
breathing difficulties and increased frequency of respiratory illnesses, anosmia
(decreased capacity to detect odors), and general cognitive impairment. Chronic
inhalant users have a higher incidence of neurobiological abnormalities including
diffuse cerebral and cerebellar atrophy, enlarged brain ventricles, and general white
matter damage. These abnormalities have been correlated with attention dysfunc-
tion, impaired motor control, and memory loss together with reduced speed of
information processing, among other detrimental effects (Yucel et al. 2008).
Inhalation of toluene-based products can cause hearing loss, visual impairment,
and severe ataxia (Filley et al. 2004).
Benzene, a component of gasoline, produces anemia and leukemia because it
impairs blood cell formation in the bone marrow. The toxicity associated with
36 Inhalant Addiction 609
gasoline inhalation may not only be linked to benzene but also to the presence of
lead in countries that do not use unleaded gasoline. Hexane, another organic solvent
used in inks and other products, causes peripheral neuropathy because it is metab-
olized to 2,5-hexanedione, a highly toxic compound.
Halogenated compounds, in other words, those containing chloride, fluoride, or
bromide in their structure, such as 1,1,1-trichloroethane, trichloroethylene (a degreasing
agent and spot remover), halothane (a liquid anesthetic), or 1,1-difluoroethane
(PC duster) can produce liver and kidney failure as well as cardiac arrest.
Repeated exposure to nitrous oxide produces a vitamin B12 deficiency, which
may lead to damage to the neuron’s myelin sheath manifested as ascending lower
extremity weakness and numbness (Lin et al. 2011). As for nitrites, chronic users of
this compound can experience bilateral vision loss due to retinal damage (Audo
et al. 2011).
The fact that the gender gap is being reduced poses specific challenges for service
providers and researchers owing to the harmful effects of inhalants in women of
reproductive age. A fetal solvent syndrome, similar to that caused by alcohol, has
been described in babies born from mothers who used inhalants during pregnancy.
This syndrome includes facial anomalies, delayed growth, and impaired
neurobehavioral development (Bowen 2011). Low weight at birth and craniofacial
abnormalities have also been documented in both clinical and preclinical studies
(Hannigan and Bowen 2010). Follow-up studies of children exposed to inhalants
during gestation have shown growth retardation, learning impairment, cerebellar
dysfunction (affecting balance), language deficiencies, and hyperactivity. It is
worth mentioning that some of these studies cannot rule out the use of other
drugs and, in fact, it is fairly common for inhalants to be used in combination
with other psychoactive substances. However, animal studies in which environ-
mental conditions are controlled and only solvents are used support these findings.
The available evidence indicates that toluene, the best-studied misused solvent, has
a complex mechanism of action, which includes effects on diverse molecular
targets. Although detailed description of toluene’s mechanism of action is beyond
the scope of this chapter and has been reviewed elsewhere (Bowen et al. 2006),
a few relevant data might be worth noting. Toluene inhibits the function of certain
channels activated by excitatory neurotransmitters such as the glutamatergic
NMDA receptors (Cruz et al. 1998) and nicotinic receptors (Bale et al. 2005a).
At similar concentrations, toluene enhances the function of inhibitory neurotrans-
mitter receptors such as GABA (Bale et al. 2005b) and glycine (Beckstead
et al. 2000). Calcium channels, potassium channels, and sodium channels are also
610 T. Real et al.
affected by toluene (Shafer et al. 2005; Cruz et al. 2003; Del Re et al. 2006). Like
other drugs of abuse, toluene increases dopamine release in key areas of the
dopaminergic mesolimbic system. Less data are available on other solvents, but
evidence indicates that at least the effects on GABAergic and glutamatergic
systems are common to many substances including the majority of inhaled gases.
Mortality is associated with this practice. Sudden sniffing death is a rare but serious
complication that may occur at any time, even after single use; in other words, it is
not necessarily associated with repeated or prolonged exposure. Death can be due to
a combination of factors including poor oxygen supply, a direct cardiac effect
(arrhythmias), and sensitization to catecholamine stimulatory effects. Sudden
death may occur when an intoxicated user is startled because catecholamines are
released, the heart function is increased, and cardiac arrest becomes more likely
(Bowen 2011). It has also been reported as a result of adrenaline surge. It can occur
during abuse or in the next few hours because solvents, dissolved in lipid-rich cell
membranes, dissipate slowly.
Other causes are derived from the interaction between the substances abused, the
user, the route of administration, and the environment. Suffocation and trauma may
occur when a user puts a plastic bag sprayed with a solvent over his or her head to
enhance the amount inhaled; the plastic bag may occlude the airway if the user loses
consciousness. Death by aspiration, usually of vomit, is similar to that observed for
alcohol and other depressants and results from a combination of a decreased level of
consciousness and the loss of protective airway reflexes. Risk of accidents is high as
users become less inhibited and less alert and oriented, which facilitates engage-
ment in risky behaviors (Williams et al. 2007).
Lifestyles of certain subgroups such as street children raise the burden
related to violence and increase the risk of HIV from sexual abuse and
prostitution (Medina-Mora et al. 1997). In a survey conducted in 100 cities
in Mexico among working children and adolescents ages 6–17, Medina-Mora
found that fewer than 1 % declared prostitution as their source of income.
Increased risk of seroconversion among the street population has been reported
in other sites (Roy et al. 2003).
The Toxic Exposure Surveillance System (TESS) database of the American
Association of Poison Control Systems showed 63 deaths in 11,670 cases of
intentional inhalant abuse reported from 1996 to 2001 to poison control centers in
that country, linked to gasoline inhalation (45 %), air fresheners (26 %), and
propane/butane (11 %) (Spiller 2004). In two particular states, Virginia and
Texas, a higher rate was found, 39 and 144, respectively, the majority linked to
fuel inhalation.
There is a wide range of diseases linked to this practice that includes ichthyosis-
like dermatitis on the extremities, decreased visual acuity, toxic hepatitis, distal
renal tubular acidosis, metabolic acidosis, leukemia, and aplastic anemia.
36 Inhalant Addiction 611
36.4 Correlates
In a review published in 2008, Medina-Mora and Real found evidence of high rates
of psychiatric comorbidity, mood, anxiety, and personality disorders being com-
mon among lifetime inhalant users. They also reported a higher prevalence of
lifetime dysthymia and anxiety disorders among female inhalant users, although
a lower prevalence of antisocial personality disorder. Among inhalant users with
comorbid disorders, those who developed social or specific phobia had experienced
the onset of these disorders prior to the initiation of inhalant use; all other mood and
anxiety disorders usually developed following the onset of inhalant use. Odds of
psychiatric disorders were higher for inhalant users who were women, poor, and
less educated and with an early onset of inhalant use, family histories of psycho-
pathology, and personal histories of substance abuse treatment.
These same authors also concluded from their review of the literature that among
incarcerated youth, compared to users of other substances, inhalant users showed
significantly higher levels of criminal behavior, antisocial attitudes, current psychi-
atric symptoms, earlier onset of offending and substance use, and more extensive
histories of head injury, kidney disease, hormonal problems, mental illness,
suicidality, trauma, and substance-related problems (Medina-Mora and Real 2008).
The complexity nature of this problem as described requires complex, culturally
sensitive interventions at the individual, familial, and community level and public
policies designed to reduce the risk associated with the substances themselves and
to control availability with a particular focus on children and adolescents, the
modification of the social determinants underlying this disorder, the reduction of
health disparities, and the promotion of development.
36.5 Prevention
Many strategies focus on educating very young children about the dangers of
inhalants and disseminating messages that depict inhalants as poison. In Texas in
the United States, some of these programs have attempted to redefine the problem
as a public health rather than a substance abuse issue. This perspective facilitates
the involvement of community partners, nurses, emergency room personnel, med-
ical associations, and poison treatment centers.
Other prevention interventions have been developed and provide educational
materials and resources for families, school, and media. Products include staff
training and curricula for schools and resources for teaching parenting skill
(NIDA 2005).
Some populations require special attention among them the Indigenous
populations. Interesting cultural adaptations can be found, for example, in programs
for Alaskan Natives aimed at making students aware of the dangers of inhalants
(Hillabrant et al. 2001). A program for young migrants from Morocco, included
attention for basic needs and identification and intervention with those recently
involved with inhalants. The program also included workshops on health promotion,
sports and art activities (Foundation Search 2002). As in treatment, prevention
includes teaching and helping children, teenagers and their families to build strengths,
increase cultural self-identity, develop social and emotional skills (Dell et al. 2003).
36.6 Treatment
Despite the impact of the negative effects of inhalant misuse reviewed in this
chapter, there is some evidence of the potential for recovery from deleterious
cognitive and neurological effects that occurs following abstinence from solvent
misuse, depending on the extension and duration of inhalant misuse (Dingwall and
Cairney 2011). Bowen and Cruz (2014) described evidence indicating that the
myeloneuropathy associated with chronic use of nitrous oxide improves with
inhalant discontinuation and vitamin B12 supplementation (Alt et al. 2011) and
that retinal damage produced by chronic nitrite inhalation can recover after cessa-
tion (Audo et al. 2011). Unfortunately, some negative sequelae, such as benzene-
induced leukemia or liver toxicity produced by halogenated compounds, would
appear to be more devastating. Support in the form of cognitive behavioral therapy,
attention to organic damage (e.g., hearing or sight loss), and treatment of psychi-
atric comorbid disorders when needed are important components of successful
treatment programs.
In this same review, Bowen and Cruz (2012) conclude that to date, there is no
available pharmacological therapy for treating this substance use disorder, but some
36 Inhalant Addiction 613
evidence of limited success has been found, such as using risperidone to control
paranoid psychosis in a man who had been inhaling gasoline and carburetor cleaner
daily for 5 years (Misra et al. 1999). Other authors have reported that the severity of
the symptoms of inhalant-induced psychotic disorder, which was reduced when
treated with either carbamazepine or haloperidol (Hernandez-Avila et al. 1998).
Moreover, daily administration of lamotrigine decreased craving in a 21-year-old
man with a 4-year history of inhalant misuse (Shen 2007). More investment in
research will lead to better pharmacological treatment.
Psychosocial interventions have proved effective. These include housing, pro-
grams aimed at promoting school attendance and retention, alternatives such as art
activities, counseling, and outreach for children at risk of becoming street children
(Echeverrı́a and Tavera 2007).
Good treatment models are an important factor in improving the quality of life of
those affected and reducing the costs for society; availability of services and service
utilization complete the equation. We know from the World Mental Health Survey
that the treatment gap for mental disorders including substance use disorders is
important, between 35.5 % and 50.3 % in developed countries and 76.3 % and
85.4 % in developing countries (Demyttenaere et al. 2004), and that the treatment
gap in some countries such as Mexico is similar for substance use disorders (Borges
et al. 2007) but few studies report rates of service utilization by type of substance in
subjects, with dependence on inhalants.
Perron and colleagues (2011) within the National Epidemiologic Survey on
Alcohol and Related Conditions (NESARC) reported that among those with depen-
dence (2.3 %), 66 % were using some sort of service, mainly 12-step programs
(68.5 %) followed by drug rehabilitation programs (61.2 %) and private practi-
tioners (55.6 %). A total of 15 % reported at least one barrier to receiving services
with the low-income group reporting more barriers (22.8 %). The most common
treatment barriers were related to a lack of understanding of what dependence
means; between 41 % and 43 % declared that “the individual should be strong
enough to handle it alone” or “thought the problem would get better by itself.” The
same proportion (42 %) reported that they did not want to seek help. In around
a third (28.8 %), barriers were related to stigma, “feeling too embarrassed to discuss
it with anyone.” Lack of resources was reported by one fifth of those with depen-
dence (23.2 %). This suggests the need to introduce policies to increase both
treatment and service utilization coverage.
36.7 Conclusion
Inhalants are the only drugs of abuse defined by the route of administration rather
than their attributes, specifically similar mechanism of actions or common phar-
macological effects. They are substances of abuse not included in the International
Regulations and are seldom a priority for health and social interventions or for
research funding. Inhalant products have legal uses in industry and households and
are therefore inexpensive and readily available. They are more commonly used by
young students and children and adolescents from poor sectors of society or heavy
drug users when they lack access to other substances.
The short-term effects of inhalants are similar to those of alcohol and other
central nervous system depressants and may produce impaired motor coordination,
emotional lability, and difficulty speaking. Chronic effects include neurotoxicity,
cognitive impairment, headaches, diminished sensorial abilities (loss of vision,
audition, and coordination), and an increase in mental disorders and sleep distur-
bances. Inhalant use prevention involves different strategies, including education,
skill building, environmental changes, and policy development. There is little
research focusing specifically on the different compounds that are included in this
heterogeneous group of substances classified as inhalants. Evidence-based treat-
ment for inhalant abuse and dependence is scarce. However, treatment should
include supportive psychotherapy, family and psychosocial interventions general
healh care, proper nutrition, and vitamins or nutritional supplements. The long-term
outcome of this addiction is usually progressive neurocognitive deterioration with
multiple medical complications.
References
Alcohol and Other Drugs Council of Australia (ADCA) (2010) Policy position, inhalants. http://
www.healthinfonet.ecu.edu.au/key-resources/organisations?oid¼403
Alt RS, Morrissey RP, Gang MA, Hoffman RS, Schaumburg HH (2011) Severe myeloneuropathy
from acute high-dose nitrous oxide (N2O) abuse. J Emerg Med 41(4):378–380
Audo I, El Sanharawi M, Vignal-Clermont C, Villa A, Morin A, Conrath J et al (2011) Foveal
damage in habitual poppers users. Arch Ophthalmol 129(6):703–708
Bale AS, Meacham CA, Benignus VA, Bushnell PJ, Shafer TJ (2005a) Volatile organic com-
pounds inhibit human and rat neuronal nicotinic acetylcholine receptors expressed in Xenopus
oocytes. Toxicol Appl Pharmacol 205(1):77–88
Bale AS, Tu Y, Carpenter-Hyland EP, Chandler LJ, Woodward JJ (2005b) Alterations in
glutamatergic and gabaergic ion channel activity in hippocampal neurons following exposure
to the abused inhalant toluene. Neuroscience 130(1):197–206
Balster RL, Cruz SL, Howard MO, Dell CA, Cottler LB (2009) Classification of abused inhalants.
Addiction 104(6):878–882
Basu D, Jhirwal OP, Singh J, Kumar S, Mattoo SK (2004) Inhalant abuse by adolescents: a new
challenge for Indian physicians. Indian J Med Sci 58:245–249
Beauvais F, Oetting ER (1988) Indian youth and inhalants: an update. NIDA research monograph
85: Epidemiology of inhalants abuse: an update, pp 34–48
616 T. Real et al.
Beckstead MJ, Weiner JL, Eger EI 2nd, Gong DH, Mihic SJ (2000) Glycine and gamma-
aminobutyric acid(A) receptor function is enhanced by inhaled drugs of abuse. Mol Pharmacol
57(6):1199–1205
Borges G, Wang P, Medina-Mora ME, Lara C, Chiu W (2007) Delay of first treatment of mental
and substance use disorders in Mexico. Am J Public Health 97(9):1638–1643
Bowen SE (2011) Two serious and challenging medical complications associated with volatile
substance misuse: sudden sniffing death and fetal solvent syndrome. Subst Use Misuse
46(Suppl 1):68–72
Bowen SE, Cruz SL (2014) Inhalants: addiction and toxic effects in the human. In: Madras B,
Kuhar M (eds) The effects of drug abuse on the human nervous system. Book 2 in the
neuroscience-net master reference book series, Academic Press, pp 553–574
Bowen SE, Batis JC, Paez-Martinez N, Cruz SL (2006) The last decade of solvent research in animal
models of abuse: mechanistic and behavioral studies. Neurotoxicol Teratol 28(6):636–647
Cairney S, Maruff P, Burns C, Currie B (2002) The neurobehavioural consequences of petrol
(gasoline) sniffing. Neurosci Biobehav Rev 26:81–89
Center for Addiction and Mental Health (CAMH) (2011) Drug use among Ontario students.
Detailed OSDUHS findings. Center for Addiction and Mental Health, Canada
Chalmers EM (1991) Volatile substance abuse. Med J Aust 154:269–274
Chávez J, Villatoro J, Robles L, Bustos M, Moreno M, Olivia N, Fregoso D, Gómez G, Medina-
Mora ME, Paredes A (2013) Encuesta escolar sobre adicciones en el Estado de Jalisco 2012.
Consejo Estatal contra las Adicciones de Jalisco. Instituto Nacional de Psiquiatrı́a Ramón de la
Fuente Muñiz, México
Cruz SL (2011) The latest evidence in the neuroscience of solvent misuse: an article written for
service providers. Subst Use Misuse 46(Suppl 1):62–67
Cruz SL, Bowen SE (2008) Inhalant abuse. In: Ubach MM, Mondragon-Ceballos R (eds) Neural
mechanisms of action of drugs of abuse and natural reinforcers. Research Signpost, Kerala,
pp 61–87
Cruz SL, Dominguez M (2011) Misusing volatile substances for their hallucinatory effects:
a qualitative pilot study with Mexican teenagers and a pharmacological discussion of their
hallucinations. Subst Use Misuse 46(Suppl 1):84–94
Cruz SL, Mirshahi T, Thomas B, Balster RL, Woodward JJ (1998) Effects of the abused solvent
toluene on recombinant N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors
expressed in Xenopus oocytes. J Pharmacol Exp Ther 286(1):334–340
Cruz SL, Orta-Salazar G, Gauthereau MY, Millan-Perez Pena L, Salinas-Stefanon EM (2003) Inhi-
bition of cardiac sodium currents by toluene exposure. Br J Pharmacol 140(4):653–660
d’Abbs P, MacLean S (2008) Volatile substance misuse: A review of interventions. National Drug
Strategy Monograph Series, p 159
Degenhardt L, Hall W (2012) Extent of illicit drug use and dependence, and their contribution to
the global burden of disease. Lancet 379:55–70
Del Re AM, Dopico AM, Woodward JJ (2006) Effects of the abused inhalant toluene on ethanol-
sensitive potassium channels expressed in oocytes. Brain Res 1087(1):75–82
Dell C, Ogborne A, Begin P (2003) Youth residential solvent treatment program design: an
examination of the role of program length and length of client stay. Canadian Center on
Substance Abuse, Ottawa
Demyttenaere K, Bruffaerts R, Posada-Villa J, Gasquet I, Kovess V, Lepine J et al (2004)
Prevalence, severity and unmet need for treatment of mental disorders in the
World Health Organization World Mental Health (WMH) surveys. J Am Med Assoc
291:2581–2590
Dingwall KM, Cairney S (2011) Recovery from central nervous system changes following volatile
substance misuse. Subst Use Misuse 46(Suppl 1):73–83
Echeverrı́a C, Tavera S (2007) Matlapa. Redes de atención para la infancia en situación de calle.
Instituto Nacional de Desarrollo Social, México
36 Inhalant Addiction 617
Filley CM, Halliday W, Kleinschmidt-DeMasters BK (2004) The effects of toluene on the central
nervous system. J Neuropathol Exp Neurol 63(1):1–12
Forster LM, Tannhauser M, Barros HM (1996) Drug use among street children in southern Brazil.
Drug Alcohol Depend 43:57–62
Fundación SEARCH (2002) Guı́a para profesionales sobre abuso de sustancias volátiles.
Fundación Search. Comunidad Europeas, 2002. http://www.lwl.org/ks-download/downloads/
searchII/Solvents-Guide_span.pdf. Accessed 22 Apr 2013
Gutiérrez R, Vega L, Medina-Mora ME (2007) La infancia “callejera” en México. In:
Echeverrı́a C, Tavera S (eds) Matlapa. Redes de atención para la infancia en situación de
calle, 1st edn. Instituto Nacional de Desarrollo Social, México, pp 17–34
Hannigan JH, Bowen SE (2010) Reproductive toxicology and teratology of abused toluene. Syst
Biol Reprod Med 56(2):184–200
Hernandez-Avila CA, Ortega-Soto HA, Jasso A, Hasfura-Buenaga CA, Kranzler HR (1998) Treat-
ment of inhalant-induced psychotic disorder with carbamazepine versus haloperidol. Psychiatr
Serv 49(6):812–815
Hillabrant W, Woodis P, Navratil C, McKenzie J, Rhoades M (2001) Inhalant abuse in Indian
country. Indian Health Service. Support Services International, Maryland, US
Johnston LD, O’Malley PM, Bachman JG (2003) Monitoring the future national survey results on
drug use, 1975–2002, vol I, Secondary School Students (NIH Publication no. 03-5375).
National Institute on Drug Abuse, Bethesda
Johnston L, O’Malley P, Bachman J, Shulenberg J (2014) Monitoring the future. National
results on drug use, 1975–2013, vol I, Secondary school students. Ann Arbor: Institute for
Social Research, The University of Michigan
Lampinen TM, Mattheis K, Chan K, Hogg RS (2007) Nitrite inhalant use among young gay and
bisexual men in Vancouver during a period of increasing HIV incidence. BMC Public Health
15:7–35
Leal H, Mejı́a L, Gómez I, Salinas de Valle O (1977) Estudio naturalı́stico sobre el fenómeno del
consumo de inhalantes en niños de la Ciudad de México. In: Contreras C (ed) Inhalación
Voluntaria de Disolventes Industriales. Trillas, México, pp 442–459
Lin RJ, Chen HF, Chang YC, Su JJ (2011) Subacute combined degeneration caused by nitrous
oxide intoxication: case reports. Acta Neurol Taiwan 20(2):129–137
Lubman D, Y€ucel M, Lawrence AJ (2008) Inhalant abuse among adolescents: neurobiological
considerations. Br J Pharmacol 154(2):316–326
MacLean S (2007) Global selves: marginalised young people and aesthetic reflexivity in inhalant
drug use. J Youth Stud 10(4):399–418
Medina-Mora ME, Berenzon S (1995) Epidemiology of inhalant abuse in Mexico. NIDA Res
Monogr 148:136–174
Medina-Mora ME, Real T (2008) Epidemiology of inhalant use. Curr Opin Psychiatry 21:247–251
Medina-Mora ME, Gutiérrez R, Vega L (1997) What happened to street kids? An analysis of the
Mexican experience. Subst Use Misuse 32(3):293–316
Medina-Mora ME, Villatoro J, Fleiz C (1999) “Estudio de niñas, niños y adolescentes trabajadores
en 100 ciudades”. En: Resultados definitivos. Informe ejecutivo. En: ¡Yo también cuento!.
Editores: UNICEF, DIF, PNUFID, ISBN: 968-826-000-2, print run: 1000, pp 11–44, México
Medina-Mora ME, Villatoro JA, Fleiz C, Domı́nguez M, Cruz SL (2014) Challenges to neurosci-
ence and public policy derived from new trends and patterns of inhalant misuse. J Drug
Alcohol Res 3:8. doi:10.4303/jdar/235842
Mesquita AM, de Andrade AG, Anthony JC (1988) Use of the inhalant lança by Brazilian medical
students. Subst Use Misuse 33(8):1667–1680
Misra LK, Kofoed L, Fuller W (1999) Treatment of inhalant abuse with risperidone. J Clin
Psychiatry 60(9):620
National Inhalant Prevention Coalition (1997) News briefs: CADCA announces national leader-
ship forum. Press Conference Marks New Inhalant PSA & Survey
618 T. Real et al.
National Institute of Drug Abuse (2005) Inhalant abuse among children and adolescents: consul-
tation on building an international research
National Institute of Drug Abuse (2012) The science of drug abuse http://www.drugabuse.gov/
drugs-abuse/inhalants. Accessed 2 Apr 2013
Oetting ER, Edwards RW, Beauvais F (1988) Social and psychological factors underlying inhalant
abuse. National Institute on Drug Abuse, Rockville
O’Malley PA (2012) This pretty balloon might kill you: the rise of inhalant abuse and resources for
practice. Clin Nurse Spec 26(4):200–202. doi:10.1097/NUR.0b013e31825d8f86
Organización de Estados Americanos (2011) Informe del Uso de Drogas en las Américas.
Organización de Estados Americanos, Washington, DC
Páez-Martı́nez N, Flores-Serrano Z, Ortiz-Lopez L, Ramirez-Rodriguez G (2013) Environmental
enrichment increases doublecortin-associated new neurons and decreases neuronal death
without modifying anxiety-like behavior in mice chronically exposed to toluene. Behav
Brain Res 256:432–440
Pagare D, Meena GS, Singh MM, Sahu R (2004) Risk factors of substance use among street
children from Delhi. Indian Pediatr 41:221–225
Perron B, Mowbray O, Bier S, Vaughn M, Krentzman A, Howard M (2011) Service use and
treatment barriers among inhalant users. J Psychoactive Drugs 43(1):69–75
Remington G, Hoffman BF (1984) Gas sniffing as a form of substance abuse. Can J Psychiatry
29(1):31–35
Rodgers D (1999) Youth gangs and violence in Latin America and the Caribbean, a literature
survey. LCR sustainable development working paper no.4. World Bank, Washington, DC
Roy E, Leclerc P, Cédras L, Weber A, Claessens CH, Boivin J (2003) HIV incidence among street
youth in Montreal, Canada. AIDS 17:1071–1075
Sanchez Z, Noto A, Anthony J (2012) Social rank and inhalant drug use: the case of lança perfume
use in São Paulo, Brazil. Drug Alcohol Depend. http://dx.doi.org/10.1016/j.
drugalcdep.2012.12.001
Secretarı́a de Salud (2013) Sistema de Vigilancia Epidemiológica de las Adicciones (SISVEA).
Informe 2011. Secretarı́a de Salud. Subsecretarı́a de Prevención y Promoción de la Salud.
Dirección General de Epidemiologı́a. México
Secretarı́a de Salud. Comisión Nacional contra las Adicciones. Instituto Nacional de Psiquiatrı́a
Ramón de la Fuente. Instituto Nacional de Salud Pública (2012) Encuesta Nacional de
Adicciones 2011
Shafer TJ, Bushnell PJ, Benignus VA, Woodward JJ (2005) Perturbation of voltage-sensitive Ca2+
channel function by volatile organic solvents. J Pharmacol Exp Ther 315(3):1109–1118
Sharp CW, Rosenber N, Beauvais F (2008) Inhalant- related disorders. In: Tasman A, Kay J,
Lieberman JA, First MB, Maj M (eds) Psychiatry, 3rd edn. Wiley, Chichester, UK,
pp 1127–1148
Shen YC (2007) Treatment of inhalant dependence with lamotrigine. Prog Neuropsychopharmacol
Biol Psychiatry 31(3):769–771
Spiller HA (2004) Epidemiology of volatile substance abuse (VSA) cases reported to US poison
centers. Am J Drug Alcohol Abuse 30:155–165
Storr CL, Chen CY, Anthony JC (2004) Unequal opportunity: neighborhood disadvantage and the
chance to buy illegal drugs. J Epidemiol Community Health 58:231–237
Takagi M, Y€ ucel M, Lubman D (2010) The dark side of sniffing: paint colour affects intoxication
experiences among adolescent inhalant users. Drug Alcohol Res 29:452–455
The European School Survey Project on Alcohol and Other Drugs (2007) The 2007 ESPAD report.
Substance use among students in 35 European countries. The Swedish Council for Information
on Alcohol and other Drugs (CAN). The European Monitoring Centre for Drugs and Drug
Addiction (EMCDDA). Council of Europe, Co-operation Group to Combat Drug Abuse and
Illicit Trafficking in Drugs (Pompidou Group)
Trotter R, Rolf J, Baldwin L (1997) Cultural models for inhalant abuse among Navajo youth.
Drugs Soc 10(1–2):39–59
36 Inhalant Addiction 619
United Nations Office on Drugs and Crime (2008) Illicit drug trends in Asia. United Nations,
Uzbekistan Republic
United Nations Office on Drugs and Crime (2010) Informe Subregional sobre Uso de Drogas en
Población Escolarizada. Segundo Estudio Conjunto. Información para el Diseño de las
Estrategias Nacionales y Regionales sobre la Problemática de Drogas en Jóvenes.
Organización de Estados Americanos. Comisión Interamericana para el Control del Abuso
de Drogas
Villatoro J, Moreno M, Olivia N, Fregoso D, Bustos M, Fleiz C, Mujica R, Mendoza MA, López
MA, Medina-Mora ME (2013) Consumo de Alcohol, Tabaco y otras Drogas en la Ciudad de
México. Medición 2012. Instituto Nacional de Psiquiatrı́a Ramón de la Fuente. Instituto para la
Atención y la Prevención de las Adicciones, Administración Federal de los Servicios
Educativos para el Distrito Federal, México
Villatoro J, Medina-Mora ME, Fleiz C, Moreno M, Oliva R, Bustos A, Fregoso D, Gutiérrez ML,
Amador N (2012) El consumo de drogas en México: Resultados de la Encuesta Nacional de
Adicciones, 2011. Salud Ment 34:447–457
Virginia Department of Education (2007) Inhalant abuse prevention: staff education and student
curriculum. Division of Special Education and Student Services, Richmond
White V, Hayman J (2004) Australian secondary students’ use of over-the-counter and illicit
substances in 2002, National drug strategy monograph series no.56. Australian Government
Department of Health and Ageing, Canberra
Williams J, Storck, M, Committee on Substance Abuse and Committee on Native American Child
Health Pediatrics (2007) 119-10009 doi: 10.1542/peds.2007-0470. http://pediatrics.
aappublications.org/content/119/5/1009.full.html. Accessed 29 Mar 2013
World Bank (2011) Crimen y Violencia en Centroamérica Un Desafı́o para el Desarrollo. Banco
Mundial, Washington, DC. www.bancomundial.org.lac
Young M, Saewyc E, Boak A, Jahrig J, Anderson B, Doiron Y, Taylor S, Pica L, Laprise P,
Clark H (2011) Cross Canada report on student alcohol and drug use: technical report Ottawa.
Canadian Centre on Substance Abuse
Yucel M, Takagi M, Walterfang M, Lubman DI (2008) Toluene misuse and long-term harms:
a systematic review of the neuropsychological and neuroimaging literature. Neurosci Biobehav
Rev 32(5):910–926
Zakocs RC, Edwards EM (2006) What explains community coalition effectiveness?: A review of
the literature. Am J Prev Med 30(4):351–361
Treatment of Anabolic-Androgenic
Steroid Related Disorders 37
Harrison G. Pope Jr. and Gen Kanayama
Contents
37.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 622
37.2 Identification and Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 624
37.2.1 Identification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 624
37.2.2 History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 624
37.2.3 Physical Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 625
37.2.4 Mental Status Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 626
37.2.5 Laboratory Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 626
37.3 AAS Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 627
37.4 AAS-Induced Hypomania and Mania . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 630
37.5 AAS-Withdrawal Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 631
37.6 Body-Image Disorders Associated with AAS Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 631
37.7 Co-occurring Substance Use Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 632
37.8 Medical Conditions Associated with AAS Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 633
37.9 AAS in Forensic Situations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 633
37.10 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 634
37.10.1 Key Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 634
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 635
Abstract
The family of anabolic-androgenic steroids (AAS) comprises the male hormone
testosterone and its many synthetic relatives. Although elite athletes have used
AAS for muscle and performance gains since the 1950s, widespread AAS use
did not emerge into the general population until the 1980s. Thus, AAS abuse is
the youngest of the world’s major forms of substance abuse, with most AAS
users still below age 50. There are now some tens of millions of AAS users
worldwide, primarily male and primarily in Western societies. Contrary to
common belief, most AAS users do not engage in competitive athletics, but
simply want to become leaner and more muscular. AAS users may occasionally
experience serious psychiatric effects, including hypomania or mania during
AAS exposure and depression during AAS withdrawal. Long-term medical
effects include especially cardiomyopathy, atherosclerotic disease, and
prolonged suppression of the hypothalamic-pituitary-gonadal axis. About 30 %
of AAS users develop dependence syndromes, likely caused by a confluence of
psychosocial factors (e.g., using AAS to “self-treat” muscle dysmorphia), neu-
roendocrine factors (e.g., repeatedly resuming AAS use to self-treat
hypogonadism during AAS withdrawal), and hedonic effects. A hedonic com-
ponent is supported by evidence that male hamsters will self-administer testos-
terone to the point of death. Treatment of AAS dependence remains largely
empirical, in part because most AAS abusers are still too young to have
developed adverse effects. Thus, few have desired or sought treatment. This
situation may change in future decades, however, as growing numbers of aging
AAS users enter the age of risk for long-term adverse effects.
37.1 Introduction
Although AAS pose important medical and psychiatric risks (see below), AAS
users rarely seek treatment. Indeed, one recent study reported that 56 % of illicit
AAS users had never disclosed their AAS use to any physician that they had seen
(Pope et al. 2004). There are several reasons for this phenomenon. First, many AAS
users perceive their use of AAS to be a positive and healthy activity, when combined
with intensive exercise and optimal diet as part of the “bodybuilding lifestyle.”
Commercial and societal forces are partly responsible for this misperception of
AAS: muscular male bodies are portrayed as an ideal in advertising, magazines,
television, and movies. Even children’s action toys, such as “G.I. Joe,” have grown
from ordinary-looking men in the 1960s and 1970s to muscle-bound specimens by
the 1990s. Advertisers sometimes tout their products as “on steroids,” but they
would never claim that their products were “on marijuana” or “on cocaine.” Given
this societal climate, it is not surprising that AAS users rarely perceive their drug use
as a psychiatric disorder requiring treatment (Kanayama et al. 2010b).
Second, AAS differ from conventional drugs of abuse. Most drugs of abuse
described in this volume deliver a prompt “reward” of intoxication immediately
after ingestion. However, AAS produce little or no reward of intoxication; instead,
the user is seeking a long-term reward in the form of a more muscular body, athletic
success, or admiration from peers or potential sexual partners. Thus, conventional
methods of treating substance abuse may be inappropriate unless modified specif-
ically for AAS users (Brower 2009).
Third, AAS users often have little respect for doctors. Internet sites for illicit
AAS users are replete with derogatory remarks about health professionals. AAS
users often regard physicians as “geeks” or “pencil necks” who have no under-
standing of the bodybuilding world. In one recent study, for example, 40 % of AAS
users reported that they trusted information about AAS from their drug dealers at
least as much as information from any physician that they had seen (Pope
et al. 2004). There is some basis for this distrust: for decades, many medical
professionals asserted that AAS were ineffective for gaining muscle mass. This
claim, based on two decades of seriously flawed studies, caused doctors to lose their
credibility among many athletes (Kanayama et al. 2008). Now, most professionals
finally concede that AAS are effective for gaining muscle mass, but still remain
largely uninformed about the extent and nature of the AAS-using subculture.
Several recent papers have stressed that clinicians should attempt to become
more familiar with AAS and AAS-associated syndromes (Kutscher et al. 2002;
Melnik 2009).
Given the above considerations, it is understandable that AAS users rarely
request treatment to stop using these drugs. Nevertheless, there are a number of
specific situations that bring AAS users to the attention of clinicians. These include
(1) AAS-dependence syndromes, (2) hypomanic and manic syndromes during
AAS exposure, (3) syndromes of depression and anxiety associated with AAS
withdrawal, (4) body-image disorders associated with AAS use, (5) co-occurring
substance use disorders, (6) medical conditions associated with long-term
AAS use, and (7) forensic situations, such as cases of AAS-induced violence
or criminality. In the sections below, we begin with a general discussion of
624 H.G. Pope and G. Kanayama
the initial identification and assessment of AAS users and continue with each of the
seven clinical issues enumerated above.
37.2.1 Identification
AAS use is one of the few types of substance use where a diagnosis is often
suggested simply by looking at the patient as he walks through the door. As we
have described elsewhere (Kouri et al. 1995), there is a fairly sharp upper limit of
muscularity that can be achieved by a lean individual without the help of drugs. We
have published a formula to calculate muscularity, expressed as the “fat-free mass
index” (FFMI), which clinicians can apply if they know the height, weight, and
approximate percentage of body fat of the patient (Kouri et al. 1995). Men who
have low body fat and display an FFMI of greater than approximately 26 kg/m2 are
almost certainly using drugs even if they deny it. Clinicians who suspect AAS use in
any patient should follow several guidelines to take a specific history.
37.2.2 History
The clinician may lead into the topic of AAS by asking about athletic or fitness-
related activities. Young men who lift weights regularly are at greatest risk to use
AAS (Brower 2009). Other lead-in questions include the use of over-the-counter
and mail-order dietary supplements such as vitamins, minerals, amino acids, and
creatine. The use of such legal performance- or image-enhancing substances is
commonly associated with use of illicit substances such as AAS (Hildebrandt
et al. 2011). Finally, has the patient ever tried AAS or thought about using them?
Patients thinking about AAS use are good candidates for prevention. Why is the
patient interested in using, and what has prevented the patient from using to date? In
addressing these questions, it is particularly critical for the clinician to be nonjudg-
mental while still discouraging use.
For patients who admit having tried AAS, both the perceived benefits and any
adverse consequences of use are important to determine. The dates of first and last
use, the names and doses of AAS used, sources of drugs, and routes of administra-
tion should be ascertained. Patients who inject AAS should be asked about needle
sharing, although fortunately this practice now appears to be rare among AAS users
(Ip et al. 2011). Sources of drugs include prescriptions, diversion from the legal
market (including the veterinary market), and the illicit market. Unlike many other
drugs of abuse such as heroin and cocaine, AAS are legally available without
a prescription in many countries outside of the United States. Thus, potential
AAS users can easily travel to nearby countries and also find Internet sites offering
to sell AAS from overseas (Brennan et al. 2013). Drugs purchased through these
sites, and then shipped by mail into the United States, often reach users without
37 Treatment of Anabolic-Androgenic Steroid Related Disorders 625
being intercepted. Patients and clinicians should remember that drugs obtained
from the illicit domestic market and from overseas sources are frequently counter-
feit, adulterated, falsely labeled, and sometimes non-sterile. Thus, the user does not
necessarily know what and how much he is taking.
Inquiry into the patterns of use is also important. Illicit AAS users typically
combine (“stack”) multiple types of AAS, including both oral and injected intra-
muscular forms, in order to achieve doses that are 10–100 times the amounts
ordinarily prescribed for therapeutic indications (Ip et al. 2011; Kanayama
et al. 2010b). Such doses may result in total AAS serum concentrations that may
exceed 50 times natural male physiologic concentrations of testosterone
(Kanayama and Pope 2012). AAS are usually taken in “cycles” (courses) of
4–16 weeks or more, often characterized by taking small doses at the beginning,
building to large doses and combinations in the middle, and tapering doses at the
end – a pattern referred to as a “pyramid.” The clinician gains useful information
when exploring the role of cycling with an individual AAS user. Does the patient
cycle off AAS to avoid testing positive on drug screening? Does the patient cycle
off AAS to give his body a rest, allowing his endogenous hormonal system a chance
to regain normal functioning? Does the patient experience depression or other
withdrawal symptoms during “off periods”? Dependent users may eliminate
cycling altogether in favor of prolonged, continuous use in order to avoid with-
drawal symptoms (see below).
Finally, a history of other drug abuse should be obtained. Users often combine other
drugs with AAS to augment performance- and image-enhancing effects (e.g., human
growth hormone, insulin-like growth factor I [IGF-I], human chorionic gonadotropin,
clenbuterol, thyroid hormones, insulin, etc.), to reduce undesirable side effects such
as gynecomastia (e.g., tamoxifen, letrozole, anastrozole), and to mask urine testing
(e.g., probenecid, diuretics) (Hildebrandt et al. 2011; Ip et al. 2011). Also, in contra-
diction to the image of the healthy bodybuilding lifestyle, a large portion of AAS users
display a history (and often an extensive history) of other forms of classical substance
abuse or dependence (Dodge and Hoagland 2011; Garevik and Rane 2010; Kanayama
and Pope 2012; Skarberg et al. 2009).
The clinician should assess the patient’s appearance for excessive muscularity as
described above, sometimes disguised by oversized clothes, especially in patients
with muscle dysmorphia who become preoccupied that they do not look big enough
and hence wish to hide their bodies (Rohman 2009). The patient’s cooperation may
vary depending on his defensiveness or denial of AAS use. Speech and sensorium
are generally normal. However, if the patient is experiencing hypomanic or manic
symptoms from current AAS use, he may display irritability, agitation, and possibly
grandiose beliefs. Patients experiencing depression from AAS withdrawal may
exhibit depressed mood, dysphoria, anxiety, psychomotor retardation, and possible
suicidal ideation.
Recent studies have increasingly documented that AAS can create a dependence
syndrome, characterized by long-term use of these drugs, often for many years, and
628 H.G. Pope and G. Kanayama
frequently in spite of adverse effects (Kanayama et al. 2009). AAS dependence may
be part of a larger pattern of dependence on appearance- and performance-
enhancing drugs, involving other agents in addition to AAS, such as human growth
hormone, insulin, and thermogenic agents such as clenbuterol, amphetamines, and
thyroid hormones (Hildebrandt et al. 2011). As many as 30 % of men who use AAS
may eventually develop such dependence syndromes (Kanayama et al. 2009), and
thus there are likely some millions of cases worldwide.
We have suggested that AAS dependence may arise via three different path-
ways, any or all of which may contribute to the syndrome in a given individual
(Fig. 37.1) (Kanayama et al. 2010a). First, there appears to be a “body-image”
pathway, in which the individual becomes preoccupied that he will lose muscle size
when he stops taking AAS and hence becomes reluctant to discontinue these drugs
even for a short interval. Treatment for such symptoms, especially the extreme case
of “muscle dysmorphia,” can be performed with cognitive behavioral therapies or
selective serotonin reuptake inhibitors (SSRIs). We discuss muscle dysmorphia in
more detail below.
Second, use of exogenous AAS leads to suppression of the hypothalamic-
pituitary-testicular (HPT) axis (de Souza and Hallak 2011; Tan and Scally 2009).
Thus, when a man discontinues a course of AAS, especially if that course has been
prolonged, he will likely experience hypogonadism, which in some cases may
persist for months or even years after AAS are discontinued. Hypogonadism may
be associated with loss of sex drive, fatigue, and occasionally serious depression;
these symptoms may prompt users to quickly resume AAS in order to make the
dysphoric feelings go away. This pathway to AAS dependence was first postulated
more than 20 years ago (Kashkin and Kleber 1989) and has been increasingly
acknowledged in recent years. Indeed, it now appears that protracted severe
hypogonadism may be much more common in long-term AAS users than previ-
ously suspected and that indeed some users may develop irreversible
hypogonadism, possibly attributable to direct toxic effects of long-term AAS
exposure on the testis or on other components of the HPT axis (de Souza and
Hallak 2011; Kanayama and Pope 2012). Therefore, in individuals displaying
AAS-withdrawal hypogonadism and expressing a genuine desire to not resume
AAS, it is desirable to institute aggressive endocrinological treatment with agents
that stimulate the HPT axis in order to “jumpstart” natural endogenous testosterone
production and thus reduce the individual’s desire to resume illicit exogenous AAS
(Tan and Scally 2009). Such treatment may include clomiphene to stimulate
pituitary secretion of luteinizing hormone and follicle-stimulating hormone,
together with human chorionic gonadotropin (HCG) to stimulate testicular produc-
tion of testosterone and spermatozoa. Initially, the patient may also require temporary
exogenous testosterone administration, typically using one of the several commercially
available testosterone gels, in order to maintain adequate testosterone levels while
waiting for clomiphene and/or HCG to stimulate resumption of endogenous function.
In a typical treatment course of this nature, one would first taper off testosterone, then
subsequently discontinue HCG, and then finally taper clomiphene, all while regularly
monitoring testosterone levels (Tan and Scally 2009). Individuals still unable to
37
Treatment of Anabolic-Androgenic Steroid Related Disorders
Fig. 37.1 Three potential pathways for the development of anabolic-androgenic steroid dependence and consequent possible treatment strategies (Adapted
from Kanayama et al. 2010a)
629
630 H.G. Pope and G. Kanayama
maintain adequate testosterone levels on their own, even after several months of
neuroendocrine treatment, may conceivably represent cases of irreversible
hypogonadism attributable to a direct toxic effect of AAS and hence may require
testosterone replacement indefinitely. Most psychiatric clinicians will likely wish to
seek endocrinological consultation for these interventions.
Third, AAS may induce a dependence syndrome via a hedonic pathway, pre-
sumably mediated by receptor sites on cell membranes, rather than by classical
anabolic or androgenic effects that are genomically mediated. Persuasive evidence
for such a hedonic pathway arises from animal studies, which have shown that rats
and mice display conditioned place preference for AAS and that male hamsters will
self-administer AAS to the point of death (Wood 2008). Interestingly, AAS self-
administration in hamsters can be blocked by administration of the opioid antago-
nist naltrexone (Wood 2008). A number of other clinical and preclinical studies
have pointed to interactions between AAS and endogenous as well as exogenous
opioids, thus suggesting that the hedonic pathway to AAS dependence may involve
opioidergic mechanisms (Nyberg and Hallberg 2012; Wood 2008). One implication
of this research is that human AAS dependence might respond, at least in part, to
treatments empirically validated for opioid dependence, such as motivational
therapies, contingency management, behavioral couples therapy, or behavioral
family counseling. In the management of opioid dependence, some of these treat-
ments have been successfully used in conjunction with naltrexone – raising the
possibility that the addition of naltrexone might be effective in AAS dependence as
well. However, these modalities have not yet been systematically tested in treat-
ment of AAS dependence. We refer the reader to the full article from which
Fig. 37.1 is taken (Kanayama et al. 2010a) for a detailed discussion of each of
these three possible pathways to AAS dependence, together with details of potential
treatment strategies.
A substantial literature over the last 20 years has demonstrated that AAS produce
hypomanic or manic syndromes in some individuals, sometimes accompanied by
aggressive or violent behavior, and very rarely psychotic symptoms (Hall
et al. 2005; Pope and Katz 2003). These effects are rare in individuals taking the
equivalent of 300 mg of testosterone per week or less, but they appear to become
progressively more common with higher doses, especially above 1,000 mg per
week (Pope and Katz 2003). These syndromes were initially noted in field studies of
illicit AAS users, and some investigators questioned whether the effects were
actually due to AAS themselves, as opposed to expectational factors, personality
variables, or subcultural influences. However, several studies have now demon-
strated that such syndromes can develop even in normal volunteers taking
supraphysiologic doses of AAS under placebo-controlled double-blind laboratory
conditions (Pope and Katz 2003). Therefore, the mood-altering effects of AAS
almost certainly have a biological basis, even though they can undoubtedly be
37 Treatment of Anabolic-Androgenic Steroid Related Disorders 631
AAS users may occasionally come to clinical attention through the courts as a result
of violent or criminal behavior. Specifically, a number of papers have described
individuals, often with no prior history of psychiatric disorder, violence, or criminal
behavior, who became uncharacteristically violent, and sometimes committed
murder while intoxicated with AAS (Hall et al. 2005; Kanayama et al. 2010b;
634 H.G. Pope and G. Kanayama
Pope and Katz 2003). In such cases, AAS are not necessarily the proximal trigger to
violence; the direction of causality may sometimes be reversed, in that some
individuals may deliberately ingest AAS in preparation for committing a crime
(Lundholm et al. 2010). A recent example of such a case was Anders Breivik,
convicted of killing 77 Norwegian civilians in the summer of 2011. In his extensive
manifesto, Breivik details his systematic use of AAS, which he ordered through the
Internet, in preparation for his terrorist attacks (Kanayama and Pope 2012).
In some cases of criminal violence, the role of AAS use may be missed because
the possibility is never considered. However, AAS use should be suspected in any
usually muscular man apprehended for violent behavior, especially if it appears
that this violence is not characteristic of his usual personality. The clinician’s
index of suspicion should be particularly raised if such a man rapidly develops
vegetative symptoms of depression after being incarcerated, but then improves
a few weeks or months later. This pattern may indicate AAS withdrawal, precip-
itated by the abrupt discontinuation of AAS following incarceration, with
a gradual remission of depressive symptoms as suppressed hypothalamic-
pituitary-testicular function gradually returns to normal. Of course, this pattern
of biological depression must be distinguished from the situational depression
associated with incarceration itself.
In cases where AAS use is acknowledged by the defendant and appears to have
been a clear precipitant of criminal behavior, forensic clinicians may be asked to
offer an opinion that the defendant exhibited “involuntary intoxication” or “dimin-
ished capacity” from AAS. The legal aspects of this defense are beyond the scope of
this chapter. However, it seems clear that if an individual is released and placed on
probation after a crime believed associated with AAS, it may be wise to require
random, unannounced, observed urine tests for AAS to ensure that he does not
resume these drugs.
37.10 Conclusion
Of the various major forms of substance abuse and dependence described in this
volume, AAS abuse and dependence may be the least familiar to the average clinician.
However, the frequency of AAS abuse and dependence, together with the various
medical and psychiatric syndromes associated with it, is now beginning to be better
recognized. Greater awareness of this problem among clinicians may lead to the
detection of many more cases, and a better understanding of how best to treat them.
• AAS users rarely see their drug use as pathological, rarely seek treatment, and
may have contempt for physicians.
• AAS users often display a history of abuse of or dependence upon other drugs,
especially opioids.
• Some individuals experience hypomanic or manic symptoms during AAS expo-
sure and depressive symptoms during AAS withdrawal.
• AAS may produce a well-documented dependence syndrome, for which an
animal model exists. This dependence syndrome may arise through several
pathways, including a “body-image” pathway, a neuroendocrine pathway, and
a hedonic pathway, each of which may dictate specific treatment interventions.
References
Brennan BP, Kanayama G, Pope HG (2013) Performance-enhancing drugs on the web: a growing
public-health issue. Am J Addict 22:158–161
Brower KJ (2009) Anabolic steroid abuse and dependence in clinical practice. Phys Sportsmed
37:1–11
de Souza GL, Hallak J (2011) Anabolic steroids and male infertility: a comprehensive review. BJU
Int 108:1860–1865
Dickerman RD, Pertusi RM, Zachariah NY et al (1999) Anabolic steroid-induced hepatotoxicity:
is it overstated? Clin J Sport Med 9:34–39
Dodge T, Hoagland MF (2011) The use of anabolic androgenic steroids and polypharmacy:
a review of the literature. Drug Alcohol Depend 114:100–109
Garevik N, Rane A (2010) Dual use of anabolic-androgenic steroids and narcotics in Sweden.
Drug Alcohol Depend 109:144–146
Hall RC, Hall RC, Chapman MJ (2005) Psychiatric complications of anabolic steroid abuse.
Psychosomatics 46:285–290
Hildebrandt T, Lai JK, Langenbucher JW et al (2011) The diagnostic dilemma of pathological
appearance and performance enhancing drug use. Drug Alcohol Depend 114:1–11
Ip EJ, Barnett MJ, Tenerowicz MJ et al (2011) The Anabolic 500 survey: characteristics of male
users versus nonusers of anabolic-androgenic steroids for strength training. Pharmacotherapy
31:757–766
Kanayama G, Pope HG (2012) Illicit use of androgens and other hormones: recent advances. Curr
Opin Endocrinol Diabetes Obes 19:211–219
Kanayama G, Hudson JI, Pope HG (2008) Long-term psychiatric and medical consequences of
anabolic-androgenic steroid abuse: a looming public health concern? Drug Alcohol Depend
98:1–12
Kanayama G, Brower KJ, Wood RI et al (2009) Anabolic-androgenic steroid dependence: an
emerging disorder. Addiction 104:1966–1978
Kanayama G, Brower KJ, Wood RI et al (2010a) Treatment of anabolic-androgenic steroid
dependence: emerging evidence and its implications. Drug Alcohol Depend 109:6–13
Kanayama G, Hudson JI, Pope HG (2010b) Illicit anabolic-androgenic steroid use. Horm Behav
58:111–121
Kanayama G, Boynes M, Hudson JI et al (2007) Anabolic steroid abuse among teenage girls: an
illusory problem? Drug Alcohol Depend 88:156–162
Kanayama G, Kean J, Hudson JI et al. (2013) Cognitive deficits in long-term anabolic-androgenic
steroid users. Drug Alcohol Depend 130:208–214
Kashkin KB, Kleber HD (1989) Hooked on hormones? An anabolic steroid addiction hypothesis.
JAMA 262:3166–3170
636 H.G. Pope and G. Kanayama
Kouri EM, Pope HG Jr, Katz DL et al (1995) Fat-free mass index in users and nonusers of
anabolic-androgenic steroids. Clin J Sport Med 5:223–228
Kutscher EC, Lund BC, Perry PJ (2002) Anabolic steroids: a review for the clinician. Sports Med
32:285–296
Lundholm L, Kall K, Wallin S et al (2010) Use of anabolic androgenic steroids in substance
abusers arrested for crime. Drug Alcohol Depend 111:222–226
Malone DA Jr, Dimeff RJ (1992) The use of fluoxetine in depression associated with anabolic
steroid withdrawal: a case series. J Clin Psychiatry 53:130–132
Melnik BC (2009) Androgen abuse in the community. Curr Opin Endocrinol Diabetes Obes
16:218–223
Nyberg F, Hallberg M (2012) Interactions between opioids and anabolic androgenic steroids:
implications for the development of addictive behavior. Int Rev Neurobiol 102:189–206
Phillips KA, Didie ER, Feusner J et al (2008) Body dysmorphic disorder: treating an
underrecognized disorder. Am J Psychiatry 165:1111–1118
Pope HG, Katz DL (2003) Psychiatric effects of exogenous anabolic-androgenic steroids. In:
Wolkowitz OM, Rothschild AJ (eds) Psychoneuroendocrinology: the scientific basis of clinical
practice. American Psychiatric Press, Washington, DC, pp 331–358
Pope HG, Kanayama G, Ionescu-Pioggia M et al (2004) Anabolic steroid users’ attitudes towards
physicians. Addiction 99:1189–1194
Rohman L (2009) The relationship between anabolic androgenic steroids and muscle dysmorphia:
a review. Eat Disord 17:187–199
Skarberg K, Nyberg F, Engstrom I (2009) Multisubstance use as a feature of addiction to anabolic-
androgenic steroids. Eur Addict Res 15:99–106
Tan RS, Scally MC (2009) Anabolic steroid-induced hypogonadism – towards a unified hypothesis
of anabolic steroid action. Med Hypotheses 72:723–728
Wood RI (2008) Anabolic-androgenic steroid dependence? Insights from animals and humans.
Front Neuroendocrinol 29:490–506
Prescription Drug Abuse: Risks
and Prevention 38
Jørgen G. Bramness
Contents
38.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 638
38.2 Prescription Drugs of Abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 640
38.2.1 Sedative Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 640
38.2.2 Analgesics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 643
38.2.3 Central Stimulants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 644
38.2.4 Other Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 645
38.3 Terminology and Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 646
38.3.1 Pseudo Therapeutic Long-Term Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 647
38.3.2 Self-Medicating Pain/Anxiety/Insomnia Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 647
38.3.3 True Prescription Drug Abuser . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 647
38.3.4 Polydrug Abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 647
38.4 Epidemiology of Prescription Drug Abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 648
38.4.1 Monitoring Patients or Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 650
38.4.2 Monitoring Sources of Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 651
38.5 Strategies for Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 653
38.6 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 655
38.6.1 Tackling the Drug-Seeking Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 655
38.6.2 Minimal Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 656
38.6.3 Tapering in the More Difficult Cases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 656
38.6.4 Tapering the Patients with Benzodiazepine Dependence . . . . . . . . . . . . . . . . . . . . . 657
38.6.5 Tapering/Detoxifying the Patients with Opioid Dependency . . . . . . . . . . . . . . . . . 657
38.6.6 Intoxications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 657
38.7 International Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 658
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 658
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 661
J.G. Bramness
Norwegian Centre for Addiction Research, University of Oslo, Oslo, Norway
e-mail: [email protected]
Abstract
Abuse of and dependence on prescription drugs is an increasing problem and
is closely related to the increasing use of prescription drugs worldwide. The
problem of prescription drug abuse includes both weak and strong opioids for
pain management; sedating drugs like benzodiazepines, barbiturates, and newer
hypnotics; and stimulant drugs used for the treatment of narcolepsy and
ADHD. Several other prescription drugs also have the potential for abuse. In
this chapter prescription drug abuse is set in an historical context. The concept of
prescription drug abuse is discussed and the types of drugs that are abused are
reviewed. The special considerations that need to be upheld when diagnosing and
understanding prescription drug abuse are highlighted. The chapter also contains
information on the epidemiology of prescription drug abuse. As prescription drugs
are effective drugs that are needed for the treatment of serious diseases, special
responsibility for the prevention of the problem of prescription drug abuse is
placed on the prescribing doctor. Lastly special considerations in treating pre-
scription drug abuse and especially long-term benzodiazepine use are reviewed.
38.1 Introduction
For as long as we have had medicinal drugs, we have had abuse of these drugs.
Similarly, drugs of abuse have long been used for their therapeutic potential, real or
perceived. Cannabis, opium and its derivatives, cocaine, and barbiturates are good
examples. Much of the legislation requiring prescription by doctors was brought in
to prevent the abuse of medicinal drugs and narcotics and even alcohol. At the time
there was a belief that having doctors administer the use of these drugs would
prevent some of the problems connected with them. This is, for good reason, still
a widely held belief. But as we shall see in the following text, requiring prescription
of these drugs does not solve the problem of abuse. Nonetheless it may be the best
system available for the distribution of these potentially harmful helpers. It does,
however, place a great deal of responsibility on the professionals entrusted with
this task.
Historically there are many examples of drugs of abuse being used as medicines.
The use of cannabis for medical purposes has its roots in the ancient civilizations of
China, Egypt, and Greece. The use of opiates for both medical and recreational
purposes went hand in hand in old cultures in the Middle and Far East. This was also
probably true for South American use of cocaine and was certainly true when the
drug came to Europe in the second half of the nineteenth century. Sigmund Freud
wrote four papers on the medical use of cocaine (Freud 1884) and developed an
addiction himself (Cohen 2011). Others developed the first local anesthetics from
it. When the first effective sleeping agents, barbiturates, were introduced, the road
to abuse was a short one, and for decades, the problem was considerable in the
Western world.
38 Prescription Drug Abuse: Risks and Prevention 639
Even today the boundaries may seem vague. Just as Freud thought that cocaine
could be a cure for morphine addiction, so heroin was introduced for the same
reason. In the 1890s many believed that heroin was not an addictive drug itself.
They could not have been more wrong! Some 70 years later Dole and Nyswander
introduced the concept of opiate maintenance treatment using long-acting opioids
(Dole and Nyswander 1967), thus sparking one of the greatest treatment options for
heroin addiction with several hundred thousand patients being treated worldwide.
This is obviously a great treatment opportunity but nevertheless is still considered
controversial in many countries. The story goes full circle with the introduction of
heroin as a substitution drug to be used for difficult-to-reach opiate addicts, an
indication that it is not the addiction per se that we seek to treat, but the adverse
effects of the addiction lifestyle, namely, criminality and social marginalization.
The boundaries are also unclear with the increasing use of medicinal drugs for
recreational purposes. These include drugs such as newer opioids, like pregabalin
(Lyrica), but also the older benzodiazepine sedatives and hypnotics and
benzodiazepine-like hypnotics. At the same time, there is a push toward the medical
use of drugs normally used for recreational purposes. Medical marijuana has
a growing following worldwide and this has formed the basis for challenging the
legislation concerning cannabis, pushed both by cannabis liberalists and also by
more scientifically oriented researchers who see the paradox in potential therapeu-
tics being outlawed. Other drugs have also been “pushed” by “drug activists”:
MDMA for the treatment of depression and psychedelics for the treatment of
other psychiatric conditions. Much of this interest appears to be fueled by special
interest groups with an agenda for liberalization and may be a romantic view of
“mind-expanding drugs.” This may be best illustrated by the interest in the use of
psychedelics in the treatment of addiction in order to “induce transcendental
experiences” as part of a cure for addiction.
Two issues should be kept in mind. Firstly, requirements for efficacy and
evidence should be just as strict toward drugs derived from narcotics as for any
medicinal drug if they are to be used therapeutically. The research concerning the
use of cannabinoids in medicine is a good example of this – showing that there is
evidence for the efficacy of cannabinoids. Secondly, the abuse potential of any drug
that is to be put on the market should be clarified as a prerequisite of any registration
process. Guidelines for such testing exist (FDA 2010). But many of these drugs
were marketed long before modern requirements to investigate their abuse potential
were in place. And even with careful testing, the real abuse potential of many drugs
may not be fully recognized. This is because preclinical and pre-marketing inves-
tigations, however meticulous, are not able to reveal a drug’s true abuse potential.
They are often tested on smaller, selected (non-abuser) populations under strictly
controlled conditions, which do not allow for spurious use. It will often take years
after a drug has come on the market before its true abuse potential becomes clear.
Post-marketing surveillance is one of the few ways of picking up abuse of drugs;
many drugs are not fully recognized for their abuse potential until they have been
on the market for many years (Arfken and Cicero 2003).
640 J.G. Bramness
This chapter will cover the most important groups and compounds. Sedatives and
hypnotics will be covered in more detail here because they are not elaborated on
elsewhere in this textbook.
This group of drugs covers many different compounds (Table 38.1). These mainly
belong to four subgroups: benzodiazepines, z-hypnotics, barbiturates, and
barbiturate-like substances. Common to all of them is that they have receptor
sites on the gamma-aminobutyric acid (GABA) receptor, subtype A. GABA is
the main inhibitory neurotransmitter in CNS and is widespread throughout the CNS.
38 Prescription Drug Abuse: Risks and Prevention 641
Table 38.1 Some commonly used sedatives marketed in many countries. Not all drugs will be
marketed in all countries
Compound Mean usual dose Mean terminal Abuse
(generic name) Main use main use (mg) half-life (h) potential
Benzodiazepines Alprazolam Anxiolytic 1 12 ***
Bromazepam Anxiolytic 9 16 **
Lorazepam Anxiolytic 4 12 ***
Oxazepam Anxiolytic 30 10 *
Chlordiazepoxide Anxiolytic 30 27 **
Clobazam Anxiolytic 30 18 **
Diazepam Anxiolytic 5 40 **
Lorazepam Hypnotic 1 12 ***
Temazepam Hypnotic 15 14 **
Flunitrazepam Hypnotic 1 25 ***
Nitrazepam Hypnotic 5 28 **
Flurazepam Hypnotic 15 60 ***
Clonazepam Antiepileptic 4 36 ***
Benzodiazepine- Zaleplon Hypnotic 10 1.5 *
like hypnotics Zopiclone Hypnotic 7,5 4.5 **
Eszopiclone Hypnotic 6 6 **
Zolpidem Hypnotic 5 2.5 **
Barbiturates Barbital Antiepileptic 750 30 ***
Fenobarbital Antiepileptic 200 80 ***
Barbiturate-like Chlomethiazole Muscle 600 6 **
drugs relaxant
Meprobamate Muscle 200 10 ***
relaxant
Methaqualone Muscle 150 74 ***
relaxant
Chlormezanone Muscle 200 40 **
relaxant
Orphenadrine Muscle 100 16 **
relaxant
Chlorzoxazone Muscle 750 1 **
relaxant
Carisoprodol Muscle 700 2 **
relaxant
Different sources of data indicate that the these drugs may be abused;
have a moderate abuse
potential; or are drugs with a high abuse potential
that they can be abused. These drugs probably have a lesser capacity to relieve anxiety
and the role of anxiety in a drug’s abuse potential should not be underestimated. It is
thus probably true to state that the abuse potential of these drugs may be lower than for
benzodiazepines, but the difference is likely to be marginal. We still see that zolpidem
is a very popular drug of abuse in many countries. A distinct metal taste following the
intake of zopiclone (also after i.v. intake) is probably preventive for abuse. Despite
many claims to the contrary, eszopiclone has no advantages over zopiclone and
probably none over benzodiazepines in terms of abuse potential. These drugs can be
and are abused (Jaffe et al. 2004; Hajak et al. 2003).
Benzodiazepines are hugely popular among injecting drug addicts. Heroin users
use them to prolong their intoxication and prevent withdrawal (Ross and Darke
2000). This may also contribute significantly to overdose deaths (Clausen
et al. 2009). Abusers of stimulants use them to land from binges or runs.
Barbiturates and barbiturate-like drugs are much less abused today than they
were before. That does not mean that they cannot be abused! Many of these drugs
are compounds that have taught us what prescription drug abuse is, like methaqua-
lone (Quaalude ®). Their high lipid solubility and resulting potential to cross the
blood-brain barrier quickly and their unlimited effect (ever-increasing effects with
higher doses and no ceiling effect, even if marked tolerance triggered massive dose
escalations) made them very popular as drugs of abuse. When this was acknowl-
edged, heavy restrictions were put on their prescribing and these drugs were
withdrawn in many countries, but they are still on the market in many others.
It is a point of discussion whether or not buspirone should be listed here. We
have opted not to do so because of the low abuse potential shown for this drug in
several studies. This is not to say that it cannot be abused in some situations or by
some patients.
38.2.2 Analgesics
Table 38.2 Some commonly used opioids marketed in many countries. Not all drugs will be
marketed in all countries
Mean terminal Abuse
Compound Main use half-life (h) potential Comment
Morphine Pain relief 2–3 ***
Ethylmorphine Cough ? **
suppression
Codeine Pain relief 3–4 * (10 % metabolized to
morphine by CYP2D6)
Fentanyl Anesthesia 1–6 *** Also much used as
a transdermal patch
Hydrocodone Pain relief 4–6 **
Oxycodone Pain relief 3–5 **
Oxymorphone Pain relief 1–2 **
Dextropropoxyphene Pain relief 8–24 ***
Hydromorphone Pain relief 2–3 **
Meperidine/ Pain relief 3–5 **
pethidine
Diphenoxylate Constipating 12–14 *
drug
Methadone Substitution in 6–8 ** High doses make once-daily
opioid intake possible
dependence
Buprenorphine Substitution in 4–6 ** Strong binding (covalent) to
opioid receptor makes once-daily
dependence intake possible
Different sources of data indicate that the these drugs may be abused; have a moderate abuse
potential; or are drugs with a high abuse potential; ? denotes an unknown abuse potential
During recent years there has been an enormous increase in the prescribing of
central stimulating drugs for treating attention deficit and hyperactivity disorder
(ADHD). Using central stimulants to treat ADHD is an effective treatment in
children (Bloch et al. 2009) and probably also in adults (Wilens et al. 2002), but
not all these drugs are used as prescribed; some are also abused. This is partly true
because patients with ADHD have an extra vulnerability to getting involved in drug
use (Groenman et al. 2013). The drugs can be abused by saving a whole week’s
worth of pills for a simultaneous intake to get a stimulant high or by selling the
drugs to friends or on the black market. A typical therapeutic use of methylpheni-
date would involve using 10–30 mg, but 50–150 mg would be common in abuse. It
is debatable whether or not buproprione should be listed here. We have opted not to
do so because of the low abuse potential of this drug shown by several studies. This
is not to say that it cannot be abused in some situations or by some patients.
Abuse of central stimulants includes using them as cognitive enhancers. This
means otherwise healthy people taking the drugs in order to optimize their
38 Prescription Drug Abuse: Risks and Prevention 645
Table 38.3 Some commonly used central stimulating drugs marketed in many countries. Not all
drugs will be marketed in all countries
Mean usual dose Mean terminal Abuse
Compound Main use main use (mg) half-life (h) potential
Methylphenidate ADHD and narcolepsy 20–30 2–3; 7–12 for **
extended release
Amphetamine ADHD and narcolepsy 20 13 ***
Dextroamphetamine ADHD and narcolepsy 20 10 ***
Ephedrine Cough medicine 20–50 3–6 *
Diet pills Weight loss Varying Varying Varying
Caffeine Narcolepsy and in Varying Varying Varying
combination for
migraine
Melanotan Illegal tanning product 10–30 1–2 ?
Different sources of data indicate that the these drugs may be abused; have a moderate abuse
potential; or are drugs with a high abuse potential; ? denotes an unknown abuse potential
Virtually any drug can be abused. No complete list will ever be compiled. As
prescribers we always need to work with others to produce early warning systems
and to remain up-to-date on the possible dangers of prescribing different drugs. We
must remember that abuse potential is often not revealed until a drug has been on
the market for a very long time (Table 38.4).
646 J.G. Bramness
Table 38.4 Miscellaneous drugs that have been reported abused. Not all drugs will be marketed
in all countries
Abuse
Compound Main use potential Comment
Marinol and other Pain and muscle *** Being a synthetic cannabinoid with very
synthetic spasms in MS patients high potency, it has a high abuse potential
cannabinoids
Sativex (cannabis Pain and muscle * Abuse potential as with other cannabis
extract) spasms in MS patients products
Pregabalin Antiepileptic ** Increasing number of case reports point to
the abuse potential of this GABA
analogue
Ketamine Anesthetic ** This anesthetic is an antagonist to the
glutamatergic NMDA receptor giving
vivid hallucinations as one of its main
effects
Quetiapine Antipsychotic * Increasing number of case reports point to
the abuse potential of this antipsychotic
drug
Xyrem GHB treatment of *** This GHB product can of course be
alcohol dependence abused as GHB
and withdrawal
Lioresal GABAB-agonist * This centrally acting muscle relaxant can
possibly be abused in higher doses, but the
euphoric and psychomotor effects are
weak
Different sources of data indicate that the these drugs may be abused;
have a moderate abuse
potential; or are drugs with a high abuse potential
Most use of prescription drugs is legitimate and therapeutically wise. The over-
whelming majority of those who receive a prescription for analgesics or for
hypnotics or sedatives use these drugs for a limited period to get through a time
of pain, insomnia, or life stress. It is important to underline this because even if we
have, for too long, overlooked the problem of abuse of these drugs, we must not go
to the other extreme and view all use of these drugs as problematic.
However, problems can and do arise. People can use too much. Some individuals
can increase their doses to high amounts. Others can use them for too long, after
their original problem is over, in order to avoid the discomforts of discontinuation
and withdrawal. The drugs can be taken for the wrong reasons. They are not meant
to be used recreationally or as part of an addiction. And some people mix different
drugs. This can be done for several reasons, but increases the addictive potential of
the drugs and also increases the chances of intoxication, often lethal.
In this context of numerous patterns of drug use, some stand out as more
archetypical.
38 Prescription Drug Abuse: Risks and Prevention 647
Sedating drugs are meant for short-term use only. The manufacturers, authorities,
and society guidelines say that the drugs should be used only for 3–4 weeks. Still
many patients continue to use the drugs for longer. This group of patients may cause
concern at the doctor’s office because of discussions about the re-prescribing of the
drugs. Many patients feel that their honesty is being questioned and many doctors
feel that they are being “forced” into prescribing for longer than necessary. These
patients, however, are not true abusers. They certainly use the drugs for longer than
intended, but seldom at high doses, most often at lower doses than prescribed, and
they seldom increase their doses. These users are often termed quasi-therapeutic
long-term users (Griffiths and Weerts 1997). They are mentioned here because they
are quite prevalent and clearly violate recommendations, but may not represent
a true problem.
Patients with anxiety disorders, but also patients with other psychiatric disorders, may
use different prescription drugs to self-medicate or treat their symptoms (McCabe
et al. 2009). It is important to acknowledge that anxiety disorders, major depression,
PTSD, personality disorders, and pain conditions may lead to overuse of prescription
drugs. The possibility of abuse should not stop the doctor from introducing effective
and necessary treatment, but the dangers of overuse should be kept in mind. Even
when drugs are used as prescribed, the patient may encounter problems such as
tolerance, abstinence, abuse, and dependence (see below).
Some patients can be labeled true prescription drug abusers. These are patients with
no or marginal reasons to use these drugs, who still keep using the drugs, often in
increasing dosages. They are involved in drug-seeking behaviors such as doctor
shopping, prescription forging, and diversion of drugs prescribed to others. The
doctor should be aware of these individuals, even though it is not a large group.
These patients resemble the next group.
Many users of heroine or central stimulants use prescription opioids as part of their
addiction (Gambi et al. 1999). Benzodiazepines are used to increase the high but
also to postpone abstinence in heroin users or to end a binge in users of central
stimulants. When such combination use occurs, it is often labeled as polydrug
abuse, but it can be argued that it in fact represents a kind of self-medication in
648 J.G. Bramness
drug abusers who have a main drug problem, be it heroin or central stimulants. This
distinction may be important for treatment choices.
The typical patterns of drug use mentioned above may or may not fulfill the
criteria for abuse or dependence on drugs. They are not, however, formal diagnoses.
The current diagnostic systems define harmful use or abuse and dependence on
drugs in the following manner (Table 38.5).
But these diagnoses may not be adequate for prescription drug problems (Kan
et al. 2001). Some have thought that these diagnoses are too normative or even
stigmatizing, as patients who only have done what the doctor has ordered would be
labeled as abusers or dependants. There have been suggestions of using another
nomenclature for prescription drugs than for other drugs. This has particularly been
advocated in the pain management community, with the increasing use of opioids
for nonmalignant pain. It has been argued that three new categories should be
introduced (Ballantyne and LaForge 2007): problematic use of prescription drugs,
addiction to prescription drugs, and iatrogenic pseudo-addiction. It is difficult to
see how the two first categories differ substantially from abuse and dependence as
defined above. The latter category, however, acknowledges the fact that some
aberrant use may be due to suboptimal treatment of the primary condition
(especially pain treatment). This kind of inappropriate use is characterized by
uncontrolled prescribing of short-acting opioids or low doses of long-acting opi-
oids. In both these cases, patients experience a slowing effect during the period
between two doses. This may cause the patient to ask for larger and/or more
frequent doses, which could lead to misconceptions of problematic opioid use
and break down the trust between the patient and the physician. This leads to
a difficult treatment situation which may gradually worsen. In such cases we are
talking about iatrogenic abuse. Pain doctors have termed this pseudo-addiction.
This terminology has been questioned by some (Manchikanti et al. 2012), who see
this way of thinking as an excuse for the large increases observed in opioid abuse.
It has been claimed that one third of the world’s drug problems stem from alcohol,
one third from narcotic drugs, and one third from prescription drugs. Even if this
statement highlights the importance of prescription drug abuse, it is obviously too
simplistic at least in underestimating problems related to alcohol. Neither does it
account for the differences between these problems. But it is difficult to get more
accurate figures. Information about aberrant use of substances is not easily avail-
able. Responders tend not to answer questions truthfully. Some are reluctant to
admit breaking the law. There may also be over-reporting; among the younger
population some will be reluctant to admit that they are the only ones who have not
tried drugs. And often the people of most interest are not available for answers; they
may be imprisoned or in treatment. Some of those you would most like to respond
to a survey never open their mailbox or do not even have an address. On the other
hand, if you choose to do your research in a prison or a treatment institution,
38 Prescription Drug Abuse: Risks and Prevention 649
Table 38.5 Diagnostic criteria according to ICD-10 and DSM-IV for harmful use/abuse and
dependence. These criteria apply to prescription drug abuse as for other substances
ICD-10 DSM-IV
Harmful The diagnosis requires that actual damage Substance abuse is defined as a maladaptive
use/abuse should have been caused to the mental or pattern of substance use leading to clinically
physical health of the user significant impairment or distress as
manifested by one (or more) of the
following, occurring within a 12-month
period
Harmful patterns of use are often criticized Recurrent substance use resulting in
by others and frequently associated with a failure to fulfill major role obligations at
adverse social consequences of various work, school, or home (such as repeated
kinds. The fact that a pattern of use or absences or poor work performance related
a particular substance is disapproved of by to substance use; substance-related
another person or by the culture, or may absences, suspensions, or expulsions from
have led to socially negative consequences school; or neglect of children or household)
such as arrest or marital arguments is not in
itself evidence of harmful use
Acute intoxication or “hangover” is not in Recurrent substance use in situations in
itself sufficient evidence of the damage to which it is physically hazardous (such as
health required for coding harmful use driving an automobile or operating
a machine when impaired by substance use)
Harmful use should not be diagnosed if Recurrent substance-related legal problems
dependence syndrome, a psychotic disorder, (such as arrests for substance related
or another specific form of drug- or alcohol- disorderly conduct)
related disorder is present Continued substance use despite
having persistent or recurrent social or
interpersonal problems caused or
exacerbated by the effects of the substance
(for example, arguments with spouse
about consequences of intoxication and
physical fights)
Dependency A definite diagnosis of dependence should usually be made only if three or more of the
following have been present together at some time during the previous year
(1) A strong desire or sense of compulsion to take the substance
(2) Difficulties in controlling substance-taking behavior in terms of its onset,
termination, or levels of use
(3) A physiological withdrawal state when substance use has ceased or have been
reduced, as evidenced by: the characteristic withdrawal syndrome for the substance; or use
of the same (or closely related) substance with the intention of relieving or avoiding
withdrawal symptoms
(4) Evidence of tolerance, such that increased doses of the psychoactive substance are
required in order to achieve effects originally produced by lower doses (clear examples of
this are found in alcohol- and opiate-dependent individuals who may take daily doses
sufficient to incapacitate or kill non-tolerant users)
(5) Progressive neglect of alternative pleasures or interests because of psychoactive
substance use, increased amount of time necessary to obtain or take the substance or to
recover from its effects
(6) Persisting with substance use despite clear evidence of overtly harmful
consequences, such as harm to the liver through excessive drinking, depressive mood
states consequent to periods of heavy substance use, or drug-related impairment of
cognitive functioning; efforts should be made to determine that the user was actually, or
could be expected to be, aware of the nature and extent of the harm
650 J.G. Bramness
you will face the problem of selection bias. Not all abusers or dependants will be
under treatment or imprisoned. The take-home message is that to study the epide-
miology of abuse, you need to draw on a variety of sources to aggregate compre-
hensive data. This is no less true for prescription drug abuse.
There are two principle types of information that we aim to gather from
epidemiological studies. The first is to look for signals of abuse in drugs not
previously recognized as drugs of abuse. This is pharmacological research. Case
reports and case series often give the first signals of such abuse potential (Arfken
and Cicero 2003; Hajak et al. 2003). These signals must be followed up by more
systematic and broader investigations. This is done both to substantiate a signal of
a drug having an abuse potential and to investigate the extent of abuse. This kind of
information is essential for grasping the size of the problem and how to cope with
it. This is epidemiological research. The different sources of data below may serve
as providers of both types of information.
Effects Database. Such databases have given us information on the abuse liability
of drugs like pregabalin (Gahr et al. 2013).
market for a drug, but also looking at weekly temporal variations in drugs, one
might get a feeling how much is used for recreational use (most at weekends and
less during weekdays) and how much is used on a regular basis (more evenly
distributed).
Where does all this leave us? Firstly, we cannot today seriously say we know the
extent of the problem of prescription drug abuse. No single source of data can
substantiate all drugs that are abused or the extent of this abuse. Some data
(surveys) will be flawed by information and selection bias; some data (databases)
will not be able to identify the clinical features of abuse or dependence. We are
therefore stuck with a number of estimates. And what do these tell us?
• These drugs are often used, but most use is clinically correct and well founded.
• Prescription drugs are, however, often abused and the problem of abuse is
increasing.
• The size of the problem is related to total sales of the drug; increased use always
comes at the price of increased abuse. Countries with a high prescribing rate
(such as the United States) have a substantial problem. In such countries the
problems following prescription drug abuse may equal those following the use of
narcotic drugs.
• Some drugs have a higher abuse potential than others. As with other drugs of
abuse, prescription drugs with high potency and a rapid effect will be more
attractive to abusers.
• Patients who have legitimate use of these drugs are also at risk for abuse, and
even use according to the doctor’s recommendations can be problematic.
Doctors should review their patient lists and take action when necessary.
• Specific populations will have more risk of abuse of prescription drugs than
others. These include drug abusers, psychiatric patients, but also patients with
somatic problems such as pain.
• It often takes a long time from when a drug is first marketed until its true abuse
potential is revealed, even with modern requirements for pre-marketing investi-
gations. Always be open to signals of a drug’s abuse potential.
Table 38.6 Prescription drug are according to US health authorities classified after their potential
for harm, including abuse. Not all drugs in this list are prescription drugs, but some are
Schedule Definition Most central drugs included
I Drugs with no currently accepted medical Cathinone, GHB, heroin, LSD, marijuana,
use in treatment in the United States and MDMA, most hallucinogens,
high potential for abuse and dependence methaqualone (Quaalude)
II Drugs with currently accepted medical use Cocaine, amphetamines, other opiates than
in treatment with severe restrictions in the heroin, some opioids, some synthetic
United States and high potential for abuse cannabinoids, barbiturates
and dependence
III Drugs with currently accepted medical use Anabolic steroids, some barbiturates,
in treatment in the United States and with buprenorphine, codeine, ketamine, GHB
a lower risk for abuse than drugs in as Xyrem, some synthetic cannabinoids
schedules I and II and low to moderate
dependence risk
IV Drugs with an accepted medical use in Benzodiazepines, benzodiazepine-like
treatment in the United States and with z-hypnotics, some barbiturates,
a low risk for abuse and dependence carisoprodol
(lower than III)
V Drugs with a current accepted medical use Codeine, pregabalin, lacosamide, atropine
in treatment in the United States and with
a low risk for abuse and dependence
(lower than IV)
within the prescribing system, under the laws of medicinal drugs. This could imply
different rules and regulations for prescribing these drugs compared to other drugs:
• The use of special prescribing.
• Only one doctor can prescribe to one patient.
• Only one pharmacy can deliver the drug.
• Only a specialist in a certain field can prescribe the drug.
• Special forms should be used for prescribing certain drugs.
• Special authorities should be informed and can perform controls/audits.
• Only certain package sizes can be prescribed.
• No telephone or Internet prescribing allowed for certain drugs.
Second, it could involve placing some medicinal drugs on narcotics lists and lists
of controlled or prohibited substances. This places the drug under jurisdiction
outside the health-care system and makes it police business. In many countries’
legislative systems, these boundaries are not so clear and (often for historical
reasons) illegal drugs and medicinal drugs are regulated by the same laws. The
scheduling system in the United States is such a system (Table 38.6). The different
degrees of scheduling can be followed by different rules or regulations for pre-
scribing as mentioned in examples above.
One could imagine that having a regime of prescribing and scheduling would
prevent widespread aberrant use, but this is not true. Aberrant use, be it abuse,
dependence, or over-consumption, is seen despite these precautions. Research
has shown us that the occurrence of overuse follows the sales of the drug in the
38 Prescription Drug Abuse: Risks and Prevention 655
38.6 Treatment
The boundary between prevention and treatment is often obvious, but sometimes it
can be unclear. Some preventive measures will be embedded in treatment and some
experiences and views from treatment will be reflected in prevention.
What kind of drug-seeking behavior physicians will encounter may vary according
to their field but also according to their place or country of work. Some common
656 J.G. Bramness
If you, as a prescriber, are worried about a patient’s use of prescription drugs, the
first step is to discuss this with your patient. Open communication is of the essence.
Even if the patient does not admit to a problematic relationship with these drugs,
just verbalizing the issue may give them food for thought. Some doctors regularly
review their patient lists and try to get a grip on who they should be concerned
about. One strategy would be to send a letter of concern to the patients in question,
just informing them of the potentially problematic sides to their drug use. Such
a simple intervention has proven very efficient in stopping or reducing drug use in
some patients (Mugunthan et al. 2011). Further support may be needed (“stepped
care”) and follow-up could include information meetings (pharmacology educa-
tion), psycho-educative programs (information about the underlying disease and
alternatives to pharmacological treatments), support groups, or even group therapy
(Voshaar et al. 2006).
Most studies show that gradual tapering of the medication is preferable to abrupt
discontinuation (Parr et al. 2009; Denis et al. 2006). The use of anticonvulsants like
carbamazepine or valproate can be of use for benzodiazepine withdrawal and
clonidine for opioid withdrawal. Also some authors suggest the use of benzodiaz-
epines for withdrawal from opioids, even if this can mean substituting one addiction
with another (Fatseas and Auriacombe 2007). The main principle is to substitute
short-acting drugs with longer-acting drugs, in order to have more control over the
withdrawal symptoms.
38 Prescription Drug Abuse: Risks and Prevention 657
A thorough evaluation must be performed of the actual dose the patient has been
using. One should aim at reducing all the different benzodiazepines and
benzodiazepine-like drugs to two different drugs at the most. Most often the
recommendation is to switch to a longer-acting drug like diazepam (in most people)
or a drug with fewer reinforcing effects like oxazepam (in drug abusers or the
elderly). Remember that some benzodiazepines (e.g., alprazolam, clonazepam, and
flunitrazepam) are 10–20 times more potent and need to be converted to equivalent
diazepam doses. For good cooperation between you and your patient, you need to
assure the patient that he/she will be adequately covered. For outpatient treatment
you may want to taper by reducing 20 % of the total daily dose during the first
months, then 10 % of the dose later, and then 5 % or less for the last weeks.
Allow the patient to reach a steady state between dose reductions and allow for time
to tackle the withdrawal symptoms. For adults with a half-life of 1–1.5 days of
diazepam, one step can be performed every second week, but for older people the
terminal elimination half-life of diazepam increases and more time should be
allowed for each step. A lot of support and encouragement may be needed,
sometimes in support groups, sometimes individually. For inpatient treatment
a more aggressive approach is recommended. Often the patient will not be given
enough time for a slow taper. The amount of withdrawal the patient needs to
manage is constant either with short- or long-term tapering. Thus, in the inpatient
situation a tapering of the whole dose within 2–3 weeks is recommended. You must
then be aware of benzodiazepine delirium.
The tapering of prescription opioids should always be done after a thorough work-up
on pain and consideration of adequate pain management. For this we refer to
textbooks on pain management. Even if inadequate pain management is the cause
of the patient’s problem, reduction or removal of the drugs will be needed. This
would involve tapering. Such tapering can be more manageable using a long-acting
opioid such as methadone or buprenorphine as a tool, even supported by clonidine
to tackle the worst withdrawal symptoms. For further information on ▶ Chap. 28,
“Opioid Addiction: Short- and Long-Acting Opioids”.
38.6.6 Intoxications
References
Arfken CL, Cicero TJ (2003) Postmarketing surveillance for drug abuse. Drug Alcohol Depend
70:S97–S105
Ator NA (2005) Contributions of GABAA receptor subtype selectivity to abuse liability and
dependence potential of pharmacological treatments for anxiety and sleep disorders. CNS
Spectrums 10:31–39
Ator NA, Griffiths RR, Weerts EM (2005) Self-injection of flunitrazepam alone and in the context
of methadone maintenance in baboons. Drug Alcohol Depend 78:113–123
Ballantyne JC (2007) Opioid misuse in oncology pain patients. Curr Pain Headache Rep
11:276–282
Ballantyne JC, LaForge KS (2007) Opioid dependence and addiction during opioid treatment of
chronic pain. Pain 129:235–255
Bloch MH, Panza KE, Landeros-Weisenberger A, Leckman JF (2009) Meta-analysis: treatment of
attention-deficit/hyperactivity disorder in children with comorbid tic disorders. J Am Acad
Child Adolesc Psychiatry 48:884–893
Bramness JG, Rossow I (2010) Can the total consumption of a medicinal drug be used as an
indicator of excessive use? The case of carisoprodol. Drugs Ed Prev Policy 17:168–180
Bramness JG, Furu K, Engeland A, Skurtveit S (2007) Carisoprodol use and abuse in Norway.
A pharmacoepidemiological study. Br J Clin Pharmacol 64:210–218
Brunette MF, Noordsy DL, Xie HG, Drake RE (2003) Benzodiazepine use and abuse among
patients with severe mental illness and co-occurring substance use disorder. Psychiatr Serv
54:1395–1401
Cai R, Crane E, Poneleit K, Paulozzi L (2010) Emergency department visits involving nonmedical
use of selected prescription drugs in the United States, 2004–2008. J Pain Palliat Care
Pharmacother 24:293–297
Clark RE, Xie HG, Brunette MF (2004) Benzodiazepine prescription practices and substance
abuse in persons with severe mental illness. J Clin Psychiatry 65:151–155
Clausen T, Waal H, Thoresen M, Gossop M (2009) Mortality among opiate users: opioid
maintenance therapy, age and causes of death. Addiction 104:1356–1362
Cohen D (2011) Freud on coke. Cutting Edge Press, London
38 Prescription Drug Abuse: Risks and Prevention 659
Kan CC, Breteler MH, van der Ven AH, Timmermans MA, Zitman FG (2001) Assessment of
benzodiazepine dependence in alcohol and drug dependent outpatients: a research report. Subst
Use Misuse 36:1085–1109
Lader M (1991) History of benzodiazepine dependence. J Subst Abuse Treat 8:53–59
Longo LP, Johnson B (2000) Addiction: part I. Benzodiazepines – side effects, abuse risk and
alternatives. Am Fam Physician 61:2121–2128
Manchikanti L, Helm S 2nd, Fellows B, Janata JW, Pampati V, Grider JS et al (2012) Opioid
epidemic in the United States. Pain Physician 15:ES9–ES38
McCabe SE (2008) Misperceptions of non-medical prescription drug use: a web survey of college
students. Addict Behav 33:713–724
McCabe SE, Boyd CJ, Teter CJ (2009) Subtypes of nonmedical prescription drug misuse. Drug
Alcohol Depend 102:63–70
Mugunthan K, McGuire T, Glasziou P (2011) Minimal interventions to decrease long-term use of
benzodiazepines in primary care: a systematic review and meta-analysis. Br J Gen Pract 61:
e573–e578
Parr JM, Kavanagh DJ, Cahill L, Mitchell G, Mc DYR (2009) Effectiveness of current treatment
approaches for benzodiazepine discontinuation: a meta-analysis. Addiction 104:13–24
Pauly V, Frauger E, Pradel V, Nordmann S, Pourcel L, Natali F et al (2011) Monitoring of
benzodiazepine diversion using a multi-indicator approach. Int Clin Psychopharmacol
26:268–277 (comparative study)
Peirce GL, Smith MJ, Abate MA, Halverson J (2012) Doctor and pharmacy shopping for
controlled substances. Med Care 50:494–500
Ragan CI, Bard I, Singh I, Independent Scientific Committee on Drugs (2013) What should we do
about student use of cognitive enhancers? An analysis of current evidence. Neuropharmacol-
ogy 64:588–595
Reid MJ, Langford KH, Morland J, Thomas KV (2011) Quantitative assessment of time dependent
drug-use trends by the analysis of drugs and related metabolites in raw sewage. Drug Alcohol
Depend 119:179–186
Ross J, Darke S (2000) The nature of benzodiazepine dependence among heroin users in Sydney,
Australia. Addiction 95:1785–1793
Rosvold EO, Vaglum P, Moum T (1998) Use of minor tranquilizers among Norwegian physicians.
A nation-wide comparative study. Soc Sci Med 46:581–590
SAMHSA (2009) Results from the 2008 National Survey on Drug Use and Health: national
findings. U.S. Department of Health and Human Services, Rockville
Schifano F, D’Offizi S, Piccione M, Corazza O, Deluca P, Davey Z et al (2011) Is there
a recreational misuse potential for pregabalin? Analysis of anecdotal online reports in com-
parison with related gabapentin and clonazepam data. Psychother Psychosom 80:118–122
Shulgin A, Shulgin A (1991) PiHKAL: a chemical love story. Transform Press, Lafayette
Skog OJ (1980) Total alcohol consumption and rates of excessive use: a rejoinder to Duffy and
Cohen. Br J Addict 75:133–145
Tan KR, Rudolph U, Luscher C (2011) Hooked on benzodiazepines: GABAA receptor subtypes
and addiction. Trends Neurosci 34:188–197
Tramer MR, Carroll D, Campbell FA, Reynolds DJ, Moore RA, McQuay HJ (2001) Cannabinoids
for control of chemotherapy induced nausea and vomiting: quantitative systematic review.
BMJ 323:16–21
Turk DC, Swanson KS, Gatchel RJ (2008) Predicting opioid misuse by chronic pain patients:
a systematic review and literature synthesis. Clin J Pain 24:497–508
UNODC (2012) World drug report 2011. United Nations Office on Drugs and Crime, Vienna
Voshaar RC, Couvee JE, van Balkom AJ, Mulder PG, Zitman FG (2006) Strategies for
discontinuing long-term benzodiazepine use: meta-analysis. Br J Psychiatry 189:213–220
Wilens TE, Spencer TJ, Biederman J (2002) A review of the pharmacotherapy of adults with
attention-deficit/hyperactivity disorder. J Atten Disord 5:189–202
38 Prescription Drug Abuse: Risks and Prevention 661
Further Reading
There are several books on recovery stories by patients who have quit the habit of benzodiazepines
or opioids. These can be illustrative and helpful for other people trying to stop taking these drugs.
One problem may be a lack of perspective in these stories of prescription-drug abuse survivors.
They often lack perspective on what drugs are harmful and what drugs are not and on the fact that
some people need these drugs for their treatment, while others are better off not using them. Two
books that can be recommended are:
• Hobson-Dupont J (2006) The Benzo book: getting safely off tranquilizers. Essex Press.
A personal story with good advice on benzodiazepine withdrawal
• Johns B (2010) Benzo-wise: a recovery companion. Campanile Publishing. A personal story
with good advice on benzodiazepine withdrawal
One piece of further reading that is not out in book form, but is readily available on the internet is
The Ashton Manual:
• Ashton H. Benzodiazepines: how they work and how to withdraw. http://www.benzo.org.uk/
manual/. This holds information about benzodiazepines and sets up schemes for tapering. The
web page (supported by Roche!) has many hints and supports for people coming off prescrip-
tion drugs
Regulatory Aspects of New Medications to
Treat Addictions: The U.S. IND Process 39
Robert L. Walsh
Contents
39.1 Regulatory Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 664
39.1.1 The Investigational New Drug (IND) Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 664
39.1.2 The Investigational New Drug (IND) Application . . . . . . . . . . . . . . . . . . . . . . . . . . 665
39.1.3 Chemistry, Manufacturing, and Controls (CMC) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 668
39.1.4 Pharmacology/Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 668
39.1.5 Previous Human Experience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 669
39.1.6 Additional Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 670
39.1.7 IND Meetings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 670
39.1.8 Drug Master File Program . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 671
39.1.9 Letters of Authorization to FDA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 673
39.1.10 Exemption from IND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 674
39.1.11 Guidance Documents for INDs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 675
39.1.12 Fast Track, Accelerated Approval, Breakthrough Therapies,
and Priority Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 676
39.2 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 679
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 679
Abstract
In most countries, for a medication to be available to treat addictions, it must first
go through a development and approval process. In the United States, the Center
of Drug Evaluation and Research (CDER), of the Food and Drug Administration
(FDA), is the Federal agency responsible for approving new addiction pharma-
cotherapies based upon their safety and efficacy. The Investigational New Drug
(IND) application is the means by which FDA allows a new medication to be
studied in humans. In order to be able to test a potential medication for addiction
in humans, FDA requires certain tests to be conducted to (1) characterize the
R.L. Walsh
Division of Pharmacotherapies and Medical Consequences of Drug Abuse, National Institute on
Drug Abuse, National Institutes of Health, USA
e-mail: [email protected]
Current US Federal law requires that a drug be the subject of an approved marketing
application before it is transported or distributed across state lines. The Federal
Food, Drug, and Cosmetic Act (FD&C Act), section 355 – New drugs states that
“No person shall introduce or deliver for introduction into interstate commerce any
new drug, unless an approval of an application filed pursuant to subsection (b) or
(j) of this section is effective with respect to such drug.” Because a sponsor often
manufactures the drug in one location and then needs to ship the investigational
drug to clinical investigators in many states and/or countries, it has to seek an
exemption from that legal requirement. The IND is the mechanism through which
the sponsor technically obtains this exemption from the FDA.
In the United States, the sponsor of an IND must have a US address or agent. The
US Code of Federal Regulations, 21 CFR 312.23 (a)(1)(ix), states that a sponsor shall
include in the IND application “The signature of the sponsor or the sponsor’s autho-
rized representative. If the person signing the application does not reside or have
a place of business within the United States, the IND is required to contain the name
and address of, and be countersigned by, an attorney, agent, or other authorized official
who resides or maintains a place of business within the United States.” Often sponsors
outside of the United States, who do not maintain offices in the United States, will use
a contract research organization (CRO) to act as their agent for the IND.
Before studies in humans can begin, an Investigational New Drug (IND) appli-
cation must be submitted to the FDA containing, among other things, information
on any risks anticipated based on the results of pharmacological and toxicological
data collected during studies of the drug in animals as outlined in 21 CFR 312.23(a)
(8). These basic safety tests are often performed in mice, rats, and dogs. The studies
are designed to allow a sponsor to identify a safe starting dose to give the drug to
humans. The studies also allow a sponsor to gain an understanding of which organs
may be the targets of toxicity, to estimate the margin of safety between a clinical
and a toxic dose, and to predict pharmacokinetic and pharmacodynamic parameters.
The central focus of the initial IND submission should be on the general investi-
gational plan and the protocols for specific human studies.
39 Regulatory Aspects of New Medications to Treat Addictions: The U.S. IND Process 665
The IND application is comprised of multiple sections which are differentiated into:
1. Cover Sheet
2. Table of Contents
3. Introductory Statement and General Investigational Plan
4. Investigator’s Brochure
5. Protocol(s) (Clinical)
6. Chemistry, Manufacturing, and Control Information
7. Pharmacology/Toxicology Information
8. Previous Human Experience
9. Additional Information
39.1.2.5 Protocol
The protocol section of the IND contains a protocol for each planned study. It is
expected that protocols for phase 1 studies may be less detailed and more flexible than
protocols for phases 2 and 3 studies. Phase 1 protocols should be directed primarily at
providing an outline of the investigation – an estimate of the number of patients to be
involved, a description of safety exclusions, and a description of the dosing plan
including duration, dose, or method to be used in determining dose – and should
specify in detail only those elements of the study that are critical to safety, such as
necessary monitoring of vital signs and blood chemistries. For phase 1 studies of
potential medications for drug addiction, it is important to also include what measures
(i.e., medications and medical equipment that will be available at all times during the
study, training and availability of staff, etc.) will be taken to anticipate for any
unexpected life-threatening events that may occur during the conduct of the study.
For phase 1 studies of potential medications for drug addiction, it is important to
also detail what measures (i.e., medications and medical equipment that will be
available at all times during the study, availability of appropriately trained medical
staff, etc.) will be taken to anticipate any unexpected life-threatening events such as
cardiac arrest or another serious adverse event that may occur during the conduct of
the study. The measures proposed need to be well thought out and should give an
FDA reviewer a sufficient level of comfort that unexpected serious adverse events
have been anticipated and planned for.
In phases 2 and 3, detailed protocols describing all aspects of the study should be
submitted. A protocol for a phase 2 or 3 investigation should be designed in such
a way that if the sponsor anticipates that some deviation from the study design may
668 R.L. Walsh
The regulations at 21 CFR 312.23 (a)(7)(i) emphasize the graded nature of chem-
istry, manufacturing, and controls (CMC) information needed as development
under an IND progresses. Although in each phase of a clinical investigational
program, sufficient information should be submitted to ensure the proper identifi-
cation, strength, quality, purity, and potency of the investigational candidate, the
amount of information needed which will provide that assurance will vary with the
phase of the investigation, the proposed duration of the investigation, the dosage
form, and the amount of information already available.
The emphasis in an initial phase 1 CMC submission should be placed on
providing information, detailing the identification and control of the raw materials
and the new drug substance. This will allow an evaluation of the safety of subjects
in the proposed study.
This section should contain a brief description of the overall plan for investigat-
ing the drug product for the following year. Detailed developmental plans are often
contingent on the outcome of the planned study(ies). In that case, sponsors should
simply state this and not try to develop overly detailed plans.
The plan should include the following:
(a) The rationale for the drug or the research study
(b) The indication(s) to be studied
(c) The general approach to be followed in evaluating the drug
(d) The kinds of clinical trials to be conducted in the first year following the submis-
sion (if plans are not developed for the entire year, the sponsor should so indicate)
(e) The estimated number of patients to be given the drug in those studies
(f) Any risks of particular severity or seriousness anticipated on the basis of
the toxicological data in animals or prior studies in humans with the drug
or related drugs
39.1.4 Pharmacology/Toxicology
evaluation include characterizing the toxic effects of the potential medication with
respect to:
• Target organs
• Dose dependence
• Relationship to exposure
• Potential reversibility
This information is important to estimate an initial safe starting dose for the
human trials and to identify parameters to allow clinical monitoring for potential
adverse effects. The nonclinical safety studies, which may be limited at the begin-
ning of clinical development, should be adequate to characterize any potential toxic
effects which may be anticipated under the conditions of the proposed clinical trial.
The pharmacology/toxicology section should contain adequate information
about the pharmacological and toxicological studies of the drug involving labora-
tory animals or in vitro, which the sponsor used as the basis for concluding that it is
reasonably safe to evaluate the potential medication in human subjects.
The kind, duration, and scope of animal and other tests required vary with the
duration and nature of the proposed clinical investigation. Such information is
required to include the identification and qualifications of the individuals who
evaluated the results of such studies and concluded that it is reasonably safe to
begin the proposed investigations and include a statement of where the investiga-
tions were conducted and where the records may be made available for inspection.
The nonclinical safety study recommendations for the marketing approval of
a pharmaceutical usually include single and repeated dose toxicity studies, repro-
duction toxicity studies, genotoxicity studies, local tolerance studies, and, for drugs
that have special cause for concern or are intended for a long duration of use, an
assessment of carcinogenic potential. Other nonclinical studies include pharmaco-
logical studies for safety assessment (safety pharmacology) and pharmacokinetic
(absorption, distribution, metabolism, and excretion (ADME)) studies.
An additional aspect of developing medications to treat addiction is the need for
animal drug-drug interactions studies with drugs of abuse. Since drug users often
abuse multiple drugs, it is necessary to know not only whether the potential
medication will interact with the specific drug of abuse it is being developed for
but also whether it will interact with other commonly co-abused drugs. To address
that concern the potential medication is tested against cocaine, morphine, and
alcohol in animals prior to initiating phase 2 studies. These studies serve to alert
the sponsor and FDA of any particular interaction that could occur in humans.
The types of studies that are summarized in the pharmacology/toxicology
section of the initial IND application are those that were conducted to support
initial and early clinical development studies.
reach agreement on the adequacy of the chemical information and animal studies
needed to initiate human testing. The meeting may also provide an opportunity for
discussing the scope and design of phase 1 testing, plans for studying the drug
product in pediatric populations, and the best approach for presentation and for-
matting of data in the IND.
CDER’s Pre-Investigational New Drug Application (IND) Consultation Pro-
gram fosters early communications between sponsors and new drug review divi-
sions to provide guidance on the data necessary to warrant IND submission. The
review divisions are organized generally along therapeutic class and can each be
contacted using the designated Pre-IND Consultation List (Fig. 39.1).
A Drug Master File (DMF) is submitted to the FDA to provide confidential, detailed
information about facilities, processes, or articles used in the manufacturing,
processing, packaging, and storing of one or more human drugs. This can be
valuable in cases where a sponsor is opening multiple INDs on the same investi-
gational drug (such as for different indications) since the sponsor can provide
a letter of authorization to allow FDA staff to cross-reference the information on
behalf of the IND applicant rather than having to provide the identical information
in each IND application. It is also useful when a sponsor wishes to support the
672
Office of Drug Evaluation I Office of Drug Evaluation II Office of Drug Evaluation III Office of Drug Evaluation IV Office of Antimicrobial Office of Hematology and
Products: Pre-IND Oncology Drug Products
Consultation Program
Pamela Lucarelli
301-796-3961
Kyong Hyon
submission of an IND by other investigators but does not wish to provide confi-
dential chemical information about the investigational drug.
A DMF is not required by law or FDA regulation. A DMF is submitted solely at
the discretion of the holder. The information contained in the DMF may be used to
support an Investigational New Drug Application (IND), a New Drug Application
(NDA), an Abbreviated New Drug Application (ANDA), another DMF, an Export
Application, or amendments and supplements to any of these.
A DMF is NOT a substitute for an IND, NDA, ANDA, or Export Application.
It is not approved or disapproved. Technical contents of a DMF are reviewed only
in connection with the review of an IND, NDA, ANDA, or an Export Application.
As stated in 21 CFR 10.90(b), this guideline does not impose mandatory
requirements. It does, however, offer guidance on acceptable approaches to meet-
ing regulatory requirements. Different approaches may be followed, but the appli-
cant is encouraged to discuss significant variations in advance with FDA reviewers
to preclude spending time and effort in preparing a submission that FDA may later
determine to be unacceptable.
Drug Master Files are provided for in 21 CFR 314.420. The guideline is intended
to provide DMF holders with procedures acceptable to the agency for preparing and
submitting a DMF. The guideline discusses types of DMFs, the information needed
in each type, the format of submissions to a DMF, the administrative procedures
governing review of DMFs, and the obligations of the DMF holder.
DMFs are generally created to allow a party other than the holder of the DMF to
reference material without disclosing to that party the contents of the file. When an
applicant references its own material, the applicant should reference the informa-
tion contained in its own IND, NDA, or ANDA directly rather than establishing
a new DMF.
There are five types of DMFs:
• Type I: Manufacturing Site, Facilities, Operating Procedures, and Personnel
• Type II: Drug Substance, Drug Substance Intermediate, and Material Used in
Their Preparation, or Drug Product
• Type III: Packaging Material
• Type IV: Excipient, Colorant, Flavor, Essence, or Material Used in Their
Preparation
• Type V: FDA Accepted Reference Information
Each DMF should contain only one type of information and all supporting data.
See Section IV.C of the guideline for more detailed descriptions of the kind of
information desired in each type. Supporting information and data in a DMF can
also be cross-referenced to any other DMF.
Before FDA can review DMF information in support of an application, the DMF
holder must submit, in duplicate to the DMF, a letter of authorization permitting
FDA to reference the DMF. If the holder cross-references its own DMF, the holder
674 R.L. Walsh
A drug that is lawfully marketed in the United States is exempt from the require-
ments for an IND if all of the following apply:
39 Regulatory Aspects of New Medications to Treat Addictions: The U.S. IND Process 675
Speeding the development and availability of drugs that treat serious diseases are in
everyone’s interest, especially when the drugs are the first available treatment or have
distinct advantages over existing treatments. The Food and Drug Administration
(FDA) has developed four distinct and successful approaches to making such drugs
available as rapidly as possible: priority review, accelerated approval, breakthrough
therapies, and fast track. Because each of these approaches implies speed, there can
be confusion about the specific meaning of each and the distinctions among them.
A request for priority review must be made by the drug company. It does not
affect the length of the clinical trial period. FDA determines within 45 days of the
drug company’s request whether a priority or standard review designation will be
assigned. Designation of a drug as “priority” does not alter the scientific/medical
standard for approval or the quality of evidence necessary.
Fast track, accelerated approval, breakthrough therapies, and priority review are
approaches that are intended to make therapeutically important drugs available at
an earlier time. They do not compromise the standards for the safety and
effectiveness of the drugs that become available through this process.
These revitalized FDA drug review approaches have yielded tangible results in
bringing safe and effective drugs to patients with serious diseases more quickly. For
example, since 1996, 68 drugs for cancer therapies have received priority review
and approval.
FDA reviewed Gleevec, a treatment for chronic myeloid leukemia, in 4 months.
Shortened review times have also brought promising treatments to patients with
HIV/AIDS more quickly. Kaletra for the treatment of HIV/AIDS was reviewed and
approved in 3.5 months. Pegasys, a combination product for the treatment of
Hepatitis C, was approved for marketing in 4 months.
Fast track, accelerated approval, breakthrough therapies, and priority review
have evolved over time. FDA has been vigilant in assuring that reducing the time
necessary for drug development has not compromised the safety and effectiveness
of drugs for patients with serious diseases.
39.2 Conclusion
References
21 CFR part 312.23 – IND content and format. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/
cfcfr/CFRSearch.cfm?fr¼312.23
21 CFR part 312.40(b)
Bioavailability and bioequivalence studies for orally administered drug products – general
considerations. (Issued October 2000). http://www.fda.gov/downloads/Drugs/Guidance
ComplianceRegulatoryInformation/Guidances/UCM070124.pdf
680 R.L. Walsh
Contents
40.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 684
40.2 Biologics Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 685
40.2.1 Nicotine Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 685
40.2.2 Cocaine Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 687
40.2.3 Methamphetamine Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 688
40.2.4 Opiate Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 688
40.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 689
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 690
Abstract
A novel approach for the treatment of substance use disorders (SUDs) is the use
of biologics. Biologics include immunotherapies, such as vaccines or antibodies,
as well as enzymes. These are usually large and complex molecules that do not
cross the blood-brain barrier and do not have effects in the central nervous
system (CNS). Biologics are investigated for the treatment of SUDs because
they prevent the access of the drug of abuse to the brain and, thus, prevent their
effect of brain reward systems. It is expected that over a period of treatment with
biologics, they will help to produce an extinction of the brain mechanisms of
drug dependence. SUDs are complex medical conditions that require multiple
therapeutic approaches and the treatment with biologics may offer a new way to
treat these disorders without directly affecting the brain. The purpose of this
chapter is to provide a general overview of the current status of research with
vaccines, antibodies, and enzymes for the treatment of SUDs.
I.D. Montoya
Division of Pharmacotherapies and Medical Consequences of Drug Abuse, National Institute on
Drug Abuse (NIDA), Bethesda, MD, USA
e-mail: [email protected]
40.1 Introduction
Substance use disorders (SUDs) are complex clinical conditions with multiple
medical and psychosocial manifestations. SUDs require multiple treatment
approaches, including the use of psychosocial interventions and often pharmaco-
therapies. Over the past 20 years, significant strides have been made in the under-
standing, development, and availability of medications to treat SUDs. Medications
such as methadone, buprenorphine, and naltrexone (oral and injectable long-acting
formulations) for opiate use disorders as well as nicotine replacement therapy,
bupropion and varenicline for nicotine dependence, have shown to be safe and
effective interventions for the respective disorders.
There is a great need for new approaches to treat SUDs because the long-term
efficacy of the approved medications to maintain drug use abstinence is far from
ideal. Also, the fact that there are no medications approved by regulatory agencies
for the treatment of cocaine, methamphetamine, and cannabis use disorders makes
this need even more urgent (Montoya and Vocci 2008). Traditionally, the develop-
ment of pharmacotherapies for SUDs has focused on small molecule approaches
that target a receptor or neurotransmitter in the brain. An alternative approach is the
use of biologics.
The Food and Drug Administration (FDA) of the United States defines biolog-
ical products as “a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood
component or derivative, allergenic product, or analogous product, or arsphena-
mine or derivative of arsphenamine (or any other trivalent organic arsenic com-
pound), applicable to the prevention, treatment, or cure of a disease or condition of
human beings” (US Food and Drug Administration 1999). Biologics are generally
“large” molecules derived from living material, complex in structure, usually not
fully characterized, which do not cross the blood-brain barrier and have no CNS
effects. Biologics can be extracted from living systems (e.g., extracted from
tissues), originated from stem cells, produced by recombinant DNA, produced in
bioreactors, or engineered in a laboratory.
The concept of using biologics to treat SUDs was first described in 1974 in
a study conducted in monkeys that received morphine immunization and showed
a reduction in heroin self-administration (Bonese et al. 1974). Subsequently, new
biologics have been discovered and tested with the goal of treating treat nicotine,
cocaine, methamphetamine, opiates, and phencyclidine use disorders (Kinsey
et al. 2009; Zheng and Zhan 2009).
It has been suggested that the mechanism of action of biologics to treat SUDs is
by preventing the access of the drug of abuse to the brain. This, in turn, prevents the
activation of brain reward systems by the drug. The long-term effect of biologics is
expected to produce a behavioral extinction of the addictive behavior. Also, by
preventing the access of the drug of abuse to the brain, biologics may help to treat
drug overdose (Peterson and Owens 2009). The biologics currently investigated
include vaccines, antibodies, and enzymes.
Vaccines stimulate the immune system to recognize the drug of abuse as
a foreign substance (antigen) and produce antibodies to combat it. Given that
40 Biologics (Vaccines, Antibodies, Enzymes) to Treat Drug Addictions 685
drugs of abuse are small molecules with low ability to stimulate the immune
response, they can become immunogenic by conjugating them on to a foreign
carrier protein. The immune system of vaccinated individuals forms an antigen
(the drug of abuse)–antibody complex in plasma. This complex is a large molecule
that does not cross the blood-brain barrier and prevents the access of the drug of
abuse to the brain (Peterson and Owens 2009; Anton et al. 2009; Gentry et al. 2010;
Orson et al. 2008). Animal studies have been conducted with vaccines against
nicotine, cocaine, amphetamine, and heroin. Human studies have been conducted
with vaccines against nicotine and cocaine.
Antibodies are being investigated to treat SUDs as well as drug overdose.
Antibodies bind directly in plasma to the drug of abuse and prevent it from reaching
the brain almost immediately after the administration. Therefore, they have the
advantage of not needing the immune system to block the access of the drugs of
abuse to the brain. This effect makes them ideal candidates for the treatment of the
neuropsychiatric complications of drug overdose. Antibodies are being investigated
for the treatment of cocaine dependence as well as cocaine, methamphetamine, and
phencyclidine overdose (Zheng and Zhan 2009; Carroll et al. 2011; Gentry
et al. 2010).
Engineered enzymes significantly more efficient than wild enzymes are being
investigated for the treatment of SUD and overdose. These enzymes can rapidly
metabolize the drug of abuse before it reaches the brain. They may be more
effective than antibodies or vaccines when the drug concentration in plasma is
high, as is the case of an overdose. They can also be treatment tools and as such
a recombinant long-acting mutated butyrylcholinesterase that is being investigated
for cocaine dependence (Gao et al. 2010; Brimijoin et al. 2008; Zheng et al. 2008;
Godin et al. 2012).
Presently, new and improved products and technologies offer vast opportunities
to advance the discovery and development of biologics to treat SUDs. Some of
these advancements include the discovery and development of nontraditional
vaccines and adjuvants, new monoclonal antibodies, and means of extending their
biological half-life, as well as highly efficient engineered enzymes that can metab-
olize a drug of abuse orders of magnitude faster than the wild enzyme. The purpose
of this chapter is to provide an overview of the current research with vaccines,
antibodies, and enzymes for the treatment of nicotine, cocaine, opiates, and
methamphetamine use disorders.
Several vaccines have been investigated with the goal of treating nicotine depen-
dence. They include NicVax™ (produced by Nabi Biopharmaceuticals), NIC002
(Nicotine Qbeta therapeutic vaccine, Cytos Biotechnology), SEL-068 (Selecta
Biosciences using a proprietary Synthetic Vaccine Particle [SVP™]),
686 I.D. Montoya
The company attributes this failure to problems with the manufacturing of the
vaccine (Celtic Pharma 2012).
IP18-KLH (Niccine) is an anti-nicotine vaccine developed by investigators in
Sweden. It is an immunoconjugate IP18-KLH that prevents the access of nicotine to
the brain and does not precipitate nicotine withdrawal in rats (de Villiers et al. 2002,
2010). A randomized, double-blind study in a sample of 355 smokers showed that
this vaccine was well tolerated but was not able to induce the production of
sufficient antibodies against nicotine. Therefore, it was considered not efficacious
for smoking relapse prevention (Tonstad et al. 2013).
effect for cocaine toxicity (McGee and Godin 2013). Currently, a randomized,
double-blind study is evaluating pharmacokinetics parameters of RBP-8000 and
cocaine to determine the effects of RBP-8000 on cocaine-induced physiologic and
behavioral effects (http://clinicaltrials.gov/ct2/show/NCT01846481).
dAd5GNC is an anti-cocaine vaccine that consists of linking the capsid
protein of an adenovirus to the cocaine molecule. The administration of
dAd5GNC to mice elicits a production of antibodies that is capable of preventing
the access of cocaine to the brain. Also, this vaccine is capable of reversing the
hyperlocomotor activity produced by the administration of cocaine. Therefore, it
may be useful to treat of cocaine dependence as well as cocaine overdose (Hicks
et al. 2011).
GNC92H2 is an immunoglobuline G (IgG) with extended half-life that may
sequester cocaine in blood and prevent its access to the brain. It appears that this
vaccine has the capacity to redistribute cocaine from the brain to serum, within the
restricted timeframe of cocaine overdose. Further research needs to be conducted to
determine the medical safety and therapeutic utility of GNC92H2 for cocaine
overdose (Treweek et al. 2011).
Currently, several groups are investigating anti-opiate vaccines (Anton and Leff
2006; Anton et al. 2009; Li et al. 2011; Pravetoni et al. 2012; Stowe et al. 2011).
M-TT is being developed by a group of investigators in Mexico (Anton and Leff
2006; Anton et al. 2009). It has been reported that it is a highly immunogenic bivalent
morphine/heroin vaccine that uses the tetanus toxoid as protein carrier. Studies
conducted in rats have shown that the vaccine was able to prevent opiate use relapse.
M-KLH is a morphine (M) and oxycodone (OXY) haptens conjugated vaccine
that may be useful for the treatment of poly-opioid dependence. A recently published
study conducted in rats showed that M-KLH alone produced high titers of antibodies
directed against heroin, 6-monoacetylmorphine (6-MAM), and morphine. Future
studies are needed to determine the efficacy of bivalent anti-opioid vaccines that
may simultaneously target multiple abusable opioids (Pravetoni et al. 2013).
40.3 Conclusion
Given the public health burden of the SUDs and overdose, there is an urgent need
for safe and effective therapeutic interventions and biologics appear to be
a promising approach. Development process include the anti-nicotine vaccine
PF-05402536. With regard to biologics against cocaine, TA-CD and TV-1380 are
the most advanced. Biologics to treat opiate and methamphetamine dependence are
far behind.
As with any other psychiatric condition, the biologic treatments must be pro-
vided in conjunction with adequate psychosocial support. The ideal biologic-based
therapy should be potent enough to block the access of the drug of abuse to the brain
for a long period of time and should have good specificity for the target drug or class
of drugs. The long-acting effect is important because individuals with SUDs usually
have poor treatment adherence and extended effects will increase the probability of
successful outcomes.
Biologics have the advantage of exerting their effect in the periphery. Unlike
pharmacotherapies that work by altering brain functions, biologics do not cross the
blood-brain barrier and therefore are unlikely to produce undesirable neuropsychi-
atric side effects. If necessary, biologics can be combined with pharmacotherapies
which may result in boosting their therapeutic effect. Given that vaccines rely on
the immune system for the production of antibodies, it is required that the immune
system of the host will have capability of producing the antibodies.
Biologics are large molecules that may have unique metabolic characteristics
and could cause a whole sort of possible adverse events such as kidney or liver
problems. Also, because they are usually originated from living organisms, there is
always a risk of anaphylactic complications. One of the drawbacks of vaccines is
that they may be contraindicated in people with SUDs who have immunodefi-
ciencies, poor nutrition, or chronic and debilitating medical conditions. The med-
ical safety is an important issue in the development of treatments with biologics.
Currently, there is a great need of safe and effective biologics to treat SUDs.
Research is needed to develop vaccines that can elicit high levels of antibody titers
690 I.D. Montoya
References
Anton B, Leff P (2006) A novel bivalent morphine/heroin vaccine that prevents relapse to heroin
addiction in rodents. Vaccine 24:3232–3240
Anton B, Salazar A, Flores A, Matus M, Marin R, Hernandez JA et al (2009) Vaccines against
morphine/heroin and its use as effective medication for preventing relapse to opiate addictive
behaviors. Hum Vaccine 5:214–229
Bonese KF, Wainer BH, Fitch FW, Rothberg RM, Schuster CR (1974) Changes in heroin self-
administration by a rhesus monkey after morphine immunisation. Nature 252:708–710
Brimijoin S, Gao Y, Anker JJ, Gliddon LA, LaFleur D, Shah R et al (2008) A cocaine hydrolase
engineered from human butyrylcholinesterase selectively blocks cocaine toxicity and rein-
statement of drug seeking in rats. Neuropsychopharmacology 33:2715–2725
Carroll FI, Abraham P, Gong PK, Pidaparthi RR, Blough BE, Che Y et al (2009) The synthesis of
haptens and their use for the development of monoclonal antibodies for treating methamphet-
amine abuse. J Med Chem 52:7301–7309
Carroll ME, Gao Y, Brimijoin S, Anker JJ (2011) Effects of cocaine hydrolase on cocaine
self-administration under a PR schedule and during extended access (escalation) in rats.
Psychopharmacology (Berl) 213:817–829
Celtic Pharma (2012a) Study of TA-NIC to assess the efficacy and safety of the vaccine as an aid to
smoking cessation. http://clinicaltrials.gov/ct2/show/NCT00633321
Celtic Pharma (2012b) TA-NIC nicotine dependence. http://www.celticpharma.com/theportfolio/
ta-nic.html
Collins GT1, Brim RL, Noon KR, Narasimhan D, Lukacs NW, Sunahara RK, Woods JH, Ko MC
(2012) Repeated administration of a mutant cocaine esterase: effects on plasma cocaine levels,
cocaine-induced cardiovascular activity, and immune responses in rhesus monkeys.
J Pharmacol Exp Ther 342(1):205–213
Cytos Biotechnology (2012a) New clinical study started with the nicotine vaccine NIC002. http://
www.cytos.com/userfiles/file/Cytos_Press_E_101105.pdf
Cytos Biotechnology (2012b) NIC002 (formerly CYT002-NicQb): a novel vaccine for nicotine
addiction. http://www.cytos.com/doc/NIC002_Nicaddiction_Facts_August07.pdf
de Villiers SH, Lindblom N, Kalayanov G, Gordon S, Malmerfelt A, Johansson AM et al (2002)
Active immunization against nicotine suppresses nicotine-induced dopamine release in the rat
nucleus accumbens shell. Respiration 69:247–253
de Villiers SH, Lindblom N, Kalayanov G, Gordon S, Baraznenok I, Malmerfelt A et al (2010)
Nicotine hapten structure, antibody selectivity and effect relationships: results from a nicotine
vaccine screening procedure. Vaccine 28:2161–2168
Duryee MJ, Bevins RA, Reichel CM, Murray JE, Dong Y, Thiele GM et al (2009) Immune
responses to methamphetamine by active immunization with peptide-based, molecular
adjuvant-containing vaccines. Vaccine 27:2981–2988
Fox BS, Kantak KM, Edwards MA, Black KM, Bollinger BK, Botka AJ et al (1996) Efficacy of
a therapeutic cocaine vaccine in rodent models. Nat Med 2:1129–1132
Gao Y, Orson FM, Kinsey B, Kosten T, Brimijoin S (2010) The concept of pharmacologic cocaine
interception as a treatment for drug abuse. Chem Biol Interact 187:421–424
40 Biologics (Vaccines, Antibodies, Enzymes) to Treat Drug Addictions 691
Gentry WB, Ruedi-Bettschen D, Owens SM (2009) Development of active and passive human
vaccines to treat methamphetamine addiction. Hum Vaccine 5:206–213
Gentry WB, Ruedi-Bettschen D, Owens SM (2010) Anti-(+)-methamphetamine monoclonal
antibody antagonists designed to prevent the progression of human diseases of addiction.
Clin Pharmacol Ther 88:390–393
Godin CS, Shemesh-Davish L, Sklair-Tavron L, Rosenstock M (2012) TV-1380 (Albumin-Fused
Mutated Bche) attenuates the cardiovascular and respiratory effects induced by cocaine in
cynomolgus monkeys. http://www.avanzalaboratories.com/abstract/Teva%20Poster%20SOT
%202010.pdf
Gorelick DA (2012) Pharmacokinetic strategies for treatment of drug overdose and addiction.
Futur Med Chem 4:227–243
Gu F, Langer R, Farokhzad OC (2009) Formulation/preparation of functionalized nanoparticles
for in vivo targeted drug delivery. Methods Mol Biol 544:589–598
Hatsukami DK, Jorenby DE, Gonzales D, Rigotti NA, Glover ED, Oncken CA et al (2011)
Immunogenicity and smoking-cessation outcomes for a novel nicotine
immunotherapeutic. Clin Pharmacol Ther 89:392–399
Hicks MJ, De BP, Rosenberg JB, Davidson JT, Moreno AY, Janda KD et al (2011) Cocaine analog
coupled to disrupted adenovirus: a vaccine strategy to evoke high-titer immunity against
addictive drugs. Mol Ther 19:612–619
Kantak KM (2003) Anti-cocaine vaccines: antibody protection against relapse. Expert Opin
Pharmacother 4:213–218
Kinsey BM, Jackson DC, Orson FM (2009) Anti-drug vaccines to treat substance abuse. Immunol
Cell Biol 87:309–314
Kinsey BM, Kosten TR, Orson FM (2010) Anti-cocaine vaccine development. Expert Rev
Vaccines 9:1109–1114
Kosten TR, Rosen M, Bond J, Settles M, Roberts JS, Shields J et al (2002) Human therapeutic
cocaine vaccine: safety and immunogenicity. Vaccine 20:1196–1204
Li QQ, Luo YX, Sun CY, Xue YX, Zhu WL, Shi HS et al (2011) A morphine/heroin vaccine with
new hapten design attenuates behavioral effects in rats. J Neurochem 119:1271–1281
Martell BA, Mitchell E, Poling J, Gonsai K, Kosten TR (2005) Vaccine pharmacotherapy for the
treatment of cocaine dependence. Biol Psychiatry 58:158–164
McCluskie MJ, Pryde DC, Gervais DP, Stead DR, Zhang N, Benoit M et al (2013) Enhancing
immunogenicity of a 30 aminomethylnicotine-DT-conjugate anti-nicotine vaccine with CpG
adjuvant in mice and non-human primates
McGee D, Godin S (2013) RBP-8000: A Dose Escalation Cocaine Interaction study in Male
Sprague Dawley Rats. Abstract. http://www.smithersavanza.com/documents/Reckitt-Poster-
Abstract-31-Oct-2013.pdf
Montoya ID, Vocci F (2008) Novel medications to treat addictive disorders. Curr Psychiatry Rep
10:392–398
Moreno AY, Mayorov AV, Janda KD (2011) Impact of distinct chemical structures for the
development of a methamphetamine vaccine. J Am Chem Soc 133:6587–6595
Nabi Pharmaceuticals (2012) NicVAX ® (Nicotine Conjugate Vaccine). http://www.nabi.com/
pipeline/pipeline.php?id¼3
Orson FM, Kinsey BM, Singh RA, Wu Y, Gardner T, Kosten TR (2008) Substance abuse vaccines.
Ann N Y Acad Sci 1141:257–269
Peterson EC, Owens SM (2009) Designing immunotherapies to thwart drug abuse. Mol Interv
9:119–124
Pfizer at USB Global Life Sciences Conference – Edited Transcript. Thomson Reuters Streetevents.
(http://www.pfizer.com/files/investors/presentations/public_ubs_transcript_092012.pdf). Accessed
Sept 2012
Pravetoni M, Le NM, Harmon TM, Tucker AM, Portoghese PS, Pentel PR (2012) An oxycodone
conjugate vaccine elicits drug-specific antibodies that reduce oxycodone distribution to brain
and hot-plate analgesia. J Pharmacol Exp Ther 341:225–232
692 I.D. Montoya
Pravetoni M, Le NM, Tucker AM, Harmon TM, Hawley TM, Portoghese PS et al (2013) Reduced
antinociception of opioids in rats and mice by vaccination with immunogens containing
oxycodone and hydrocodone haptens. J Med Chem 56:915–923
Selecta Biosciences (2012) Selecta biosciences initiates phase 1 clinical study of SEL-068, a first-
in-class synthetic nicotine vaccine for smoking cessation and relapse prevention http://www.
selectabio.com/news/recent-news/Selecta-Biosciences-Initiates-Phase-1-Clinical-Study-of-
SEL-068.cfm
Stowe GN, Vendruscolo LF, Edwards S, Schlosburg JE, Misra KK, Schulteis G et al (2011)
A vaccine strategy that induces protective immunity against heroin. J Med Chem
54:5195–5204
Tonstad S, Heggen E, Giljam H, Lagerbäck PÅ, Tønnesen P, Wikingsson LD, Lindblom N,
de Villiers S, Svensson TH, Fagerström KO (2013) Niccine1, a nicotine vaccine, for relapse
prevention: a phase II, randomized, placebo-controlled, multicenter clinical trial. Nicotine Tob
Res 15(9):1492–1501
Treweek JB, Roberts AJ, Janda KD (2011) Immunopharmacotherapeutic manifolds and modula-
tion of cocaine overdose. Pharmacol Biochem Behav 98:474–484
U.S. Food and Drug Administration (1999) Regulation of biological products. 42USC262
[On-line]. http://www.fda.gov/RegulatoryInformation/Legislation/ucm149278.htm
Unknown (2012) Swedish scientists working on Niccine, a vaccine to fight against http://
healthvox.info/?p¼33
Zheng F, Zhan CG (2009) Recent progress in protein drug design and discovery with a focus on
novel approaches to the development of anti-cocaine medications. Futur Med Chem 1:515–528
Zheng F, Yang W, Ko MC, Liu J, Cho H, Gao D et al (2008) Most efficient cocaine hydrolase
designed by virtual screening of transition states. J Am Chem Soc 130:12148–12155
Recent Advances in Drug Development
41
Frank J. Vocci
Contents
41.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 694
41.2 Medications in Development for Treatment of Substance Use Disorders . . . . . . . . . . . . . 695
41.2.1 Pharmacological Treatments for Alcohol Dependence . . . . . . . . . . . . . . . . . . . . . . . 695
41.2.2 Pharmacotherapy of Cannabis Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 698
41.2.3 Pharmacotherapy of Cocaine and Amphetamine/Methamphetamine
Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 700
41.2.4 D3 Dopamine Receptors and Buspirone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 701
41.2.5 Medications for the Treatment of Amphetamine/Methamphetamine
Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 702
41.2.6 Medications for the Treatment of Opioid Dependence . . . . . . . . . . . . . . . . . . . . . . . 704
41.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 707
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 708
Abstract
Encouraging findings are being reported in the development of drugs for the
treatment of addictive disorders. This chapter reviews drug development for
the treatment of alcohol, cannabis, cocaine, opiates, and methamphetamine
dependence. Gabapentin, pregabalin, ondansetron, and sertraline have been
investigated for the management of alcohol dependence in double-blind,
placebo-controlled designs. Gabapentin has been shown in two studies to
reduce the emergence and percentage of heavy drinking days following
alcohol detoxification treatment. Pregabalin was shown to reduce withdrawal
F.J. Vocci
Friends Research Institute, Inc., Baltimore, MD, USA
e-mail: [email protected]
41.1 Introduction
The development of medications for the treatment of addictive disorders has had
some successes in the treatment of alcohol dependence (acamprosate, oral and
extended-release naltrexone, and disulfiram), nicotine dependence (nicotine
replacement therapies and bupropion), and opioid dependence (methadone, oral
and extended-release naltrexone, buprenorphine, and buprenorphine/naloxone),
while there are no marketed pharmacotherapies for the treatment of cannabis,
cocaine, or methamphetamine dependence. There are 26 medications in develop-
ment for addictive disorders by the pharmaceutical industry (Pharmaceutical
Research Manufacturers Association [PhRMA] report 2012). Some of these
development projects are partially supported by funding from the US National
Institutes of Health. Of these 26 medications, some are being investigated for
multiple drug dependencies. Thus, there are seven medications being evaluated
for each of cocaine, opiate, and nicotine dependencies, while there are five
medications being developed for alcohol dependence treatment and three for
methamphetamine dependence treatment. Additionally, the medications develop-
ment programs of the National Institute on Drug Abuse and the National Institute
on Alcohol Abuse and Alcoholism support clinical studies of investigational and
marketed medications that are not on the list from the PhRMA. Reviewing all the
medications on the PhRMA list is beyond the scope of this chapter. This review
will survey developments for the treatment of alcohol, cannabis, cocaine, opiates,
and methamphetamine dependence that were recently published in the medical
literature.
41 Recent Advances in Drug Development 695
Table 41.1 Clinical studies of the efficacy of GPN in the treatment of alcohol dependence
GPN dose
and Comparator
Study design Sample size duration medication Results Reference
Randomized, 60 males 300 mg bid Placebo GPN reduced the Furieri and
double blind for 30 days number of drinks per Nakamura-
day, % heavy drinking Palacios
days both (p ¼ 0.02) and (2007)
increased % days
abstinent (p ¼ 0.008)
Randomized, 11 males Titration up Placebo GPN reduced onset to Brower
double blind and to 1,500 mg heavy drinking effect et al. (2008)
10 females per day. relative to placebo;
Dosed for effect persisted for
6 weeks 6 weeks (p ¼ 0.003 at
12 weeks)
Randomized, 60 Titration up Placebo GPN GPN differential Anton
double blind to 1,200 mg; and placebo efficacy: better et al. (2009)
dosed for flumazenil modulation of
39 days. withdrawal in those with
2 doses of more severe withdrawal,
flumazenil more % days abstinent
(2 mg) on and more time to first
2 successive heavy drinking episode.
days Effects persisted for
8 weeks post-dosing
Randomized, 150; Titration up Respective First 6 weeks: Anton
double blind 119 male to 1,200 mg placebos GPN/naltrexone group et al. (2011)
per day with had longer delay to
or without heavy drinking
50 mg (p ¼ 0.04) and less
naltrexone heavy drinking days
per day than naltrexone only
group (p ¼ 0.0002) and
less drinks/drinking day
than naltrexone only
group (p ¼ 0.02) and
placebo group
(p ¼ 0.01)
Randomized, 190 evaluated, Up to 450 mg per Lorazepam up to All groups had significant withdrawal score Martinotti
multicenter, 111 enrolled 69 males day for 2 weeks 10 mg/day for 14 days; reduction on the CIWA alcohol scale with et al. (2010a)
single blind 42 females, tiapride up to a greater effect of pregabalin on headache and
N ¼ 37/group 800 mg/day for 14 days orientation (p < 0.001); all groups reported less
craving; less relapse in the pregabalin group
(p < 0.05); less retention in the tiapride group
(p < 0.05)
Randomized, 71 enrolled 54 males, Up to 450 mg/day, Naltrexone 50 mg/day; No group differences in abstinence or craving Martinotti
double blind 59 detoxed X ¼ 275.8 mg/day for 16 weeks; 21/28 scores; % of abstinent pregabalin patients with et al. (2010b)
N ¼ 31 pregabalin, for 16 weeks; 27/31 completed dual diagnosis was significantly higher than in the
N ¼ 28 naltrexone completed naltrexone group (p < 0.05); CIWA-AR scores
Both groups have had reduced in both groups, with a greater reduction
equivalent Axis in the pregabalin group (p < 0.05)
I comorbid patients
697
698 F.J. Vocci
Relative to the findings in the placebo group, GPN reduced cannabis use
as determined by weekly urine toxicology (p ¼ 0.001) and self-report results
(p ¼ 0.004). GPN also significantly reduced withdrawal symptoms (p ¼ 0.001),
craving (p ¼ 0.001), and Beck Depression Inventory scores (p ¼ 0.009). Sleep was
also improved in the GPN group as determined by the Pittsburgh Sleep Quality
Index (p < 0.001). The GPN medicated group showed improvement, relative to
their baseline scores, on the Marijuana Problems Scale score (p ¼ 0.02). The GPN
group also showed greater improvement relative to placebo on a composite score of
the three executive function tests (p ¼ 0.029). GPN is a promising candidate
medication for the treatment of cannabis dependence. The results need to be replicated
before GPN can be recommended as a treatment for cannabis dependence.
Nabilone is a synthetic cannabinoid medication. It has been compared to THC
(dronabinol) in a clinical pharmacology study of its subjective, cognitive, and cardio-
vascular effects in ten current adult marijuana smokers (Bedi et al. 2012). Nabilone
(2 mg) decreased systolic blood pressure and higher doses (4, 6, 8 mg) produced
cannabinoid-like subjective effects. Doses of 6 or 8 mg of nabilone decreased psycho-
motor speed. Nabilone had a slower time to peak effects than THC and its effects were
more dose-related than THC. The authors speculated that the dose-relatedness might be
due to nabilone having more reliable bioavailability that THC.
A second study evaluated nabilone’s ability to affect marijuana withdrawal
symptoms and a measure of relapse (Haney et al. 2013). Eleven marijuana smokers
were administered three doses of nabilone (0, 6, and 8 mg) in a counterbalanced
order during times of marijuana abstinence (three consecutive days of placebo
marijuana) in the clinical pharmacology laboratory. Both active doses of nabilone
decreased marijuana withdrawal-related irritability and sleep disruptions (p < 0.05).
700 F.J. Vocci
Food intake was increased relative to placebo when 6 or 8 mg doses of nabilone were
administered during the marijuana withdrawal period. Participants engaged in more
eating sessions (p < 0.01) and increased the caloric intake during each eating session.
Nabilone doses of 6 and 8 mg also reduced self-administration of marijuana puffs,
a laboratory measure of marijuana relapse. Interestingly, nabilone did not produce
“liking” or a desire to take the nabilone capsules.
The data from the two studies discussed above suggest that nabilone should be
evaluated as a treatment for cannabis dependence. The clinical pharmacology
studies provide a rationale and the dose range for a phase II outpatient study.
There was no difference in cocaine usage across the three study groups by the
GEE analysis. The study also replicated the analysis used by Dackis et al. (2005)
wherein missing urines were counted as positive for cocaine. This analysis also did
not reveal a treatment effect favoring the modafinil groups. A secondary analysis of
participants who did not have an alcohol dependence history or current alcohol
dependence (n ¼ 125) revealed a significant increase (p ¼ 0.02) in cocaine nonuse
days for the 200 mg (8.9 %) and 400 mg (8.5 %) modafinil groups relative to
placebo. These non-alcohol-dependent modafinil subgroups also had a greater
number of consecutive nonuse days, relative to the placebo group (p ¼ 0.01).
Craving was reduced in the 200 mg modafinil group although the effect was not
statistically significant when corrected for multiple comparisons.
The second trial was a randomized, double-blind placebo-controlled trial of
210 cocaine-dependent participants who were randomized to a 200 mg modafinil
(n ¼ 65), 400 mg modafinil (n ¼ 70), or a placebo group (n ¼ 75) (Dackis
et al. 2012). Unlike the Anderson et al. 2009 trial, prospective participants were
excluded if they had any other drug dependencies. Thus, this group was a better
match for the patient population from the first Dackis et al. (2005) study. The
primary outcome variable was cocaine abstinence inferred by urine drug screens.
Missing urines were imputed as positive. Other outcome measures assessed were
withdrawal signs and symptoms, cocaine craving, and study retention.
There were no significant differences in cocaine abstinence across the three
groups. The only trend (p ¼ 0.06) seen favoring modafinil was in males in the
400 mg group versus males receiving placebo. There were no significant differ-
ences across groups on the other variables of interest.
The results of these two studies must be viewed as a disappointment as neither
provided a robust signal of efficacy. It is conceivable that a combined analysis of
these data sets could boost the power to determine differences across treatment
groups.
D3 dopamine receptors are located in limbic areas associated with cue- and drug-
induced drug reward (Micheli and Heidbreder 2008). Cocaine produces an increase
in D3 receptor mRNA and D3 receptor density in the rodent brain. Increases in D3
mRNA and receptors have been reported following cocaine cue-induced locomo-
tion in mice (Le Foll et al. 2002) and a course of cocaine self-administration in rats
(Neisewander et al. 2004). Upregulation of D3 mRNA (Segal et al. 1997) and D3
receptors have been reported in cocaine overdose fatalities (Staley and Mash 1996).
These cocaine-induced neurobiological changes in D3 receptor density (and pre-
sumably, sensitivity to dopamine) may be a major determinant of cocaine-seeking
behavior, in that they may enhance the reinforcing effects of cocaine use. D3
dopamine antagonists can block cue-induced, drug-primed, and stress-induced
reinstatement of cocaine self-administration in rodents (Heidbreder 2008).
702 F.J. Vocci
Two clinical trials have been conducted that suggest bupropion can reduce meth-
amphetamine use in light users (Elkashef et al. 2008; Shoptaw et al. 2008). Both of
these studies evaluated 150 mg bid versus a placebo. Although the primary end-
point of statistically significant reduction of methamphetamine use was not
achieved in either study, Elkashef et al. showed that bupropion significantly
reduced methamphetamine use (p < 0.001) in light to moderate users (1–18 days
of use per month at baseline). Similarly, Shoptaw et al. reported that bupropion also
significantly reduced methamphetamine use (p < 0.001) in light methamphetamine
users (defined as having 0–2 positive urines uses out of a possible six during
the baseline period). McCann and Li (2012) conducted an analysis of individuals
within groups who achieved multiple weeks of abstinence. In this analysis,
bupropion significantly facilitated abstinence (p ¼ 0.0176). Brensilver et al.
(2012) reanalyzed the data on light to moderate users in the Elkashef et al.
and Shoptaw et al. trials. These authors concluded that the inability to achieve at
least three methamphetamine negative urine samples predicted a greater than
90 % likelihood of treatment failure. Thus, the primary trials and their reanalyses
41 Recent Advances in Drug Development 703
suggest a patient population that may be responsive to bupropion and the time
frame that at least a partial response should be seen.
Methylphenidate has been evaluated as a treatment agent for amphetamine depen-
dence in a study in Finland (Tiihonen et al. 2007). In this study 53 intravenous
amphetamine users were randomized to aripiprazole (15 mg/day), methylphenidate
(54 mg per day), or placebo. The medication portion of the trial was 20 weeks. The
primary outcome measure was amphetamine use as measured by urine toxicology.
There were fewer amphetamine positive urines in the methylphenidate-treated group.
A follow-up trial to assess the efficacy of extended-release methylphenidate was
conducted in Finland and New Zealand (Miles et al. 2013). Seventy-nine partici-
pants were randomized to either the methylphenidate (54 mg/day) or placebo group.
The trial duration of 20 weeks was identical to the initial Tiihonen et al. (2007)
study. There was no difference seen in amphetamine use between the two groups
although retention was superior in the methylphenidate group (p < 0.05).
Naltrexone (50 mg/day, po) was found to reduce relapse in amphetamine-
dependent trial participants (Jayaram-Lindstrom et al. 2008). Although no direct
confirmatory trials have been reported in the extant literature, there are two
publications that utilized naltrexone implants. The first was a study that randomized
100 amphetamine and opiate dually dependent participants to a naltrexone or
placebo rod (Tiihonen et al. 2012). The primary outcome variables were urines
negative for amphetamine and opiates and retention in the study. Missing urines
were imputed as positive for the analysis. The naltrexone group had more drug-free
urines (38 %) versus the placebo group (16 %) (p ¼ 0.01). The number of
amphetamine free urines was not statistically different across groups in a weekly
drug use analysis. However, the number of times used per week was almost
statistically significant (p ¼ 0.06) with less days of use in the naltrexone group.
Retention was greater in the naltrexone group (p ¼ 0.01). Kelty et al. (2013)
conducted a retrospective review of amphetamine-dependent users who were
treated with naltrexone implants in Australia. Forty-four patients who received
naltrexone implants gave self-report data on their amphetamine use. Almost 70 %
claimed to be abstinent for at least 1 month. Of the 29 patients claiming abstinence
at 1 month, 14 claimed to be abstinent at 6 months. The authors correlated
abstinence with naltrexone blood levels and reported a direct relationship between
blood levels and abstinence: those with a blood level greater than 2 ng/mL,
1–2 ng/mL, and less than 1 ng/mL had reported abstinence rates of 91 %, 43 %,
and 39 %, respectively. Future trials need to incorporate urinalysis confirming
abstinence with blood levels above 2 ng/mL as a threshold target in future trials.
Elkashef and colleagues (2012) evaluated the potential efficacy of topiramate
versus placebo in the treatment of methamphetamine dependence in a randomized,
double-blind, multicenter trial. One hundred forty methamphetamine-dependent
adults received topiramate in a titrating dose schedule. The initial dose of 25 mg
per day was ramped up to a maximum of 200 mg per day by the end of week
6. Doses were then kept constant for the next 6 weeks. The primary outcome
measure was negative “methamphetamine use week” during weeks 6–12, analyzed
using a GEE method.
704 F.J. Vocci
There were no differences in methamphetamine use in weeks 6–12 across the two
groups. However, when those participants in each group whose last baseline urine
before randomization was negative (n ¼ 13 in both the topiramate and placebo
groups) were analyzed, the topiramate group had less methamphetamine use
(p ¼ 0.02). This finding suggests that topiramate should be reevaluated as a relapse
prevention agent in methamphetamine-dependent populations (Vocci 2012).
seen during the screening period when buprenorphine dosing was administered
sublingually (0.72 0.30 ng/mL). The terminal plasma half-life of buprenorphine
post-removal of the implants was 23.8 8.6 h.
A multicenter trial of the buprenorphine implant was performed in 18 centers in
the United States (Ling et al. 2010). One hundred sixty-three male and nonpregnant
female opioid-dependent study participants were randomized under double-blind
conditions to the buprenorphine rods (four implants) or placebo (four implants) in
a 2:1 ratio. All study participants were inducted onto 12–16 mg of sublingual
buprenorphine and had to be maintained at that dose for 3 days before
randomization.
In this trial supplemental sublingual buprenorphine, up to 12 mg, was allowed if
participants experienced significant withdrawal or craving. An additional implant
was also permitted if participants required supplemental buprenorphine more
than 3 days in 1 week or 8 days over a 4-week period. Sixty-four of the
108 buprenorphine-implanted participants received supplemental buprenorphine
for a median time of 7.5 days, whereas 91 % of the placebo group was
supplemented with buprenorphine for a median time of 19.5 days during the first
16 weeks. The implants were removed after 6 months.
In addition to urine toxicology to determine opiate use, the Clinician Opiate
Withdrawal Scale (COWS), the SOWS, a visual analog scale for craving, and
Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) were
obtained at baseline, 16 and 24 weeks.
Participants in the buprenorphine implant group used less opiates (40.4 % opiate
negative versus 28 % negative in the placebo group) as measured by urine toxicol-
ogy results (p ¼ 0.04). Additionally, the buprenorphine implant group had lower
scores on the COWS (p < 0.001), SOWS (p ¼ 0.004), and the visual analog craving
scale (p < 0.001). Lower scores were recorded in the buprenorphine group on
the CGI-S (p < 0.001) with a corresponding improvement on the CGI-I scale
(p < 0.001). Retention favored the buprenorphine implant versus placebo groups
with 67.5 % and 30 % retention, respectively (p < 0.001).
Two serious adverse events (SAEs) were reported in the buprenorphine group
and four were reported in the placebo group. One of the SAEs in the buprenorphine
group was thought to be possibly treatment-related: one participant with a history of
chronic obstructive pulmonary disease and embolism experienced an exacerbation
of these conditions. One placebo participant developed a cellulitis at the implant
site that required hospitalization, debridement, and drainage. The other SAEs in
either group were not treatment-related. Most of the adverse events in the
buprenorphine group were implant site-related; three participants discontinued
due to implant site pain (n ¼ 1) or pain and infection (n ¼ 2). No placebo
participants discontinued due to adverse events.
A second, multicenter trial of the buprenorphine implants was conducted in
20 sites in the United States (Ling and Beebe 2013). Opiate-dependent, adult males
and nonpregnant females (n ¼ 287) were randomized in a double-blind fashion to
a buprenorphine implant group (four implants) or a placebo group (four implants)
and a sublingual buprenorphine group in an open-label fashion. The primary
706 F.J. Vocci
outcomes were the comparison of the two implant groups and the comparison of the
buprenorphine implant group to the open-label buprenorphine/naloxone group.
At the conclusion of the 6-month trial, all study completers were allowed to
enroll in a 6-month open-label extension of the buprenorphine implants.
In the comparison of the implant groups, the buprenorphine implant group had
a greater percentage of opiate negative urines (p < 0.0001) and greater retention
(64 % vs. 25 %, p < 0.0002). The implant group response was also shown to be
non-inferior to the sublingual buprenorphine group response at a pre-specified
non-inferiority level of 15 %.
A long-acting, injectable preparation of buprenorphine is being developed by
Camurus (2013). Depending on the lipid composition of the controlled-release
matrix, an injection could produce therapeutic blood levels last for 1 week or
1 month. A safety, efficacy, and pharmacokinetics study of the 1-week preparation
in 41 opiate-dependent individuals was reported on the company’s website. Dose-
proportional and dose-linear kinetics were observed after a single injection of
buprenorphine (CAM2038). SOWS and COWS assessments were “well controlled
for up to 10 days after single dose injection of CAM2038.” These results obviously
need to be published in a peer-reviewed journal but, if verified, would give clinician’s
another option to treat opioid dependence with minimal concern about diversion.
Methadone is available as a racemic mixture for treatment of opioid dependence.
Besides an effect on respiratory depression, racemic methadone has effects on cardiac
repolarization by virtue of its ability to block the inwardly rectifying K+ channel (IKr)
in the myocardium. The human ether-a-go-go-related (HERG) gene encodes the
potassium channel current. Methadone blocks the HERG channel at Cmax concen-
trations seen in human populations (Katchman et al. 2002). The delayed repolariza-
tion produced by methadone (and other medications that block the IKr channel)
results in a prolongation of the QT interval in the ECG. There are numerous case
reports in the literature of methadone’s ability to prolong the QT interval (Andrews
et al. 2009) along with cohort studies (Maremmani et al. 2005; Ehret et al. 2006;
Fanoe et al. 2007). The QT interval associated with chronic methadone treatment at
a fixed dose has been reported to increase (Andrews et al. 2009). Martell et al. (2005)
reported that methadone increased the QTc by an average of 12 ms and the increase
was correlated to both trough and peak methadone serum levels. Roy et al. (2012)
reported that 11.1 % of 180 patients enrolled in a methadone clinic had QTc intervals
greater than 450 ms. In the cohort reported by Ehret et al. (2006), 16 % of the group
has a QTc >500 ms, and 3.6 % developed torsades de pointes (TdP). Fanoe
et al. (2007) calculated that each 1 mg increase in methadone dose increased the
QTc by 0.14 ms. Thus, methadone may produce toxicity through both respiratory and
cardiac mechanisms (QT prolongation that could lead to TdP).
The R-isomer (l-methadone or levomethadone) has been reported to be ten times
more potent at mu receptor binding sites than the S-isomer (Kristensen et al. 1995)
and twice as potent as racemic (R,S) methadone. The S-isomer has been reported to
be 3.5 times more potent than the R-isomer in blocking the HERG channel (Eap
et al. 2007). Thus, the S-isomer is likely to be a greater contributor to QT prolon-
gation than the R-isomer when the racemic mixture is given. In 39 patients
41 Recent Advances in Drug Development 707
41.3 Conclusion
References
Ait-Daoud N, Roache JD, Dawes MA, Liu L, Wang XQ, Javors MA, Seneviratne C, Johnson BA
(2009) Can serotonin transporter genotype predict craving in alcoholism? Alcohol Clin Exp
Res 33:1329–1335
Anderson AL, Reid MS, Li SH, Holmes T, Shemanski L, Slee A, Smith EV, Kahn R, Chiang N,
Vocci F, Ciraulo D, Dackis C, Roache JD, Salloum IM, Somoza E, Urschel HC 3rd, Elkashef
AM (2009) Modafinil for the treatment of cocaine dependence. Drug Alcohol Depend
104:133–139
Andrews CM, Krantz MJ, Wedam EF, Marcuson MJ, Capacchione JF, Haigney MC (2009)
Methadone-induced mortality in the treatment of chronic pain: role of QT prolongation.
Cardiol J 16:210–217
Ansermot N, Albayrak O, Schlapfer J, Crettol S, Croquette-Krokar M, Bourquin M, Deglon JJ,
Faouzi M, Scherbaum N, Eap CB (2010) Substitution of (R, S)-methadone by (R)-methadone:
impact on QTc interval. Arch Intern Med 170:529–536
Anton RF, Myrick H, Baros AM, Latham PK, Randall PK, Wright TM, Stewart SH, Waid R,
Malcolm R (2009) Efficacy of a combination of flumazenil and gabapentin in the treatment of
alcohol dependence: relationship to alcohol withdrawal symptoms. J Clin Psychopharmacol
29:334–342
Anton RF, Myrick H, Wright TM, Latham PK, Baros AM, Waid LR, Randall PK
(2011) Gabapentin combined with naltrexone for the treatment of alcohol dependence.
Am J Psychiatry 168:709–717
41 Recent Advances in Drug Development 709
Beardsley PM, Shelton KL, Hendrick E (2010) Effects of ATDP 30,120 on stress-induced
reinstatement of level pressing previously reinforced by cocaine in the rat. [Unpublished
Work]. NIDA Contract N01DA-8-8889
Bedi G, Cooper ZD, Haney M (2012) Subjective, cognitive and cardiovascular dose-effect profile
of nabilone and dronabinol in marijuana smokers. Addict Biol. doi:10.1111/j.1369-
1600.2011.00427.x [Epub ahead of print]
Bergman J, Roof RA, Furman CA, Conroy JL, Mello NK, Sibley DR, Skolnick P (2013)
Modification of cocaine self-administration by buspirone (buspar ®): potential involvement of
D3 and D4 dopamine receptors. Int J Neuropsychopharmacol 16:445–458
Brensilver M, Heinzerling KG, Swanson AN, Shoptaw SJ (2012) A retrospective analysis of two
randomized trials of bupropion for methamphetamine dependence: suggested guidelines for
treatment discontinuation/augmentation. Drug Alcohol Depend 125:169–172
Brower KJ, Myra Kim H, Strobbe S, Karam-Hage MA, Consens F, Zucker RA
(2008) A randomized double-blind pilot trial of gabapentin versus placebo to treat alcohol
dependence and comorbid insomnia. Alcohol Clin Exp Res 32:1429–1438
CAMURUS (n.d.) Cam2038 drug addiction. Resource document. http://www.camurus.com/index.
asp?DocumentID¼2&DocumentIDSub¼5&Lang¼sv&ShowSub¼(4)&Show¼(2)&main
¼Products&searchres¼CAM2038. Accessed 11 Mar 2013
Dackis CA, Kampman KM, Lynch KG, Pettinati HM, O’Brien CP (2005) A double-blind,
placebo-controlled trial of modafinil for cocaine dependence. Neuropsychopharmacology
30:205–211
Dackis CA, Kampman KM, Lynch KG, Plebani JG, Pettinati HM, Sparkman T, O’Brien CP
(2012) A double-blind, placebo-controlled trial of modafinil for cocaine dependence. J Subst
Abus Treat 43:303–312
Dasgupta N, Bailey EJ, Cicero T, Inciardi J, Parrino M, Rosenblum A, Dart RC (2010) Post-
marketing surveillance of methadone and buprenorphine in the United States. Pain Med
11:1078–1091
Drugs.com (2013) Top 100 drugs for 2012 by sales. Resource document. http://www.drugs.com/
stats/top100/2012/sales. Accessed 2 Apr 2013
Eap CB, Crettol S, Rougier JS, Schlapfer J, Sintra Grilo L, Deglon JJ, Besson J, Croquette-
Krokar M, Carrupt PA, Abriel H (2007) Stereoselective block of hERG channel by
(S)-methadone and QT interval prolongation in CYP2B6 slow metabolizers. Clin Pharmacol
Ther 81:719–728
Ehret GB, Voide C, Gex-Fabry M, Chabert J, Shah D, Broers B, Piguet V, Musset T, Gaspoz JM,
Perrier A, Dayer P, Desmeules JA (2006) Drug-induced long QT syndrome in injection drug
users receiving methadone: high frequency in hospitalized patients and risk factors. Arch
Intern Med 166:1280–1287
Elkashef AM, Rawson RA, Anderson AL, Li SH, Holmes T, Smith EV, Chiang N, Kahn R,
Vocci F, Ling W, Pearce VJ, McCann M, Campbell J, Gorodetzky C, Haning W, Carlton B,
Mawhinney J, Weis D (2008) Bupropion for the treatment of methamphetamine dependence.
Neuropsychopharmacology 33:1162–1170
Elkashef A, Kahn R, Yu E, Iturriaga E, Li SH, Anderson A, Chiang N, Ait-Daoud N, Weiss D,
McSherry F, Serpi T, Rawson R, Hrymoc M, Weis D, McCann M, Pham T, Stock C,
Dickinson R, Campbell J, Gorodetzky C, Haning W, Carlton B, Mawhinney J, Li MD,
Johnson BA (2012) Topiramate for the treatment of methamphetamine addiction: a multi-
center placebo-controlled trial. Addiction 107:1297–1306
Fanoe S, Hvidt C, Ege P, Jensen GB (2007) Syncope and QT prolongation among patients
treated with methadone for heroin dependence in the city of copenhagen. Heart
93:1051–1055
Furieri FA, Nakamura-Palacios EM (2007) Gabapentin reduces alcohol consumption and craving:
a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 68:1691–1700
Giannini AJ, Loiselle RH, Graham BH, Folts DJ (1993) Behavioral response to buspirone in
cocaine and phencyclidine withdrawal. J Subst Abus Treat 10:523–527
710 F.J. Vocci
Haney M, Cooper ZD, Bedi G, Vosburg SK, Comer SD, Foltin RW (2013) Nabilone decreases
marijuana withdrawal and a laboratory measure of marijuana relapse. Neuropsychophar-
macology. doi:10.1038/npp.2013.54 [Epub ahead of print]
Heidbreder C (2008) Selective antagonism at dopamine D3 receptors as a target for drug addiction
pharmacotherapy: a review of preclinical evidence. CNS Neurol Disord Drug Targets
7:410–421
Homberg JR, Arends B, Wardeh G, Raaso HS, Schoffelmeer AN, de Vries TJ (2004) Individual
differences in the effects of serotonergic anxiolytic drugs on the motivation to self-administer
cocaine. Neuroscience 128:121–130
Jayaram-Lindstrom N, Hammarberg A, Beck O, Franck J (2008) Naltrexone for the treatment of
amphetamine dependence: a randomized, placebo-controlled trial. Am J Psychiatry
165:1442–1448
Johnson BA, Ait-Daoud N, Seneviratne C, Roache JD, Javors MA, Wang XQ, Liu L, Penberthy
JK, DiClemente CC, Li MD (2011) Pharmacogenetic approach at the serotonin transporter
gene as a method of reducing the severity of alcohol drinking. Am J Psychiatry 168:265–275
Katchman AN, McGroary KA, Kilborn MJ, Kornick CA, Manfredi PL, Woosley RL, Ebert SN
(2002) Influence of opioid agonists on cardiac human ether-a-go-go-related gene K(+)
currents. J Pharmacol Exp Ther 303:688–694
Kelty E, Thomson K, Carlstein S, Sinclair R, Hulse G (2013) A retrospective assessment of the use
of naltrexone implants for the treatment of problematic amphetamine use. Am J Addict 22:1–6
Kranzler HR, Armeli S, Tennen H, Covault J, Feinn R, Arias AJ, Pettinati H, Oncken C (2011)
A double-blind, randomized trial of sertraline for alcohol dependence: moderation by age of
onset [corrected] and 5-hydroxytryptamine transporter-linked promoter region genotype.
J Clin Psychopharmacol 31:22–30
Kranzler HR, Armeli S, Tennen H (2012) Post-treatment outcomes in a double-blind, randomized
trial of sertraline for alcohol dependence. Alcohol Clin Exp Res 36:739–744
Kristensen K, Christensen CB, Christrup LL (1995) The mu1, mu2, delta, kappa opioid receptor
binding profiles of methadone stereoisomers and morphine. Life Sci 56:PL45–PL50
Le Foll B, Frances H, Diaz J, Schwartz JC, Sokoloff P (2002) Role of the dopamine D3 receptor in
reactivity to cocaine-associated cues in mice. Eur J Neurosci 15:2016–2026
Ling W, Beebe KL (2013) Results of a six month, randomized, controlled, confirmatory phase III
trial comparing the efficacy and safety of buprenorphine implants to placebo implants, and
sublingual buprenorphine/naloxone for opioid addiction. Presented at the American Society of
Addiction Medicine. Chicago
Ling W, Casadonte P, Bigelow G, Kampman KM, Patkar A, Bailey GL, Rosenthal RN, Beebe KL
(2010) Buprenorphine implants for treatment of opioid dependence: a randomized controlled
trial. JAMA 304:1576–1583
Maremmani I, Pacini M, Cesaroni C, Lovrecic M, Perugi G, Tagliamonte A (2005) QTc interval
prolongation in patients on long-term methadone maintenance therapy. Eur Addict Res
11:44–49
Mariani JJ, Pavlicova M, Bisaga A, Nunes EV, Brooks DJ, Levin FR (2012) Extended-release
mixed amphetamine salts and topiramate for cocaine dependence: a randomized controlled
trial. Biol Psychiatry 72:950–956
Martell BA, Arnsten JH, Krantz MJ, Gourevitch MN (2005) Impact of methadone treatment on
cardiac repolarization and conduction in opioid users. Am J Cardiol 95:915–918
Martinotti G, Di Nicola M, Tedeschi D, Mazza M, Janiri L, Bria P (2008) Efficacy and safety of
pregabalin in alcohol dependence. Adv Ther 25:608–618
Martinotti G, di Nicola M, Frustaci A, Romanelli R, Tedeschi D, Guglielmo R, Guerriero L,
Bruschi A, De Filippis R, Pozzi G, Di Giannantonio M, Bria P, Janiri L (2010a) Pregabalin,
tiapride and lorazepam in alcohol withdrawal syndrome: a multi-centre, randomized, single-
blind comparison trial. Addiction 105:288–299
Martinotti G, Di Nicola M, Tedeschi D, Andreoli S, Reina D, Pomponi M, Mazza M, Romanelli R,
Moroni N, De Filippis R, Di Giannantonio M, Pozzi G, Bria P, Janiri L (2010b) Pregabalin
41 Recent Advances in Drug Development 711
Toll L, Berzetei-Gurske I, Polgar W, O’Brien A, Rodriguez L (2008) Receptor activity testing for
medication discovery [Unpublished Work]. NIDA contract N01DA-7-8072
Verthein U, Ullmann R, Lachmann A, During A, Koch B, Meyer-Thompson HG, Schmidt R,
Reimer J, Haasen C (2005) The effects of racemic D, L-methadone and L-methadone in
substituted patients – a randomized controlled study. Drug Alcohol Depend 80:267–271
Vocci F (2012) Commentary on Elkashef et al.: just enough efficacy for a second look. Addiction
107:1307–1308
White J, Bell J, Saunders JB, Williamson P, Makowska M, Farquharson A, Beebe KL
(2009) Open-label dose-finding trial of buprenorphine implants (probuphine) for treatment of
heroin dependence. Drug Alcohol Depend 103:37–43
Winchell C, Rappaport BA, Roca R, Rosebraugh CJ (2012) Reanalysis of methamphetamine
dependence treatment trial. CNS Neurosci Ther 18:367–368
Winhusen T, Brady KT, Stitzer M, Woody G, Lindblad R, Kropp F, Brigham G, Liu D,
Sparenborg S, Sharma G, Vanveldhuisen P, Adinoff B, Somoza E (2012) Evaluation of
buspirone for relapse-prevention in adults with cocaine dependence: an efficacy trial conducted
in the real world. Contemp Clin Trials 33:993–1002
Evaluating the Therapeutic Utility of
Hallucinogens for Substance Use 42
Disorders
Elias Dakwar
Contents
42.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 714
42.2 Classifications, Properties, and Historical Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 715
42.2.1 Classifications and Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 715
42.2.2 Psychoactive Properties and Risks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 717
42.2.3 Historical Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 719
42.3 Hallucinogen-Based Treatment Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 721
42.3.1 Negative Reinforcement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 721
42.3.2 Psycholytic Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 721
42.3.3 Psychedelic Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 722
42.3.4 Hallucinogen-Facilitated Therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 723
42.3.5 Neurobiological Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 724
42.4 Evidence for Efficacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 724
42.4.1 Clinical Evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 724
42.4.2 Mechanism-Oriented Evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 725
42.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 726
42.5.1 Medicine, or Drugs of Abuse? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 727
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 729
Abstract
Hallucinogens represent a promising but controversial treatment for substance
use disorders. Research into their efficacy and clinical feasibility has been
hampered, however, by legal, cultural, and political restrictions since the late
1960s, when many of these substances were criminalized. In light of these
substantial limitations, this chapter evaluates what is known about the uses of
hallucinogens in the treatment of substance use disorders. First, the neurobio-
logical and psychoactive effects of hallucinogens are summarized. The relevance
E. Dakwar
New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons,
New York, NY, USA
e-mail: [email protected]
42.1 Introduction
a Phenethylamines H
OCH3 OCH3
H3CO NH2 NH2 NH2 O N CH3
H CH3 H2C
H3CO “R” “R”
O CH3
OCH3 OCH3 OCH3
Mescaline “2C” compounds “Amphetamines” 3, 4-Methylenedioxymethamphetamine
R = CH3; DOM (MDMDA)
R = Br; DOB
R = I, DOI
R = CF3; DOTFM
b Indoleamines
N(C2H5)2 NH2
O O
HN HN
N N
LSD LSA
(H3C)2HC
N N NH2 N N CH(CH3)2
OH
O
P OH
O NH NH NH NH NH
HO H3CO H3CO
Psilocybin DMT Bufotenine 5-MeO-DMT 5-MeO-DIPT
N N
N N
NH NH
NH
NH
and functional connectivity are consistent with brain activity associated with other
altered states, such as meditation and psychosis, as well as with the subacute effects of
sub-anesthetic ketamine (Scheidegger et al. 2012). The diminution in prefrontal CBF
and activity found with IV psilocybin, however, has yet to be replicated by other
groups. It is also unclear whether this effect on CBF is indeed crucial to the
psychoactive effects of psilocybin or whether it is an epiphenomenon of
tryptamine-like vasoconstriction.
with individuals continuing to report 1 year later that the experience was among the
most important in their lives (Griffiths et al. 2006, 2008).
As we will see later, these various alterations in consciousness are believed by
some treatment models to serve as the psychological mechanisms by which clinical
improvement for addictive disorders occurs. However, these same alterations also
represent the greatest source of toxicity, especially when the hallucinogen is
consumed by unprepared or unstable individuals, or in the absence of a supportive,
responsive framework. In such circumstances, hallucinogens may lead to acute
behavioral disturbances or persistent distress that may require emergency treat-
ment. Common adverse effects of hallucinogens include anxiety or dysphoria,
generally circumscribed to the period of intoxication; loss of behavioral control
during acute intoxication, including passivity, disorganization, indecision, and
suboptimal functioning; and more rarely, precipitation of persistent anxiety, affec-
tive, or psychotic disturbances in vulnerable individuals (Bakalar and Grinspoon
1997; Vollenweider and Kometer 2010; Johnson et al. 2008; Imperi et al. 1968).
The criminalization of hallucinogens was buttressed by various claims of risk that
are now recognized as false, but which have managed to persist despite no supportive
evidence (Bakalar and Grinspoon 1997). These unsubstantiated claims include
concerns that classical hallucinogens cause chromosomal damage (Cohen and
Shiloh 1977–1978); that they lead to suicide, murder, or debauchery, even when
used in appropriate clinical settings (Malleson 1971; Studerus et al. 2011); or that
they engender schizotypal personality changes or lasting psychotic disturbances in
individuals without a preexisting vulnerability (Malleson 1971; Studerus et al. 2011;
Vardy and Kay 1983).
Though hallucinogens may be used irresponsibly or abused (e.g., repeatedly
ingested despite the emergence of behavioral distress or other adverse effects),
classical hallucinogens do not present a risk for dependence according to animal
models; they are not self-administered, do not create conditioned place preference
or physiological dependence, and do not lead to dopamine release from reward
pathways (Fantegrossi et al. 2008).
Recent polls in the United States parallel these findings and strongly suggest that
hallucinogens are infrequently used and do not create dependence phenomena.
Hallucinogens are used most commonly in late adolescence and young adulthood,
with up to 11 % of 12th graders having used at least once, and their use is generally
sporadic, clustered, or infrequent. Even heavy users do not use more than two or
three times a week, and it is uncommon for hallucinogen use to persist beyond young
adulthood. Barring atypical substances such as ketamine, nitrous oxide, certain
phenethylamines (i.e., MDMA), and cannabis, hallucinogens do not create physio-
logical dependence or tolerance, and dependence phenomena, such as an inability to
stop using, are rarely seen (Galanter and Kleber 2008; Fantegrossi et al. 2008; Passie
et al. 2002).
Research suggests that the behavioral and psychoactive risks associated with
hallucinogens may be effectively minimized and managed by the context in which
the agents are administered. It has been recognized that hallucinogenic alterations
are shaped, to an extent, by the past experience, expectations/intentions, preparation,
42 Evaluating the Therapeutic Utility of Hallucinogens for Substance Use Disorders 719
and attributes of the individual (the set), as well as by the context (including other
individuals, medical staff, or a guide) in which the experience occurs (the setting)
(Bakalar and Grinspoon 1997; Malleson 1971; Vollenweider and Kometer 2010;
Imperi et al. 1968; Studerus et al. 2012). The set and setting may play a primary role
in whether the hallucinogen experience is pleasant and enriching or dysphoric and
upsetting. Most importantly, the set and setting also constitute the most salient
modifiable variables affecting whether or not hallucinogen-related toxicity occurs.
Many reports from the heyday of hallucinogen research – the 1950s and 1960s – have
consistently shown that with appropriate patient selection, preparation, guidance,
and follow-up care, hallucinogens can be safely administered in medical settings,
with minimal reports of behavioral toxicity or persistent adverse effects (Bakalar and
Grinspoon 1997; Malleson 1971; Vollenweider and Kometer 2010; Studerus
et al. 2011). Indeed, most accounts of behavioral toxicity or persistent distress
occur outside of medical settings, when these substances are used irresponsibly.
These findings are now being replicated by more recent investigations as human-
oriented hallucinogen research carefully resumes (Johnson et al. 2008).
Set and setting also provide a valuable lens by which to understand the historical use
of hallucinogens. As is the case with many psychoactive substances, hallucinogens
have been accorded an important, and sometimes sacramental, place in various
cultural traditions. The use of the hallucinogen might be ritualized or ceremonialized,
symbolically integrated into the group’s beliefs and traditions, or invested with
supernatural importance (Fig. 42.2). The unique psychoactive profile of hallucino-
gens, and particularly their capacity to engender mystical-type experiences, has made
them especially well suited to religious, initiation, or healing ceremonies (Bakalar
and Grinspoon 1997; Hofmann and Schultes 1979).
Indigenous groups in the Americas have a robust and diverse history of incorpo-
rating hallucinogens into their rituals and ceremonies, likely because of the wealth of
naturally occurring psychoactive substances in these continents. The Aztecs ritual-
ized the use of psilocybin-containing mushrooms for millennia; peyote (mescaline)
and salvia are used by groups in Mexico; and DMT, in the form of ayahuasca or yage,
is central to Shamanic or religious ritual in various indigenous and syncretic Ama-
zonian traditions. Despite DMT and mescaline being illegal in the United States, they
can be licitly used in their naturally occurring forms by members of certain religions
that are recognized by the US government as requiring these substances for proper
worship. Of note, both DMT (as ayahuasca) and mescaline (as peyote) are used by
their respective communities to promote health and address certain ailments, such as
addiction. The spiritually oriented set and setting implicated in the therapeutic use of
hallucinogens have led some researchers to propose that psychospiritual mechanisms
account for their putative benefits. Researchers have accordingly proposed
hallucinogen-based treatment models that aim to elicit mystical states similar to
those cultivated in hallucinogen-oriented rituals (Bakalar and Grinspoon 1997;
720 E. Dakwar
Fig. 42.2 Various mushroom stones. These stones, dating from 1,000 BC to 500 CE, are
approximately 1 ft in height. They suggest the religious and cultural importance accorded to
psychoactive mushrooms by groups that consume them sacramentally, ritually, or ceremonially
(Image adapted from Plant of the Gods by Schultes and Hofmann)
Hofmann and Schultes 1979). (These will be discussed in greater detail in the next
section, alongside other hallucinogen-based treatment models.)
The widespread use of hallucinogens in the United States and Europe among the
young during the 1960s is also worth discussing. Alongside being privileged for their
potent ability to alter and enhance sensory experience, hallucinogens (and primarily
LSD) were celebrated by the counterculture as tools for self-discovery, direct
mystical communion, and transcendence from ordinary, consensus experience.
This attitude towards hallucinogens, fueled by such popular figures as Aldous
Huxley, Timothy Leary, and Alan Watts among many others, gained particular
momentum in the context of the social problems and generational conflicts that
characterized the late 1950s and 1960s, with many people, and particularly the
young, disillusioned by the belligerent imperialism, consumerism, materialism,
and conformity that had come to shape their societies. In this troubled time, hallu-
cinogens came to represent, much as in some indigenous cultures, a means by which
to access deeper truths and initiate communal renewal. Unlike these indigenous
cultures, however, the United States and other Western countries lacked the cultural
framework to effectively incorporate hallucinogen use, support those who sought to
use them, and respond creatively to the powerful experiences occasioned by them.
Instead, unsupervised and irresponsible use proliferated; traumatic or sensational
adverse events made headlines; and the substances were condemned as dangerous
and bereft of benefit. The importance of a supportive and guided framework that
adequately screens and prepares the individual before hallucinogen administration
42 Evaluating the Therapeutic Utility of Hallucinogens for Substance Use Disorders 721
cannot be overstated and should guide both the clinical and cultural use of these
compounds to minimize the risks associated with them, as well as optimize their
benefits (Bakalar and Grinspoon 1997; Leuner 1994).
Fig. 42.3 These drawings by trained artists are visual representations of experiences that
occurred during LSD-assisted psychotherapy. They demonstrate the psychological depth and
intensity of the conflicts that might emerge during psychedelic experience, as well as how readily
these conflicts might lend themselves to psychodynamic exploration. In these images, the artists
may be depicting their conflicted attitude towards sexual desire, and anxieties about how sexual
desire and union may threaten individual identity (Adapted from LSD Psychotherapy by Stanislav
Grof)
LSD was thought to be most effective at a low dose for these purposes. The
therapeutic framework was the typical one of psychoanalysis, with sessions occur-
ring several times a week and with the analyst seated out of sight of the generally
supine patient so as to facilitate transference reactions, free association, and fantasy.
Frequency of LSD administration varied from a few times weekly to monthly, and
the goal was to raise to conscious reflection the unconscious processes that perpetuate
addictive behaviors. This model was primarily used, however, to address depressive
and anxiety symptoms, not substance use disorders (Bakalar and Grinspoon 1997;
Malleson 1971; Vollenweider and Kometer 2010; Hoffer 1970; Abramson 1967).
during the indigenous ceremonies discussed earlier. Furthermore, they are similar to
the spontaneous experiences described by addicted individuals who undergo a trans-
formative experience, be it “hitting rock bottom” or “having a moment of clarity,”
that serves to provide an experiential foundation for subsequent abstinence (Hoffer
1970; Abramson 1967; Krupitsky and Grinenko 1997; Miller and C’de Baca 2001).
Psychedelic therapy involves a high level of rapport, preparation, guidance, and
post-session integration. It is typically carried out over many encounters, with several
sessions occurring before the hallucinogen is administered so as to ensure that the
participant is adequately prepared and comfortable with his/her treatment team. In
current psychedelic therapy models, the team is generally composed of a male and
female who engage with the patient as a dyad during the hallucinogen session. The
role of the dyad is to provide gentle support and reassurance throughout the session,
particularly when distressing phenomena may occur (Johnson et al. 2008).
Psychedelic therapy with high-dose LSD became the dominant hallucinogen-
based model for treating alcohol dependence in the 1960s, and enough comparable
controlled studies were completed as to produce sufficient data for a recent meta-
analysis, which will be discussed later. KPT, mentioned above, was used in Russia
in the 1980s and 1990s and was intended to trigger near-death and rebirth experi-
ences with ketamine to treat opioid or alcohol dependence. Ibogaine is found in the
root bark of an African shrub iboga and continues to be used by the Bwiti for
healing, pleasure, initiation, and spiritual communion. Ibogaine as a treatment for
opioid dependence emerged from the psychedelic/experiential model in the 1950s,
but was investigated preclinically with government funding in the 1980s and 1990s
with greater emphasis on neurobiological mechanisms. Ayahuasca (a brew com-
posed of plants containing DMT and an MAOI, which serves to inhibit first-pass
DMT metabolism) is beginning to be investigated in small pilot studies in Spain and
Brazil for treating various addictive disorders. More recently, researchers in
the United States are testing the feasibility of embedding psychedelic therapy
using psilocybin in more conventional addiction-oriented therapies, such as
cognitive-behavioral therapy (CBT) or motivational enhancement (ME), to treat
nicotine and alcohol dependence (ClinicalTrials.gov Identifier: NCT01534494)
(Bakalar and Grinspoon 1997; Malleson 1971; Hoffer 1970; Abramson 1967;
Krupitsky and Grinenko 1997; Alper and Glick 2001).
Recent research has served to clarify the neurobiological effects associated with
hallucinogens and has broadened the scope of clinical research with these
compounds by suggesting that they might target some of the neural, synaptic, or
functional deficits associated with addiction as well as other psychiatric disorders.
While classical hallucinogens and their nonclassical counterparts initiate their psy-
choactive effects by different mechanisms, they may have comparable downstream
effects, particularly on prefrontal regions. These effects include the promotion of
neural plasticity, improvement of prefrontal glutamate homeostasis, modulation of
glutamatergic neurotransmission, attenuation of problematic cortical excitation, and
regulation of DMN activity and functional connectivity (Vollenweider and Kometer
2010; Carhart-Harris et al. 2012a; Scheidegger et al. 2012). Many of these mecha-
nisms have direct relevance to the deficits associated with substance use disorders.
Ibogaine was investigated in this way for opioid dependence, with the hypoth-
eses that NMDAr effects were implicated in its anti-addictive properties and
reduction in withdrawal symptoms (Vollenweider and Kometer 2010; Alper and
Glick 2001). However, an analog iboga compound with less toxicity,
18-methoxycoronaridine (18-MC), has been found to exert comparable anti-
addictive effects but with negligible NMDAr activity, suggesting that the main
mechanism of action may not be what was thought previously (Glick et al. 2000).
Similarly, the NMDAr antagonist ketamine is being investigated along neurobio-
logical lines as a treatment for various substance use disorders.
Most of the clinical research conducted with hallucinogens for substance use disorders
occurred in the 1950s and 1960s, focused on LSD for alcohol dependence, and lacked
the rigorous design characteristics that have come to characterize modern research
methodology. It is therefore not possible to draw conclusions from these early prelim-
inary studies, though there may be some promising signals. A literature search, for
example, reveals many clinical anecdotes, case studies, and trials of varying degrees of
scientific rigor that suggest the feasibility of LSD as an antidipsotropic agent.
Case studies and open trials, however, cannot establish efficacy on their own.
The gold standard in clinical research is widely recognized to be randomized
controlled trials (RCTs). As such, a recent meta-analysis pooled results from
seven comparable studies conducted in the 1960s that best approximate modern
standards of RCT design (Krebs and Johansen 2012). The authors found that LSD,
42 Evaluating the Therapeutic Utility of Hallucinogens for Substance Use Disorders 725
42.5 Conclusion
References
Abramson H (1967) The use of LSD in psychotherapy and alcoholism. Bobbs-Merrill, New York
Alper KR, Glick SD (2001) Ibogaine: a review. Alkaloids Chem Biol 56:1–38 (San Diego:
Academic)
Bakalar J, Grinspoon L (1997) Psychedelic drugs reconsidered, 3rd edn. The Lindesmith Center,
New York
Bisaga A, Aharonovich E, Cheng WY, Levin FR, Mariani JJ, Raby WN, Nunes EV (2010) A
placebo-controlled trial of memantine for cocaine dependence with high-value voucher incen-
tives during a pre-randomization lead-in period. Drug Alcohol Depend 111(1–2):97–104
Carhart-Harris RL, Erritzoe D, Williams T, Stone JM, Reed LJ, Colasanti A, Tyacke RJ, Leech R,
Malizia AL, Murphy K, Hobden P, Evans J, Feilding A, Wise RG, Nutt DJ (2012a) Neural
correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc Natl
Acad Sci U S A 109(6):2138–2143
Carhart-Harris RL, Leech R, Erritzoe D, Williams TM, Stone JM, Evans J, Sharp DJ, Feilding A,
Wise RG, Nutt DJ (2012b) Functional connectivity measures after psilocybin inform a novel
hypothesis of early psychosis. Schizophr Bull 39(6):1343–1351
Cohen MM, Shiloh Y (1977–1978) Genetic toxicology of lysergic acid diethylamide (LSD-25).
Mutat Res 47(3–4):183–209
Collins ED, Ward AS, McDowell DM, Foltin RW, Fischman MW (1998) The effects of
memantine on the subjective, reinforcing, and cardiovascular effects of cocaine in human.
Behav Pharmacol 9(7):587–598
Dakwar E, Levin FR, Foltin R, Nunes EV, Hart CL (2014) The effects of subanesthetic ketamine
infusions on motivation to quit and cue-induced craving in cocaine-dependent research volun-
teers. Biol Psychiatry 76(1):40–46
Fantegrossi WE, Murnane KS, Reissig CJ (2008) The behavioral pharmacology of hallucinogens.
Biochem Pharmacol 75(1):17–33
Galanter M, Kleber HD (eds) (2008) Textbook of substance abuse treatment, 4th edn. American
Psychiatric Press, Washington, DC
Glick SD, Maisonneuve IM, Szumlinski KK (2000) 18-Methoxycoronaridine (18-MC) and
ibogaine: comparison of antiaddictive efficacy, toxicity, and mechanisms of action. Ann N Y
Acad Sci 914:369–386
Goldstein RZ, Volkow ND (2002) Drug addiction and its underlying neurobiological basis: neuro-
imaging evidence for the involvement of the frontal cortex. Am J Psychiatry 159:1642–1652
Goldstein RZ, Tomasi D, Rajaram S, Cottone LA, Zhang L, Maloney T, Telang F, Alia-Klein N,
Volkow ND (2007) Role of the anterior cingulate and medial orbitofrontal cortex in processing
drug cues in cocaine addiction. Neuroscience 144(4):1153–1159
Gouzoulis-Mayfrank E et al (1999) Neurometabolic effects of psilocybin,
3,4-methylenedioxyethylamphetamine (MDE) and d-methamphetamine in healthy volunteers.
A double-blind, placebo-controlled PET study with [18 F]FDG. Neuropsychopharmacology
20:565–581
Griffiths RR, Richards WA, McCann U, Jesse R (2006) Psilocybin can occasion mystical-type
experiences having substantial and sustained personal meaning and spiritual significance.
Psychopharmacology (Berl) 187(3):268–283 (discussion. pp 284–292, 2006)
Griffiths RR, Richards W, Johnson M, McCann U, Jesse R (2008) Mystical-type experiences
occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance
14 months later. J Psychopharmacol 22:621–632
Hoffer A (1970) Treatment of Alcoholism with Psychedelic therapy. In: Aaronson B,
Osmond H (eds) The uses and implications of Hallucinogenic drugs. Hogarth Press, London,
pp 357–366
Hofmann A, Schultes RE (1979) Plants of the Gods. McGraw-Hill, Maidenhead
Imperi LL, Kleber HD, Davie JS (1968) Use of hallucinogenic drugs on campus. JAMA
204(12):1021–1024
730 E. Dakwar
Johnson M, Richards W, Griffiths R (2008) Human hallucinogen research: guidelines for safety.
J Psychopharmacol 22(6):603–620
Kalivas PW (2009) The glutamate homeostasis hypothesis of addiction. Nat Neurosci 10:561–572
Kosten TA, SCanley BE, Tucker KA, Oliveto A, Prince C, Sinha R, Potenza MN, Skudlarski P,
Wexler BE (2006) Cue-induced brain activity changes and relapse in cocaine dependent
patients. Neuropsychopharmacology 31:644–650
Krebs TS, Johansen PO (2012) Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of
randomized controlled trials". J Psychopharmacol 26(7):994–1002
Krupitsky EM, Grinenko AY (1997) Ketamine psychedelic therapy (KPT): a review of the results
of ten years of research. J Psychoactive Drugs 29(2):165–183
Leuner H (1994) Hallucinogens as an aid in psychotherapy: basic principles and results. In:
Pletscher A, Ladewig D (eds) 50 years of LSD: current status and perspectives of Hallucinogen
research. Parthenon, New York
Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghahanian G, Duman RS
(2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of
NMDA antagonists. Science 20:959–964
MacLean KA, Johnson MW, Griffiths RR (2011) Mystical experiences occasioned by the hallu-
cinogen psilocybin lead to increases in the personality domain of openness. J Psychopharmacol
25(11):1453–1461
Malleson N (1971) Acute adverse reactions to LSD in clinical and experimental use in the United
Kingdom. Br J Psychiatry 118:229–230
Mathew SJ, Shah A, Lapidus K, Clark C, Jarun N, Ostermeyer B, Murrough JW (2012) Ketamine
for treatment-resistant unipolar depression: current evidence. CNS Drugs 26(3):189–204
Miller WR, C’de Baca J (2001) Quantum change: when epiphanies and sudden insights transform
ordinary lives. Guilford, New York
Passie T, Seifert J, Schneider U, Emrich HM (2002) The pharmacology of psilocybin. Addict Biol
7(4):357–364
Scheidegger M, Walter M, Lehmann M, Metzger C, Grimm S, Boeker H, Boesiger P, Henning A,
Seifritz E (2012) Ketamine decreases resting state functional network connectivity in healthy
subjects: implications for antidepressant drug action. PLoS One 7(9):e44799. doi:10.1371/
journal.pone.0044799
Schreckenberger M et al (1998) The psilocybin psychosis as a model psychosis paradigm for acute
schizophrenia: a PET study with 18-FDG. Eur J Nucl Med 25:877
Studerus E, Kometer M, Hasler F, Vollenweider FX (2011) Acute, subacute and long-term
subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.
J Psychopharmacol 25(11):1434–1452
Studerus E, Gamma A, Kometer M, Vollenweider FX (2012) Prediction of psilocybin response in
healthy volunteers. PLoS One 7(2):e30800
Vardy MM, Kay SR (1983) LSD psychosis or LSD-induced schizophrenia? A multimethod
inquiry. Arch Gen Psychiatry 40(8):877–883
Vollenweider FX, Kometer M (2010) The neurobiology of psychedelic drugs: implications for the
treatment of mood disorders. Nat Rev Neurosci 11(9):642–651
Addiction Treatment with Acupuncture
43
Markos Emmanouel
Contents
43.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 732
43.2 Acupuncture Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 732
43.2.1 The NADA Ear Protocol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 732
43.2.2 Research and the NADA Protocol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 733
43.2.3 Applications and Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 734
43.2.4 Special Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 735
43.2.5 International Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 735
43.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 736
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 736
Abstract
The National Acupuncture Detoxification Association auricular acupuncture pro-
tocol is used around the world to help people deal with and recover from substance
abuse. The NADA protocol has been shown in a variety of clinical settings to be
beneficial in the process of detoxification from substance abuse as well as to help
with the emotional, physical, and psychological attributes involved in addictions.
The NADA protocol has been effective in a wide range of addictive disorders that
include opiates, alcohol, cocaine, cannabis, methamphetamine, and benzodiaze-
pines. Clinical reports have indicated that the NADA protocol has been effective
for dually diagnosed patients. Patients report a decrease in anxiety and depression
and a reduction in violence, improvement in compliance with medication pro-
tocols, and reduction of adverse reactions to psychotropic medications. Since the
beginning of the new millennium, in the age of evidenced-based medicine, the use
of this modality has increased significantly worldwide, despite the lack of a large
amount of randomized controlled trials indicating its efficacy.
M. Emmanouel
Department of Psychiatry, NYU Langone Medical Center, New York, NY, USA
e-mail: [email protected]
43.1 Introduction
Acupuncture is a modality of treatment practiced in China for the past 2,500 years.
In 1972, Dr. H. L. Wen, a neurosurgeon from Hong Kong, discovered that one of his
patients reported reduced withdrawals and cravings for opiates following auricular
acupuncture utilized for analgesia. Dr. Wen and Dr. Cheung published their results
of treating 40 heroin and opium addicts with electropotentiated ear acupuncture in
the Asian Journal of Medicine.
The following year Dr. Michael Smith, medical Director of the Lincoln Hospital
Detox Program, began using acupuncture as an adjunct treatment for their patients,
following a 10-day methadone detoxification cycle. Clients reported less malaise,
feeling more relaxed, and a reduction of opiate withdrawal symptoms. It was
accidentally discovered that simple manual needling produced a more prolonged
effect compared to electric stimulation. In 1978, the clinic discontinued the use of
methadone as a part of its detoxification protocol. During the crack cocaine
epidemic of the 1980s, the protocol was utilized with some success to treat these
patients as well.
Chinese medical theory, though scientific in its own right, is built on the foundation
of ancient philosophical thought. The theory of the yin and yang is one such
philosophy. The basic premise of this theory is that in nature there is constant
change. Yin and yang represent two broad categories of opposite yet complemen-
tary concepts. More specifically, yin is what maintains and endures, is nourishing,
and supports growth. Some examples of yin are earth, autumn, cold, and moisture.
On the other hand, yang is what is creative and generating. Some examples of yang
are heaven, spring and summer, heat, and dryness.
Auriculotherapy is a therapeutic modality of acupuncture in which external ear
stimulation is utilized to treat health conditions in other parts of the body. The
needling takes place with five thin, sterile, stainless steel needles under the surface
of the skin of the outer ear. The practice of ear acupuncture is based on the fact that
there is an anatomical arrangement of points on the external ear that represent an
inverted homunculus. More specifically, the head is represented in the lower part of
the ear, the hands and feet towards the top, and the internal organs within the
depressions of the outer ear.
The NADA five points are the sympathetic, shen men (spirit gate), kidney point,
liver point, and lung point. These were chosen based on Chinese medical theory and
clinical indication, as well as lower electrical resistance and pain sensitivity.
They are located on the deep, dark, cavernous parts of the ear, i.e., the yin side.
The combination of all five points has the result of a yin tonification, restoring the
calm inner qualities akin to serenity.
43 Addiction Treatment with Acupuncture 733
The needling of the sympathetic and shen men points produces calming,
relaxing, and centering effects. The kidney, liver, and lung points correspond to
yin organs. The yin organs are deemed as nourishing, restorative, and supportive. In
modern Western medicine, these organs are the organs of elimination in the body
and, hence, relate to detoxification and cleansing.
Dr. Michael Smith at the Lincoln Recovery Center developed sleepmix tea
which is used in prior to the NADA protocol. It contains three parts chamomile
and one part each peppermint, yarrow, hops, skullcap, and catnip. It is believed to
calm and soothe the nervous system, stimulate circulation, and eliminate waste
products.
Dr. H. L. Wen was the first physician to report successful treatment of withdrawal
symptoms with acupuncture in 1973. He initially observed an opiate addict receiv-
ing electroacupuncture for presurgical analgesia and, as a result, reported relief of
withdrawal symptoms.
In 1987, Bullock studied 54 patients with alcohol dependence in an inpatient
program that were randomly assigned to either the NADA treatment protocol or
needling at nearby ear points (the “sham” group). The receivers of the NADA
protocol treatment showed better outcomes for cravings of alcohol and subsequent
relapses. These results were replicated by the same group in 1989 during which
80 patients were divided randomly in two groups, 40 in the NADA group and 40 in
the “sham” group. After 8 weeks, 21 patients in the first group remained in the
program compared to one in the latter group.
Washburn in 1993 reported that opiate addicts receiving the NADA treatment
protocol had better program attendance than subjects receiving acupuncture on
placebo sites.
Konefal in 1995 conducted a study during which 321 subjects were randomly
assigned to three groups: a one-needle shen men point, the NADA protocol five-point
treatment, and a NADA protocol five-point treatment plus selected body points
for self-reported symptoms. All three groups showed a reduction in the percentage
of positive urine drug screens, with the latter two groups showing the largest
reduction.
Shwartz, Saitz, Mulvey, and Brannigan in 1999 published a retrospective cohort
study of 8,000 clients discharged from detoxification programs in Boston,
MA. Outpatients that received acudetox treatment had statistically significant
lower rates of readmission than residential patients who did not receive acudetox
treatment.
A pilot study in 2000 by Russell, Sharp, and Gilbertson of 86 subjects with
a history of addiction and multiple arrests found a statistically significant increase
in program retention and positive trend towards fewer arrests and fewer positive
urine toxicology results of the group that received acudetox treatment compared to
the group that did not.
734 M. Emmanouel
While originally intended for use in opioid abuse and dependence, the NADA
protocol has been effective in a wide range of addictive disorders that include
opiates, alcohol, cocaine, cannabis, methamphetamine, and benzodiazepines. For
the most part, this form of treatment has been effective as adjunctive to standard
treatment protocols.
Substance abuse treatment programs that treat groups such as adolescents; elderly;
women; culturally defined populations; gay/lesbian/transgender patients; homeless;
veterans; incarcerated patients; patients with significant medical comorbidities such
as HIV/AIDS, hepatitis, and mental illness; and trauma survivors have found the
NADA protocol particularly helpful. These groups have more trouble maintaining
their sobriety due to added stressor of discrimination and marginalization. In
pregnant women, acudetox has been an effective alternative to treatment especially
when medication-based treatment is not indicated or available. The Lincoln Recov-
ery Center has been treating more than 100 pregnant cocaine users per year.
Clinical reports have indicated that the NADA protocol has been effective for
dually diagnosed patients. Patients report a decrease in anxiety and depression, and
programs a reduction in violence, improvement in compliance with medication
protocols, and reduction of adverse reactions to psychotropic medications.
personnel in India. In Northern Europe, 3,000 nurses have been trained in 100 dif-
ferent government facilities. The Drug Abuse Resistance Education (D.A.R.E.)
program in Thailand has provided ear acupuncture for Burmese tribes in border
camps.
In May 2008, at the Kiryandongo Refugee Settlement Camp in Uganda, 21 for-
mer healthcare worker refugees were trained in the NADA protocol to treat the
Kenyan refugee population that fled their country and entered Uganda due to the
postelection violence that erupted in Kenya. Over 500 refugees were treated, with
improvements in mood and sleep, decreased aggression and grief, and decreased
substance abuse (mostly alcohol and tobacco use), and in children a decrease in
bedwetting. Within a week, the temporary camp was moved to a permanent camp
where the Kenyan refugees joined Sudanese and Ugandan refugees. Acudetox
treatments continued at the camp with the participation of all three national groups.
The community leaders reported that issues such as domestic abuse, stress, and
alcoholism were significantly reduced since the implementation of acudetox treat-
ments. In a period of 18 months, over 29,000 acupuncture treatments were
provided.
43.3 Conclusion
References
Avants S, Margolin A, Holford T, Kosten T (2000) A randomized controlled trial of auricular
acupuncture for cocaine dependence. Arch Intern Med 160(5):2305–2312
Bier I, Wilson J, Studt P, Shakleton M (2002) Auricular acupuncture, education smoking cessa-
tion: a randomized, sham controlled trial. Am J Public Health 92:1642–1647
Bullock M, Ulmen A, Culliton P (1987) Acupuncture treatment of alcohol recidivism: a pilot
study. Alcohol Clin Exp Res 11(3):292–295
Bullock M, Culliton P, Olander R (1989) Controlled trial of acupuncture for severe recidivistic
alcoholism. Lancet 1:1435–1439
Konefal J, Duncan R, Clemence C (1995) Comparison of three levels of auricular acupuncture in
an outpatient substance abuse program. Altern Med J 2(5):1
Margolin A, Avants S, Chang P, Kosten T (1993) Acupuncture for the treatment of cocaine
dependence in methadone-maintained patients. Am J Addict 2(3):194–201
Margolin A, Kleber H, Avants S et al (2002) Acupuncture for the treatment of cocaine addiction:
a randomized controlled trial. JAMA 287(1):55–63
43 Addiction Treatment with Acupuncture 737
Russell L, Sharp B, Gilbertson B (2000) Acupuncture for addicted patients with chronic histories
of arrest. A pilot study of the Consortium Treatment Center. J Subst Abus Treat 19:199–205
Shwartz M, Saitz R, Mulvey K, Brannigan P (1999) The value of acupuncture detoxification
programs in a substance abuse treatment system. J Subst Abus Treat 17(4):305–312
Voyles C, Toomim R (2008) National acupuncture detoxification training manual
Washburn A, Fullilove R, Fullilove M et al (1993) Acupuncture heroin detoxification: a single
blind clinical trial. J Subst Abus Treat 10(4):345–351
Wen H, Cheng S (1973) Treatment of drug addiction by acupuncture and electrical stimulation.
Asian J Med 9:138–141
Transcraneal Magnetic Stimulation (TMS)
as Treatment for Substance Addiction 44
David A. Gorelick
Contents
44.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 740
44.2 TMS Treatment of Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 740
44.2.1 rTMS and Nicotine (Tobacco) Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 741
44.2.2 rTMS and Cocaine Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 743
44.2.3 rTMS and Alcohol Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 743
44.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 743
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 744
Abstract
Transcranial magnetic stimulation (TMS) is a rapidly developing noninvasive
physical approach to psychiatric treatment, including substance use disorders. It
involves projecting a fluctuating magnetic field (magnetic pulses), usually repet-
itively (rTMS), through the skull into the brain, which generates electrical currents
in brain tissue and, thus, modulates neuronal firing. TMS treatment of addiction is
still in an early stage and must be considered experimental. The mechanism of
TMS therapeutic action in addiction is not definitively established, but may
include modulation of neurotransmitter activity (especially dopamine and gluta-
mate) in brain regions mediating addiction, such as the dorsolateral prefrontal
cortex (Hayashi et al. Proc Natl Acad Sci USA 110:4422–4427, 2013), and
disruption of cue-induced drug craving. Most, but not all, studies found reduced
drug craving in the active TMS group vs. the sham group. TMS does appear
well tolerated by individuals with addiction; there are no reported serious or
unexpected adverse events. Research is being conducted to evaluate the safety
and efficacy of this novel intervention.
D.A. Gorelick
Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
e-mail: [email protected]
44.1 Introduction
Table 44.1 Published studies of repetitive transcranial magnetic stimulation (rTMS) and nicotine
craving
TMS parameters
Pulse
Site of frequency # Total #
pulses N (Hz) Sessions pulses Outcome Authors
Superior 15 10 1 4,500 " cue-induced craving Rose
frontal gyrus # spontaneous craving et al. (2011)
Superior 15 1 1 450 No D cue-induced Rose
frontal gyrus craving et al. (2011)
" spontaneous craving
L DLPFC 14 20 2 2,000 # smoking Eichhammer
No D spontaneous et al. (2003)
craving
L DLPFC 11 20 1 1,000 # spontaneous craving Johann
et al. (2003)
L DLPFC 48 10 10 10,000 # smoking Amiaz
# cue-induced craving et al. (2009)
L& 15a 20 20 15,000 # spontaneous craving Wing
R DLPFC per side first week only et al. (2012)
No D smoking
L DLPFC 16 10 1 3,000 # cue-induced craving Li et al. (2013)
L DLPFC 10 1 1 1,800 # cue-induced craving Hayashi
et al. (2013)
N number receiving active rTMS, DLPFC dorsolateral prefrontal cortex, L left, R right, NRT
nicotine replacement therapy
a
Comorbid schizophrenia receiving nicotine replacement therapy and weekly counseling
no effect on cigarette smoking (Wing et al. 2012). Thus, the effectiveness of TMS
for smoking cessation in a realistic clinical setting remains uncertain.
We identified two published and one unpublished study using rTMS to treat cocaine
addiction (Table 44.2), including one small, open-label outpatient trial (Politi
et al. 2008) and one double-blind, sham-controlled outpatient clinical trial (Ribeiro
et al. 2013). Both trials applied high-frequency rTMS pulses (10 or 20 Hz, respec-
tively) to the left DLPFC for multiple daily sessions (2 or 4 weeks). Both trials
reported significantly decreased spontaneous craving – developing only in the second
week of treatment in the open-label trial and linearly over time in the controlled
clinical trial. The controlled clinical trial also reported significantly decreased cocaine
use, verified by urine drug testing (drug use wasn’t reported by the open-label trial).
Thus, there is limited clinical trial evidence that at least one week of high-frequency
TMS applied to the left DLPFC reduces cocaine craving and use.
44.3 Conclusion
Acknowledgment Dr. Gorelick was supported by the Intramural Research Program, National
Institute on Drug Abuse, US National Institutes of Health. He has no conflicts of interest to report.
744 D.A. Gorelick
References
Amiaz R, Levy D, Vainiger D, Grunhaus L, Zangen A (2009) Repeated high-frequency
transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette
craving and consumption. Addiction 104:653–660
Bellamoli E, Manganotti P, Schwartz RP, Rimondo C, Gomma M, Serpelloni G (2013) rTMS in
the treatment of drug addiction: an update about human studies. Behav Neurol, in press
Bestmann S, Ruff CC, Blankenburg F, Weiskopf N, Driver J, Rothwell JC (2008) Mapping causal
interregional influences with concurrent TMS-fMRI. Exp Brain Res 191:383–402
Camprodon JA, Martinez-Raga J, Alonso-Alonso M, Shih MC, Pascual-Leone A (2007) One
session of high frequency repetitive transcranial magnetic stimulation (rTMS) to the right
prefrontal cortex transiently reduces cocaine craving. Drug Alcohol Depend 86:91–94
Cho SS, Strafella AP (2009) rTMS of the left dorsolateral prefrontal cortex modulates
dopamine release in the ipsilateral anterior cingulate cortex and orbitofrontal cortex. PLoS
ONE 4:e6725
De Ridder D, Vanneste S, Kovacs S, Sunaert S, Dom G (2011) Transient alcohol craving
suppression by rTMS of dorsal anterior cingulate: an fMRI and LORETA EEG study. Neurosci
Lett 496:5–10
Denslow S, Lomarev M, George MS, Bohning DE (2005) Cortical and subcortical brain effects of
Transcranial Magnetic Stimulation (TMS)-induced movement: an interleaved TMS/functional
magnetic resonance imaging study. Biol Psychiatry 57:752–760
Eichhammer P, Johann M, Kharraz A, Binder H, Pittrow D, Wodarz N et al (2003) High-frequency
repetitive transcranial magnetic stimulation decreases cigarette smoking. J Clin Psychiatry
64:951–953
Fitzgerald PB (2011) The emerging use of brain stimulation treatments for psychiatric disorders.
Aust N Z J Psychiatry 45:923–938
Hayashi T, Ko JH, Strafella AP, Dagher A (2013) Dorsolateral prefrontal and orbitofrontal cortex
interactions during self-control of cigarette craving. Proc Natl Acad Sci USA 110:4422–4427
Herremans SC, Baeken C, Vanderbruggen N, Vanderhasselt MA, Zeeuws D, Santermans
L et al (2012) No influence of one right-sided prefrontal HF-rTMS session on alcohol craving
in recently detoxified alcohol-dependent patients: results of a naturalistic study. Drug Alcohol
Depend 120:209–213
Herremans SC, Vanderhasselt MA, De RR, Baeken C (2013) Reduced intra-individual reaction
time variability during a Go-NoGo task in detoxified alcohol-dependent patients after one
right-sided dorsolateral prefrontal HF-rTMS session. Alcohol Alcohol 48:552–557
Hoppner J, Broese T, Wendler L, Berger C, Thome J (2011) Repetitive Transcranial
Magnetic Stimulation (rTMS) for treatment of alcohol dependence. World J Biol Psychiatry
12(Suppl 1):57–62
Johann M, Wiegand R, Kharraz A, Bobbe G, Sommer G, Hajak G et al (2003) Transcranial
magnetic stimulation for nicotine dependence. Psychiatr Prax 30(Suppl 2):S129–S131
Kammer T, Spitzer M (2012) Brain stimulation in psychiatry: methods and magnets, patients and
parameters. Curr Opin Psychiatry 25:535–541
Kluger BM, Triggs WJ (2007) Use of transcranial magnetic stimulation to influence behavior. Curr
Neurol Neurosci Rep 7:491–497
Li X, Nahas Z, Kozel FA, Anderson B, Bohning DE, George MS (2004) Acute left prefrontal
transcranial magnetic stimulation in depressed patients is associated with immediately
increased activity in prefrontal cortical as well as subcortical regions. Biol Psychiatry
55:882–890
Li X, Hartwell KJ, Owens M, Lematty T, Borckardt JJ, Hanlon CA et al (2013) Repetitive
transcranial magnetic stimulation of the dorsolateral prefrontal cortex reduces nicotine cue
craving. Biol Psychiatry 73:714–720
Mishra BR, Nizamie SH, Das B, Praharaj SK (2010) Efficacy of repetitive transcranial magnetic
stimulation in alcohol dependence: a sham-controlled study. Addiction 105:49–55
44 Transcraneal Magnetic Stimulation (TMS) as Treatment for Substance Addiction 745
Contents
45.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 748
45.2 Nutrients, Phytomedicines, and Mind-Body Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 748
45.2.1 Nutrients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 748
45.2.2 Herbal Medicines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 756
45.2.3 Mind-Body Practices in the Treatment of Substance Abuse . . . . . . . . . . . . . . . . . 758
45.2.4 Fetal Alcohol Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 764
45.2.5 Integrative Approaches to the Treatment of Substance
Abuse Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 766
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 767
Abstract
Substance abuse programs continue to search for nonpharmacological treatments
to assist patients during withdrawal and for relapse prevention. The craving,
dysphoria, insomnia, and discomfort that drive addictions cannot be adequately
treated with pharmacological agents which may be addictive or contraindicated
due to comorbid conditions. The treatment of addictions is often complicated by
physical pain; poor nutrition; emotional disorders such as depression, anxiety
disorders, and posttraumatic stress disorder; and medical problems such as trau-
matic brain injury, neurological deterioration, lung disease, liver disease, and
HIV. Nutrients, herbs, and mind-body practices that ameliorate physical and
psychological aspects of addiction as well as its medical complications are gaining
acceptance commensurate with their growing evidence base.
R.P. Brown
Columbia University College of Physicians and Surgeons, New York, NY, USA
e-mail: [email protected]
P.L. Gerbarg (*)
New York Medical College, Valhalla, NY, USA
e-mail: [email protected]
45.1 Introduction
Nutrients, including vitamins, minerals, omega-3 fatty acids, and metabolites, can
be beneficial in the treatment of substance abuse and its many comorbidities.
Among the advantages of using nutrients, herbs, and mind-body practices are the
following: little or no risk for dependence or withdrawal symptoms; fewer and less
severe side effects than most prescription drugs; beneficial effects on comorbid
conditions; and less risk of exacerbating abuse-related disorders such as alcoholic
cirrhosis, hepatitis, or HIV. Furthermore, vitamins and nootropics (cognitive
enhancers) may improve brain functions that have been compromised by substance
abuse, poor nutrition, and traumatic brain injuries. Nutrients also have a role in the
prevention and treatment of fetal alcohol syndrome. Dysphoria, anxiety, depres-
sion, and anger are major factors that contribute to substance abuse. Certain mind-
body practices can rapidly reduce the effects of such negative emotions, improve
emotion regulation, and provide new tools for dealing with stress.
This chapter focuses on treatments supported by an evidence base and by
plausible physiological mechanisms of action. The relatively small scale of
research on many natural treatments reflects the imbalance of funding and the
difficulty of patenting natural products. In contrast, patentable, synthetic pharma-
ceuticals can be sold at a large profit to offset the costs of high-quality research.
Taking into consideration that the playing field for research is far from level and
that nutrients, herbs, and mind-body treatments tend to have fewer side effects, the
evidential threshold for trying natural treatments could be lowered, particularly for
patients who do not respond well or who are unable to tolerate standard treatments.
The same principles used in treatment with prescription medications apply to the
use of nutrients and phytomedicines. Documentation of physician-patient discus-
sion of risks, benefits, and the pros and cons of both standard and alternative
approaches is advisable (Brown et al. 2009). The risk of adverse effects can be
minimized by starting with lower doses in patients who are elderly, frail, or
sensitive to medications and monitoring for side effects while increasing doses
over a period of days to weeks, depending on tolerance. Herbs and nutrients can be
strategically combined for synergistic effects.
45.2.1 Nutrients
Vitamins, minerals, fatty acids, amino acids, and metabolites have been shown to be
beneficial in all phases of substance abuse treatment. In addition to reducing
craving and relapse, many supplements prevent or ameliorate adverse effects of
drinking on the liver, brain, and other organ systems. Vitamin B12 and folate are
important for the antidepressant effects of S-adenosylmethionine (SAMe) and
prescription medications (see below). Vitamin B6 is essential for SAMe
hepatoprotection.
45 Nutrients, Phytomedicines, and Mind-Body Treatments for Substance Abuse 749
45.2.1.2 Magnesium
Acute alcohol administration can cause sudden severe vasoconstriction and
decreased cerebral blood flow. Alcohol use, particularly “binge drinking,” is asso-
ciated with headaches, strokes, sudden death, and worse outcomes in patients with
brain injury. Low levels of intracellular and extracellular magnesium modulate
a cascade of events involved in cerebrovascular constriction. In animal studies,
magnesium infusion attenuated alcohol-induced vasoconstriction. In humans, intra-
venous magnesium sulfate relieved alcohol-associated headaches (Altura and
Altura 1999; Barbour et al. 2002).
In a 12-week randomized controlled trial (RCT), magnesium-l-aspartate
723 mg/day given to heroin addicts undergoing treatment with methadone
decreased the percentage of positive urinary tests and the rate of relapse to heroin
use during methadone maintenance. Preclinical in vitro and animal studies point to
a role for Mg2+ in reducing the intensity of dependence on nicotine, cocaine,
amphetamine, ethanol, and other drugs. Magnesium has moderate stimulative
effects on the reward system and reinforcement without causing dependence
(Nechifor 2008). It is thought to reduce caffeine and nicotine dependence by release
of dopamine and glutamate. A 4-week RCT found that magnesium enabled heavy
smokers to reduce the number of cigarettes smoked per day (Nechifor et al. 2004).
Cocaine-dependent patients given mg-L-aspartate 732 mg/day in a 12-week RCT
showed decreased cocaine craving and cocaine use (Margolin et al. 2003).
45.2.1.5 N-Acetylcysteine
Animal studies have indicated that N-acetylcysteine (NAC) inhibits cocaine-
seeking behavior. In a double-blind randomized placebo-controlled (DBRPC)
cross-over trial, 15 hospitalized nontreatment-seeking patients with cocaine depen-
dence were given four doses of either NAC (600 mg) or placebo. In rating their
responses to watching slides depicting cocaine and cocaine use, subjects reported
less interest and less desire to use cocaine while they were taking NAC. This study
suggests that NAC may reduce cocaine cue reactivity (LaRowe et al. 2007).
A 4-week open pilot study in 23 treatment-seeking cocaine-dependent patients
tested NAC in doses of 1,200 mg/day, 2,400 mg/day, or 3,600 mg/day. The two
higher doses of NAC were associated with better retention rates. A majority of the
16 subjects who completed the study either terminated use of cocaine completely or
significantly reduced their use of cocaine during NAC treatment. All three doses
were well tolerated. These findings support the value of further trials of NAC as an
adjunct for treating individuals with cocaine dependence (Mardikian et al. 2007).
Reducing marijuana use may be more appealing to young adults than giving it up
completely, as demonstrated in a pilot trial of NAC. Men (n¼18) and women
(N ¼ 6) ages 18–21 years, who wanted to reduce marijuana smoking, but not stop
it entirely, took NAC 1,200 mg b.i.d. for 4 weeks. The subjects reported significant
reductions in three out of four domains on the Marijuana Craving Questionnaire.
Semiquantitative urine cannabinoid levels did not change (Gray et al. 2010). In an
8-week DBRPC study of 15–21-year-old marijuana users, the treatment group
received NAC 1,200 mg/day with a contingency management intervention and
brief weekly cessation counseling. During treatment participants receiving NAC
had more than twice the odds of having negative urine cannabinoid tests compared
to the placebo group (odds ratio ¼ 2.4, 95 % CI ¼ 1.1–5.2) (Gray et al. 2012).
45.2.1.7 S-Adenosylmethionine
S-adenosylmethionine (SAMe) has significant potential as a valuable treatment for
all stages of alcoholism because it has both antidepressant and hepatoprotective
effects. Many alcoholics suffer from depression. SAMe is as effective as prescription
antidepressants, but it has fewer side effects. Unlike prescription drugs, it does not
burden liver metabolic systems and does not cause liver enzyme elevations
(a common side effect of SSRI’s). SAMe has been shown to improve liver function
and to reduce alcohol-induced liver toxicity through several mechanisms. First,
SAMe reduces serum alcohol levels, but does not increase serum acetaldehyde levels.
Second, SAMe protects liver mitochondria from damage by alcohol (Lieber 2002).
Third, SAMe maintains supplies of the body’s primary antioxidant, glutathione. The
US Department of Health and Human Services Research and Quality Assessment
report (AHRQ 2007) concluded that SAMe was as effective as prescription antide-
pressants but with fewer side effects and that it improved indicators of hepatic
dysfunction (for reviews of SAMe, see Brown et al. 2002; Bottiglieri 2002, 2013).
• SAMe blocks CYP2E1 effects on alcohol oxidation and the associated increase
in reactive oxygen species (ROS).
• SAMe prevents alcohol upregulation of Toll-like receptor (TLR) signaling
pathways that mediate proinflammatory response, fibrogenesis, and carcinogen-
esis in alcoholic liver disease (ALD) and other chronic liver diseases in animal
models (Oliva et al. 2011).
The mechanisms of SAMe hepatoprotection against injury by alcohol and CYP2E1
have been reviewed (Cederbaum 2010). Dehydrogenase oxidizes most of the
alcohol that is ingested, but at elevated ethanol concentrations and with chronic
consumption, CYP2E1 has a greater role in oxidizing ethanol and generates acet-
aldehyde and hepatotoxic ROS. SAMe is a reversible, noncompetitive inhibitor of
the catalytic effect of CYP2E1 on ethanol oxidation. Thus, SAMe blocks CYP2E1
oxidation of alcohol, reducing production of ROS that damage mitochondria and
membranes.
Chronic alcohol consumption by baboons for 18–36 months significantly
depleted hepatic SAMe and glutathione and increased circulating levels of the
mitochondrial enzyme glutamic dehydrogenase. SAMe attenuated the ethanol-
induced increase in plasma glutamic dehydrogenase and was associated with
a decrease in the number of giant mitochondria (Lieber et al. 1990).
In a 30-day DBRPC study of 64 subjects with at least a 6-year history of alcohol
abuse, those given SAMe 200 mg IM/day (equivalent to 400 mg p.o.) showed
significant improvements in anxiety, depression, liver function tests, fatigue,
anorexia, insomnia, nausea/vomiting, treatment compliance, and abstinence com-
pared to placebo. The group given SAMe had lower gamma-GT levels and lower
serum alcohol levels compared to no change in the placebo group (Cibin
et al. 1988).
A review of 17 clinical studies (Osman et al. 1993) found that SAMe improved
biochemical markers (e.g., serum bilirubin, liver enzymes, cysteine, taurine, and
hepatic glutathione) and symptoms (e.g., pruritus, fatigue, and jaundice) of liver
disease regardless of etiology (alcoholic, nonalcoholic, infectious hepatitis, cirrho-
sis, cholestasis, metabolic disorders, and hepatotoxicities).
Mato and colleagues (Mato et al. 1999) conducted a 2-year DBRPC study of
123 patients with alcohol-induced liver cirrhosis reporting that patients with Child-
Pugh class A or B given oral pharmaceutical-grade SAMe (AdoMet) 1,200 mg/day
for at least 1 year had a mortality/liver transplantation rate of 12 % versus 29 %
(p ¼ 0.025) in the placebo group. At 2-year follow-up, the SAMe group continued
to have lower mortality/liver transplantation rates (p ¼ 0.046). In Child-Pugh C, the
more severe cases, there was a trend toward reduced mortality/liver transplantation
that did not reach significance. These results indicate that long-term treatment with
SAMe may improve survival or delay liver transplantation in patients with alco-
holic liver cirrhosis, especially in those with less advanced liver disease.
In contrast, a 24-week DBRPC study of SAMe treatment in 37 outpatients with
alcoholic liver disease (ALD) included baseline liver biopsies in 24 subjects. The
group given 400 mg t.i.d. of SAMe (SD4 by Abbot Laboratories) found SAMe to be
no more effective than placebo in reducing liver function tests (LFTs) or fibrosis on
45 Nutrients, Phytomedicines, and Mind-Body Treatments for Substance Abuse 753
liver biopsy (Medici et al. 2011). The authors acknowledged that the absence of
SAMe effects observed in this study may be due in part to the following limitations.
The small number of completers, 13 in each group, was marginally adequate to
detect meaningful effects. The number of posttreatment biopsies was even smaller
(n¼14). Although an attempt was made to exclude patients with severe ALD, the
biopsies showed a high level of fibrosis. The authors noted that this would result in
a smaller number of potentially responsive hepatocytes. Therefore, the effective-
ness of SAMe would depend upon its transport, retention, and metabolism by
damaged hepatocytes. Furthermore, glutathione production requires vitamin B6.
The ALD subjects had subnormal B6 levels throughout the study which were not
corrected. Moreover, sobriety was not guaranteed in outpatients. Subjects admitted
relapse to drinking, and those whose drinking exceeded the protocol limit were
dropped from the study. The reported alcohol abuse and the possibility of
unreported drinking would reduce the effectiveness of SAMe and the validity of
the findings. Finally, the short duration of this study, 24 weeks, may not have
allowed sufficient time for SAMe benefits in patients with fibrosis of ALD. The
study by Mato and colleagues (Mato et al. 1999) reported significant results after
1 year of SAMe treatment for alcoholic liver cirrhosis.
A review of 8 RCTs of ALD did not find sufficient evidence to support or refute
treatment with SAMe (Rambaldi and Gluud 2006). Overall, the evidence suggests
that SAMe is beneficial to liver function and repair but that in more severe cases, it
requires augmentation for effectiveness. One of the weaknesses of research is the
predominance of single-agent trials even when it is known that essential cofactors
are deficient, for example, low B6 levels. Liver protection and repair require the
rehabilitation of multiple metabolic pathways and cellular structures. Expecting
a robust response to SAMe monotherapy in patients with serious ALD may be
unrealistic. Further SAMe research on hepatic diseases should include more com-
plex regimens (see below). Current treatments for ALD are quite limited, and the
morbidity, mortality, and costs of hepatic disease are high. In this context, clini-
cians can offer patients with ALD low-risk treatments that will improve their
chances for recovery by using higher doses of SAMe as the treatment foundation.
The benefits of SAMe can be augmented with vitamin B6 and the nutrients and
herbs discussed below.
had antifibrinogenic effects in hepatic stellate cells, effects that could be explained by
the inhibition of collagen-producing mRNA and other mechanisms. In addition,
SAMe blocked the generation of H2O2 (free radical) and restored the reduced
glutathione (GSH) levels (Cao et al. 2006).
To date, no clinical trials of SAMe with PLPC augmentation have been published.
In clinical practice, one of the authors (RB) finds that the addition of PLPC and
Chinese herbal combinations containing Bupleurum (see below) to higher doses of
SAMe (1,200–2,400 mg/day) substantially increases the benefits of SAMe in the
treatment of patients with mild to severe alcohol-induced liver disease. Correction of
subnormal B6 levels is also important. In future studies of patients with alcohol-
related hepatic dysfunction, including fibrosis, it would be worthwhile to supplement
SAMe with PLPC, B6, and Bupleurum-containing preparations.
effects of prescription drugs and does not have adverse interactions with med-
ications (Torta et al. 1988).
SAMe has been shown to be useful as a monotherapy and as an adjunct to other
antidepressants. An open trial of SAMe (800–1,600 mg/day) augmentation to
antidepressant treatment for 30 depressed patients who had failed to respond to
either SRIs or venlafaxine yielded a response rate of 50 % and a remission rate of
43 % (Alpert et al. 2004). In a 6-week DBRCT of 73 serotonin reuptake inhibitor
(SRI) nonresponders with major depressive disorders, adjunctive SAMe (800 mg b.i.d.)
significantly improved response rates and was well tolerated (Papakostas et al. 2010).
The US Agency for Healthcare Research and Quality Assurance report based
on a systematic review of SAMe research found no statistically significant
difference in outcomes between patients treated with SAMe compared to prescription
antidepressants, but SAMe caused fewer side effects (AHRQ 2007).
In an 8-week DBRPC study of 18 schizophrenic patients, oral SAMe
(800 mg/day) significantly improved depression and ameliorated aggressive symp-
toms (Strous et al. 2009). Oral SAMe treatment for 8 weeks also significantly reduced
depressive symptoms in 20 HIV-seropositive patients with a history of drug abuse
and a diagnosis of major depressive disorder (Shippy et al. 2004). The evidence for
antidepressant effects of SAMe is compelling (Brown et al. 2009; Bottiglieri 2013).
Considerable evidence indicates hepatoprotective effects. Although the one small
recent study cited above did not corroborate hepatoprotection, this may have been
due to the short term of treatment, low B6 levels, patient selection, or the lack of
SAMe augmentation. At the very least, SAMe does no harm to the liver and, in that
regard, is superior to other antidepressants. Although further studies of oral SAMe in
the treatment of alcoholism are needed, the evidence base is sufficient to justify its
use treating depression, anxiety, and hepatic dysfunction in alcoholics.
Mentat
Mentat is a traditional Ayurvedic formula containing ashwagandha (Withania
somnifera), Bacopa (Bacopa monnieri), gotu kola (Centella asiatica), Indian Vale-
rian (Valeriana jatamansi), Triphala churna, and other medicinal herbs. One small
open series suggested it reduced relapse in abstinent alcoholics (Trivedi 1999). In
animal studies, ashwagandha decreased opiate withdrawal symptoms (Kulkarni and
Ninan 1997).
The desire to avoid or escape from negative thoughts, feelings, and painful sensa-
tions is a key factor in substance abuse and relapse. Difficulty regulating affects
such as anxiety, fear, and anger is a common finding in substance abusers. Mind-
body practices which are known to improve affect tolerance and affect regulation
have the potential to help patients deal with difficult emotions without resorting to
substance abuse. The treatment of addictions is often complicated by physical pain;
emotional problems such as depression, anxiety disorders, and posttraumatic stress
disorder; and medical conditions such as traumatic brain injury, neurological
deterioration, lung disease, liver disease, and HIV. Studies indicate benefits of
mind-body practices in recovery from substance abuse, anxiety, depression, phys-
ical injuries, and pain syndromes. Key neurophysiological mechanisms that under-
lie addictions are targeted by therapeutic mind-body practices.
45 Nutrients, Phytomedicines, and Mind-Body Treatments for Substance Abuse 759
breath practices (4.5–6 breaths per minute) such as coherent breathing, ujjayi
(ocean breath), and alternate nostril breathing reduce anxiety and induce a state
of calm alertness (Brown and Gerbarg 2009, 2012). Preliminary neurophysiological
data are consistent with improvements in attention, cognitive integration, and
learning.
treatment (counseling and benzodiazepine for sleep). The SKY intervention was
breath practices for 45 min every other day. In the SKY group mean reductions in
BDI scores and cortisol levels were greater than in the standard treatment controls
(Vedamurthachar et al. 2006). This study suggests that SKY may reduce anxiety
and cortisol levels in recently detoxed alcoholic patients. Methodological issues
limit its impact.
Fetal alcohol spectrum disorders (FASD) due to brain damage from prenatal
alcohol exposure include children with mental retardation, hyperactivity, behav-
ioral and sexual disorders, and abnormal craniofacial development. Neurotoxicity
45 Nutrients, Phytomedicines, and Mind-Body Treatments for Substance Abuse 765
Understanding the modes of action, the evidence base, and the high safety profile of
the approaches described above will enable clinicians and researchers to judiciously
integrate phytomedicines and mind-body practices with standard treatments for
optimal patient outcomes. Here is a sample of an integrative plan for treatment of
substance abuse.
Integrative Plan for Treatment of Substance Abuse
1. Correct nutritional imbalances: thiamine (B1), folate, B vitamin complex, and
an A–Z multivitamin. Brewer’s yeast in two rounded tbsps twice a day (Lewis
Labs) is an inexpensive source of B vitamins and trace minerals.
2. For neuroprotection: 3,000–6,000 mg/day fish oils (omega-3 fatty acids)
(eicosapentaenoic acid + docosahexaenoic), 600–800 mg/day magnesium,
1,800 mg b.i.d. N-acetylcysteine (NAC), and 1,000–3,000 mg/day acetyl-
L-carnitine.
3. Refer to self-help support groups: Alcoholics Anonymous, Adult Children of
Alcoholics, and Al-Anon.
4. Prescription medications as appropriate:
a. Naltrexone, acamprosate, or both for alcohol dependence
b. Topiramate 200–400 mg/day or isradipine to reduce craving for alcohol,
cocaine, and other drugs
c. Valproate for bipolar patients who abuse alcohol or marijuana
5. Evaluation for possible ADD/ADHD. In such cases, stimulants may reduce
drug dependence.
6. Mind-body-spirit practices such as yoga, qigong, vipassana meditation, MBRP
or mindfulness meditation with CBT, MBSR, a DBT.
7. SAMe to improve mood, liver function, immune function, for neuroprotection,
and to help reduce alcohol intake. To enhance hepatoprotective effects of
SAMe: B6, polyenophosphatidylcholine, betaine, and Bupleurum. SAMe is
contraindicated in bipolar patients.
8. Formulation of the treatment plan: Discussion with the patient about the
treatment options and prioritizing of the target symptoms. Documentation of
this discussion in the medical record.
9. Assessment of the feasibility of doing the intervention, taking into account
patient motivation, costs, and likelihood of compliance.
10. Time Frame and Treatment Phase
a. The first 2 weeks: detoxification, physical stabilization, and engagement
in treatment. Initiate nutrients, herbs, and slow breathing practices to
correct nutritional deficiencies and reduce anxiety, insomnia, withdrawal
symptoms, and pain. Cranial electrotherapy stimulation (CES) can
help to relieve anxiety, agitation, insomnia, and pain (Kirsch and Nichols
2013).
b. The first 3 months: relapse prevention and keeping the patient in treatment.
Continue nutrients, herbs, and mind-body practices to reduce dysphoria and
45 Nutrients, Phytomedicines, and Mind-Body Treatments for Substance Abuse 767
References
Agency for Healthcare Research and Quality (AHRQ) (2007) S-adenosyl-L-methionine for treat-
ment of depression, osteoarthritis, and liver disease. Summary, evidence report/technology
assessment: number 64. AHRQ publication no. 02-E033, August 2002. http://www.ahrq.gov/
clinic/epcsums/samesum.htm. Retrieved 8 Oct 2007
Akhondzadeh S, Kashani L, Mobaseri M, Hosseini SH, Nikzad S, Khani M (2001) Passionflower
in the treatment of opiates withdrawal: a double-blind randomized controlled trial. J Clin
Pharm Ther 26(5):369–373
Alpert JE, Papakostas G, Mischoulon D, Worthington JJ 3rd, Petersen T, Mahal Y, Burns A,
Bottiglieri T, Nierenberg AA, Fava M (2004) S-adenosyl-L-methionine (SAMe) as an adjunct
for resistant major depressive disorder: an open trial following partial or nonresponse to
selective serotonin reuptake inhibitors or venlafaxine. J Clin Psychopharmacol 24(6):661–664
Altura BM, Altura BT (1999) Association of alcohol in brain injury, headaches, and stroke with
brain-tissue and serum levels of ionized magnesium: a review of recent findings and mecha-
nisms of action. Alcohol 19(2):119–130
Arciniegas DB (2003) The cholinergic hypothesis of cognitive impairment caused by traumatic
brain injury. Curr Psychiatry Rev 5(5):391
Ashare RL, Sinha R, Lampert R, Weinberger AH, Anderson GM, Lavery ME, Yanagisawa K,
McKee SA (2012) Blunted vagal reactivity predicts stress-precipitated tobacco smoking.
Psychopharmacology (Berl) 220(2):259–268. doi:10.1007/s00213-011-2473-3
Ballard MS, Sun M, Ko J (2012) Vitamin A, folate, and choline as a possible preventive
intervention to fetal alcohol syndrome. Med Hypotheses 78(4):489–493. doi:10.1016/j.
mehy.2012.01.014
Barbour RL, Gebrewold A, Altura BT, Altura BM (2002) Optical spectroscopy and prevention of
deleterious cerebral vascular effects of ethanol by magnesium ions. Eur J Pharmacol
447(1):79–86
Bhattacharya SK (1994) Nootropic effect of BR-16A (Mentat), a psychotropic herbal formulation,
on cognitive deficits induced by prenatal undernutrition, postnatal environmental impoverish-
ment and hypoxia in rats. Indian J Exp Biol 32(1):31–36
Bottiglieri T (2002) S-Adenosyl-L-methionine (SAMe): from the bench to the bedside–molecular
basis of a pleiotropic molecule. Am J Clin Nutr 76(5):1151S–1157S
Bottiglieri T (2013) Folate, B12 and S-adenosylmethionine. Psychiatr Clin N Am March 36(1):1–13
Brown RP, Gerbarg PL (2009) Yoga breathing, meditation, and longevity. Ann N Y Acad Sci
1172:54–62. doi:10.1111/j.1749-6632.2009.04394.x
Brown RP, Gerbarg PL (2012) The healing power of the breath. Simple techniques to reduce stress
and anxiety, enhance concentration, and balance your emotions. Shambhala Publications,
Boston
768 R.P. Brown and P.L. Gerbarg
Brown RP, Gerbarg PL (2005) Sudarshan Kriya yogic breathing in the treatment of stress, anxiety,
and depression: part I-neurophysiologic model. J Altern Complement Med 11(1):189–201.
doi:10.1089/acm.2005.11.189
Brown RP, Gerbarg PL, Bottiglieri T (2002) S-adenosylmethionine (SAMe) for depression:
biochemical and clinical evidence. Psychiatr Ann 32(1):29–44
Brown RP, Gerbarg PL, Muskin PR (2009) How to use herbs, nutrients, and yoga in mental health
care. W. W. Norton, New York
Brown RP, Gerbarg PL, Muench F (2013) Breathing practices for the treatment of psychiatric and
stress-related medical conditions. Psychiatr Clin N Am March 36(1):121–140
Busch V, Magerl W, Kern U, Haas J, Hajak G, Eichhammer P (2012) The effect of deep and slow
breathing on pain perception, autonomic activity, and mood processing – an experimental
study. Pain Med 13(2):215–228. doi:10.1111/j.1526-4637.2011.01243.x
Buydens-Branchey L, Branchey M (2006) n-3 polyunsaturated fatty acids decrease anxiety
feelings in a population of substance abusers. J Clin Psychopharmacol 26(6):661–665
Calabrese P, Perrault H, Dinh TP, Eberhard A, Benchetrit G (2000) Cardiorespiratory interactions
during resistive load breathing. Am J Physiol Regul Integr Comp Physiol 279(6):R2208–R2213
Calabrese V, Scapagnini G, Ravagna A, Fariello RG, Giuffrida Stella AM, Abraham NG
(2002) Regional distribution of heme oxygenase, HSP70, and glutathione in brain: relevance
for endogenous oxidant/antioxidant balance and stress tolerance. J Neurosci Res 68(1):65–75
Cao Q, Mak KM, Lieber CS (2006) DLPC and SAMe prevent alpha1(I) collagen mRNA
up-regulation in human hepatic stellate cells, whether caused by leptin or menadione. Biochem
Biophys Res Commun 350(1):50–55
Cederbaum AI (2010) Hepatoprotective effects of S-adenosyl-L-methionine against alcohol- and
cytochrome P450 2E1-induced liver injury. World J Gastroenterol 16(11):1366–1376
Chang LR, Lin YH, Kuo TB, Ho YC, Chen SH, Chang HCW, Liu CM, Yang CC (2012)
Cardiac autonomic modulation during methadone therapy among heroin users: a pilot
study. Prog Neuropsychopharmacol Biol Psychiatry 37(1):188–193. doi:10.1016/j.
pnpbp.2012.01.006
Chen KW, Comerford A, Shinnick P, Ziedonis DM (2010) Introducing qigong meditation into
residential addiction treatment: a pilot study where gender makes a difference. J Altern
Complement Med 16(8):875–882. doi:10.1089/acm.2009.0443
Cibin M, Gentile N, Ferri M (1988) S-Adenosylmethionine (SAMe) is effective in reducing
ethanol abuse in an outpatient program for alcoholics. In: Kuriyama K, Takada A, Ishii
M (eds) Biomedical and social aspects of alcohol and alcoholism. Proceedings of the 4th
Congress. Elsevier Science Publishers, BV, Amsterdam, pp 357–360
Cooney CA, Wise CK, Poirier LA, Ali SF (1998) Methamphetamine treatment affects blood and
liver S-adenosylmethionine (SAM) in mice. Correlation with dopamine depletion in the
striatum. Ann N Y Acad Sci 844:191–200
Das UN (2006) Fetal alcohol syndrome and essential fatty acids. PLoS Med 3(5):e247, author
reply e248
Das SK, Balakrishnan V, Vasudevan DM (2006) Alcohol: its health and social impact in India.
Natl Med J India 19(2):94–99
Dhawan K, Dhawan S, Chhabra S (2003) Attenuation of benzodiazepine dependence in mice by
a tri-substituted benzoflavone moiety of Passiflora incarnata Linneaus: a non-habit forming
anxiolytic. J Pharm Pharm Sci 6(2):215–222
Dimeff LA, Linehan MM (2008) Dialectical behavior therapy for substance abusers. Addict Sci
Clin Pract 4(2):39–47
Di Rocco A, Rogers JD, Brown R, Werner P, Bottiglier T (2000) S-adenosyl-methionine improves
depression in patients with Parkinson’s disease in an open-label clinical trail. Mov Disord
15(6):1225–1229
Elibero A, Janse Van Rensburg K, Drobes DJ (2011) Acute effects of aerobic exercise and Hatha
yoga on craving to smoke. Nicotine Tob Res 13(11):1140–1148. doi:10.1093/ntr/ntr163
45 Nutrients, Phytomedicines, and Mind-Body Treatments for Substance Abuse 769
Gerbarg PL (2008) Yoga and neuro-psychoanalysis. In: Anderson FS (ed) Bodies in treatment: the
unspoken dimension. The Analytic Press, Hillsdale, pp 127–150
Gray KM, Watson NL, Carpenter MJ, Larowe SD (2010) N-acetylcysteine (NAC) in young
marijuana users: an open-label pilot study. Am J Addict 19(2):187–189. doi:10.1111/j.1521-
0391.2009.00027.x
Gray KM, Carpenter MJ, Baker NL, Desantis SM, Kryway E, Hartwell KJ, McRae-Clark AL, Brady
KT (2012) A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent
adolescents. Am J Psychiatry. Aug 1;169(8):805–812. doi:10.1176/appi.ajp.2012.12010055
Haaga DA, Grosswald S, Gaylord-King C, Rainforth M, Tanner M, Travis F, Nidich S, Schneider
RH (2011) Effects of the transcendental meditation program on substance use among univer-
sity students. Cardiol Res Pract 2011:537101. doi:10.4061/2011/537101
Halsted CH (2013) B-Vitamin dependent methionine metabolism and alcoholic liver disease.
Clin Chem Lab Med 51(3):457–465. doi:10.1515/cclm-2012-0308
Halsted CH, Medici V (2012) Aberrant hepatic methionine metabolism and gene methylation in
the pathogenesis and treatment of alcoholic steatohepatitis. Int J Hepatol 2012:959746.
doi:10.1155/2012/959746
Henry BL, Minassian A, Perry W (2012) Effect of methamphetamine dependence on heart rate
variability. Addict Biol 17(3):648–658. doi:10.1111/j.1369-1600.2010.00270.x
Horrocks LA, Yeo YK (1999) Health benefits of docosahexaenoic acid (DHA). Pharmacol Res
40(3):211–225. doi:10.1006/phrs.1999.0495
Hote PT, Sahoo R, Jani TS, Ghare SS, Chen T, Joshi-Barve S, McClain CJ, Barve SS (2008)
Ethanol inhibits methionine adenosyltransferase II activity and S-adenosylmethionine biosyn-
thesis and enhances caspase-3-dependent cell death in T lymphocytes: relevance to alcohol-
induced immunosuppression. J Nutr Biochem 19(6):384–391
Ieraci A, Herrera DG (2006) Nicotinamide protects against ethanol-induced apoptotic
neurodegeneration in the developing mouse brain. PLoS Med 3(4):e101. doi:10.1371/jour-
nal.pmed.0030101
Ikeda H (1977) Effects of taurine on alcohol withdrawal. Lancet 2(8036):509
Jang MH, Shin MC, Kim YJ, Chung JH, Yim SV, Kim EH, Kim Y, Kim CJ (2001) Protective
effects of puerariae flos against ethanol-induced apoptosis on human neuroblastoma cell line
SK-N-MC. Jpn J Pharmacol 87(4):338–342
Khalsa SB, Khalsa GS, Khalsa HK, Khalsa MK (2008) Evaluation of a residential Kundalini yoga
lifestyle pilot program for addiction in India. J Ethn Subst Abuse 7(1):67–79. doi:10.1080/
15332640802081968
Kirsch DL, Nichols F (2013) Cranial Electrotherapy Stimulation (CES) for treatment of anxiety,
depression and insomnia. Psychiatr Clin N Am March 36(1):169–176
Kulkarni SK, Ninan I (1997) Inhibition of morphine tolerance and dependence by Withania
somnifera in mice. J Ethnopharmacol 57:213–217
Lange H, Suryapranata H, De Luca G, Borner C, Dille J, Kallmayer K, Pasalary MN, Scherer E,
Dambrink JH (2004) Folate therapy and in-stent restenosis after coronary stenting. N Engl
J Med 350(26):2673–2681. doi:10.1056/NEJMoa032845
LaRowe SD, Myrick H, Hedden S, Mardikian P, Saladin M, McRae A, Brady K, Kalivas PW,
Malcolm R (2007) Is cocaine desire reduced by N-acetylcysteine? Am J Psychiatry
164(7):1115–1117. doi:10.1176/appi.ajp.164.7.1115
Larsen S, Sherlin L (2013) Neurofeedback: an emerging technology for treating CNS
dysregulation. Psychiatr Clin N Am March 36(1):163–168
Lee CY, Wang JY, Chen TC, Jiang JK, Peng CH, Kuo CD, Chang WC, Chiu JH, Wu CW
(2011) Effects of S/B remedy containing Scutellaria baicalensis and Bupleurum scorzoner-
ifolfium on hepatic interleukin-6 related signal transducer and activator of transcription 3 acti-
vation in mice through cell-cell interaction. Biol Pharm Bull 34(5):727–733
Li M, Chen K, Mo Z (2002) Use of qigong therapy in the detoxification of heroin addicts. Altern
Ther Health Med 8(1):50–54, 56–59
770 R.P. Brown and P.L. Gerbarg
Libby DJ, Worhunsky PD, Pilver CE, Brewer JA (2012) Meditation-induced changes in high-
frequency heart rate variability predict smoking outcomes. Front Hum Neurosci 6:54.
doi:10.3389/fnhum.2012.00054
Lieber CS (2002) S-adenosyl-L-methionine: its role in the treatment of liver disorders. Am J Clin
Nutr 76(5):1183S–1187S
Lieber CS, Casini A, DeCarli LM, Kim CI, Lowe N, Sasaki R, Leo MA (1990) S-adenosyl-
L-methionine attenuates alcohol-induced liver injury in the baboon. Hepatology 11(2):165–172
Lukas SE, Penetar D, Berko J, Vicens L, Palmer C, Mallya G, Macklin EA, Lee DY (2005) An
extract of the Chinese herbal root kudzu reduces alcohol drinking by heavy drinkers in
a naturalistic setting. Alcohol Clin Exp Res 29(5):756–762
Mangano NG, Clementi G, Costantino G, Calvani M, Matera M (2000) Effect of
acetyl-L-carnitine on ethanol consumption and alcohol abstinence syndrome in rats.
Drugs Exp Clin Res 26(1):7–12
Mardikian PN, LaRowe SD, Hedden S, Kalivas PW, Malcolm RJ (2007) An open-label trial of
N-acetylcysteine for the treatment of cocaine dependence: a pilot study. Prog Neuropsycho-
pharmacol Biol Psychiatry 31(2):389–394. doi:10.1016/j.pnpbp.2006.10.001
Margolin A, Kantak K, Copenhaver M, Avants SK (2003) A preliminary, controlled investigation
of magnesium L-aspartate hydrochloride for illicit cocaine and opiate use in methadone-
maintained patients. J Addict Dis 22(2):49–61. doi:10.1300/J069v22n02_04
Mato JM, Camara J, Fernandez de Paz J, Caballeria L, Coll S, Caballero A, Garcia-Buey L,
Beltran J, Benita V, Caballeria J, Sola R, Moreno-Otero R, Barrao F, Martin-Duce A, Correa
JA, Pares A, Barrao E, Garcia-Magaz I, Puerta JL, Moreno J, Boissard G, Ortiz P, Rodes
J (1999) S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled,
double-blind, multicenter clinical trial. J Hepatol 30(6):1081–1089
Medici V, Virata MC, Peerson JM, Stabler SP, French SW, Gregory JF 3rd, Albanese A, Bowlus
CL, Devaraj S, Panacek EA, Richards JR, Halsted CH (2011) S-adenosyl-L-methionine
treatment for alcoholic liver disease: a double-blinded, randomized, placebo-controlled trial.
Alcohol Clin Exp Res 35(11):1960–1965. doi:10.1111/j.1530-0277.2011.01547.x
Monk BR, Leslie FM, Thomas JD (2012) The effects of perinatal choline supplementation on
hippocampal cholinergic development in rats exposed to alcohol during the brain growth spurt.
Hippocampus 22(8):1750–1757. doi:10.1002/hipo.22009
Morse NL (2012) Benefits of docosahexaenoic acid, folic acid, vitamin D and iodine on foetal and
infant brain development and function following maternal supplementation during pregnancy
and lactation. Nutrients 4(7):799–840. doi:10.3390/nu4070799
Navder KP, Baraona E, Lieber CS (1997) Polyenylphosphatidylcholine attenuates alcohol-
induced fatty liver and hyperlipidemia in rats. J Nutr 127(9):1800–1806
Nechifor M (2008) Interactions between magnesium and psychotropic drugs. Magnes Res
21(2):97–100
Nechifor M, Chelarescu D, Mandreci I, Cartas N (2004) Magnesium influence on nicotine
pharmacodependence and smoking. Magnes Res 17(3):176–181
Neese S, La Grange L, Trujillo E, Romero D (2004) The effects of ethanol and silymarin treatment
during gestation on spatial working memory. BMC Complement Altern Med 4:4
Nespor K (2005) Yoga for treatment of substance abuse (Electronic Version). Yoga Magazine:
n.p., http:yogamag.net/archives/2000/6nov/yogadds.shtml, Retrieved on 10 May 2013
Oliva J, Bardag-Gorce F, Li J, French BA, French SW (2011) S-adenosylmethionine prevents the
up regulation of Toll-like receptor (TLR) signaling caused by chronic ethanol feeding in rats.
Exp Mol Pathol 90(3):239–243. doi:10.1016/j.yexmp.2011.01.005
Osman E, Owen JS, Burroughs AK (1993) Review article: S-adenosyl-L-methionine – a new
therapeutic agent in liver disease? Aliment Pharmacol Ther 7(1):21–28
Papakostas GI, Mischoulon D, Shyu I, Alpert JE, Fava M (2010) S-adenosyl methionine (SAMe)
augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major
depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry
167(8):942–948. doi:10.1176/appi.ajp.2009.09081198
45 Nutrients, Phytomedicines, and Mind-Body Treatments for Substance Abuse 771
Ward J, Rosenbaum C, Hernon C, McCurdy CR, Boyer EW (2011) Herbal medicines for the
management of opioid addiction: safe and effective alternatives to conventional pharmaco-
therapy? CNS Drugs 25(12):999–1007
Watanabe A, Hobara N, Nagashima H (1985) Lowering of liver acetaldehyde but not ethanol
concentrations by pretreatment with taurine in ethanol-loaded rats. Experientia
41(11):1421–1422
Westbrook C, Creswell JD, Tabibnia G, Julson E, Kober H, Tindle HA (2011) Mindful attention
reduces neural and self-reported cue-induced craving in smokers. Soc Cogn Affect Neurosci
8(1):73–84
Witkiewitz K, Lustyk MK, Bowen S (2012) Retraining the addicted brain: a review of hypothe-
sized neurobiological mechanisms of mindfulness-based relapse prevention. Psychol Addict
Behav 27(2):351–365
Yadav S, Dhawan A, Sethi H, Chopra A (2006) Effect of AOL breathing process on heroin users.
In: Proceedings world conference on expanding paradigms: science, consciousness & spiritu-
ality, 24–25 Feb 2006. AIIMS, New Delhi, pp 169–177
Yen MH, Weng TC, Liu SY, Chai CY, Lin CC (2005) The hepatoprotective effect of Bupleurum
kaoi, an endemic plant to Taiwan, against dimethylnitrosamine-induced hepatic fibrosis in rats.
Biol Pharm Bull 28(3):442–448
Section IV
Behavioural Approaches
Abstract
Over the past 30 years, numerous empirically tested behavioral approaches to
substance use disorders (SUDs) have been adopted by treatment settings. A key
focus of many of these approaches is the retention of patients in treatment. This
Introduction provides an overview of the chapters in this section on behavioral
approaches to SUDs, including psychodynamic psychotherapy, 12-step pro-
grams, Motivational Interviewing, Cognitive Behavioral Therapy, Contingency
Management, Behavioral Couples Therapy, Multidimensional Family Therapy,
Network Therapy, the Community Reinforcement Approach, the Community
Reinforcement Approach and Family Training, Mindfulness Meditation, and
physical exercise. The final section discusses the dissemination of behavioral
approaches to other parts of the world and the importance of adapting
approaches in culturally sensitive ways while maintaining fidelity to the original
model.
In every society where substance use disorders (SUDs) are treated in some system-
atic manner, behavioral approaches, including “talk therapies,” are at least one
element of the treatment approach. In many parts of the world where treatment for
SUDs is just emerging, the behavioral treatments consist of advice-giving or
commonsense generic counseling. In some areas, including the United States
during the 1960s and 1970s, behavioral approaches consisting primarily of con-
frontational therapies designed to “break through denial” were usually delivered
within the context of residential therapeutic communities. These harsh, unpleasant,
R.A. Rawson
Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, USA
e-mail: [email protected]
M. Galanter (*)
Division of Alcoholism and Drug Abuse, NYU School of Medicine, New York, NY, USA
e-mail: [email protected]
and occasionally abusive techniques had no empirical support but were widely
adopted, frequently with patient populations that had extensive involvement in the
criminal justice system. During the 1980s, when these techniques were applied in
outpatient settings with a noncriminal justice population, they proved to be inef-
fective and, frankly, counterproductive, as they resulted in poor patient compliance
and low retention rates, a serious problem in outpatient treatment settings.
Over the past 30 years, a collection of behavioral interventions and approaches
that were developed and evaluated in research trials have gradually been adopted
into a wide variety of treatment settings. As outpatient settings have increasingly
become the location for SUD services, a key guiding principle in the development
of these approaches is that they should improve retention in treatment. For this
reason, in many of the approaches described in this section, extensive use of
positive reinforcement is emphasized to reinforce positive behavioral change,
including retention in treatment.
The behavioral approaches and strategies described in the section now represent
the foundational treatment paradigm for much of the SUD treatment delivered in
the world. For the treatment of SUDs that have effective pharmacotherapies,
including the treatment of opioid dependence with methadone and buprenorphine,
these behavioral approaches are frequently employed in combination with these
medications. For other SUDs, such as stimulant dependence, these approaches
represent the only empirically supported techniques currently available.
A limiting factor in the rapid dissemination of these approaches is that
a significant training effort is needed for the successful transfer of the knowledge
and skills needed to deliver these treatments. An ongoing challenge in the interna-
tional dissemination of these approaches is balancing fidelity to the evidence-based
principles and methods of the approach, while allowing for adaptation to the
context and values of new cultures. These training and adaptation issues are
covered within this section.
Section IV includes a comprehensive set of chapters on the behavioral
approaches that have been developed and evaluated for the treatment of SUDs.
Psychodynamic psychotherapy has long been used to understand how people use
drugs and alcohol to modify hedonic states and self-regulate moods. Khantzian
describes how drugs and alcohol are used to cope with suffering and emotional
pain. He emphasizes the importance of the therapeutic alliance as an important
element in promoting change and describes the key elements of this alliance as
kindness, support, empathy, respect, patience, and instruction. Donovan and Daley
describe a therapeutic approach developed for the seminal study, Project Match,
which promotes the engagement and use of the 12-step program of Alcoholics
Anonymous (and other related self-help programs) as a method for achieving and
maintaining recovery from drugs and alcohol. The chapter reviews the empirical
evidence for the benefits of participation in a 12-step program and provides
guidance to physicians and other professionals regarding how they can effectively
encourage patients to participate in a 12-step program.
During the past 20 years, three behavioral approaches, Motivational
Interviewing, Cognitive Behavioral Therapy, and Contingency Management,
46 Behavioural Approaches: An Introduction 777
have been the most extensively researched, evaluated, and widely disseminated
behavioral approaches. Motivational Interviewing (MI), conceived and presented in
a 1991 text authored by Miller and Rollnick, is reviewed in the chapter by Tober
(▶ Chap. 47, “Motivational Interviewing and Behaviour Change in Addiction
Treatment”). Motivational Interviewing is arguably the most important behavioral
strategy ever developed for the treatment of SUDs, as it has been applied in a very
extensive array of settings and with a wide variety of patient populations. Tober’s
chapter reviews the skills that are needed by therapists to effectively employ the MI
approach. Clinical examples are given to illustrate the use of key MI concepts, and
training and supervision strategies are described to promote the application of MI
with fidelity. Lee reviews the learning-theory underpinnings of Cognitive Behav-
ioral Therapy (CBT) and the skills needed by therapists to effectively deliver
CBT. She describes the variety of ways that CBT can be applied, with specific
guidelines for how sessions can be constructed. She also provides a comprehensive
array of CBT models and variations as developed by various authors/researchers,
and she reviews the evidence that supports the efficacy of CBT. Roll and Fruci
describe the operant-conditioning rationale for Contingency Management
(CM) and methods used to apply CM principles in the treatment of addiction.
They review the variety of specific modifications that can be used to practically
apply CM in clinical settings. Of all the behavioral approaches, CM has the
strongest empirical evidence of efficacy. Roll and Fruci organize their review of
the research evidence to reflect the key factors that impact the effectiveness of CM
interventions. They finish their review by addressing the implementation barriers
and limitations of CM.
Three of the chapters in Section IV describe behavioral approaches involving
multiple participants. In many parts of the world, group therapy plays a major role
in addiction treatment. McHugh, Park, and Weiss review the variety of group
therapies used in SUD treatment and the data that supports the value of group
therapy. O’Farrell reviews the evidence from studies conducted in the United States
and internationally on Behavioral Couples Therapy (BCT). He describes some
specific techniques, including couples contracts and communication exercises, as
well as some of the possible limitations of BCT resulting from the training and
supervision requirements needed to ensure fidelity. Multidimensional Family Ther-
apy (MDFT) is one of the few behavioral approaches that have been evaluated in
a large multisite international trial. Rigter and colleagues describe the rationale and
elements of MDFT and the methodology and results of that multisite implementa-
tion trial. The chapter describes the challenges and limitations of adapting
a dissemination model for a complex therapy across different cultures and
languages.
Section IV also includes three chapters that describe multielement outpatient
approaches. Galanter describes the rationale and elements of Network Therapy and
the importance of social support as part of successful treatment. The chapter
explains how networks are created and how 12-step program involvement and
medication can be valuable as elements of the network. Research evidence for
support of Network Therapy is provided. The Community Reinforcement Approach
778 R.A. Rawson and M. Galanter
Contents
47.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 780
47.2 Understanding the Nature of Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 780
47.3 What Are the Effective Mechanisms of Change? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 781
47.4 In Which Treatments Can These Effective Mechanisms of Change
Be Found? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 782
47.5 The Social Focus of Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 786
47.6 Treatment Protocols and Their Inclusion in Manuals to Guide Practice . . . . . . . . . . . . . . 787
47.7 Who Treats Addiction Problems? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 788
47.8 Implementing Effective Treatment: Getting Competent Practitioners . . . . . . . . . . . . . . . . . 789
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 789
Abstract
This chapter explores social and psychological routes into addiction and the natu-
rally occurring and assisted routes to recovery. Evidence for effective mechanisms
of change points to specific components of structured treatment and its delivery,
practitioner behaviors, and client attributes. The extent to which these specific
components are in turn contained in usually delivered treatment methods is explored.
Motivational interviewing practice as a style of consultation contains a number of
effective practitioner behaviors, while other important mechanisms are found in
cognitive behavioral coping skills training and in socially based network treatment
approaches. Examples of dialogue and of interactions with clients are given.
The specification of treatment protocols in practice manual format provides the
basis for training and maintaining practice standards. Supervision and the rating of
competence can be based on the use of a validated practice delivery rating method.
G. Tober
Leeds Addiction Unit, Leeds and York Partnership NHS Foundation Trust/University of Leeds,
Leeds, UK
e-mail: [email protected]
47.1 Introduction
For all the evidence for the effectiveness of psychosocial interventions, it is perhaps
surprising that a consensus on the optimal or standard treatment, albeit with variants
to suit different addiction problems, has yet to be forged. A hundred years of
behavioral research has provided both the framework for understanding addictive
behavior and the evidence for treating it. There is, however, the perennial challenge
of translating research findings into practice, and this is further complicated by the
enduring negative attitudes to people with addiction problems, a lack of consensus
about the nature of addiction problems, and about who should treat them. Different
countries have different expectations of the provision of care and how to intervene,
some taking the view that only professionals – medics, psychologists, social
workers, and allied professions – are the right people to provide treatment, others
taking the view that primarily people who have had the problem themselves are the
right treatment providers or that it is the criminal justice system and possibly most
commonly a combination of all of these. This makes for a situation in which
a shared view of the concept of good practice, let alone the specifics, can be hard
to find and effective practice quite difficult to implement.
This raises the question of what is addiction treatment for. Research reports that
people seek treatment because they have lost control over an addictive behavior or
have a sense that they have lost control over their life. There may be greater or
lesser elements of coercion involved in help seeking whether external or somehow
self-imposed, and these are combined with the ambition to achieve some sort of
change. Thus, there is a need to ensure that treatment seekers have a sense of being
helped to reassert control, and so it follows that treatment needs to be an active,
task-oriented process. Help seekers will generally have tried to reach their own
solutions: they may have appealed to family and friends for help, will intuitively
have tried different coping strategies, or tried various kinds of self-help and mutual
aid, and turned to other forms of social capital such as religion or spiritual
inspiration. The challenge is for the helping professional to build on the individual’s
own resources, thus harnessing the processes of “natural recovery” into treatment-
assisted recovery.
point that harmful side effects of treatment are not confined to pharmaceutical
or invasive treatments and he estimates that about 10 % of those receiving psycho-
social treatments will be harmed as a consequence of that treatment. Among the
possible explanations is a loss of optimism about the possibility of change. Help
seeking is always to some extent an expression of optimism about the possibility of
change and having a sense of failure following help seeking damages self-efficacy,
a belief in one’s ability to achieve a particular goal, on which successful change
depends. It is not just doing the wrong thing that can cause harm, but doing nothing,
it can be argued, is equally likely to result in harm.
Michie and colleagues (2012) have used a different starting point in the search
for active ingredients or the effective mechanisms of behavior change treatments,
by examining practice manuals and protocols for the treatment of alcohol problems.
A list of behavior change techniques was extracted and applied to the findings of the
Cochrane Review of brief alcohol interventions, and associations between the
effective interventions and the identified behavior change techniques were exam-
ined using meta-regression. This method yielded the finding that brief interventions
which incorporated ‘prompting self monitoring’ were associated with larger effect
sizes. This is a small finding but one that demonstrates the further potential for
identifying those behavior change techniques that are likely to make a difference
and should be incorporated in routine addiction treatment.
The effective mechanisms of change reported here are supported by service user
accounts of what helps recovery from addiction problems. In their analysis of 1,484
post treatment session questionnaires administered in the UK Alcohol Treatment
Trial (UKATT 2005a, b), Orford and colleagues (2009a) found that, regardless of
treatment received, service users found talking to the therapist, belief in their
progress, and the future focus of treatment to be the most useful elements of the
session. In a longer-term follow-up of UKATT service users, face-to-face inter-
views with 397 participants from several services in different parts of the UK asked
questions about the factors to which they attributed change in their drinking. These
revealed that they thought social factors, the involvement of others in their treat-
ment, motivational factors resulting from knowing the consequences of their
drinking through feedback, personal factors of determination, commitment and
decision making, access to detoxification and medication and feeling comfortable
talking were key (Orford et al. 2009b).
In his first paper on motivational interviewing, Miller (1983) argued that it was the
understanding of client motivation, based in perceived reinforcement and shifting
consequences of the behavior, which would guide the practitioner in delivering
good and useful practice in treating problem drinkers. Ignoring motivation, he
claimed, was counterproductive, while identifying current motivation to continue
47 Motivational Interviewing and Behaviour Change in Addiction Treatment 783
drinking, mixed feelings about it, and allowing the service user to express their own
reservations about their drinking and explore the potential advantages to the service
user of change might help to shift the behavioral status quo. It was a simple
argument, elegantly stated and enthusiastically received. It unlocked the therapeutic
paralysis that characterized attempts to treat people who lacked motivation to
change and often resulted in negative attitudes to the treatment of addiction that
endure in many settings to this day. Miller went on to describe how this facilitation
might be done, with a set of Rogerian (Rogers 1959) principles including listening
to the client, not telling the client what to do, asking for the client’s perspective, and
reflecting their thoughts. Miller however developed the Rogerian principles with
a critical new element: he introduced the idea of direction that is of the practitioner
having an agenda that focused on change and improvement in the client’s health
and social well-being through the medium of stopping or changing drinking. In
order to pursue this agenda, Miller suggested that reflections should be selective,
highlighting negative thoughts about drinking, positive thoughts about the out-
comes of change, and about ability to change.
Miller’s proposed style of consultation owes its popularity to the context in
which it was presented: the equally popular and contemporaneous development by
Prochaska and Diclemente (1984) of a model of change that described the fluctu-
ating nature of motivation which determines continuation or modification of addic-
tive disorders (and not just these behaviors) and drew attention to the imperative to
address this motivation if change was to be facilitated. Miller operationalized
a method of helping people move forward toward making a decision to change,
instead of becoming entrenched in arguments for continuing the behavior (manifest
as denial, rationalization, or justification).
Thus, motivational interviewing with its support for the client, its structure, and
goal directness embodies effective mechanisms of change outlined by Moos.
Furthermore, it is designed to increase self-efficacy by exploring the client’s beliefs
in their ability to change and the resources they need to enhance these beliefs. More
recent research on what happens in motivational interviewing by Amrhein and
colleagues (2003) deepens our knowledge of how to harness the method to optimize
change by ensuring that an expression of commitment to change is the goal of the
motivational dialogue. In their analysis of the discourse between practitioners
working in a motivational interviewing style and their clients’ responses, Amrhein
et al. (2003) found that the statement of a commitment to change made by the client
predicted that change was more likely to occur than when no such statement of
commitment was made. The contribution of this work was to distinguish different
kinds of “change talk,” where the client expresses the desire to change, the ability to
change, the need to change, and reasons for change, and identify “commitment
talk,” defined as the statement of an intention to change. They found that it was the
presence and the strength of this commitment talk or expressed concrete intention
to change which predicted that change was more likely to occur. Apodaca and
Longabough (2009) reviewed the mechanisms of change in motivational
interviewing and their findings support the importance of client change talk that
784 G. Tober
expresses intention to change. How the practitioner achieves this is less specifically
defined; but one thing seems clear. Hours are spent in the average clinic or
counselling room talking about the importance of change, that it needs to happen,
that it ought to happen, and that life would be so much better if it did happen.
Talking about change and its benefits is not enough. Making a commitment to
change is the point that needs to be reached in order for change to have a chance of
happening, at least in the consultation or counselling setting.
In general terms, the weight of the evidence points to the likelihood that
motivational interviewing as a style of consultation enhances treatment engagement
and treatment adherence (Hettema et al. 2005). People are more likely to come into
addiction treatment where they experience being listened to and more likely to stay
where they feel that their own thoughts and feelings are being addressed. What the
practitioner should be trying to achieve is clear, but how exactly they might achieve
this is less clear and the evidence on the specific components of motivational
interviewing that make a difference is equivocal. Apodaca and Longabough
(2009) claim that practitioner behaviors thought to be inconsistent with motiva-
tional interviewing, described as confronting, directing, and warning, were found to
be associated with worse outcomes across treatment for problem drinking and illicit
substance use, while Miller and colleagues (1993) in comparing motivational
interviewing with a confrontational style of treatment as usual found that the latter
tended to result in in-session conflict, which in turn predicted worse drinking
outcomes up to 2 years after treatment.
Based on these findings, the core skills of motivational interviewing which
facilitate the accurate assessment of motivation, enhance motivation to decide
upon and pursue a change goal, are thought to be characterized by open questions
and selective reinforcement:
If you want to assess the individual’s motivation regarding their drinking, ask
them, and do it in such a way as to communicate interest in what they have to say;
avoid telling them what you think, either verbally, in the tone of your voice, or in your
body language. This is open questioning. It makes intuitive sense and it is a learned
behavior in itself, one that is difficult for clinicians who are trained to make differ-
ential diagnoses by questioning whether a list of things is present or not:
Tell me about your recent drinking
What has recently happened when you have been drinking this amount?
What are your thoughts about this?
What would you like to be different?
This second skill is more difficult for the nondirective counsellor, or the “person-
centered” counselling practitioner where the counsellor is required to follow any
agenda set by the client; rather it is the skill of contingent or selective reflection.
The task is to reflect the things that are relevant to the question of drinking, or drug
use, or the health behavior that justifies the conversation. The difference between
reflection in this style of motivational dialogue and nondirective reflective listening
is that selective reflection facilitates the forward movement of the dialogue in
a combination of the directiveness and support to which Moos referred as active
mechanisms for change:
47 Motivational Interviewing and Behaviour Change in Addiction Treatment 785
The combination of open questions and selective reflections enables the practi-
tioner to move the dialogue forward through change talk about their desire to
change, to reach the point of an expression of optimism about the possibility and
outcomes of change, and then a commitment to change. But how does this work?
Why do people change their view of their drinking? Some studies have shown that
the provision of feedback that is objective and personalized, such as described in the
Drinker’s Check-up (Miller et al. 1988) which formalized the process of heighten-
ing concerns about use, a key component of change talk, is what makes motiva-
tional interviewing effective. Thus, neuropsychological tests can be useful, as
demonstrated in Miller et al.’s study and liver function tests as demonstrated in
the UK Alcohol Treatment Trial (2005a). The distinguishing features of using
feedback from test results in a way that is more likely to enhance motivation for
change are that the tests themselves are objective and valid, produce results that are
measurable against population norms or well-functioning people, are personalized,
and are presented in a manner that enables the recipient to understand both their
meaning and their potential for change. Importantly, they need to be perceived to be
a result of drinking, drug use, or whatever the target behavior is and to be
improvable as a result of a change in the target behavior.
Avoiding confrontation and conflict in the consulting room and establishing
collaborative working with the client toward a common goal are supported by
research on the therapeutic alliance, where collaboration between therapist and
client encourages a feeling of mutual respect enabling the therapist to be a helping
agent and creating conditions for the client to explore opportunities and enhance
self-efficacy for change. Those elements of communicating respect and positive
regard, listening to the client, and agreeing the goal of treatment, which are shown
to make a difference, highlight the contribution of the motivational interviewing
method in the operationalization of this professional conduct or the way to achieve
this therapeutic alliance.
The same skills are used throughout the next steps of the process: when moti-
vation to change has been heightened, the decision to make a commitment to
change is prompted; thus, if there are, for example, negative thoughts about
drinking or drug use and positive thoughts about stopping, a goal can be formulated
in a dialogue that follows the open question: How would you like or prefer things to
be? and then using selective reflections to narrow down the response to a clearly
articulated goal. This articulation of the goal may be the result of statements like
I want to stop arguing with my partner; I want to stop taking time off work; and
I want to be someone my children can look up to, when the practitioner asks the
further question about how this can be achieved, eliciting the response I want
to stop drinking. The requirements of the goal are that it is specific and well
defined, measurable, realistic, and achievable and has a time frame attached to it.
786 G. Tober
This is well-trodden territory, and yet many of these key elements are often missing
in addiction treatment. It helps the practitioner as well as the service user to stay
focused if the goal is regularly reviewed and restated, enabling repeated assess-
ments of motivation to change: change “but not just yet” is weak commitment, and
so are loosely defined goals, unrealistic goals, and goals that cannot be measured.
It is not difficult to check that the key criteria are met.
How to implement the behavior change required to achieve the goal takes us into
the territory of applying effective behavior change techniques, as the next step
involves making short-term behavior change plans. Thinking about the rest of life is
too difficult. Listen to the mantras of followers of the 12-step approach. One day at
a time is popular because it is manageable. In describing the implementation of the
active mechanisms of change in behavioral treatments of addiction, Carroll and
Rounsaville (2006) point to increasingly robust evidence for key components. Skill
rehearsal involves the client trying out the new behavior and rehearsing the
thoughts that precede and accompany the behavior. In reviewing these rehearsals,
one can decide whether they are realistic approximations of what can happen. Next
comes the setting of homework, or skills practice in vivo; the definition of tasks
needs to be concrete and specific for time and place; and then monitoring the
method. The effectiveness of giving homework is in the monitoring and reporting
back of it, without which, the research tells us the setting of homework makes no
difference to the learning of new skills.
People with social networks of family and friends who are supportive of change
have a greater chance of changing than those whose social networks support heavy
drinking or drug use. Some of the behavioral interventions based on recruiting and
mobilizing such a support network are the community reinforcement approach
(Meyers and Smith 1995), network therapy (Galanter 1993), and social behavior
and network therapy (Copello et al. 2009). While all of these have an evidence base,
they are not universally practiced; they do, though, provide a strong argument for
moving away from individualized treatment and ensuring that every intervention is
delivered to an individual in a social network.
The process of getting other people involved, people who are available, willing,
and able to help put the plan into practice, involves a set of skills not always familiar
to the addiction practitioner trained in delivering individually based treatments.
This approach has been identified repeatedly by clinical researchers: McCrady
(2006) emphasizes the importance of the family in each step of the helping-seeking
journey. Like Moos, she describes the central role of the family in protecting
against or increasing the risk of substance misuse problems, thus highlighting the
opportunity for harnessing their support in recovery. The wider search for sources
of support beyond the family was at the heart of the development of social behavior
and network therapy (Copello 2007) in which “think network” is a key practitioner
skill. Good network plans are made by people who want to work together, who want
47 Motivational Interviewing and Behaviour Change in Addiction Treatment 787
to give and get support from each other, and who want the same outcome.
The pharmacological components of treatment and compliance with them can be
incorporated into the network plan, and the behavioral principles of rehearsal and
reporting back and modifying behaviors in the light of feedback can be pursued.
The importance of positive role models is addressed in the network approach.
A well-functioning network will include modelling of behaviors and positive
experiences of rewarding activities not associated with drinking or drug use.
If such role models are to be found outside the network, for example, in a local
Alcoholics Anonymous meeting, or other mutual help fellowship, the network can
provide the support to make the initial contact which people can find so difficult.
Treatment staff have variable attitudes to encouraging attendance at and affiliation
with mutual aid when the evidence for their effectiveness is gathering momentum.
In each of the sets of skills described, the active mechanisms identified by Moos
and others are included. Thus, the network-based support, change plan, and relapse
prevention plan enhance self-efficacy (there are always people there to help) and
coping (everyone learns new coping skills in the network); it is focused on the goal
and support is explicit; its direction is enshrined in its future focus (how are things
going to be different from now on?). This set of skills, a combination of motiva-
tional enhancement for change and behavior change skills delivered in a network
supportive of change, can be adopted in a variety of addictive behavior change
settings, whether there is an addiction problem in isolation or in combination with
other disorders, at each stage of behavior change, decision making, planning, and
maintenance of change, in the context of pharmacological, psychological, and
social interventions, and whether the treatment goal is abstinence, control, or
harm reduction.
Effective methods for helping the client to change their addictive behavior have
been incorporated into treatment manuals, self-help materials, training guides, and
numerous forms of brief interventions. Let us get the problems with treatment
manuals out of the way. The first is that they are not often published and so are
difficult to find. Where they have been developed as part of clinical trials, they are
likely to be placed in the public domain. The three treatment manuals which were
used in Project MATCH: Motivational Enhancement Therapy (Miller et al. 1992)
which gives useful examples of worksheets for delivering feedback from tests and
monitoring behavior; Cognitive Behavioral Coping Skills Training (Kadden et al.
1992) combines the core and elective sessions of behavior change treatments with
adaptable worksheets; and Twelve Step Facilitation (Nowinski et al. 1995) focuses
on an introduction to the 12-step philosophy and practice and encouragement to
embark on that recovery journey, all available from NIAAA. Treatment manuals used
in subsequent US trials for different substance dependencies such as cocaine, heroin,
and cannabis are published by the US Clinical Trials Network via Internet media.
788 G. Tober
Monti et al. (2002) have developed their manual for the treatment of alcohol
dependence and incorporated developments in clinical research. Manuals may also
be published as books giving extensive examples of practice (e.g., Copello
et al. 2009; Tober and Raistrick 2007).
Rigid adherence to manual-based protocols is counterproductive. Indeed in their
meta-analysis, Hettema et al. (2005) found that motivational interviewing was more
effective when practiced without a manual. The strongest message to come from the
use of manuals in guiding treatment is that they are useful for ensuring practitioners
adhere to a structure, the prescribed content and style of treatment delivery, but they
are not useful when practitioners follow them “blindly.” Manuals do not compen-
sate for lack of knowledge and experience, and the best use of them is by more
experienced practitioners. Every treatment session needs to be adapted to the
individual client, their motivation, social circumstances, and the severity of their
condition, and a good manual will be designed to be used in this way.
Manuals can provide the basis for detailed scrutiny of practice where video or
audio recordings of practice form the basis for detection and analysis of the
components of treatment and the quality of their delivery. There are validated
methods to rate competence and practitioner adherence to practice protocols.
These can be used for the dual purpose of independent rating of treatment delivery
and for supervision to improve and maintain good practice. Such ratings ensure that
the active mechanisms of change are present and make it possible to identify
differences in practice and explore whether and perhaps why practitioners success-
fully engage service users in treatment and change (see, e.g., Tober et al. 2008).
Practitioner competence is the key to effective treatment; time and money can be
saved by focusing on just doing those things that make a difference.
Everybody who works in health and social care can contribute to addictive behavior
change. Successful outcomes are not just the result of formal treatment but also the
accumulated effect of small but positive “nudges” toward motivation to change.
There is no sense in thinking that busy staff with other responsibilities on their
minds can screen or deliver brief treatments to people with drinking or drug
problems: the liver transplant surgeon, the nurse looking after the patient with
pancreatitis, the emergency room doctor dealing with trauma, and the social worker
handling a child protection case can all see where drinking or drugs are causal
agents. What these staff need to be able to do is help to build motivation; in part,
this is by working in a motivational style, that is, being empathic, using open-ended
questions where possible, and reinforcing change talk, and it is also by simple
motivational enhancement techniques like asking a question such as “what differ-
ence do you think your drinking is making?”. Making the specialist addiction
services as available as is possible is going to be more fruitful than trying to get
staff with other jobs to do to screen and treat people with addiction problems.
Promoting optimism for and confidence in the outcomes of specialist treatment may
47 Motivational Interviewing and Behaviour Change in Addiction Treatment 789
What are the necessary conditions for being a competent specialist addiction
practitioner? Knowledge of the nature of addictive disorders, as well as understand-
ing of the experience of having an addiction disorder, gained from listening to
people who have them, and of the illnesses and other consequences that result from
them are the foundations for accurately assessing the problem and its various
consequences and making the right treatment decisions. Understanding the behav-
ioral principles that drive the addiction itself and the evidence-based effective
mechanisms of change provides the building blocks for the specific intervention.
Utilizing a manual that incorporates these and gives guidance for practice that is
context specific and culturally relevant gives the prototype against which to mea-
sure competence and will enable practitioners to maintain treatment protocol
adherence, once this has been established through training followed by supervised
practice and the rating of competence (Tober et al. 2005).
Those practitioners who are perceived to be authoritative in their knowledge of
the problem and their knowledge of effective treatment and who are perceived by
the client to be competent in effective treatments will be likely to deliver better
outcomes, so the research has shown. Knowledge and then practice of behavior
change techniques, moving from the key components to the complex business of
practicing in addiction treatment settings, are not as simple as the description of
skills suggests. Addiction problems are by definition complex, and people present
with multiple complexities such as dual diagnosis with mental illness, physical
illness, pregnancy and child care concerns, and criminal and other antisocial
behavior. Competence will be achieved through continually supervised practice
in a supportive environment where there is an ambition to implement the evolving
science as a matter of routine.
References
Amrhein PC, Miller WR, Yahne CE, Palmer M, Fulcher L (2003) Client commitment language
during motivational interviewing predicts drug use outcomes. J Cons Clin Psych 71:862–878
Apodaca TR, Longabough R (2009) Mechanisms of change in motivational interviewing: a review
and preliminary evaluation of the evidence. Addiction 104:705–715
Carroll KM, Rounsaville BJ (2006) Behavioral therapies the glass would be half full if only we had
a glass. In: Miller WR, Carroll KM (eds) Rethinking substance abuse. The Guilford Press,
New York, pp 223–239
790 G. Tober
Copello A, Orford J, Hodgson R, Tober G (2009) Social behaviour and network therapy for
alcohol problems. Hove, Routledge
Galanter M (1993) Network therapy for substance abuse: a clinical trial. Psychother Theory Res
Pract Train 30:251–258
Heather N, Robertson I (1997) Problem drinking, 3rd edn. Oxford University Press, Oxford
Hettema J, Steele J, Miller WR (2005) Motivational interviewing. Ann Rev Clin Psych 1:91–111
Kadden R, Carroll K, Donovan D, Cooney N, Monti P, Abrams D, Litt M, Hester R (eds) (1992)
Cognitive behavioral coping skills therapy manual. Project MATCH monograph series.
NIAAA, Rockville
McCrady B (2006) Family and other close relationships. In: Miller WR, Carroll KM (eds)
Rethinking substance abuse. The Guilford Press, New York, pp 166–181
Meyers RJ, Smith JE (1995) Clinical guide to alcohol treatment: the community reinforcement
approach. Guilford Press, New York
Michie S, Whittington C, Hamoudi Z, Zarnani F, Tober G, West R (2012) Identification of
behaviour change techniques to reduce excessive alcohol consumption. Addiction
107:1431–1440
Miller (1983) Motivational interviewing with problem drinkers. Behav Psychother 11:147–172
Miller WR, Carroll KM (2006) Rethinking substance abuse. Guilford, New York
Miller WR, Sovereign RG, Krege B (1988) Motivational interviewing with problem
drinkers: II. The drinker’s check-up as a preventive intervention. Behav Psychother
16:251–268
Miller WR, Zweben A, DiClemente CC, Rychtarik RG (1992) Motivational enhancement therapy
manual: a clinical research guide for therapists treating individuals with alcohol abuse and
dependence, Project MATCH monograph series. NIAAA, Rockville
Miller WR, Benefield RG, Tonigan JS (1993) Enhancing motivation for change in problem
drinking: a controlled comparison of two therapist styles. J Consult Clin 61:455–461
Monti PM, Kadden RM, Rohsenow DJ, Cooney NL, Abrams DB (2002) Treating alcohol
dependence a coping skills training guide. Guilford, New York
Moos RH (2007) Theory based active ingredients of treatment for substance use disorders. Drug
Alc Dep 88:109–121
Nowinski J, Baker S, Carroll K (1995) Twelve step facilitation therapy manual, Project MATCH
monograph series. NIAAA, Rockville
Orford J (2001) Excessive appetites; a psychological view of addictions, 2nd edn. Wiley,
New York
Orford J, Hodgson R, Copello A, Krishnan M, de Madariaga M, Coulton S (2009a) What was
useful about that session? Clients and therapists’ comments after sessions in the UK Alcohol
Treatment Trial. Alc Alc 44:306–313
Orford J, Hodgson R, Copello A, Wilton S, Slegg G (2009b) To what factors do clients attribute
change? Content analysis of follow-up interviews of clients in the UK Alcohol Treatment Trial.
J Subst Abus Treat 36:49–58
Prochaska JO, DiClemente CC (1984) The transtheoretical approach: crossing traditional bound-
aries of therapy. Dow/Jones Irwin, Homewood
Rogers C (1959) A theory of therapy, personality and interpersonal relationships as developed in
the client-centered framework. In: Koch S (ed) Psychology: a study of a science. Vol. 3:
formulations of the person and the social context. McGraw Hill, New York
Rotgers F (2003) Cognitive behavioral theories of substance abuse. In: Rotgers F, Morgenstern J,
Walters ST (eds) Treating substance abuse theory and technique, 2nd edn. Guilford, New York,
pp 166–189
Russell MAH (1971) Cigarette smoking: natural history of a dependence disorder. Brit J Med
Psych 44:1–16
Russell MAH, Peto J, Patel UA (1974) The classification of smoking by factorial structure of
motives. J Royal Stat Soc 137:313–333
Siegel S (1999) Drug anticipation and drug addiction. Addiction 94:1113–1124
47 Motivational Interviewing and Behaviour Change in Addiction Treatment 791
Contents
48.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 794
48.1.1 A Brief History of CBT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 794
48.2 The Cognitive Behavioral Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 796
48.2.1 Description of the General CBT Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 796
48.2.2 Application of CBT to Alcohol and Other Drug Treatment . . . . . . . . . . . . . . . . . . 799
48.2.3 Evidence to Support CBT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 803
48.2.4 International Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 805
48.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 806
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 806
Abstract
Cognitive behavior therapy (CBT) is an umbrella term that describes a group of
therapies, that although many in number and broad in their approach, have in
common a focus on thoughts and beliefs (cognitions) as the central driver of, and
the solution to, effective emotion regulation. The early CBT models (sometimes
referred to as the “first wave”) focused primarily on response to stimuli and
included the theories of B.F. Skinner and Joseph Wolpe. The “second wave”
introduced the concept of cognition into the behavioral models; the most well
known of these models were developed by Aaron Beck (Cognitive Therapy) and
Albert Ellis (Rational Emotive Behavior Therapy). The “third wave” models
are primarily the mindfulness-based cognitive therapies, although a range of
other integrative therapies, such as Schema Focused Therapy and Emotion
Focused Therapy, are sometimes included in the group of newer CBT models.
N.K. Lee
National Centre for Education and Training on Addiction (NCETA), Flinders University,
Adelaide, Australia
LeeJenn Health Consultants, Melbourne, Australia
e-mail: [email protected]
This chapter describes how these models work and how they have been adapted
to substance use treatment, ranging from intensive to brief and low-intensity
interventions. The evidence shows that CBT is one of the most effective
interventions for substance use issues, as well as for co-occurring substance
use and mental health problems. Traditional (second wave) CBT has the most
evidence for its effectiveness, and the mindfulness therapies have a growing
body of evidence that shows that they potentially have similar outcomes for
substance use disorders. CBT has been adapted and applied across a range of
cultures and countries.
“We are what we think. All that we are arises with our
thoughts. With our thoughts we make the world.”
Shakyamuni Buddha
48.1 Introduction
traditional CBT approaches in that, rather than analyzing or controlling them, the
aim of therapy is accepting the thoughts and letting them pass.
This chapter focuses on the second and third waves of cognitive behavioral
therapies.
Like any other therapy, CBT is not merely a manualized set of techniques but
is based on well-researched theoretical models that share the underlying assump-
tion that our thoughts, behaviors, and emotional reactions are learned and that
the path to well-being is through managing thoughts and beliefs in some way.
The fact that CBT is often manualized is an artifact of its structured and scientific
approach rather than a fundamental part of the approach. There is some evidence
that a single-focused approach is more effective than an eclectic one (e.g., Moos
et al. 1999), suggesting that a sound basis in a single therapy is most effective.
Therefore, it is important to understand the underlying theoretical structure
of CBT, not merely the strategies or techniques, to apply the interventions
effectively.
Strategies to manage thoughts and beliefs may differ between different styles of
CBT. For example, in Cognitive Therapy, change is facilitated through strategies to
analyze and change thoughts, while in mindfulness approaches the focus is on
becoming aware of, and accepting, thoughts.
In general, cognitive and behavioral therapies are relatively brief (usually
10–20 sessions), and even briefer therapy versions have been developed that are
designed for delivery in between 1 and 6 sessions.
2. Pattern and onset: What is the current pattern of substance use, how did it start,
and how do the pattern and history of use impact on current strengths and
vulnerabilities?
3. Predisposing factors: What are the client’s vulnerability and risk factors (e.g.,
family history of drinking or drug use; trauma; or neglect in childhood)? Under-
standing these risk factors can help tailor treatment and indicate the need for
referral. For example, if a client has a history of trauma, ensuring that treatment is
“trauma informed” and does not inadvertently re-traumatize the client is not only
client sensitive but can also assist in reducing the client’s risk of relapse.
4. Precipitating factors: What are the client’s immediate triggers to substance use
(e.g., anxiety or stress, external cues)? Identifying immediate- and longer-term
triggers for use can focus treatment substantially.
5. Perpetuating factors: What variables maintain substance use (e.g., homelessness,
friendship circles, dependence)?
6. Protective factors: What protective factors does the client currently have at their
disposal (e.g., friendship circle, attendance at meetings, clear insight)? These
protective factors can be used to support treatment and can also be further
developed in treatment.
7. Prognosis: What is the likely outcome of treatment for this client? Prognosis
helps practitioners understand how to modify treatment options to realistically
address client’s needs. For example, if the client is highly likely to relapse given
the current circumstances, harm reduction strategies may be most helpful at this
stage, while trying to engage the client in 12-step groups may be setting them up
for failure.
Core Beliefs
Trigger
Automatic
Thoughts
Proximal situational
factors
Feelings Actions
has not shown the same effectiveness in substance use treatment as it has in other
mental health areas, such as post-traumatic stress and obsessive-compulsive and
panic disorders (e.g., Kavanagh et al. 2006), and CST is more commonly practiced
as a stand-alone treatment.
The four main components of stand-alone CST are relapse prevention training,
social and communication skills training, training in coping with urges and
cravings, and mood management. Project MATCH, the largest alcohol treatment
outcome study, used a modified CST as the cognitive behavioral arm of the study
(Kadden et al. 2003) and found modified CST equally as effective as motivational
enhancement and 12-step facilitation.
(Bennett-Levy et al. 2010) and can be used to address a range of substance use
problems from prevention to tertiary treatment. Cognitive behavioral therapies are
ideally suited to the low-intensity environment because they are typically brief,
structured, and easily manualized.
There have been a number of different types of low-intensity interventions
developed in recent years. Advice clinics, for example, operate in mental health
services in the UK (White 2010) as a one-off 30-min appointment with a clinician.
Guided self-help CBT (Kenwright 2010) involves either paper-based or Internet-
based self-directed learning materials that are supplemented by lower-intensity
guidance from a practitioner as required. The practitioner is available to answer
questions about the material, but otherwise the client works through a brief program
essentially on their own.
While brief telephone counseling has been accessible for decades in some
countries, more recently there has been development of a number of similar
services using email and online media. An online service in Australia
(counsellingonline.com.au), for example, uses live online chat-style environment
to provide brief interventions for people with substance use problems. An early
review of the service showed that the types of clients and the types of presenting
issues are markedly different from telephone counseling, with younger people and
methamphetamine users making up a greater proportion of online clients (Swan and
Tyssen 2009), suggesting that these types of interventions do indeed increase reach
and access to hard-to-reach populations.
In addition, interventions have been developed for SMS (mobile phone text
messaging) (Shapiro and Bauer 2010), mail (Kavanagh et al. 2010), and online-
facilitated peer support (Griffiths and Reynolds 2010) (see www.theshedonline.org.
au for an example).
The inconsistent use of the term “cognitive behavior therapy” to describe both
interventions based on common general principles and specific treatments makes it
difficult to distinguish outcomes between the different styles. However, overall,
CBT appears to be both effective and long lasting when compared with general
drug counseling, treatment as usual, and no treatment controls and is effective in
both individual and group formats (McHugh et al. 2010).
A number of studies have examined specific relapse prevention treatments,
including a systematic review of psychosocial interventions for substance use
disorders (Dutra et al. 2008), which included five studies of RP that
showed positive but modest outcomes on retention in treatment and substance
use. Compared to other types of behavioral therapies, RP was most effective in
maintaining abstinence post treatment (39 % abstinent post treatment), suggesting
that if abstinence is the treatment goal, RP may be the treatment of choice.
Other treatments that draw heavily from the RP model have also been found to
be effective. The matrix model (Rawson et al. 1995), for example, is a 16-week
manualized group-focused outpatient intervention that includes many components
of RP, plus a range of other behavioral interventions such as contingency manage-
ment and 12-step participation. It has been found to be effective for a range of drug
users, including amphetamine and cocaine users (Shoptaw et al. 2009).
In a review of CBT, RP, and contingency management, Dutra et al. (2008) found
that the group referred to as “CBT therapies” (which included cognitive therapy and
therapies drawn from CT such as dialectical behavior therapy) had lower dropout rates
(35 %) than RP (57 %), equivalent effect sizes, but lower abstinence rates post treatment.
CBT appears to be more effective with the addition of contingency management,
although the evidence is mixed and limited (McHugh et al. 2010). Project
COMBINE (Anton et al. 2006) showed that in combination with medical manage-
ment, “combined behavioral intervention” (including CBT) was as effective as
naltrexone, and both were more effective than placebo for alcohol dependence.
(using the AUDIT) and 5-min brief intervention in primary care (McAvoy
et al. 2001). Computer-assisted CBT has been found to improve abstinence and
treatment engagement compared to standard outpatient treatment for substance
dependence (Kay-Lambkin et al. 2009) and for co-occurring mental health and
substance use problems with some studies showing equivalent or better outcomes
than treatment with a psychologist face-to-face.
Cognitive behavior therapy has its origins in the developed world and is
heavily based on Western concepts and models of illness (Rathod and Kingdon 2009).
However, it is a broad and flexible model of care based on a well-grounded treatment
formulation that can accommodate cultural and other influences and as a result has
been adapted and successfully used across a number of cultures.
For example, in some cultures, such as many Indigenous groups, collective
history is an important component of their world view (Rathod and Kingdon
2009) or, in CBT terms, their core beliefs. Although CBT does not tend to delve
deeply into the past to routinely reappraise it, past issues are not precluded when
they are driving or maintaining current problems, and CBT can easily accommo-
date these types of cultural differences.
Similarly, Hodges and Oei (2007) have examined the compatibility of CBT with
Chinese values and have identified a number of potential issues for CBT, including the
value Chinese and other Asian cultures place on conformity, certainty and discipline,
persistence and a strong work ethic, and respect for authoritarian systems. In Asia more
broadly, there is also a high level of stigma around mental health issues and a tendency
for somatization (i.e., expressing mental health issues as physical symptoms).
Hodges and Oei (2007) argue that because CBT is structured and can be adapted
to a more instructive rather than collaborative style, it may suit cultural contexts
needing a directive and structured therapy style. This adaptation may suit the need
for certainty and authority in these cultures and can also reduce the stigma of mental
health treatment by using a more “coaching” style of therapy. Finally, they note that
with the expansion of CBT using Eastern and Buddhist mindfulness strategies, CBT
is well suited to Asian cultures.
806 N.K. Lee
CBT for mental health problems has been applied successfully in a range of
diverse cultures and countries including, but not limited to, Pakistan (Rahman
et al. 2008), Japan (Chen et al. 2007), and China (Williams et al. 2006) and among
Latina women in the USA (Amaro et al. 2010), Muslims (Williams et al. 2006), and
Aboriginal Australians (Laliberté et al. 2010), using a more narrative style of delivery
sometimes referred to as “bush CBT” (Rickwood 2006). Although many of these
studies are not specifically related to substance use disorders, the cross-cultural
applications still apply.
48.3 Conclusion
CBT is an umbrella term that describes a wide range of therapies that have in
common a focus on thoughts and beliefs as the central driver of, and the solution to,
effective emotion regulation.
It tends to be relatively brief and highly collaborative. It is collaboration that is
considered to be key in the development of the therapeutic alliance, an essential
component of the application of CBT. It comes in a wide range of formats,
including group and individual therapy, longer-term and brief therapy, and
low-intensity interventions such as computerized CBT.
It is one of the most researched treatments in the world; both traditional (e.g.,
cognitive therapy) and newer (e.g., dialectical behavior therapy) models have
shown effectiveness for treating substance use disorders.
Its structured and theoretical base makes it ideally suited to issues that co-occur
with substance use problems, including common mental health problems, cognitive
impairment, and trauma.
It has been adapted and applied across a range of cultures and countries. CBT is
ideal for adaptation to non-Western cultures because of its flexible collaborative
style and its reliance on effective case formulation.
References
Amaro H, Magno-Gatmaytan C, Meléndez M, Cortés DE, Arevalo S, Margolin A (2010)
Addiction treatment intervention: an uncontrolled prospective pilot study of spiritual self-
schema therapy with Latina women. Subst Abus 31(2):117–125
Anton RF, O’Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, Gastfriend DR,
Hosking JD, Johnson BA, LoCastro JS, Longabaugh R, Mason BJ, Mattson ME, Miller WR,
Pettinati HM, Randall CL, Swift R, Weiss RD, Williams LD, Zweben A (2006) Combined
pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study:
a randomized controlled trial. JAMA 295(17):2003–2017
Baker A, Kay-Lambkin F, Lee NK, Claire M, Jenner L (2003) A brief cognitive behavioural
intervention for regular amphetamine users – a treatment guide. Australian Government
Department of Health and Ageing, Canberra
Baker A, Lee NK, Claire M, Lewin TJ et al. (2005) Brief cognitive behavioural interventions for
regular amphetamine users: a step in the right direction. Addiction 100(3):367–378
48 Cognitive Behavioural Therapies for Substance Use Problems 807
Ball SA, Young JE (2000) Dual focus schema therapy for personality disorders and substance
dependence: case study results. Cogn Behav Pract 7(3):270–281
Bandura A (1977) Social learning theory. Prentice Hall, Englewood Cliffs
Bates ME, Bowden SC, Barry D (2002) Neurocognitive impairment associated with alcohol use
disorders: Implications for treatment. Exp Clin Psychopharmacol 10(3):193–212
Beck JS (2011) Cognitive therapy: basics and beyond. The Guilford Press, New York
Beck AT, Wright FD, Newman CF, Liese BS (1993) Cognitive therapy of substance abuse. The
Guilford Press, New York
Bennett-Levy J, Richards D, Farrand P, Christensen H, Griffiths KM, Kavanagh DJ, Klein B, Lau
MA, Proudfoot J, Ritterband L, White J, Williams C (2010) Oxford guide to low intensity CBT
interventions. Oxford University Press, New York
Beshai S, Clark CM, Dobson KS (2013) Conceptual and pragmatic considerations in the use of
cognitive-behavioral therapy with Muslim clients. Cognit Ther Res 37:197–206
Bowen S, Chawla N, Collins SE, Witkiewitz K, Hsu S, Grow J, Clifasefi S, Garner M, Douglass A,
Larimer ME (2009) Mindfulness-based relapse prevention for substance use disorders: a pilot
efficacy trial. Subst Abus 30(4):295–305
Bowen S, Chawla N, Marlatt GA (2010) Mindfulness-based relapse prevention for addictive
behaviors: a clinician’s guide. The Guilford Press, New York
Carroll KM (1998) A cognitive-behavioral approach: treating cocaine addiction. National Institute
on Drug Abuse, Rockville
Chen J, Nakano Y, Ietzugu T, Ogawa S, Funayama T, Watanabe N, Noda Y, Furukawa TA
(2007) Group cognitive behavior therapy for Japanese patients with social anxiety disorder:
preliminary outcomes and their predictors. BMC Psychiatry 7(1):69
Copeland J, Swift W, Roffman R, Stephens R (2001) A randomized controlled trial of brief
cognitive–behavioral interventions for cannabis use disorder. J Subst Abus Treat 21(2):55–64
Currie SR, Clark S, Hodgins DC, El-Guebaly N (2004) Randomized controlled trial of brief
cognitive–behavioural interventions for insomnia in recovering alcoholics. Addiction
99(9):1121–1132
Dore G, Mills K, Murray R, Teeson M, Farrugia P (2012) Post-traumatic stress disorder,
depression and suicidality in inpatients with substance use disorders. Drug Alcohol Rev
31(3):294–302
Dutra L, Stathopoulou G, Basden S, Leyro T, Powers M, Otto M (2008) A meta-analytic review of
psychosocial interventions for substance use disorders. Am J Psychiatry 165(2):179–187
Griffiths KM, Reynolds J (2010) Online mutual support bulletin boards. In: Bennett-Levy J,
Richards D, Farrand P, Christensen H, Griffiths KM, Kavanagh DJ, Klein B, Lau MA,
Proudfoot J, Ritterband L, White J, Williams C (eds) Oxford guide to low intensity CBT
interventions. Oxford University Press, New York
Hayes SC (2004) Acceptance and commitment therapy and the new behavior therapies:
mindfulness, acceptance and relationship. In: Hayes SC, Follette VM, Linehan M (eds)
Mindfulness and acceptance: expanding the cognitive behavioral tradition. The Guilford
Press, New York, pp 1–29
Hayes SC, Strosahl KD (2011) Acceptance and commitment therapy, second edition: the process
and practice of mindful change. The Guilford Press, New York
Hodges J, Oei TP (2007) Would Confucius benefit from psychotherapy? The compatibility of
cognitive behaviour therapy and Chinese values. Behav Res Ther 45(5):901–914
Hofmann SG, Sawyer AT, Fang A (2010) The empirical status of the “new wave” of
CBT. Psychiatr Clin North Am 33(3):701
Hoppes K (2006) The application of mindfulness-based cognitive interventions in the treatment of
co-occurring addictive and mood disorders. CNS Spectrums 11(11):829
Kadden R, Carroll K, Donovan D, Cooney N, Monti P, Abrams D, Litt M, Hester R (2003)
Cognitive behavioral coping skills therapy manual – a clinical research guide for therapists
treating individuals with alcohol abuse and dependence. U.S. Department of Health and
Human Services Public Health Service National Institutes of Health, Rockville
808 N.K. Lee
Kavanagh DJ, Sitharthan G, Young RM, Sitharthan T, Saunders JB, Shockley N, Giannopoulos
V (2006) Addition of cue exposure to cognitive-behaviour therapy for alcohol misuse:
a randomized trial with dysphoric drinkers. Addiction 101(8):1106–1116
Kavanagh DJ, Connolly J, White A, Kelly A, Parr J (2010) Low intensity CBT by mail. In:
Bennett-Levy J, Richards D, Farrand P, Christensen H, Griffiths KM, Kavanagh DJ, Klein B,
Lau MA, Proudfoot J, Ritterband L, White J, Williams C (eds) Oxford guide to low intensity
CBT interventions. Oxford University Press, New York
Kay-Lambkin FJ, Baker AL, Lewin TJ, Carr VJ (2009) Computer-based psychological treatment
for comorbid depression and problematic alcohol and/or cannabis use: a randomized controlled
trial of clinical efficacy. Addiction 104(3):378–388
Kenwright M (2010) Introducing and supporting written and internet-based guided CBT. In:
Bennett-Levy J, Richards D, Farrand P, Christensen H, Griffiths KM, Kavanagh DJ, Klein B,
Lau MA, Proudfoot J, Ritterband L, White J, Williams C (eds) Oxford guide to low intensity
CBT interventions. Oxford University Press, New York
Laliberté, Arlene, Nagel, Tricia, and Haswell, Melissa (2010) Low intensity CBT with indigenous
consumers: creative solutions for culturally appropriate mental health care. In: Bennet-Levy J,
Richards DA, Farrand P, Christensen H, Griffiths KM, Kavanagh DJ, Klein B, Lau MA,
Proudfoot J, Ritterband L, White J, Williams C, (eds.) Oxford Guide to Low Intensity CBT
Interventions. Oxford Guides in Cognitive Behavioural Therapy . Oxford University Press,
Oxford, UK, pp. 577–585
Linehan M (1993) Borderline personality disorder: concepts, controversies, and definitions. In:
Linehan M (ed) Cognitive-behavioral treatment of borderline personality disorder. The
Guilford Press, New York
Luoma JB, Kohlenberg BS, Hayes SC, Bunting K, Rye AK (2008) Reducing self-stigma in
substance abuse through acceptance and commitment therapy: model, manual development,
and pilot outcomes. Addict Res Theory 16(2):149–165
Magill M, Ray LA (2009) Cognitive-behavioral treatment with adult alcohol and illicit drug users: a -
meta-analysis of randomized controlled trials. J Stud Alcohol Drugs 70(4):516–527
Marlatt AG, Donovan DM (2005) Relapse prevention: maintenance strategies in the treatment of
addictive behaviors. The Guilford Press, New York
Marlatt AG, Gordon JR (1985) Relapse prevention: maintenance strategies in the treatment of
addictive behaviors. The Guilford Press, New York
Marlatt AG, Larimer ME, Witkiewitz K (2012) Harm reduction, second edition: pragmatic
strategies for managing high-risk behaviors, 2nd edn. The Guilford Press, New York
McAvoy BR, Donovan RJ, Jalleh G, Saunders JB, Wutzke SE, Lee N, Kaner EF, Heather N,
McCormick R, Barfod S, Gache P (2001) General practitioners, prevention and alcohol-a
powerful cocktail? Facilitators and inhibitors of practising preventive medicine in general and
early intervention for alcohol in particular: a 12-nation key informant and general practitioner
study. Drugs Educ Prev Policy 8(2):103–117
McHugh RK, Hearon BA, Otto MW (2010) Cognitive-behavioral therapy for substance use
disorders. Psychiatr Clin North Am 33(3):511
Mills K, Deady M, Proudfoot H, Sannibale C, Teesson M, Mattick R, Burns L (2009) Guidelines
on the management of co-occurring mental health conditions in alcohol and other drug
treatment settings. National Drug and Alcohol Research Centre, University of New South
Wales, Sydney
Mitcheson L, Maslin J, Meynen T, Morrison T, Hill R, Wanigaratne S (2010) Applied cognitive
and behavioural approaches to the treatment of addiction: a practical treatment guide. Wiley,
Chichester
Monti PM, Rohsenow DJ (1999) Coping-skills training and cue-exposure therapy in the treatment
of alcoholism. Alcohol Res Health 23(2):2–2
Moos RH, Finney JW, Ouimette PC, Suchinsky R (1999) A comparative evaluation of substance
abuse treatment: I. Treatment orientation, amount of care, and 1-year outcomes. Alcohol Clin
Exp Res 23(3):529–536
48 Cognitive Behavioural Therapies for Substance Use Problems 809
Contents
49.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 812
49.2 Addiction as a Self-regulation Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 813
49.2.1 Disordered Emotions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 813
49.2.2 Disordered Relations with Self and Others . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 814
49.2.3 Disordered Self-care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 815
49.3 Implications for Psychodynamic Psychotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 816
49.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 818
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 819
Abstract
An understanding of addiction to drugs and alcohol and their treatment is
reviewed from a modern-day psychodynamic perspective drawing on ego/self-
psychology and object relations and attachment theory. The author places
emphasis on addictions as a self-regulation disorder. Deficits in regulating
emotions, self-esteem, relationship, and self-care interact variably and cause
individuals so affected to relieve their pain and suffering associated with these
deficits with addictive substances and to become addicted to them. The author
considers addictive drugs to be appealing not so much as pleasure producing but
rather as agents that create and foster comfort and contact for individuals who
are discomforted and disconnected. Alcohol and drugs relieve and/or change
states of anhedonia, dysphoria, and unbearable painful emotional states. Indi-
viduals so affected discover that depending on the particular emotional pain with
which they suffer, they discover a preference for a particular class of drugs. The
action of each class of drugs is linked to how individuals discover these specific
effects in relation to the suffering associated with their self-regulation problems.
E.J. Khantzian
Harvard Medical School, Boston, MA, USA
e-mail: [email protected]
49.1 Introduction
experiencing their feelings as cut off or vacuous (Khantzian 1975, 1985, 1997).
Weider and Kaplan (1969) coined the term “drug of choice,” elaborating on how
individuals self-select addictive drugs as a “prosthetic” to cope with overwhelming
adolescent anxiety. The works of Wurmser (1974) and Khantzian (1985) empha-
sized the calming or muting action of opiates or obliterating doses of alcohol,
especially for feelings of rage and aggression. What should be emphasized here is
that these reports better focused on and appreciated how addictive drugs were used
not for pleasure or self-destructive motives as early psychoanalytic studies stressed,
but more precisely to selectively alleviate or make more tolerable affects that were
confusing, unbearable, or intolerable.
More recently, Khantzian (2012) has considered some of the more subtle
psychodynamics of addictive behavior that are insufficiently considered, namely,
why so much of addictive behavior unfortunately continues to be linked to pleasure
seeking (especially by neuroscientists) and how and why seeking relief from
addictive drugs most usually produces more suffering than it relieves, and yet
addicted individuals persist in the use of their drugs. In the former instance,
especially those who are alexithymic and confused about their feelings, addicted
individuals wittingly and unwittingly substitute the suffering which they perpetuate
and control with use for the suffering they do not understand or control. The
operative changes from simply relieving suffering, for one of control where they
better understand and control it. In the second case, Khantzian (2012) has specu-
lated, based on clinical observations, that addicted individuals often suffer with
pervasive anhedonia and that the often magical relief they first experience with their
drug of choice is experienced as euphoric, which is interpreted as pleasure, when in
fact it is the result of relief of the anhedonia.
Khantzian (2012) and Khantzian and Mack (1983) have described a fundamental
ego function involved in life and in addictive vulnerability, namely, a capacity for
self-care.1 Self-care functions ensure safety, well-being, and survivability. They are
underdeveloped or deficient in substance-dependent individuals. Early in his career,
Khantzian (2012) cites his experience working with intravenous heroin users in
1
The following sections on self-care and treatment are based in part on a recent report by
Khantzian (2012).
816 E.J. Khantzian
The psychodynamic findings that have been outlined previously are considered
in what follows, not only in reference to individual psychotherapy but also as they
apply to considering other treatments, especially psychodynamic group therapy, as
they can enhance individual therapy or be considered as alternatives when there are
psychodynamic indications to do so.
Remembering how cut off addicted patients can be with their thoughts and
feelings, therapists can help significantly with these dysfunctions by actively
drawing out, identifying, and labeling feelings that begin to surface or seem
evident to the therapist. When patients protest they do not know what they are
feeling, treating clinicians should avoid concluding it is resistance or denial but
rather use such interactions to invite and support the patient to consider the
challenge of exploring, discovering, and understanding their feelings and emo-
tions. Allen, Fonagy and Bateman (2008) have coined the term mentalization to
emphasize one of the most basic aspects of psychotherapeutic work in general,
but the concept preeminently applies to work with addicted patients, namely, to
persistently focus on helping patients to access feelings, put them into words,
and sustain them. Beyond individual therapy, the narrative and storytelling
traditions that occur in group therapy and 12-step meetings are often very
beneficial in helping patients to develop a capacity to recognize, express, and
practice their own thoughts and feelings.
For those patients who struggle with and self-medicate intense and threaten-
ing emotions, particularly anger and rage, considerations and efforts should be
made to help them contain and moderate the feelings that can feel so dangerous
to self and others. It is worth noting how the positive treatment relationship and
the therapist’s concern for the safety of the patient is in and of itself a containing
influence. For those whose rage and violent feeling derive from trauma and neglect,
it is crucial to acknowledge and validate the legitimacy of such reactions and help
them to understand how and why they have resorted to addictive drugs to contend
with such intense emotions. Carefully timed and gentle explorations of the experi-
ences that engender such emotions can gradually diminish or resolve such intense
affect. In this context, judicious use of legitimate psychotropic medications
targeting these affects can significantly attenuate the intensity to make the working
through of these affects in psychotherapy more doable.
The support and empathy exhibited by the therapist in response to drug patients’
pervasive sense of shame and broken self-esteem (predisposing and consequential)
are a vital element in engaging and retaining such patients in psychotherapy. Such
an approach helps in gaining inroads on the confusing and elusive ways in which
the sense of self and others is experienced by substance users. Openings are created
to focus on and help identify and resolve feelings of powerlessness, defensive rage,
and reactions of omnipotence that are experienced and often surface in treatment.
Patience, support, and kindness remain of paramount importance and allow
for opportunities to therapeutically address and help the patient and the therapist,
understand, and better work out problems with off-putting characteristics.
These characteristics are more often reactive and defensive secondary to feelings
of helplessness as well as feelings of unimportance (Dodes 1996; Director 2005).
818 E.J. Khantzian
And for those who are seemingly void of emotions and disengaged, the therapist
may draw on their own energy and liveliness to help activate and enliven patients
who are so affected. Again, group therapy experiences often can be invaluable in
this respect in instilling and validating a better sense of self/self-esteem.
The issue of low self-esteem of substance abusers is related to their tendency to
be avoidant of relationships and interpersonally isolated. They feel undeserving of
the care and connection to others. Remaining interactive, engaging, and empathic
are important elements in responding to patients’ fear of and ambivalence about
relationship. Impassivity and detached interpretations can be counter-therapeutic
and devastating. Tactful focus on the ambivalence can materially stimulate possi-
bilities of beneficial connections to others. It is in this respect that the connections
stimulated by individual and group therapy are extraordinarily helpful in addressing
and ameliorating the attachment difficulties and sense of alienation with which
substance-dependent individuals struggle.
The thoughtless and unfeeling behaviors of substance-dependent patients that
are characteristic of self-care deficits become manifest in the treatment relation-
ship by the alarm stirred in the therapist by patients’ risky or dangerous behav-
iors. Such reactions and interactions can alert the therapist and patient to how
such deficits are major factors for patients to use and relapse to additive behav-
iors. The therapist should be unhesitant in using their reactions of alarm and
concern that patients stir to identify the lack of such reaction in the patient.
Constant attention to patients’ poor self-care can help to instill a growing
awareness of how their self-care deficits continuously leave those so affected
continuously in harm’s way, especially those involved with the harm and dangers
associated with addictive substances. Long-term therapy often helps in getting at and
understanding the developmental and environmental roots of these deficits, but
a here-and-now, active, instructive approach is essential in order to stimulate and
better develop a better capacity to recognize, anticipate, and avoid self-harm,
particularly related to addictive substances. Finally, “We need to help patients use
self-respect, feelings of apprehension/worry, relationships with others, and thought-
fulness as a guide for safe behavior and self-preservation” (Khantzian 2012, p. 278).
49.4 Conclusion
References
Allen JG, Fonagy P, Bateman AW (2008) Mentalizing in clinical practice. American Psychiatric
Publishing, Washington, DC
Director L (2005) Encounters with omnipotence in the psychoanalysis of substance users.
Psychoanal Dialog 15:567–586
Dodes LM (1996) Compulsion and addiction. J Am Psychoanal Assoc 44:815–835
Dodes LM (2002) The heart of addiction. Harper Collins, New York
Dodes LM, Khantzian EJ (2005) Individual psychodynamic psychotherapy. In: Frances RJ,
Miller SI, Mack AH (eds) Clinical textbook of addictive disorders, 3rd edn. Guilford Press,
New York, pp 457–473
Dodes LM, Khantzian EJ (in press) Individual psychodynamic psychotherapy. In: Frances RJ,
Miller SI, Mack, AH (eds) Clinical textbook of addictive disorders, 4th edn. Guilford Press,
New York
Flores PJ (2004) Addiction as an attachment disorder. Jason Aronson, New York
Gedo J (1986) Conceptual issues in psychoanalysis: essays in history and method. The Analytic
Press, Hillsdale
Khantzian EJ (1975) Self-selection and progression in drug dependence. Psychiatry Digest
10(1):9–22
Khantzian EJ (1978) The ego, the self and opiate addiction: theoretical and treatment consider-
ations. Int Rev Psychoanal 5:189–198
Khantzian EJ (1985) The self-medication hypothesis of addictive disorders. Am J Psychiatr
142:1259–1264
Khantzian EJ (1997) The self-medication hypothesis of substance use disorders: a reconsideration
and recent applications. Harv Rev Psychiatry 4:231–244
Khantzian EJ (2003) Understanding addictive vulnerability: an evolving psychodynamic perspec-
tive. Neuro-Psychoanalysis 5:5–21
Khantzian EJ (2012) Reflections on treating addictive disorders: a psychodynamic perspective.
Am J Addict 21:274–279
Khantzian EJ, Mack JE (1983) Self-preservation and the care of the self: ego instincts
reconsidered. Psychoanal Study Child 38:209–232
Kohut H (1971) The analysis of the self. International Universities Press, New York
Kohut H (1977) The restoration of the self. International Universities Press, New York
Krystal H (1988) Integration and self-healing: affect, trauma. Alexithymia. The Analytic Press,
Hillsdale
Krystal H, Raskin HA (1970) Drug dependence: aspects of ego functions. Wayne State University
Press, Detroit
Lichtenberg JD (1983) Psychoanalysis and infant research. The Analytic Press, Hillsdale
McDougall J (1984) The ‘disaffected’ patient: reflections on affect pathology. Psychoanal Q
53:386–409
Milkman H, Frosch WA (1973) On the preferential abuse of heroin and amphetamine. J Nerv Ment
Dis 156:242–248
Shedler J (2010) The efficacy of psychodynamic psychotherapy. Am Psychol 65:98–109
Walant KB (2002) Creating the capacity for attachment: treating addictions and the alienated self.
Jason Aronson, New York
Weider H, Kaplan E (1969) Drug use in adolescents. Psychoanal Study Child 24:399–431
Wurmser L (1974) Psychoanalytic considerations of the etiology of compulsive drug use. J Am
Psychoanal Assoc 22:820–843
Mindfulness as Behavioural Approach
in Addiction Treatment 50
Marianne T. Marcus
Contents
50.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 822
50.1.1 Mindfulness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 823
50.1.2 Mindfulness-Based Approaches to Substance Use Disorders . . . . . . . . . . . . . . . . 823
50.1.3 Mindfulness-Based Stress Reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 824
50.1.4 Mindfulness-Based Cognitive Therapy (MBCT) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 825
50.1.5 Dialectical Behavioral Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 826
50.1.6 Acceptance and Commitment Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 827
50.1.7 Addiction-Specific Mindfulness Treatment Approaches . . . . . . . . . . . . . . . . . . . . . 829
50.2 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 832
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 835
Abstract
This chapter discusses the concept of mindfulness and reviews the theoret-
ical and empirical evidence for the use of mindfulness-based strategies as
behavioral approaches to addiction treatment. Mindfulness is defined as
bringing nonjudgmental, intentional awareness to present-moment experi-
ences. Mindfulness encourages the individual to acknowledge and accept
thoughts, feelings, and bodily sensations as they arise, recognizing their
impermanence. Mindfulness training as a component of addiction treatment
is particularly compelling because it fosters acceptance of one’s moment-to-
moment thoughts and experiences rather than engaging in substance use to
avoid or suppress distressing thoughts and emotions. Various psychological
constructs associated with substance abuse, including experiential avoid-
ance, stress, thought suppression, craving, self-compassion, and coping,
M.T. Marcus
University of Texas Health Science Center, Houston, TX, USA
e-mail: [email protected]
50.1 Introduction
Substance use disorders (SUDs) continue to be a public health problem across the
globe. An estimated 230 million individuals, or 5 % of the adults across the world,
had used an illicit drug in 2010. Twenty-seven million adults worldwide are
estimated to be problem drug users (World Drug Report 2012). The World Health
Organization reports that 2.5 million deaths result from harmful alcohol use each
year, 320,000 of which are young people between the ages of 15 and 29 (WHO
2012). In the United States 58.3 million people aged 12 or older reported heavy
drinking, 20.6 million were classified with substance dependence, and 68.2 million
were current users of a tobacco product in 2011 (SAMSHA 2012). Substance use
disorders are a major cause of disability and death worldwide. While the scope of
SUD and the impact of the problem on health are incontrovertible, effective
treatment and prevention of relapse pose challenges to researchers and clinicians.
Addiction is defined as a chronic relapsing brain disease involving reward, moti-
vation, memory, and related circuitry which leads to biological, psychological,
social, and spiritual manifestations (ASAM 2012). Much has been learned about
addiction and its underlying neurobiology over the past few decades. Addiction
changes the brain causing characteristic behavior changes associated with enhanced
motivational drive for the substance and weakening of control over this drive
(Volkow et al. 2011). There has been increasing interest in the utility of
mindfulness-based strategies in addressing the cognitive and emotional
processes and behavioral urges underlying addiction (Dakwar and Levin 2009).
The purpose of this chapter is to discuss mindfulness and review the theoretical and
empirical evidence for use of mindfulness as a behavioral approach to addiction
treatment.
50 Mindfulness as Behavioural Approach in Addiction Treatment 823
50.1.1 Mindfulness
a negative mood. MBCT sessions are outlined in Segal et al. (2002). No formal set
of qualifications have been proposed for MBCT therapists, but training in counsel-
ing, psychotherapy, or cognitive therapy is considered important (Baer and
Krietemeyer 2006). MBCT has been found to decrease relapse of depressive
disorders in several studies (Teasdale et al. 2000; Ma and Teasdale 2004; Teasdale
and Ma 2004; Teasdale and Williams 2000).
perspectives on craving, biological, cognitive, and affective and suggest that a focus
on all three may be important in understanding the impact of MBRP on craving.
The authors stress that research which integrates information from brain to behavior
is necessary to determine the various mechanisms of behavior change following
mindfulness-based treatments such as MBRP (Witkiewitz et al. 2012).
50.2 Conclusion
While meditation practices were added to addiction treatment well over four
decades ago, it was only in early 2000 that empirical reports of mindfulness
meditation began to appear in the literature (Black 2012). Since that time there
have been an increasing number of studies, and two systematic reviews, indicating
the potential benefit of mindfulness approaches to the treatment of SUDs (Zgierska
et al. 2009; Chiesa and Serretti 2013). Chiesa and Serretti (2014) note that the
reasons why mindfulness may be of benefit to SUD treatment are related to the
potential of mindfulness training to develop a nonjudgmental attitude toward
distressing thoughts and feelings, adapt to one’s own thought patterns, and accept
present-moment experiences without attempting to suppress unpleasant experi-
ences by using substances of abuse. These authors reviewed 24 quantitative, con-
trolled studies of mindfulness-based or associated treatments for SUDs. The study
interventions included MBSR, MBCT, MBRP, DBT, and ACT. Control conditions
involved nonspecific educational support groups and wait-list controls. All four of
the studies of smoking cessation reviewed showed significant benefits for the
mindfulness condition over controls. While there was limited evidence that mind-
fulness interventions can reduce substance use over controls in studies of other
substances such as alcohol, opiates, cannabis, methamphetamines, and
50
Manual
Acceptance and Behavioral and cognitive content to increase Mindfulness content directed at Craving, negative affect, emotional
commitment psychological flexibility, behaviors linked to values, reducing experiential avoidance reactivity, stress, positive affect,
therapy (ACT) varying length of sessions across studies psychological well-being, mindfulness,
Therapist qualifications: experience in addiction successful detoxification
treatment and mindfulness-based interventions
Manual
(continued)
833
834
References
Adinoff B, Iranmanesh A, Veldhuis J, Fisher L (1998) Disturbances of the stress response: the role of
the HPA axis during alcohol withdrawal and abstinence. Alcohol Health Res World 22(1):67–72
Alexander W (1997) Cool water: alcoholism, mindfulness and ordinary recovery. Shambhala, Boston
Alterman AI, Koppenhaver JM, Mulholland E, Ladden LJ, Baime MJ (2004) Pilot trial of
effectiveness of mindfulness meditation for substance abuse patients. J Subst Use
9(6):259–268
American Society of Addiction Medicine (2012) Definition of addiction http://www.asam.org/
research-treatment/defintion-of-addiction. Accessed 29 June 2012
Baer RA, Krietemeyer J (2006) Overview of mindfulness and acceptance based treatment
approaches. In: Baer RA (ed) Mindfulness-based treatment approaches: clinicians guide to
evidence-based treatment applications. Academic, New York, pp 3–27
Black DS (2012) Mindfulness and substance use intervention. Subst Use Misuse 47(3):199–201
Bowen S, Chawla N, Collins SE, Witkiewitz K, Hsu S, Grow J, Clifasefi S, Garner M, Douglass A,
Larimer ME, Marlatt A (2009) Mindfulness-based relapse prevention for substance use
disorders: a pilot efficacy trial. Subst Abus 30(4):295–305
Brewer JA, Elwafi HM, Davis JH (2012) Craving to quit: psychological models and neurobiolog-
ical mechanisms of mindfulness training as treatment for addiction. Psychol Addict Behav
27:366–379
836 M.T. Marcus
Brown SA, Vik PW, Patterson TL, Grant I, Schuckit MA (1995) Stress, vulnerability and adult
alcohol relapse. J Stud Alcohol 56:538–545
Carlson LE, Speca M, Patel KD, Goodey E (2003) Mindfulness-based stress reduction in relation
to quality of life, mood, symptoms of stress, and immune parameters in breast and prostate
cancer outpatients. Psychosom Med 65:571–581
Carroll D, Lange B, Liehr B, Raines S, Marcus M (2008) Evaluating mindfulness-based stress
reduction: analyzing stories of stress to formulate focus group questions. Arch Psychiatr Nurs
22(2):107–109
Center for Mindfulness. Teacher certification in MBSR review. http://www.umassmed.edu/cfm/
certification/index.aspx. Accessed 12 April 2013
Chawla N, Collins S, Bowen S, Hsu S, Grow J, Douglass A, Marlatt GA (2010) The mindfulness-
based relapse prevention adherence and competence scale: development, interrater reliability,
and validity. Psychother Res 20(4):388–397
Chiesa A, Serretti A (2014) Are mindfulness-based interventions effective for substance use
disorders? A systematic review of the evidence. Subst Use Misuse 19:492–512
Dakwar E, Levin FR (2009) The emerging role of meditation in addressing psychiatric illness,
with a focus on substance use disorders. Harv Rev Psychiatry 17(4):254–267
DeLeon G (2000) The therapeutic community: theory, model, and method. Springer, New York
DeVylder JE (2010) Dialectical behavior therapy for the treatment of borderline personality
disorder: an evaluation of the evidence. Int J Psychosoc Rehabil 15(1):61–70
Dimeff LA, Linehan MM (2008) Dialectical behavior therapy for substance abusers. Addict Sci
Clin Pract 4(2):39–47
Farb NAS, Segal ZV, Mayberg H, Bean J, McKeon D, Fatima Z, Anderson AK (2007) Attending
to the present: mindfulness meditation reveals distinct neural modes of self-reference. Soc
Cognit Affect Neurosci 2(4):313–322
Fiore MC, Bailey WC, Cohen SJ, Dorfman SF, Goldstein MG, Gritz ER (2000) Treating
tobacco use and dependence: clinical practice guideline. U.S. Department of Health and
Human Services (USDHHS), Rockville. Public Health Service (PHS). Report No.: 1-58763-
007-9
Garland EL, Gaylord SA, Boettiger CA, Howard MO (2010) Mindfulness training modifies
cognitive, affective, and physiological mechanisms implicated in alcohol dependence: results
of a randomized controlled pilot trial. J Psychoactive Drugs 42(2):177–192
Garland EL, Schwarz NR, Kelly A, Whitt A, Howard MO (2012) Mindfulness-oriented recovery
enhancement for alcohol dependence: therapeutic mechanisms and intervention acceptability.
J Social Work Pract Addict 12(3):242–263
Gordon HW (2002) Early environmental stress and biological vulnerability to drug abuse.
Psychoneuroendocrinology 27:115–126
Hayes SC, Stroshal K, Wilson KG (1999) Acceptance and commitment therapy. Guilford Press,
New York
Hayes SC, Levin ME, PlumbVilardaga J, Villatte JL, Pistorello J (2011) Acceptance and com-
mitment therapy and contextual behavioral science: Examining the progress of a distinctive
model of behavioral and cognitive therapy. Behav Ther 44:180–198
Hayes SC, Pistorello J, Levin ME (2012) Acceptance and commitment therapy as a unified model
of behavior change. Couns Psychol 40(7):976–1002
Hides L, Samet S, Lubman DI (2010) Cognitive behaviour therapy (CBT) for the treatment of
co-occurring depression and substance use: current evidence and directions for future research.
Drug Alcohol Rev 29(5):508–517
Kabat-Zinn J (1990) Full catastrophe living: using the wisdom of your body and mind to face
stress, pain and illness. Dell Publishing, New York
Kabat-Zinn J (1994) Wherever you go there you are: mindfulness meditation in everyday life.
Hyperion, New York
50 Mindfulness as Behavioural Approach in Addiction Treatment 837
Kabat-Zinn J (2003) Mindfulness-based interventions in context: past, present, and future. Clin
Psychol Sci Pract 10(2):144–156
Kabat-Zinn J, Lipworth L, Burney R, Sellers W (1986) Four year follow-up of a meditation-based
program for the self-regulation of chronic pain: treatment outcomes and compliance. Clin
J Pain 2:159–173
Kabat-Zinn J, Massion AD, Kristeller J, Peterson LG, Fletcher KE, Pbert L, Lenderking WR,
Santorelli SF (1992) Effectiveness of a meditation-based stress reduction program in the
treatment of anxiety disorders. Am J Psychiatry 149(7):936–943
Kaplan KH, Goldenberg DL, Galvin-Nadeau M (1993) The impact of a meditation- based stress
reduction program on fibromyalgia. Gen Hosp Psychiatry 15(5):284–289
Kreek MJ, Koob GF (1998) Drug dependence: stress and dysregulation of brain reward pathways.
Drug Alcohol Depend 51:23–47
Kristeller JL, Halleh CB (1999) An exploratory study of a meditation-based intervention for binge
eating disorder. J Health Psychol 4:357–363
Liehr P, Marcus MT, Carroll D, Granmayeh LK, Cron SG, Pennebaker JW (2010) Linguistic
analysis to assess the effect of a mindfulness intervention on self-change for adults in substance
use recovery. Subst Abus 31(2):79–85
Linehan MM (1993) Cognitive-behavioral treatment of borderline personality disorder. Guilford
Press, New York
Linehan MM (1999) Skills training manual for treating borderline personality disorder. Guilford
Press, New York
Linehan MM, Dimeff LA, Reynolds SK, Comtois KA, Welch SS, Heagerty P, Kivlahan DR
(2002) Dialectical behavior therapy versus comprehensive validation therapy plus 12-step for
the treatment of opioid dependent women meeting criteria for borderline personality disorder.
Drug Alcohol Depend 67(1):13
Linehan MM, Comtois KA, Murray AM, Brown MZ, Gallop RJ, Heard HL, Korslund KE,
Titek DA, Reynolds SK, Lindenboim L (2006) Two-year randomized controlled trial and
follow-up of dialectical behavior therapy vs therapy by experts for suicidal behaviors and
borderline personality disorder. Arch Gen Psychiatry 63(7):757–766
Ludwig DS, Kabat-Zinn J (2008) Mindfulness in medicine. JAMA 300(11):1350–1352
Ma SH, Teasdale JD (2004) Mindfulness-based cognitive therapy for depression: replication
and exploration of differential relapse prevention effects. J Consult Clin Psychol 72:31–40
Marcus M (1998) Changing careers: becoming clean and sober in a therapeutic community. Qual
Health Res 8(4):466–480
Marcus M, Liehr P, Schmitz J, Moeller FG, Swank P, Fine M, Cron S, Granmayeh L, Carroll D
(2007) Behavioral therapies trials: a case example. Nurs Res 56(3):210–216
Marcus MT, Schmitz J, Moeller G, Liehr P, Cron SG, Swank P, Bankston S, Carroll D,
Granmayeh LK (2009) Mindfulness-based stress reduction in therapeutic community treat-
ment: a stage 1 trial. Am J Drug Alcohol Abuse 35(2):103–108
Marlatt GA, Gordon JR (1985) Relapse prevention: maintenance strategies in the treatment of
addictive behaviors. Guilford Press, New York
McLellan AT, Luborsky L, Cacciola J, Griffith J (1985) New data from the addiction severity
index: reliability and validity in three centers. J Nerv Ment Dis 173:412–423
McMahon RC (2001) Personality, stress, and social support in cocaine relapse prediction. J Subst
Abuse Treat 21(2):77–87
Miller JJ, Fletcher K, Kabat-Zinn J (1995) Three-year follow-up and clinical implications of
a mindfulness-based stress reduction intervention in the treatment of anxiety disorders. Gen
Hosp Psychiatry 17(3):192–200
Neacsiu AD, Rizvi SL, Linehan MM (2010) Dialectical behavior therapy skills use as
a mediator and outcome of treatment for borderline personality disorder. Behav Res Ther
48(9):832–839
838 M.T. Marcus
Reibel DK, Greeson JM, Brainard GC, Rosenzweig S (2001) Mindfulness-based stress reduction
and health-related quality of life in a heterogeneous patient population. Gen Hosp Psychiatry
23:183–192
Ruiz FJ (2010) A review of acceptance and commitment therapy (ACT) empirical evidence:
correlational, experimental psychopathology, component and outcome studies. Int J Psychol
Psychol Ther 10(1):125–162
Segal ZV, Williams JMG, Teasdale JD (2002) Mindfulness-based cognitive therapy for depres-
sion: a new approach to preventing relapse. The Guilford Press, New York
Shapiro SL, Schwartz GE, Bonner G (1998) Effects of mindfulness-based meditation stress
reduction on medical and premedical students. J Behav Med 21:581–599
Shapiro SL, Carlson EE, Astin JA, Freedman D (2006) Mechanisms of mindfulness. J Clin
Psychol 62:373–386
Short EB, Kose S, Mu Q, Borckardt J, Newberg A, George MS, Kozel FA (2010) Regional brain
activation during meditation shows time and practice effects: an exploratory FMRI study{.
Evid Complement Altern Med (eCAM) 7(1):121–127
Simpson DD, Joe DW, Brown BS (1997) Treatment retention and follow-up out-come in the Drug
Abuse Treatment Outcome Study (DATOS). Psychol Addict Behav 11:294–307
Sinha R (2001) How does stress increase risk of drug abuse and relapse? Psychopharmacology
(Berl) 158:343–359
Smout MF, Longo M, Harrison S, Minniti R, Wickes W, White JM (2010) Psychosocial
treatment for methamphetamine use disorders: a preliminary randomized controlled trial
of cognitive behavior therapy and acceptance and commitment therapy. Subst Abus
31(2):98–107
Speca M, Carlson LE, Goodey E, Angen M (2000) A randomized, wait-list controlled trial: the
effect of a mindfulness meditation-based stress reduction program on mood and symptoms of
stress in cancer outpatients. Psychosom Med 62:613–622
Stotts AL, Green C, Masuda A, Grabowski J, Wilson K, Northrup TF, Schmitz JM (2012)
A stage I pilot study of acceptance and commitment therapy for methadone detoxification.
Drug Alcohol Depend 125(3):215–222
Substance Abuse and Mental Health Services Administration (2012) Results from the 2011
national survey on drug use and health: summary of national findings, NSDUH Series H-44,
HHS Publication No. (SMA) 12–4713. Substance Abuse and Mental Health Services Admin-
istration, Rockville
Teasdale JD, Ma SH (2004) Mindfulness-based cognitive therapy for depression:
replication and exploration of differential relapse prevention effects. J Consult Clin Psychol
72(1):31–40
Teasdale JD, Williams JM (2000) Prevention of relapse/recurrence in major depression by
mindfulness-based cognitive therapy. J Consult Clin Psychol 68(4):615
Teasdale JD, Segal ZV, Williams JMG, Ridgeway VA, Soulsby JM, Lau MA (2000) Prevention of
relapse/recurrence in major depression by mindfulness-based cognitive therapy. J Consult Clin
Psychol 68(4):615–623
Vidrine JI, Businelle MS, Cinciripini P, Li Y, Marcus MT, Waters AJ, Wetter DW (2009) Asso-
ciations of mindfulness with nicotine dependence, withdrawal, and agency. Subst Abus
30(4):318–327
Vieten C, Astin JA, Buscemi R, Galloway GP (2010) Development of an acceptance-based coping
intervention for alcohol dependence relapse prevention. Subst Abus 31(2):108–116
Volkow N, Baler R, Goldstein R (2011) Addiction: pulling at the neural threads of social
behaviors. Neuron 69(4):599–602
Westbrook C, Creswell JD, Tabibria G, Julson E, Kober H, Tindle H (2013) Mindful attention
reduces neural and self-reported cue-induced craving in smokers. Social cognitive and Affec-
tive Neuroscience 8(1):73–84
Wexler HK, Melnick G, Lower L, Peters J (1999) Three-year reincarnation outcomes of Amity
in-prison therapeutic community and aftercare in California. Prison J 79:321–336
50 Mindfulness as Behavioural Approach in Addiction Treatment 839
Contents
51.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 842
51.2 Contingency Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 845
51.2.1 Underlying Logic of CM Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 845
51.2.2 Prototypic Examples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 846
51.2.3 Key Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 849
51.2.4 Barriers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 851
51.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 852
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 853
Abstract
This chapter describes the underpinnings of the contingency management inter-
ventions for treating substance use disorders. It presents historical data
establishing the efficacy of the procedures. Sections addressing key factors for
the use of these protocols and current limitations are also included. In no way is
the chapter meant to be an exhaustive review of the contingency management
literature. Nor is the chapter intended to provide the necessary level of detail
needed to implement these procedures. Instead, this chapter is a brief introduc-
tion to contingency management. Resources for implementation are included in
the suggested reading section of this chapter. Contingency management inter-
ventions have shown remarkable promise for promoting the initiation of
abstinence. The use of these protocols may increase overall treatment efficacy.
The chapter is intended to introduce the reader to this class of interventions with
the hope that they will be motivated to dig deeper into the extensive literature
surrounding contingency management-based treatment of substance use
disorders and associated comorbidities.
51.1 Introduction
In this case food reinforces lever pressing and the lever pressing increases until the
behavior has been mastered. Most would consider the food to be an example of
positive reinforcement. That is to say the behavior produces a stimulus (food)
which increases the homeostatic “good” of the rat. Another type of reinforcement
that can be demonstrated in a laboratory preparation is negative reinforcement. An
example of this would be a rat placed in an operant chamber that receives a shock
every 2 min regardless of what the rat did, in other words, the shock is inescapable.
However, if a lever is placed in the box and the rat presses the lever, the next
scheduled shock can be avoided. As in the positive reinforcement example, the rat
will acquire the lever-pressing behavior over time until it has mastered the behavior
and maintains it at a level that avoids shocks. Negative reinforcement, which is
reinforcement that removes an aversive state, like this occurs when a behavior
eliminates a noxious stimulus.
The forgoing is not merely a historical footnote. The use of the operant chamber
opened many avenues for the study of how drugs influence behavior. Early exam-
ples of this work were conducted by Skinner and Heron (Skinner and Heron 1937)
who examined how caffeine and amphetamine (Benzedrine) impacted food-
reinforced behavior and the extinction of that behavior.
However, the aspect of operant psychology that is of the most relevance to this
chapter was the demonstration that naı̈ve animals would self-administer most of the
same drugs abused by humans. In an early study, Thomson and Schuster demon-
strated that drug-naı̈ve monkeys would self-administer morphine (Thompson and
Schuster 1964). This was a seminal demonstration that drugs of abuse could serve
as positive reinforcers analogous to other positive reinforcers like food and water.
Since this demonstration, thousands of studies in which drugs are provided to
organisms (human and nonhuman) contingent on an operant response have
demonstrated the robustness of this phenomenon (e.g., Roll 2014). It is one of the
more unambiguous and well-accepted facts that drugs of abuse act as sources of
positive reinforcement. Similarly, it has been demonstrated in laboratory paradigms
that drugs of abuse can also serve as powerful sources of negative reinforcement
(e.g., Holz and Gill 1975; Kandel and Schuster 1977; Thompson and Schuster 1968;
Negus 2006; Negus and Banks 2013). In brief, drug-dependent organisms will
increase their responding for a drug when they are in a state of withdrawal
(see especially the body of work of Negus for discussion of this). That is, the
animal, or person, will increase their consumption of a drug to escape from
a negative state. In situations such as this, the drug may function as a negative
reinforcer.
This observation that drugs of abuse serve as sources of reinforcement, both
positive and negative, has been an important observation in our quest to understand,
treat, and prevent addiction. Many would argue that the goal of treatment (and
prevention) efforts should be the diminution of the reinforcing efficacy of the drug
of abuse.
To relate this operant framework back to the opening discussion about a drug
user’s quest to feel good, we can refine that description so that instead of describing
a quest to feel good, we can describe a quest for reinforcement. This could be
844 J.M. Roll and B. Fruci
positive reinforcement, which some might equate with euphoria or negative rein-
forcement, for example, the diminution of withdrawal symptoms. This conceptu-
alization now allows us to place drug addiction and its associated sequela into the
operant psychology framework.
To appreciate the utility of this operant framework for addressing addiction, one
more point needs consideration, that is, that primary, or naturalistic, reinforcers are
biologically important for the survival of the organism and hence the species. Food,
water, and sex are crucial to survival and these are powerful sources of natural
reinforcement. Human biology has evolved to be maximally sensitive to sources of
reinforcement such as these. A detailed discussion of the neurobiology underpin-
ning reinforcement is well beyond the scope of this chapter. Suffice it to say that an
impressive array of neurobiological systems are in play. When a thirsty person
takes a drink of water, it is a powerful source of reinforcement, and our neurobi-
ology guarantees that in a similar state of thirst, we will again seek a drink of water.
Unfortunately, most drugs of abuse interact with the same neurobiological system
that governs our reinforcing relationship to primary sources of reinforcement. As
popularized by a past director of the National Institute on Drug Abuse, Dr. Alan
Leshner, drugs of abuse hijack this neurobiological system and insidiously shift
a user’s motivation toward a compulsive focus on drug-derived reinforcement. The
result is that an addicted person develops a compulsive motivation to seek drug-
based reinforcement and that that reinforcement is of exceptional strength.
While daunting, this conceptualization does point toward an effective treatment
mechanism. In order to help an individual enter into recovery from drug addiction,
it is necessary to reduce the reinforcing efficacy of the drug. We would argue that
this is the goal of all drug abuse treatment efforts at some level. The cognitive
behavior treatments seek to restructure thoughts about drugs or to reorganize
a user’s cognitions so that they conceptualize the negative aspects of drug use as
being more salient than the positive aspects. Motivational therapies seek to alter the
user’s motivation to seek the drug reinforcement; pharmacologic and immunother-
apeutic approaches seek to block the drug from ever interacting with the user’s
reward-related neurobiology. While some will surely disagree, we postulate that all
successful treatment approaches can be couched in terms of lowering the abused
drug’s reinforcing efficacy. One approach that takes this as its stated goal is
contingency management (CM). The remainder of this chapter will focus on this
approach. We will briefly describe the basic science supporting the approach and
discuss prototypic examples of how to use the approach, key factors to consider
when using the approach, populations for which the approach has been used,
barriers to implementation, and finally potential limitations to the use of the
approach. A series of meta-analyses supports the use of CM (Dutra et al. 2008;
Lussier et al. 2006; Prendergast et al. 2006). The interested reader is encouraged to
consult these publications as they are much more detailed than this chapter. There
also exist a number of books on the topic of CM. We especially encourage the
interested reader to consult those listed in Table 51.1. This brief chapter can provide
only a glimpse of the wealth of research on CM. Consulting these other texts is
crucial prior to actual implementation of the procedure.
51 Contingency Management as Behavioural Approach in Addiction Treatment 845
Contingency management can take many forms, but in all cases it is a technique that
clinicians use to engineer a drug user’s environment so that the drug user must
choose between drug use (maintained by the drug’s reinforcing efficacy) and other
nondrug reinforcers. The salient nondrug reinforcers that have often been employed
included access to housing (Milby et al. 1996), access to employment (Silverman
et al. 2012), provision of vouchers which can be exchanged for monetarily based
goods and services (Higgins et al. 1994b), access to prizes which are valued by the
user (e.g., Petry and Martin 2002), escape from judicial sanctions (Prendergast
et al. 2008), and access to one’s monetary resources (Ries et al. 2004). Several
research groups have developed potential lists of other types of reinforcers that can
be employed, and these include such things as reduced clinic fees, access to clinic-
sponsored social events, fee rebates, and donated goods and services (e.g., Amass
and Kamien 2008; Roll et al. 2005).
While the CM class of interventions have been used for most types of drug abuse
treatment (Higgins et al. 2008), they have, in our opinion, been most successful for
those types of addictions for which no viable pharmacotherapy exists. This largely
excludes opioid addiction and nicotine addiction as both of these disorders can
be controlled with pharmacotherapy (e.g., opioids: Bart 2012; nicotine: Aubin
et al. 2013). That is not to say that CM cannot be a useful adjunct for the management
of opiate addiction. For example, take-home doses of methadone that are delivered
contingent on compliance with clinic regulations and the continued provision of
51 Contingency Management as Behavioural Approach in Addiction Treatment 847
drug-free urine tests is a relatively common practice (e.g., Stitzer et al. 1992).
Contingency management may also have utility in treating nicotine addiction
(Ledgerwood 2008), but in our experience CM is usually a secondary focus to the
pharmacotherapy, which is the first-line treatment of these disorders. Please note that
even when good pharmacotherapy is available, some populations (such as pregnant
women) may not be able to use the pharmacotherapy. In cases such as this, CM may
become a very important treatment modality (e.g., Higgins et al. 2012. However, we
still do not have accepted pharmacotherapies for psychostimulant addiction
(excluding nicotine addiction), especially cocaine and methamphetamine. It is for
these disorders that we believe CM is a useful first-line approach. There are two types
of CM that are most commonly employed in the treatment of psychostimulant
addiction. The first, popularized by Higgins (e.g., Higgins et al. 1994b), is perhaps
best described as voucher-based reinforcement therapy (VBRT) and the second
popularized by Petry (e.g., Petry and Martin 2002) is variously referred to as the
fishbowl technique and prize-based CM, but is more accurately known as variable
magnitude of reinforcement CM (e.g., Silverman et al. 2008). Examples of each are
provided below, and in the following section the key factors related to the efficacy of
the procedures are discussed.
Steve Higgins at the University of Vermont first demonstrated the efficacy of
VBRT in a relatively large randomized clinical trial designed to assess the inter-
vention’s impact on cocaine-using individuals (Higgins et al. 1991). The basic
procedures for this type of intervention are as follows: patients receive vouchers
for the provision of biological samples (urine or breath) that indicate no recent drug
use. Participants receive a voucher each time they test negative for the target drug.
These vouchers can then be exchanged for goods or services. The initial voucher
value is set at a low value (e.g., $2.50). Each consecutive instance of abstinence
increases the magnitude of the voucher by a small amount (e.g., $1.50). Three
consecutive abstinences result in the delivery of an additional bonus (e.g., $10.00).
A drug-positive urine sample, or failure to test, results in a reset of the voucher
magnitude back to its original level (i.e., $2.50), from which the escalation can
begin again.
Nancy Petry at the University of Connecticut popularized the variable magni-
tude of reinforcement procedure (Petry et al. 2005). This procedure involves
making “draws” from a bowl of chips representing different prize/reinforcer
magnitudes. These chips can be exchanged for goods that are available on-site.
Typically about half of the chips say “good job” and do not result in the delivery of
any tangible reinforcement. 41.8 % of the chips result in a small reinforcer (worth
about $1.00), 8 % result in a large reinforcer (worth about $20.00), and 0.2 % result
in a jumbo reinforcer (worth about $80.00). Participants earn at least one draw for
each urine sample submitted that is drug negative. The number of draws awarded at
each urine collection escalates by with consecutive instances of drug-negative urine
tests. Missing or drug-positive urine samples result in a reset to one draw available
when the next negative sample is submitted.
Both of these (VBRT and variable magnitude of reinforcement) procedures are
quite effective at treating psychostimulant addiction. In fact, the United States
848 J.M. Roll and B. Fruci
In summary, both of these procedures work well and have improved the lives of
many individuals who have benefited from treatment that utilized these approaches.
There is no immediate reason to prefer one approach over the other. Both are
effective if delivered with high degrees of fidelity. There is good evidence that the
procedures work for most types of addiction (Dutra et al. 2008; Hartzler et al. 2012;
Higgins and Silverman 1999; Lussier et al. 2006; Prendergast et al. 2006) and for
many populations including adolescents (Branson et al. 2012), polysubstance
abusers (Downey et al. 2000), pregnant women (Higgins et al. 2012), and those
afflicted with both substance use disorders and serious and persistent mental health
issues (McDonell et al. 2013). There is also evidence that the procedures work best
for those who rapidly initiate abstinence during treatment (Yoon et al. 2009) and for
those who begin treatment in a drug-free state (Stitzer et al. 2007). The utility of
the CM procedures for treatment in the criminal justice system is less compelling
(e.g., Hall et al. 2009; although see De Fulio et al. 2013). This is perhaps not
surprising as most criminal justice systems are punishment based. While punish-
ment is usually to be avoided in therapeutic contexts because of the proclivity of
the person being punished to escape the punisher (e.g., terminate the treatment
interaction), that is not an option in a criminal justice setting in which the person is
compelled to engage in treatment. Given these circumstances contingent punish-
ment should be quite effective in controlling behavior. For example, if a cocaine
user is clearly informed that if they use cocaine they will be incarcerated, it is
a powerful contingency management protocol based on punishment. This is the
norm in many criminal justice systems (punishers range from mild sanction in some
countries to death in others!). In such a milieu it is unlikely that a reinforcement-
based CM procedure will garner much additional control over a user’s behavior
unless very high-magnitude reinforcers are employed. In criminal justice systems
where behavior is less controlled, however, CM interventions should be effective.
In this section we briefly describe what we believe are four key factors for the
successful implementation of any variety of CM. For a detailed discussion of these
factors and others, please consult Petry (2012) and Tuten et al. (2012).
The first factor to consider is the procedure by which vouchers or prizes
(henceforth both referred to as reinforcers) are disbursed. This is known in parlance
of operant psychology as the schedule of reinforcement. Schedules of reinforce-
ment have been extensively studied and it has been repeatedly demonstrated that
schedule changes can have profound impacts on behavior (Ferster et al. 1957).
Higgins developed the basic schedule that is routinely employed in CM procedures.
This has two key components. First, as outlined in the examples in the previous
section, there is an escalation in reinforcement magnitude for consecutive instances
of abstinence. Secondly, as described above, there is a reset in reinforcer magnitude
(voucher value or number of prize draws) following a failure to abstain. The
combination of these components seems to provide the greatest likelihood for
850 J.M. Roll and B. Fruci
achieving a successful treatment outcome (Roll et al. 1996; Roll and Higgins 2000).
While we do not precisely know why these components are operative, it is likely
that they function to integrate individual instances of abstinence into a consecutive
period of abstinence. If each abstinence were reinforced independently of those that
preceded or followed it, the behavioral target would be individual instances of
abstinence. By linking consecutive instances of abstinence via the escalation and
reset procedure, the target becomes consecutive instances of abstinence, which
should be the goal of all treatment efforts. Whenever it is possible, CM procedures
should try to incorporate both of these schedule components to have the greatest
likelihood of success.
The second factor to consider is the magnitude, or value, of the reinforcers used.
There exists an extensive body of literature from both laboratory and clinical trials
and with different species, including humans, that unambiguously demonstrates
that higher magnitudes of reinforcement are better at controlling behavior
(Nader and Woolverton 1991; Packer et al. 2012; Wong et al. 2003). Clinically,
this means that the higher the value of the reinforcer employed, the more effective it
is likely to be. Use of reinforcer magnitudes that are too low to control behavior
(e.g., Packer et al. 2012) will result in failure of the intervention. Unfortunately, this
could be interpreted as a failure of the CM protocol, when in fact it is a lack of
fidelity to the protocol that is responsible for the failure. One should not expect
a low-magnitude reinforcer procedure to be very effective. This often poses
a significant challenge to the implementation of CM (Roll et al. 2009). Treatment
centers are often underresourced and do not have the means to employ high-
magnitude monetary reinforcers such as vouchers and prizes. In this case, other
noncash-based reinforcers can be used (as described above), or community dona-
tions can be sought (e.g., Amass and Kamien 2004). It is our belief that funders are
beginning to embrace CM interventions as many insurance companies employ
CM-based efforts to control health behaviors and as the United States Veterans’
Administration adopts CM as a primary treatment strategy (Rash et al. 2013b).
Hopefully, this will reduce the difficulty surrounding the provision of reinforcement
of sufficient magnitude.
It should be noted that what is reinforcing for one person may not be reinforcing
for another. Thus, when using noncash-based reinforcers, it is incumbent on the
clinician to find reinforcers that are salient to individual consumers. This can be
done by identifying a functional relationship between behavior and reinforcers as
described in Johnston and Pennypacker (1993). Also of note is that reinforcement
magnitude can be changed during treatment, if necessary, to garner more control
over a user’s behavior. In a study by Robles and colleagues (2000), it was demon-
strated that even treatment-resistant cocaine users would abstain if relatively high-
magnitude vouchers were used.
The third factor to consider when developing, or delivering, a CM protocol is
delay (Petry 2000; Roll et al. 2000; Packer et al. 2012). There are two types of delay
that are common in CM protocols. The first is the delay between earning
a reinforcer (e.g., providing biological evidence of drug abstinence) and receiving
the reinforcer, that is, how long after someone provides a drug-negative urine
51 Contingency Management as Behavioural Approach in Addiction Treatment 851
sample until they receive their prize or voucher. In order to be maximally effective,
this delay should be minimized. Another type of delay encountered when using
vouchers is an exchange delay, that is, the delay between telling the counselor what
you want to exchange your voucher for and the actual receipt of the item. Again, in
order to maximize protocol efficacy, this delay should be minimized.
The fourth and final factor we wish to mention is intervention duration. While it
is quite understandable that clinicians, consumers and their families, and funders
want short, effective treatment, it is important to remember that addicts spend
a lifetime developing an addiction; it may not be reasonable to think that the
behavioral patterns established in order to support compulsive drug taking behavior
can be terminated quickly. For this reason, we recommend that the longest possible
duration of treatment be employed. There is evidence to suggest that longer
treatments are more effective than shorter ones (Roll et al. 2013) and that long-
term treatment is acceptable to consumers (Silverman et al. 2004).
51.2.4 Barriers
Given the widely accepted efficacy and relative ease of implementation, one could
reasonably ask why CM is not more widely employed. To begin with, it is often
employed although perhaps not as frequently as one would expect. In our experi-
ence, three common barriers are raised that hinder effective implementation of the
procedure. These barriers have been discussed in detail and interested readers
should consult the literature for a thorough vetting (e.g., Rash et al. 2012;
Roll et al. 2009).
Primary among the barriers is the perceived cost of the CM interventions. We
have touched on this in several of the above sections. Cost is an issue, but
nonmonetary reinforcers can be employed. Some work has even demonstrated
unanticipated benefits such as decreased hospitalizations and improved comorbid
psychiatric functioning which result in significant cost savings (McDonell
et al. 2013).
It has also been argued that CM protocols are too complex. Proponents of this
argument claim that busy, poorly resourced clinicians do not have the time needed
to calculate reinforcer value and carry out prize draws or voucher exchanges. While
we certainly agree that clinicians are overworked and underpaid, we find this class
of argument to be repugnant. It is akin to a surgeon declining to operate on someone
because the surgical procedure was too complex and they were too busy with other
procedures. Moreover, the advent of computerized programs to aid clinicians with
the delivery of CM (www.bettertxoutcomes.org) and the ability to conduct
online voucher exchanges (Meredith and Dallery 2013) obviate most of these
concerns.
The final perception we wish to discuss is one of consumer resources. It has been
suggested that CM-based interventions will only work for those who have limited
financial resources. While it is undeniable that drug addiction eats away at
a person’s resources until they are depleted and that most abusers are financially
852 J.M. Roll and B. Fruci
51.2.4.1 Limitations
While we are strong proponents for the use of CM-based interventions, we are also
realistic. As of yet there is no silver bullet for the treatment of psychostimulant
addiction, including CM. In our experience, however, CM is a great treatment
modality for initiating abstinence. While some have demonstrated encouraging
long-term maintenance of abstinence post-CM-based treatment (e.g., Higgins
et al. 2000), a perception lingers that long-term effects are difficult to demonstrate.
As discussed above, we believe that VBRT provides a mechanism for bringing
consumers in contact with nondrug sources of reinforcement than can serve to
maintain abstinence, but in our experience this is not an automatic occurrence.
Once individuals are treated for their addiction, they often find themselves right
back in the same environment that occasioned their drug use in the first place. In
this environment, the same pressures began to re-exert their influence and a risk of
relapse is high. This brings us to our second limitation. We do not believe that CM
should be a stand-alone intervention in most instances. Instead, we recommend
pairing it with other evidence-based treatment. Drug abusers have complicated
chaotic lives. They need help navigating affective, legal, and cognitive aspects of
their addiction. While CM initiates abstinence and provides a sober client for the
clinician to work with, it does nothing to inherently address these other concerns.
These need to be addressed in the therapeutic relationship in order to maximize
the likelihood of maintaining the abstinence which CM is so effective at initiating.
One of the clearly most effective treatment strategies, the MATRIX model, does
combine CM with other psychosocial modalities (Rawson et al. 2002).
51.3 Conclusion
An impressive array of basic science research supports the notion that drugs of
abuse serve as potent reinforcers. Further, the hallmark of successful drug abuse
51 Contingency Management as Behavioural Approach in Addiction Treatment 853
Acknowledgment The authors would like to extend their appreciation to Arlana Buyers and
Dr. Donelle Howell. The authors were funded by the WA State Life Sciences Discovery Fund
during the time when this chapter was produced.
References
Alessi SM, Roll JM, Reilly MP, Johanson CE (2002) Establishment of a diazepam preference in
human volunteers following a differential-conditioning history of placebo versus diazepam
choice. Exp Clin Psychopharmacol 10(2):77–83. doi:10.1037//1064-1297.10.2.77
Amass L, Kamien J (2004) A tale of two cities: financing two voucher programs for substance
abusers through community donations. Exp Clin Psychopharmacol 12(2):147–55
Amass L, Kamien JB (2008) Funding contingency management in community treatment clinics:
use of community donations and clinic rebates. Contingency Manag Subst Abus Treat
34:280–297
Andrade LF, Petry NM (2014) Contingency management. In: McSweeney FK, Murphy ES (eds)
Wiley-Blackwell handbook of operant and classical conditioning. Wiley-Blackwell, Oxford
Aubin HJ, Luquiens A, Berlin I (2013) Pharmacotherapy for smoking cessation: pharmacological
principles and clinical practice. Br J Clin Pharmacol 77:324. doi:10.1111/bcp.12116
Bart G (2012) Maintenance medication for opiate addiction: the foundation of recovery. J Addict
Dis 31(3):207–225
Boakes RA (1984) From Darwin to behaviourism: psychology and the minds of animals.
Cambridge University Press, New York
Branson CE, Barbuti AM, Clemmey P, Herman L, Bhutia P (2012) A pilot study of low cost
contingency management to increase attendance in an adolescent substance abuse program.
Am J Addict 21(2):126–129
Carroll ME, Lac ST, Nygaard SL (1989) A concurrently available nondrug reinforcer prevents the
acquisition or decreases the maintenance of cocaine-reinforced behavior. Psychopharmacology
97(1):23–29
Crowley TJ (1984) Contingency contracting treatment of drug-abusing physicians, nurses, and
dentists. NIDA Res Monogr 46:68–83
De Fulio A, Stitzer M, Roll J, Petry N, Nuzzo P, Schwartz RP, Stabile P (2013) Criminal justice
referral and incentives in outpatient substance abuse treatment. J Subst Abus Treat 45:70–75
Downey KK, Helmus TC, Schuster CR (2000) Treatment of heroin-dependent poly-drug abusers
with contingency management and buprenorphine maintenance. Exp Clin Psychopharmacol
8(2):176–184
Dutra L, Stathopoulou G, Basden SL, Leyro TM, Powers MB, Otto MW (2008) A meta-analytic
review of psychosocial interventions for substance use disorders. Am J Psychiatry
165(2):179–187. doi:10.1176/appi.ajp.2007.06111851
Ferster BF, Skinner CB, Ferster C (1957) Schedules of reinforcement. Appleton, New York
Hall EA, Prendergast ML, Roll JM, Warda U (2009) Reinforcing abstinence and treatment
participation among offenders in a drug diversion program: are vouchers effective. Crim
Justice Behav 36(9):935–953
Hartzler B, Lash SJ, Roll JM (2012) Contingency management in substance abuse treatment:
a structured review of the evidence for its transportability. Drug Alcohol Depend 122(1):1–10
854 J.M. Roll and B. Fruci
Higgins ST, Bickel WK, Hughes JR (1994a) Influence of an alternative reinforcer on human
cocaine self-administration. Life Sci 55(3):179–187. doi:10.1016/0024-3205(94)00878-7
Higgins ST, Budney AJ, Bickel WK, Foerg FE, Donham R, Badger GJ (1994b) Incentives improve
outcome in outpatient behavioral treatment of cocaine dependence. Arch Gen Psychiatry
51(7):568–576
Higgins ST, Delaney DD, Budney AJ, Bickel WK, Hughes JR, Foerg F, Fenwick JW
(1991) A behavioral approach to achieving initial cocaine abstinence. Am J Psychiatry
148(9):1218–1224
Higgins ST, Silverman K (1999) Motivating behavior change among illicit-drug abusers: research
on contingency management interventions. American Psychological Association, Washington,
DC
Higgins ST, Silverman K, Heil SH (2008) Contingency management in the treatment of substance
use disorders: a science-based treatment innovation. Guilford Press, New York
Higgins ST, Washio Y, Heil SH, Solomon LJ, Gaalema DE, Higgins TM, Bernstein IM
(2012) Financial incentives for smoking cessation among pregnant and newly postpartum
women. Prev Med 55:S33–S40
Higgins ST, Wong CJ, Badger GJ, Ogden DEH, Dantona DL (2000) Contingent reinforcement
increases cocaine abstinence during outpatient treatment and 1 year of follow-up. J Consult
Clin Psychol 68(1):64–72. doi:10.1037//0022-006x.68.1.64
Holz WC, Gill CA (1975) Drug injections as negative reinforcers. Pharmacol Rev 27(3):437–446
Johnston JM, Pennypacker HS (1993) Strategies and tactics of behavioral research, 2nd edn.
Lawrence Erlbaum, Hillsdale
Kandel DA, Schuster CR (1977) An investigation of nalorphine and perphenazine as negative
reinforcers in an escape paradigm. Pharmacol Biochem Behav 6(1):61–71
Ledgerwood DM (2008) Contingency management for smoking cessation: where do we go from
here? Curr Drug Abus Rev 1(3):340–349
Lussier JP, Heil SH, Mongeon JA, Badger GJ, Higgins ST (2006) A meta-analysis of voucher-
based reinforcement therapy for substance use disorders. Addiction 101(2):192–203.
doi:10.1111/j.1360-0443.2006.01311.x
McDonell MG, Srebnik D, Angelo F, McPherson S, Lowe JM, Sugar A, Short RA, Roll JM, Ries
RK (2013) Randomized controlled trial of contingency management for stimulant use in
community mental health patients with serious mental illness. Am J Psychiatr 170(1):94–101
McSweeney FK, Murphy ESE (2014) Wiley-Blackwell handbook of operant and classical condi-
tioning. Wiley-Blackwell, Oxford
Meredith SE, Dallery J (2013) Investigating group contingencies to promote brief abstinence from
cigarette smoking. Exp Clin Psychopharmacol 21(2):144–154. doi:10.1037/a0031707
Milby JB, Schumacher JE, McNamara C, Wallace D, McGill T, Stange D, Michael M (1996)
Abstinence contingent housing enhances day treatment for homeless cocaine abusers. Natl Inst
Drug Abuse Res Monogr Ser 74:39–45
Nader MA, Woolverton WL (1991) Effects of increasing the magnitude of an alternative rein-
forcer on drug choice in a discrete-trials choice procedure. Psychopharmacology
105(2):169–174. doi:10.1007/Bf02244304
Negus SS (2006) Choice between heroin and food in nondependent and heroin-dependent rhesus
monkeys: effects of naloxone, buprenorphine, and methadone. J Pharmacol Exp Ther
317(2):711–723
Negus SS, Banks ML (2013) Medications development for opioid abuse. Cold Spring Harb
Perspect Med 3(1):a012104
Packer RR, Howell DN, McPherson S, Roll JM (2012) Investigating reinforcer magnitude and
reinforcer delay: a contingency management analog study. Exp Clin Psychopharmacol
20(4):287–292
Petry N (2012) Contingency management for substance abuse treatment: a guide to implementing
this evidence based-practice. Taylor and Francis, New York
51 Contingency Management as Behavioural Approach in Addiction Treatment 855
Roll JM, Reilly MP, Johanson CE (2000) The influence of exchange delays on cigarette versus
money choice: a laboratory analog of voucher-based reinforcement therapy. Exp Clin
Psychopharmacol 8(3):366–370. doi:10.1037//1064-1297.8.3.366
Silverman K, DeFulio A, Sigurdsson SO (2012) Maintenance of reinforcement to address the
chronic nature of drug addiction. Prev Med 55:S46–S53
Silverman K, Robles E, Mudric T, Bigelow GE, Stitzer ML (2004) A randomized trial of long-
term reinforcement of cocaine abstinence in methadone-maintained patients who inject drugs.
J Consult Clin Psychol 72(5):839–854
Silverman K, Roll JM, Higgins ST (2008) Introduction to the special issue on the behavior analysis
and treatment of drug addiction. J Appl Behav Anal 41(4):471–480. doi:10.1901/jaba.2008.41-471
Skinner BF (1938) The behavior of organisms: an experimental analysis. Copley Publishing
Group, Acton
Skinner BF, Heron WT (1937) Effects of caffeine and benzedrine upon conditioning and extinc-
tion. Psychol Rec 1:340–346
Stitzer ML, Iguchi MY, Felch LJ (1992) Contingent take-home incentive: effects on drug use of
methadone maintenance patients. J Consult Clin Psychol 60(6):927–934
Stitzer ML, Petry N, Peirce J, Kirby K, Killeen T, Roll J, Hamilton J, Stabile PQ, Sterling R,
Brown C, Kolodner K, Li R (2007) Effectiveness of abstinence-based incentives: interaction
with intake stimulant test results. J Consult Clin Psychol 75(5):805–811
Thompson T, Schuster CR (1964) Morphine self-administration, food-reinforced, and avoidance
behaviors in rhesus monkeys. Psychopharmacology 5(2):87–94
Thompson T, Schuster CR (1968) Behavioral pharmacology. Prentice Hall, Englewood Cliffs
Tuten M, Jones HE, Schaffer CM, Stitzer ML (2012) Reinforcement-based treatment for substance
use disorders: a comprehensive behavioral approach. Am J Addict 21(5):499–500
Wong CJ, Sheppard J-M, Dallery J, Bedient G, Robles E, Svikis D, Silverman K (2003) Effects of
reinforcer magnitude on data-entry productivity in chronically unemployed drug abusers
participating in a therapeutic workplace. Exp Clin Psychopharmacol 11(1):46–55
Yoon JH, Higgins ST, Bradstreet MP, Badger GJ, Thomas CS (2009) Changes in the relative
reinforcing effects of cigarette smoking as a function of initial abstinence. Psychopharmacol-
ogy 205(2):305–318
Twelve Step Facilitation as Behavioural
Approach in Addiction Treatment 52
Dennis M. Donovan and Dennis C. Daley
Contents
52.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 858
52.2 12-Step Approaches: An Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 859
52.2.1 What Are 12-Step Programs? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 859
52.2.2 Effectiveness of 12-Step Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 860
52.2.3 Interventions to Facilitate 12-Step Involvement in Specialty Treatment
Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 861
52.2.4 The Physician’s Role in Educating Patients and Families in Promoting
12-Step Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 862
52.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 869
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 869
Abstract
Hazardous and harmful alcohol use, illicit drug use, and the misuse of prescription
medications represent major public health concerns that affect a large segment of
the population. These highly prevalent conditions are associated with medical,
social, and psychiatric comorbidities that bring them to the attention of practi-
tioners in a variety of health-care and social service settings. While many such
individuals will benefit from brief interventions or more formal specialty sub-
stance abuse treatment, many also might choose to engage in a mutual support
program to seek assistance or gain additional support in their communities to help
them achieve and maintain their goal of reducing or discontinuing their substance
use. The present chapter reviews 12-step mutual support programs that serve as
widely available, no-cost resources in substance abuse recovery. It reviews evi-
dence about the effectiveness of such support groups and of specific interventions
designed to facilitate engagement in them. It also describes the physician’s role in
educating patients and families in promoting 12-step programs. Important steps
for physicians include understanding 12-step mutual support programs, preparing
patients or family members to engage in a mutual support program, monitoring
attendance and engagement, exploring patient resistances to mutual support pro-
grams, knowing the components and “tools” of the program, and being aware of
alternatives for patients who will not use 12-step programs.
52.1 Introduction
Hazardous and harmful alcohol use, illicit drug use, and the misuse of prescription
medications represent major public health concerns that affect a large segment of
the population. These highly prevalent conditions are associated with medical,
social, and psychiatric comorbidities that bring them to the attention of practitioners
in a variety of health-care and social service settings (Kelly and McCrady 2008;
Schulden et al. 2012). With an increased emphasis on conducting screening, brief
intervention, and referral to treatment in primary care, emergency medicine, HIV and
STI, and psychiatric clinics, the likelihood is high that medical and psychiatric
practitioners will encounter individuals with substance use disorders (SUDs). While
brief interventions in such settings may be sufficient to lead to behavior change for
many, with a move toward either abstinence or reduced use and harm reduction, many
other individuals will be referred for more intensive specialty substance use disorder
treatment. Individuals might also choose to engage in a mutual support program to
seek assistance or gain additional support in their communities to help them achieve
and maintain their goal of reducing or discontinuing their substance use.
One such source of support is the large number mutual support programs based
on the 12-step philosophy and principles, which originated with Alcoholics Anon-
ymous (AA), but now includes Narcotics Anonymous (NA), Cocaine Anonymous
(CA), and a number of others (Laudet 2008). These programs involve no cost and
only require a desire to stop drinking or using drugs as a condition of membership,
making them highly accessible and readily available, thus serving as important
resources in substance abuse recovery. It is estimated that there are nearly 64,000
AA groups with 1.4 million members in the United States and Canada and over
114,000 groups and 2.1 million members worldwide (Alcoholics Anonymous
2012b). Similarly, NA and CA have meetings available throughout many countries
internationally. All of these mutual support programs have also expanded their
services through the availability of Internet-based meetings and “chat rooms” that
provide an additional, supplemental source of support.
Given that many individuals who are in need of treatment never seek specialty
SUD care, 12-step programs have served as the primary, if not only, source of
52 Twelve Step Facilitation as Behavioural Approach in Addiction Treatment 859
behavior change for many individuals dependent on alcohol or drugs. They have
also been incorporated into specialty SUD treatment programs, either as
a component of or as an adjunct to formal treatment, and have served as continuing
care and community support following treatment. Of the over five million adoles-
cents and adults in the United States that attended substance-focused mutual
support groups during 2006 and 2007, approximately two-thirds were not involved
in formal treatment during this period, while the remaining one-third were also
involved in some type of specialty SUD treatment over that same period (Substance
Abuse and Mental Health Services Administration 2008).
Alcoholics Anonymous and other mutual support programs that are based on AA
have their foundation in 12 steps, which represent a general philosophy, principles,
beliefs, and behavioral guidelines for individuals seeking to discontinue their
alcohol or drug use. The AA 12 steps are found in Table 52.1. The underlying
philosophy reflected by these steps emphasizes a particular view of the recovery
process. Acceptance of addiction as a disease that can be arrested but never
eliminated, enhancing individual maturity and spiritual growth, minimizing self-
centeredness, and providing help to other addicted individuals are all viewed as
essential components (Humphreys et al. 2004). The 12 steps represent a series of
self-reflective and behavioral activities that substance abusers engage in during
their recovery. As noted in Table 52.1, individuals seeking to overcome their SUD
should admit their powerlessness over alcohol and drugs, take a moral inventory of
themselves, admit the nature of their wrongs, make a list of individuals whom they
have harmed, and make amends to those people. The essence of recovery activities
and guiding principles has been described as the 12-step “six pack”: don’t drink or
use drugs, go to meetings, ask for help, get a sponsor, join a group, and get active
(Caldwell and Cutter 1998).
In addition to the general philosophy and behavioral guidelines, 12-step
approaches place a considerable emphasis on “fellowship” or the social network
that is associated with 12-step group membership (Kaskutas et al. 2002). One of the
characteristic features of a substance dependence syndrome is a narrowing of the
drinking repertoire, which most often includes a narrowing of the friends and
associates the individual has to those who are drinking/drug-using friends and
acquaintances who tend to reinforce continued use. By joining a 12-step program,
the individual begins to shift one’s social network away from those who support
drinking/drug use to an expanding network of those who support abstinence and
promote recovery (Bond et al. 2003; Groh et al. 2008; Kelly et al. 2012, 2011;
Longabaugh et al. 1998). There is an increased sense of bonding with other
members in the fellowship who are also working toward a common goal of
abstinence. This new social network provides a set of behavioral norms and role
models for how to work toward abstinence and follow a personal recovery plan, the
development and engagement in non-substance-related activities that are rewarding
and can take the place of substance-related activities, a decreased exposure to
drinking/drug-related activities and cues that induce craving, and rewarding social
relationships (Kelly et al. 2011, 2012). Consistent with this, greater attendance at
AA meetings was associated with decreases in social ties with individuals who
supported the individuals’ drinking and in drinking-related activities while also
increasing social ties with those supporting abstinence and engaging in nondrinking
activities, all of which contributed to better outcomes with respect to abstinence
(Kelly et al. 2011). These social aspects of 12-step programs may be as important, if
not more so, as 12-step specific factors or spiritual mechanisms in the positive
benefits of 12-step mutual support groups (Groh et al. 2008; Kelly et al. 2012).
A number of interventions have been developed for use in substance abuse treat-
ment programs to facilitate 12-step meeting attendance and engagement in 12-step
862 D.M. Donovan and D.C. Daley
activities (Cloud and Kingree 2008; Donovan and Floyd 2008; Donovan
et al. 2013). These differ with respect to their primary focus but share the common
goal of getting individuals actively involved in 12-step groups. Twelve-Step Facil-
itation (TSF) therapy, developed in Project MATCH with alcohol-dependent
individuals (Nowinski et al. 1992) and subsequently adapted for use with drug-
dependent patients (Baker 1998; Carroll et al. 1998), focuses on helping individuals
better understand and appreciate 12-step philosophy and the first three of the
12 steps, which focus on acceptance and surrender. The underlying assumption of
TSF, which can be delivered in either individual or group formats, is that this
increased appreciation will lead to subsequent engagement. Making AA Easier
(MAAEZ) (Kaskutas et al. 2009b), a six-session group intervention, does not focus
explicitly on 12-step philosophy and concepts. Rather, it attempts to facilitate
12-step engagement by familiarizing individuals with the “culture” of 12-step
meetings, helping them identify potential barriers to engagement, and minimizing
their resistance by helping them anticipate and learn ways to deal with issues in
12-step meetings and programs that often lead them to reject future participation.
The intensive referral intervention (Timko and DeBenedetti 2007; Timko
et al. 2006) focuses on a much more active and direct process of engaging individuals
in meeting attendance. In a three-session, individually delivered intervention, an
attempt is made to link the alcohol- or drug-dependent individual with a member
of a community-based 12-step program who will accompany the individual to
a 12-step meeting, thus helping reduce the potential fear of not knowing anyone at
a meeting that can serve as a barrier to attendance. The volunteer helps prepare and
“socialize” the patient, answering questions, introducing them to other group mem-
bers, and serving as a transitional support. As with MAAEZ, the assumption of the
intensive referral is that getting the individual to a meeting is paramount and that
understanding of 12-step concepts and principles will follow. The STAGE-12 inter-
vention (Stimulant Abuser Groups to Engage in 12 Step) (Daley et al. 2011; Donovan
et al. 2012), consisting of three individual sessions and five group sessions, attempts
to combine the active engagement process based on the intensive referral linkage
with 12-step volunteers with TSF therapy content focused on better understanding
12-step concepts. The underlying assumption of STAGE-12 is that, given the high
rates of early attrition, getting people to meetings may be insufficient to maintain
involvement without an understanding of the philosophy and steps of the program;
thus, a combined approach that focuses both on meeting attendance and active
participation and on 12-step practices and principles may be needed. Each of these
four interventions has demonstrated an ability to increase attendance and/or engage-
ment in 12-step activities with a resultant decrease in alcohol or drug use.
The physician can also encourage medical students, residents, and others involved
in patient care to attend meetings and read literature (online or in written publica-
tions) describing these programs. Reading program literature can help the physician
and medical staff understand these programs as well as serve as resources to
recommend to patients interested in learning about and engaging in these programs
(Alcoholics Anonymous 2001, 2009; Narcotics Anonymous 1993, 2008). Alco-
holics Anonymous has developed a special brochure and video to help familiarize
physicians and health-care providers about the program and ways to facilitate
referrals to it (Alcoholics Anonymous 1992).
Following are some key issues in understanding 12-step programs and facilitat-
ing their use by patients or their family members:
• These programs consist of many components: meetings, the 12 steps of recovery,
sponsorship, recovery slogans, recovery literature, supportive activities (e.g.,
holiday events, conventions, sober social events), and service.
• Meetings are free and accessible in many countries and communities and follow
a similar format, depending on the type of meeting (open or closed; speaker or
discussion meeting). Attending different meetings can help the patient find ones
that fit his or her recovery needs.
• No one is in charge of the 12-step fellowship and all members are equal.
Discussion meetings have chairpersons to lead discussions, but these are mem-
bers of the program. Meetings are “anonymous” and no records are kept.
• People from all walks of life can attend, even if they are not yet abstinent
from alcohol or drugs. The only requirement is a “desire to stop” using alcohol
or drugs.
• Members become educated about addiction, recovery, and other topics/issues.
Some may even learn social and/or recovery skills such as how to self-disclose
(cravings, problems, feelings, and thoughts) and to accept or give support.
• The emphasis of 12-step programs is one alcoholic or drug-addicted individual
helping another. Newcomers are welcomed and accepted, which helps reduce
their shame. Program members help them learn to work a “we” versus an “I”
program.
• Members help each other by sharing their experience with addiction and recov-
ery, thereby sharing hope and strength. This is done at the meetings, at “meetings
after the meeting” (e.g., members go out for tea or coffee after a meeting to
support each other in recovery), and via sponsorship.
• Members who connect with others can reduce their isolation. They can receive
social support and help from other members “who have been there” and are
managing the common challenges faced in recovery from alcoholism or drug
addiction.
• Groups and other program activities are a positive replacement for drinking or
drug use. In early recovery, addicted patients often struggle with boredom and
not knowing what to do with their time. Some lack non-substance leisure
interests.
• Group members can give participants (especially newcomers) a “dose” of reality
to reduce their distorted or “stinking” thinking as well as recovery sabotaging
52 Twelve Step Facilitation as Behavioural Approach in Addiction Treatment 865
comfortable to attend discussion meetings, sharing was easier for them. What do
you think about this idea?”
• Higher Power refers to “something greater than oneself” to help in the recovery
journey. Many of the 12 steps (steps 2, 3, 5, 6, 7, 12) focus on spirituality and
how to use a Higher Power to deal with the challenges of recovery. However, for
those who do not believe in God as a Higher Power, the fellowship of AA or NA
can be the suggested source of an “outside” support to the patient.
• 12 steps of AA, NA, or other programs provide a way to actively engage in the
recovery journey by understanding the spiritual principles of the program. The
12 steps focus on the following: (a) acceptance of addiction and negative effects
on life (e.g., powerlessness and unmanageability), (b) spirituality (e.g., relying
on a “Higher Power”), (c) self-assessment (e.g., looking at one’s character
defects and strengths via a personal inventory), (d) making amends to loved
ones and others hurt by one’s addiction, and (e) service by carrying the message
of the program to others with alcoholism or drug addiction.
• Slogans refer to sayings or ways of thinking to help the member think more like
a person in recovery and less like an addicted person. These can be used to coach
oneself through stressful times such as when the member has a strong craving for
alcohol or drugs or is obsessed about using. Some of the more common sayings
include “One day at a time,” “easy does it,” “this too [craving/desire] shall pass,”
“let go and let God,” and “put off the first drink (or drug),” to name a few.
• Providing or recommending literature about these programs or common
issues faced by members is a helpful intervention. AA has the “Big Book” and
NA has the “Basic Text,” as well as many other books and information pam-
phlets or tapes on addiction or recovery. AA, NA, Al-Anon, Nar-Anon, and other
12-step programs all have a rich selection of recovery literature for all phases of
recovery. Many members continue to use this literature on a daily basis years
(or even decades) into their recovery.
• Events sponsored by these programs include those that take place during the
holidays to provide extra support during high-risk times for some members (e.g.,
Christmas and New Year), as well as social events such as picnics or attending
some activity of mutual interest (e.g., bowling or a sports event). In addition, there
are a number of Alano Clubs and Recovery Cafes found in many cities. These
venues, in addition to hosting recovery group meetings, provide alcohol- and drug-
free environments in which recovering individuals and their families can engage
in social and recreational activities. These activities reinforce the belief that is
possible to have fun without being under the influence of alcohol or drugs.
52.2.4.6 Alternatives for Patients Who Will Not Use 12-Step Programs
It is not unusual for some patients to state that they have tried 12-step programs to
no avail, they are simply not interested, or they have difficulties accepting the basic
philosophy and spirituality of the programs. If, after exploring the resistances to
find out what did not help or any other experiences that impacted on not wanting to
use program, the physician believes an alternative mutual support approach could
help, then options for non-12-step programs can be provided. These include, but are
not limited to, the following: Women for Sobriety, Men for Recovery, Rational
Recovery, SMART Recovery, Secular Organizations for Sobriety/Save Our Selves
52 Twelve Step Facilitation as Behavioural Approach in Addiction Treatment 869
or SOS, and others. One potential limitation is that these groups are less readily
available than are 12-step groups, with many towns or cities having few or none of
these programs available.
52.3 Conclusion
Mutual support programs (12-step and others) are an excellent resource for indi-
viduals with alcohol or drug addictions as well as loved ones or significant others
adversely affected by an addiction. These programs are available at no cost, and
each provides a framework for recovery, based on the philosophy of the program.
The most widely used and available programs are AA, NA, An-Anon, and
Nar-Anon. Becoming familiar with these programs, educating patients about
them, providing literature or meeting lists, facilitating attendance, and monitoring
involvement are some of the helpful strategies for physicians and their medical
staffs to help patients with alcohol and drug problems and affected family members.
Acknowledgment This chapter was supported by a series of grants from the United States
National Institutes of Health/National Institute on Drug Abuse (NIDA) as part of the Cooperative
Agreement on National Drug Abuse Treatment Clinical Trials Network: Pacific Northwest Node
(U10DA13714) and Appalachian/Tri-States Node (U10DA20036). Its contents are solely the
responsibility of the authors and do not necessarily represent the official views of NIDA.
References
Alcoholics Anonymous (1991) Bridging the gap between treatment and AA through temporary
contact programs. Alcoholics Anonymous World Services, New York
Alcoholics Anonymous (1992) AA as a resource for the health care professional. Alcoholics
Anonymous World Service, New York
Alcoholics Anonymous (2001) Alcoholics Anonymous: the big book, 4th edn. Alcoholics
Anonymous World Services, New York
Alcoholics Anonymous (2009) Twelve steps and twelve traditions. Alcoholics Anonymous World
Services, New York
Alcoholics Anonymous (2012a) 2011 membership survey. Alcoholics Anonymous World
Services, New York
Alcoholics Anonymous (2012b) Estimates of A.A. groups and members as of January 1, 2012.
A.A. General Service Office, New York
Alcoholics Anonymous (Producer). A.A. video for healthcare professionals. Retrieved from http://
www.videostreamingservices.com/aa/cpc/health/index.php
Baker S (1998) Twelve step facilitation for drug dependence. Psychotherapy Development Center,
Department of Psychiatry, Yale University, New Haven
Blondell RD, Looney SW, Northington AP, Lasch ME, Rhodes SB, McDaniels RL (2001a) Can
recovering alcoholics help hospitalized patients with alcohol problems? J Fam Pract 50(5):447
Blondell RD, Looney SW, Northington AP, Lasch ME, Rhodes SB, McDaniels RL (2001b)
Using recovering alcoholics to help hospitalized patients with alcohol problems. J Fam Pract
50(5):E1
Bond J, Kaskutas LA, Weisner C (2003) The persistent influence of social networks and alcoholics
anonymous on abstinence. J Stud Alcohol 64(4):579–588
870 D.M. Donovan and D.C. Daley
Caldwell PE, Cutter HS (1998) Alcoholics Anonymous affiliation during early recovery. J Subst
Abuse Treat 15(3):221–228
Carroll KM, Nich C, Ball SA, McCance E, Rounsavile BJ (1998) Treatment of cocaine and alcohol
dependence with psychotherapy and disulfiram. Addiction 93(5):713–727
Cloud RN, Kingree JB (2008) Concerns about dose and underutilization of twelve-step
programs: models, scales, and theory that inform treatment planning. Recent Dev Alcohol
18:283–301
Connors GJ, Tonigan JS, Miller WR, Project MATCH Research Group (2001) A longitudinal
model of intake symptomatology, AA participation and outcome: retrospective study of the
Project MATCH outpatient and aftercare samples. J Stud Alcohol 62(6):817–825
Daley DC, Donovan DM (2007) Using 12-Step programs in recovery: for individuals with alcohol
and drug addiction. Daley Publications, Export
Daley DC, McDonald J (2013) Online resources for substance use disorders and co-occurring
psychiatric disorders: resources for clients, family members and professionals. Appalachian
Tri-State Node of the NIDA Clinical Trials Network, University of Pittsburgh, Pittsburgh
Daley DC, Baker S, Donovan DM, Hodgkins CC, Perl H (2011) A combined group and individual
12-step facilitative intervention targeting stimulant abuse in the NIDA Clinical Trials Network:
STAGE-12. J Groups Addict Recover 6(3):228–244
Donovan DM, Floyd AS (2008) Facilitating involvement in twelve-step programs. Recent Dev
Alcohol 18:303–320
Donovan DM, Daley DC, Brigham GS, Hodgkins CC, Perl HI, Garrett SB, Zammarelli L (2012)
Stimulant abuser groups to engage in 12-Step: a multisite trial in the National Institute on Drug
Abuse Clinical Trials Network. J Subst Abuse Treat 44(1):103–114
Donovan DM, Ingalsbe MH, Benbow J, Daley DC (2013) Twelve-step interventions and mutual
support programs for substance use disorders: an overview. Soc Work Public Health
28(3–4):313–332
Gossop M, Stewart D, Marsden J (2008) Attendance at Narcotics Anonymous and Alcoholics
Anonymous meetings, frequency of attendance and substance use outcomes after residential
treatment for drug dependence: a 5-year follow-up study. Addiction 103(1):119–125
Groh DR, Jason LA, Keys CB (2008) Social network variables in alcoholics anonymous:
a literature review. Clin Psychol Rev 28(3):430–450
Humphreys K (2003) Alcoholics Anonymous and 12-step alcoholism treatment programs. Recent
Dev Alcohol 16:149–164
Humphreys K, Moos R (2001) Can encouraging substance abuse patients to participate in self-help
groups reduce demand for health care? Alcohol Clin Exp Res 25(5):711–716
Humphreys K, Moos RH (2007) Encouraging posttreatment self-help group involvement to reduce
demand for continuing care services: two-year clinical and utilization outcomes. Alcohol Clin
Exp Res 31(1):64–68
Humphreys K, Wing S, McCarty D, Chappel J, Gallant L, Haberle B, Weiss R (2004) Self-help
organizations for alcohol and drug problems: toward evidence-based practice and policy.
J Subst Abuse Treat 26(3):151–158
Kaskutas LA (2009) Alcoholics anonymous effectiveness: faith meets science. J Addict Dis
28(2):145–157
Kaskutas LA, Bond J, Humphreys K (2002) Social networks as mediators of the effect of
Alcoholics Anonymous. Addiction 97(7):891–900
Kaskutas LA, Ammon L, Delucchi K, Room R, Bond J, Weisner C (2005) Alcoholics anonymous
careers: patterns of AA involvement five years after treatment entry. Alcohol Clin Exp Res
29(11):1983–1990
Kaskutas LA, Bond J, Avalos LA (2009a) 7-year trajectories of Alcoholics Anonymous attendance
and associations with treatment. Addict Behav 34(12):1029–1035
Kaskutas LA, Subbaraman MS, Witbrodt J, Zemore SE (2009b) Effectiveness of making Alco-
holics Anonymous easier: a group format 12-step facilitation approach. J Subst Abuse Treat
37(3):228–339
52 Twelve Step Facilitation as Behavioural Approach in Addiction Treatment 871
Kelly JF, McCrady BS (2008) Twelve-step facilitation in non-specialty settings. Recent Dev
Alcohol 18:321–346
Kelly JF, Stout RL, Magill M, Tonigan JS (2011) The role of Alcoholics Anonymous in mobilizing
adaptive social network changes: a prospective lagged mediational analysis. Drug Alcohol
Depend 114(2–3):119–126
Kelly JF, Hoeppner B, Stout RL, Pagano M (2012) Determining the relative importance of the
mechanisms of behavior change within Alcoholics Anonymous: a multiple mediator analysis.
Addiction 107(2):289–299
Krentzman AR, Robinson EA, Moore BC, Kelly JF, Laudet AB, White WL, Strobbe S (2010)
How Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) work: cross-disciplinary
perspectives. Alcohol Treat Q 29(1):75–84
Laudet AB (2008) The Impact of Alcoholics Anonymous on other substance abuse related twelve
step programs. Recent Dev Alcohol 18:71–89
Longabaugh R, Wirtz PW, Zweben A, Stout RL (1998) Network support for drinking, Alcoholics
Anonymous and long -term matching effects. Addiction 93(9):1313–1333
Magura S, Cleland CM, Tonigan JS (2013) Evaluating Alcoholics Anonymous’s effect on
drinking in Project MATCH using cross-lagged regression panel analysis. J Stud Alcohol
Drugs 74(3):378–385
Manning V, Best D, Faulkner N, Titherington E, Morinan A, Keaney F, Strang J (2012) Does
active referral by a doctor or 12-Step peer improve 12-Step meeting attendance? Results from
a pilot randomised control trial. Drug Alcohol Depend 126(1–2):131–137
McKellar J, Stewart E, Humphreys K (2003) Alcoholics anonymous involvement and positive
alcohol-related outcomes: consequence, or just a correlate? A prospective 2-year study of
2,319 alcohol-dependent men. J Consult Clin Psychol 71(2):302–308
Moos RH, Moos BS (2006) Participation in treatment and alcoholics anonymous: a 16-year
follow-up of initially untreated individuals. J Clin Psychol 62(6):735–750
Mundt MP, Parthasarathy S, Chi FW, Sterling S, Campbell CI (2012) 12-Step participation
reduces medical use costs among adolescents with a history of alcohol and other drug
treatment. Drug Alcohol Depend 126(1–2):124–130
Narcotics Anonymous (1993) It works: how and why. The twelve steps and twelve traditions of
Narcotics Anonymous. Narcotics Anonymous World Services, Chatsworth
Narcotics Anonymous (2008) Basic text, 6th edn. Narcotics Anonymous World Services,
Chatsworth
Nowinski J, Baker S, Carroll K (1992) Twelve step facilitation therapy manual: a clinical research
guide for therapists treating individuals with alcohol abuse and dependence, vol 1. National
Institute on Alcohol Abuse and Alcoholism, Rockville
Owen PL, Slaymaker V, Tonigan JS, McCrady BS, Epstein EE, Kaskutas LA, Miller WR
(2003) Participation in alcoholics anonymous: intended and unintended change mechanisms.
Alcohol Clin Exp Res 27(3):524–532
Pagano ME, Friend KB, Tonigan JS, Stout RL (2004) Helping other alcoholics in alcoholics anony-
mous and drinking outcomes: findings from Project MATCH. J Stud Alcohol 65(6):766–773
Pagano ME, Post SG, Johnson SM (2010) Alcoholics Anonymous-related helping and the helper
therapy principle. AlcoholTreat Q 29(1):23–34
Pagano ME, White WL, Kelly JF, Stout RL, Tonigan JS (2013) The 10-year course of Alcoholics
Anonymous participation and long-term outcomes: a follow-up study of outpatient subjects in
Project MATCH. Subst Abus 34(1):51–59
Schulden JD, Lopez MF, Compton WM (2012) Clinical implications of drug abuse epidemiology.
Psychiatr ClinN Am 35(2):411–423
Substance Abuse and Mental Health Services Administration (2008) The NSDUH report: partic-
ipation in self-help groups for alcohol and illicit drug use: 2006 and 2007. Substance Abuse and
Mental Health Services Administration, Rockville
Timko C, DeBenedetti A (2007) A randomized controlled trial of intensive referral to 12-step
self-help groups: one-year outcomes. Drug Alcohol Depend 90(2–3):270–279
872 D.M. Donovan and D.C. Daley
Timko C, DeBenedetti A, Billow R (2006) Intensive referral to 12-Step self-help groups and
6-month substance use disorder outcomes. Addiction 101(5):678–688
Weiss RD, Griffin ML, Gallop RJ, Najavits LM, Frank A, Crits-Christoph P, Luborsky L (2005)
The effect of 12-step self-help group attendance and participation on drug use outcomes among
cocaine-dependent patients. Drug Alcohol Depend 77(2):177–184
Whelan PJ, Marshall EJ, Ball DM, Humphreys K (2009) The role of AA sponsors: a pilot study.
Alcohol Alcohol 44(4):416–422
Witbrodt J, Mertens J, Kaskutas LA, Bond J, Chi F, Weisner C (2012) Do 12-step meeting
attendance trajectories over 9 years predict abstinence. J Subst Abuse Treat 43(1):30–43
World Health Organization (2012) Role of mutual help groups such as Alcoholics Anonymous
(AA). Retrieved May 19, 2013, from http://www.who.int/mental_health/mhgap/evidence/
alcohol/q6/en/
Zemore SE, Subbaraman M, Tonigan JS (2013) Involvement in 12-Step activities and treatment
outcomes. Subst Abus 34(1):60–69
Group Therapy for Substance Use
Disorders 53
R. Kathryn McHugh, Sara Park, and Roger D. Weiss
Contents
53.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 874
53.2 Efficacy and Effectiveness of Group Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 875
53.2.1 Is Group Therapy Effective for the Treatment of SUDs? . . . . . . . . . . . . . . . . . . . . 875
53.2.2 Is Group Therapy as Good as Individual Therapy? . . . . . . . . . . . . . . . . . . . . . . . . . . . 877
53.2.3 What Types of Group Therapy Are Most Effective? . . . . . . . . . . . . . . . . . . . . . . . . . 878
53.2.4 Comparing Group Therapies for Co-occurring Disorders . . . . . . . . . . . . . . . . . . . . 880
53.2.5 How Can We Maximize Outcomes in Group Therapy? . . . . . . . . . . . . . . . . . . . . . . 881
53.2.6 Summary and Integration of the Literature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 883
53.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 884
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 885
Abstract
Group therapy is the predominant type of behavioral therapy offered in sub-
stance use disorder treatment settings. This chapter provides an overview of the
research literature on the efficacy of group therapy for substance use disorders
and discusses research challenges and important future directions in the study of
group therapy. Research on the efficacy of group therapy for substance use
disorders has generally found that it is associated with superior outcomes
compared to no treatment or treatment as usual. Studies examining the combi-
nation of group therapy with other forms of treatment, such as pharmacotherapy,
have been mixed, with some studies finding additive benefits and others finding
no benefit. However, group therapy appears to be equally as effective as indi-
vidual therapy and may offer cost benefits relative to individual treatment.
Group therapy for co-occurring substance use disorders and other psychiatric
disorders, such as bipolar disorder and posttraumatic stress disorder, is associ-
ated with benefits for both disorders. Due to a number of difficulties with
conducting research on group therapy, this treatment modality remains
understudied compared to individual therapy. Additional research is needed to
identify the most effective types of group therapy and its optimal delivery
method, either alone or in combination with other therapies.
53.1 Introduction
The term “group therapy” encompasses a number of treatment approaches that share in
common the presence of at least two independent (i.e., not related) patients and
a therapist who conduct meetings with the goal of eliminating or reducing substance
use or substance use disorder (SUD) symptoms (Weiss et al. 2004). Specific treatments
falling under this umbrella term may emphasize the interactions among members and
the therapist (process or supportive therapy groups), the provision of information and
skills (psychoeducational or behavioral therapy groups), or both. The content of groups
also varies and may include components such as psychoeducation, cognitive-
behavioral or motivational interventions, “check-ins” about use and other symptoms,
encouragement to attend 12-step or other mutual help groups, relational interventions,
skills training, and contingency management, among others.
The vast majority of programs that specialize in treating SUDs report offering some
form of group therapy (more than 94 %; United States Department of Health and
Human Services 2010). The predominance of group therapy in these settings may be
attributable – at least in part – to the potential cost savings of a group rather than an
individual approach. Cost analyses have suggested that group therapy is associated
with substantially less therapist time per patient compared to individual therapy
(Sobell et al. 2009) and that it has both the lowest cost and best cost-effectiveness
ratio of psychosocial treatment approaches (French et al. 2008). In addition, patients
are generally satisfied with group therapy as indicated by similar (if not superior)
retention rates compared to individual therapy and strong self-ratings of treatment
satisfaction (e.g., Sobell et al. 2009). Studies of patient preference for group versus
individual therapy are few; however, at least one study has identified preference for
group therapy over individual therapy (Schmitz et al. 1994). Thus, group therapy
appears to be a highly acceptable and low-cost approach to treating SUDs.
53 Group Therapy for Substance Use Disorders 875
Despite the widespread use of group therapy, this approach has been studied far less
extensively than individual therapies. In this review, we aim to characterize the current
research on the use of group therapy for patients with SUDs, with a focus on random-
ized controlled trials. We will limit our definition of group therapy to treatments that
focus on substance use or associated symptoms and not on treatments targeted specif-
ically to other symptoms or co-occurring disorders (e.g., group cognitive-behavioral
therapy for depression in patients with SUDs). Where possible, we will attempt to
characterize the nature of the group therapy approach from a content (e.g., cognitive-
behavioral, psychoeducational, etc.), composition (e.g., targeted substance, single or
mixed gender, dual diagnosis), and timing (e.g., acute care, aftercare) perspective.
We conclude with a commentary on limitations and challenges in conducting research
on group therapy and an integration of findings from the literature to date.
Although the majority of group therapy studies have compared two (or more) types
of group therapy, several studies have attempted to answer the basic question of
whether group therapy leads to improvement in SUD symptoms. These studies
compare either treatment as usual (usual care at a facility) to treatment as usual plus
group therapy or group therapy to no group therapy.
Several studies have tested whether the same type of treatment is more effective
when delivered in a group or individual format. The largest well-controlled study of
this association was conducted by Sobell and colleagues (2009) in a sample of
264 individuals with “non-severe” alcohol and drug use problems (those with
a history of severe dependence were excluded). Participants were randomly assigned
to four sessions of a cognitive-behavioral or motivational intervention in a group or
individual format. Participants experienced significant reductions in self-reported
alcohol and drug use and consequences of substance use. Results also indicated no
differences in substance use outcomes for individual versus group administration for
either alcohol or drug use and no differences in treatment retention.
In another study of group versus individual delivery of a motivational therapy,
John and colleagues (2003) randomized 343 alcohol-dependent inpatients in
German psychiatric hospitals to receive either three sessions of individual therapy
or nine sessions of group therapy for enhancing motivation for alcohol abstinence
following detoxification. Those in the group therapy condition reported more self-
help group attendance; however, there were no differences in other forms of
treatment-seeking and overall service utilization between groups. There were also
no differences in alcohol outcomes between these groups, with fewer than 30 % in
each group reporting abstinence at 6 months after detoxification.
Studies comparing individual and group cognitive-behavioral therapy have
yielded similar results. A study of the use of 9 weeks (12 sessions) of cognitive-
behavioral relapse prevention in group or individual format for 47 cocaine-
dependent patients following inpatient treatment found similar outcomes for both
groups over time on rates of abstinence as well as drug-related problems and
measures of functioning (Schmitz et al. 1997). By the end of treatment, fewer
than 50 % of both groups had remained abstinent, although gains in functioning and
impairment were largely sustained over 24 weeks of follow-up; at the final
878 R.K. McHugh et al.
assessment point, the average days of cocaine use in the previous month were low
(2 days for individual and less than 1 day for group).
A similar study also compared individual to group relapse prevention as part of
an aftercare program for 132 patients with alcohol and drug dependence (Graham
et al. 1996). Patients received 12 weekly sessions of either 45–60 min individual or
60–90 min group therapy. Group and individual therapy had similar outcomes for
treatment adherence and retention and self-reported alcohol and drug use. However,
group therapy was associated with better social support at 12-month follow-up.
A study conducted in Brazil randomized 155 mixed alcohol- and drug-dependent
patients to receive 17 sessions of cognitive-behavioral therapy in either group or
individual format (Marques and Formigoni 2001). This study also found no signif-
icant differences in session attendance or in self-reported alcohol or drug use
outcomes between groups when controlling for baseline levels of use.
A Norwegian study tested 12 weeks of 90-min group therapy (with same-gender
composition) or 7 h of individual delivery of a short-term therapy based on social
learning theory, focusing on skill acquisition toward individualized treatment goals
(abstinence or harm reduction) (Duckert et al. 1992). Study participants who responded
to advertisements and reported “alcohol problems” were randomized to one of these
conditions and followed for 21 months. Although there was a higher rate of abstinence
among women in individual therapy at the 3-month follow-up, there were no differ-
ences between groups at any subsequent time throughout the follow-up period. At the
end of 21 months, almost 70 % had reduced their alcohol consumption from
pretreatment levels and half of the total sample reduced alcohol use by at least 50 %.
Although relatively few studies have specifically tested individual versus group
therapies using the same group content, the available research very clearly suggests
that individual and group therapies are generally equivalent in terms of both
retention and clinical outcomes. Thus, it seems that high-quality treatment can be
administered as effectively in group as in individually delivered formats.
The majority of studies examining group therapy for SUDs have focused on
comparing two or more types of group therapy that vary in terms of content or
approach. For example, several studies have compared skills training to other
interventions and have yielded mixed results. Eriksen et al. (1986) randomized
24 alcohol-dependent participants to eight sessions of social skills training or
counseling. The social skills training group reported fewer drinking days, drank
less alcohol overall, and had better employment outcomes. A comparison of coping
skills and interactional (interpersonal) groups for alcohol use disorders found no
overall differences between the conditions in terms of alcohol use; however,
individuals rated high on psychopathy had better outcomes with the coping skills
group and those low on psychopathy had better outcomes in the interactional group,
both following treatment (Kadden et al. 1989) and at 2-year follow-up (Cooney
et al. 1991). A later study by this group randomized 250 alcohol-dependent patients
53 Group Therapy for Substance Use Disorders 879
Other psychiatric disorders commonly co-occur with SUDs (Conway et al. 2006;
Grant et al. 2004). Accordingly, numerous studies of group therapy for SUDs have
examined therapies targeted to both the SUD and the co-occurring psychiatric
disorder.
Weiss et al. (2000) compared usual care to usual care plus 12–20 sessions of an
integrated group therapy for SUDs and bipolar disorder in a sample of 45 partici-
pants. Results indicated that the group therapy was associated with significantly
lower SUD severity, more months abstinent, and longer durations of abstinence
relative to usual care alone. In a subsequent study, 62 outpatients with co-occurring
bipolar disorder and substance dependence were randomly assigned to 20 sessions
of either the integrated treatment or group drug counseling (Weiss et al. 2007).
Patients in the integrated group therapy had fewer days of substance use following
treatment and throughout 3 months of follow-up; however, mood outcomes were
similar between groups. Weiss and colleagues (2009) then tested the implementa-
tion of a 12-session version of the treatment with drug counselors without previous
training in cognitive-behavioral therapy. Sixty-one participants were randomized to
the integrated treatment or group counseling and results indicated better outcomes
for both substance (e.g., likelihood of abstinence) and mood symptoms (e.g., greater
reduction in risk for a mood episode) in the integrated treatment group.
In a study comparing dialectical behavioral therapy (DBT), which included
a group therapy component, to treatment as usual for 28 women with
co-occurring borderline personality disorder and substance dependence, there was
significantly greater treatment adherence, more days abstinent, and more negative
urine screens in the DBT group (Linehan et al. 1999). These findings for benefits of
DBT were replicated in heroin-dependent women when compared to individual
therapy (Linehan et al. 2002).
In a study conducted in Australia, James et al. (2004) randomized 63 participants
with co-occurring alcohol or drug use and a psychotic disorder to receive either
usual care and one session of substance use education or six sessions of an
integrated treatment for both disorders. The integrated dual disorder treatment
group was associated with significantly greater improvement in psychiatric symp-
toms, substance use, and SUD severity. In a similar study, Bellack et al. (2006)
randomized 129 outpatients with a diagnosis of drug dependence and serious
mental illness (psychotic or major affective disorder) to receive an integrated
behavioral treatment (Behavioral Treatment for Substance Abuse in Severe and
Persistent Mental Illness) or supportive group discussion twice weekly for 6 months.
Results indicated that the integrated treatment was associated with more negative
urine screens as well as better treatment retention and functional outcomes
(e.g., quality of life).
Results for co-occurring depression and anxiety disorders have been more
mixed. Lydecker and colleagues (2010) compared an integrated cognitive-
behavioral therapy for co-occurring depression and SUDs to 12-step facilitation
in a sample of 206 veterans with a current substance dependence diagnosis and
53 Group Therapy for Substance Use Disorders 881
Because the evidence generally supports the effectiveness of group therapy for
SUDs, recent research has begun to examine ways to maximize its effectiveness.
Several studies have tested ways to enhance group therapy by adding adjunctive
interventions or manipulating group factors.
outcomes and that those who are not able to achieve abstinence in group therapy
alone may benefit from individual therapy. Nonetheless, additional research is
needed to better understand the potential benefits of combining group and individ-
ual therapies.
Although research on group therapy for SUDs varies widely in the types of group
therapy, substance of abuse, population of interest, and timing and delivery of
treatment, several trends emerge from the existing literature. In general, studies
adding group treatment to minimal or no treatment suggest that group therapy is
associated with improved substance use and often also functional outcomes (e.g.,
Stephens et al. 2000; Weiss et al. 2000). Although not all studies have found
evidence for this effect (e.g., Razavi et al. 1999), studies predominantly support
group therapy as an effective intervention for SUDs. Results are mixed for adding
group therapy to more powerful treatments (e.g., certain pharmacotherapies), with
some evidence for no benefit for adding group therapy (e.g., Tucker et al. 2004) and
others finding benefits for some outcomes or in certain subgroups (e.g., Luthar and
Suchman 2000; Schmitz et al. 2007). However, many of these studies have been
limited by either small sample sizes or uncontrolled designs (e.g., no limitations on
additional adjunctive treatments); it thus remains unclear whether group therapy
can achieve additive benefits when combined with pharmacotherapy.
Likewise, comparisons of different types of group therapy have generally
yielded variable results. The relative effectiveness of different types of group
treatment may depend on the fit of the intervention to the target population. For
example, several integrated group therapies (such as those for SUD patients with
co-occurring psychosis or bipolar disorder) have been associated with better out-
comes than general alcohol and drug counseling therapies (e.g., Bellack et al. 2006;
Weiss et al. 2007). Thus, the degree to which the treatment “fits” the population
may be critical to understanding which treatment works best for what population.
Studies comparing individual to group delivery of substance abuse treatment
(predominantly motivational enhancement or cognitive-behavioral therapy) have
not found significant differences between individual and group therapy on sub-
stance use or other functional outcomes or differences in treatment retention.
Although there is limited evidence for greater social functioning following group
therapy (Graham et al. 1996) and greater patient preference for individual therapy
(Sobell et al. 2009), the evidence overall seems to support the equivalence of these
approaches for both drug and alcohol use disorders.
Given the mixed findings on effectiveness, strategies to maximize outcomes are
of particular importance. The addition of incentives for attending treatment appears
to improve retention, maximizing the “dose” of therapy that patients receive.
Because the findings examining the addition of individual therapy to group therapy
have been mixed, contingency management may be the best available strategy to
enhance outcomes of group therapy.
884 R.K. McHugh et al.
The mixed outcomes reported above are likely due in part to the heterogeneity of
studies and populations, including the dose (i.e., number of sessions) administered
and the timing of when treatment occurs. In addition, many studies have used small
sample sizes, which substantially limit the ability to identify differences in out-
comes, particularly when comparing two active treatments, such as pharmacother-
apy versus pharmacotherapy plus group therapy, or two types of group therapy.
Thus, it is clear that more research is needed to understand what types of group
therapy are most effective and under what conditions.
53.3 Conclusion
particularly when the treatment is specific and well-defined; group treatment may
be a particularly effective option for those with co-occurring psychiatric and
substance use disorders. Studies suggest that group therapy is generally as effective
as individual therapy, although the specific types of group therapy associated with
the optimal outcomes remain somewhat unclear.
Acknowledgments Dr. Weiss’s effort on this chapter was supported in part by award K24
DA022288 from the National Institute on Drug Abuse.
References
Alessi SM, Hanson T, Wieners M, Petry NM (2007) Low-cost contingency management in
community clinics: delivering incentives partially in group therapy. Exp Clin
Psychopharmacol 15:293–300
Bellack AS, Bennett ME, Gearon JS, Brown CH, Yang Y (2006) A randomized clinical trial of
a new behavioral treatment for drug abuse in people with severe and persistent mental illness.
Arch Gen Psychiatry 63:426–432
Carroll KM, Chang G, Behr H, Clinton B, Kosten TR (1995) Improving treatment outcome in pregnant,
methadone-maintained women: results from a randomized clinical trial. Am J Addict 4:56–59
Conway KP, Compton W, Stinson FS, Grant BF (2006) Lifetime comorbidity of DSM-IV mood
and anxiety disorders and specific drug use disorders: results from the National Epidemiologic
Survey on Alcohol and Related Conditions. J Clin Psychiatry 67:247–257
Cooney NL, Kadden RM, Litt MD, Getter H (1991) Matching alcoholics to coping skills or
interactional therapies: two-year follow-up results. J Consult Clin Psychol 59:598–601
Copeland J, Hall W, Didcott P, Biggs V (1993) A comparison of a specialist women’s alcohol and
other drug treatment service with two traditional mixed-sex services: client characteristics and
treatment outcome. Drug Alcohol Depend 32:81–92
Coviello DM, Alterman AI, Rutherford MJ, Cacciola JS, McKay JR, Zanis DA (2001) The
effectiveness of two intensities of psychosocial treatment for cocaine dependence. Drug
Alcohol Depend 61:145–154
Crits-Christoph P, Siqueland L, Blaine J, Frank A, Luborsky L, Onken LS, Muenz LR, Thase ME,
Weiss RD, Gastfriend DR, Woody GE, Barber JP, Butler SF, Daley D, Salloum I, Bishop S,
Najavits LM, Lis J, Mercer D, Griffin ML, Moras K, Beck AT (1999) Psychosocial treatments
for cocaine dependence: National Institute on Drug Abuse Collaborative Cocaine Treatment
Study. Arch Gen Psychiatry 56:493–502
Crits-Christoph P, Siqueland L, McCalmont E, Weiss RD, Gastfriend DR, Frank A, Moras K,
Barber JP, Blaine J, Thase ME (2001) Impact of psychosocial treatments on associated
problems of cocaine-dependent patients. J Consult Clin Psychol 69:825–830
Duckert F, Amundsen A, Johnsen J (1992) What happens to drinking after therapeutic interven-
tion? Br J Addict 87:1457–1467
Eriksen L, Bjornstad S, Gotestam KG (1986) Social skills training in groups for alcoholics:
one-year treatment outcome of groups and individuals. Addict Behav 11:309–329
French MT, Zavala SK, McCollister KE, Waldron HB, Turner CW, Ozechowski TJ (2008) Cost-
effectiveness analysis of four interventions for adolescents with a substance use disorder.
J Subst Abuse Treat 34:272–281
Graham K, Annis HM, Brett PJ, Venesoen P (1996) A controlled field trial of group vs. individual
cognitive-behavioural training for relapse prevention. Addiction 81:1127–1139
Grant BF, Stinson FS, Dawson DA, Chou SP, Dufour MC, Compton W, Pickering RP, Kaplan
K (2004) Prevalence and co-occurrence of substance use disorders and independent mood and
anxiety disorders. Arch Gen Psychiatry 61:807–816
886 R.K. McHugh et al.
Greenfield SF, Trucco EM, McHugh RK, Lincoln M, Gallop RJ (2007) The Women’s Recovery
Group Study: a stage I trial of women-focused group therapy for substance use disorders versus
mixed-gender group drug counseling. Drug Alcohol Depend 90:39–47
Greenfield SF, Potter JS, Lincoln MF, Popuch RE, Kuper L, Gallop RJ (2008) High psychiatric
symptom severity is a moderator of substance abuse treatment outcomes among women in
single vs. mixed gender group treatment. Am J Drug Alcohol Abuse 34:594–602
Hien DA, Wells EA, Jiang H, Suarez-Morales L, Campbell AN, Cohen LR, Miele GM, Killeen T,
Brigham GS, Zhang Y, Hansen C, Hodgkins C, Hatch-Maillette M, Brown C, Kulaga A,
Kristman-Valente A, Chu M, Sage R, Robinson JA, Liu D, Nunes EV (2009) Multisite
randomized trial of behavioral interventions for women with co-occurring PTSD and substance
use disorders. J Consult Clin Psychol 77:607–619
Ito JR, Donovan DM, Hall JJ (1988) Relapse prevention in alcohol aftercare: effects on drinking
outcome, change process, and aftercare attendance. Br J Addict 83:171–181
James W, Preston NJ, Koh G, Spencer C, Kisely SR, Castle DJ (2004) A group intervention which
assists patients with dual diagnosis reduce their drug use: a randomized control trial. Psychol
Med 34:983–990
Joanning H, Thomas F, Quinn W, Mullen R (1992) Treating adolescent drug abuse: a comparison of
family systems therapy, group therapy, and family education. J Marital Fam Ther 18:345–356
John U, Veltrup C, Driessen M, Wetterling T, Dilling H (2003) Motivational intervention: an
individual counseling vs a group treatment approach for alcohol-dependent in-patients. Alco-
hol Alcohol 38:263–269
Kadden RM, Cooney NL, Getter H, Litt MD (1989) Matching alcoholics to coping skills or
interactional therapies: post-treatment results. J Consult Clin Psychol 57:698–704
Kadden RM, Litt MD, Cooney NL, Kabela E, Getter H (2001) Prospective matching of alcoholic
clients to cognitive-behavioral or interactional group therapy. J Stud Alcohol 62:359–369
Kaminer Y, Burleson JA, Goldberger R (2002) Cognitive-behavioral coping skills and
psychoeducation therapies for adolescent substance abuse. J Nerv Ment Dis 190:737–745
Ledgerwood DM, Alessi SM, Hanson T, Godley MD, Petry NM (2008) Contingency management
for attendance to group substance abuse treatment administered by clinicians in community
clinics. J Appl Behav Anal 41:517–526
Linehan MM, Schmidt H 3rd, Dimeff LA, Craft JC, Kanter J, Comtois KA (1999) Dialectical
behavior therapy for patients with borderline personality disorder and drug-dependence. Am
J Addict 8:279–292
Linehan MM, Dimeff LA, Reynolds SK, Comtois KA, Welch SS, Heagerty P, Kivlahan DR
(2002) Dialectical behavior therapy versus comprehensive validation therapy plus 12-step for
the treatment of opioid dependent women meeting criteria for borderline personality disorder.
Drug Alcohol Depend 67:13–26
Luthar SS, Suchman NE (2000) Relational psychotherapy mothers’ group: a developmentally
informed intervention for at-risk mothers. Dev Psychopathol 2:235–253
Luthar SS, Suchman NE, Altomare M (2007) Relational psychotherapy mothers’ group:
a randomized clinical trial for substance abusing mothers. Dev Psychopathol 19:243–261
Lydecker KP, Tate SR, Cummins KM, McQuaid J, Granholm E, Brown SA (2010) Clinical outcomes of
an integrated treatment for depression and substance use disorders. Psychol Addict Behav 24:453–465
Marques AC, Formigoni ML (2001) Comparison of individual and group cognitive-behavioral
therapy for alcohol and/or drug dependent patients. Addiction 96:835–846
McKay JR, Alterman AI, Cacciola JS, Rutherford MJ, O’Brien CP, Koppenhaver J (1997) Group
counseling versus individualized relapse prevention aftercare following intensive outpatient
treatment for cocaine dependence: initial results. J Consult Clin Psychol 65:778–788
Najavits LM (2002) Seeking safety: a treatment manual for PTSD and substance abuse. Guilford,
New York
Najavits LM, Gallop RJ, Weiss RD (2006) Seeking safety therapy for adolescent girls with
PTSD and substance use disorder: a randomized controlled trial. J Behav Health Serv
Res 33:453–463
53 Group Therapy for Substance Use Disorders 887
Olson PR, Devine VT, Ganley R, Dorsey GC (1981) Long-term effects of behavioral versus
insight-oriented therapy with inpatient alcoholics. J Consult Clin Psychol 49:866–877
Omer H, Winch G, Dar R (1998) Therapeutic impact in treatments for smoking and test-anxiety.
Psychother Res 8:439–454
Petry NM, Weinstock J, Alessi SM (2011) A randomized trial of contingency management
delivered in the context of group counseling. J Consult Clin Psychol 79:686–696
Pomerleau OF, Pertschuk M, Adkins D, Brady JP (1978) A comparison of behavioral and
traditional treatment for middle-income problem drinkers. J Behav Med 1:187–200
Razavi D, Vandecasteele H, Primo C, Bodo M, Debrier F, Verbist H, Pethica D, Eerdekens M,
Kaufman L (1999) Maintaining abstinence from cigarette smoking: effectiveness of group
counseling and factors predicting outcome. Eur J Cancer 35:1238–1247
Santa Ana EJ, Wulfert E, Nietert PJ (2007) Efficacy of group motivational interviewing (GMI) for
psychiatric in patients with chemical dependence. J Consult Clin Psychol 75:816–822
Schmitz JM, Oswald LM, Baldwin L, Grabowski J (1994) A survey of posthospitalization
treatment needs and preferences in cocaine abusers. Am J Addict 3:227–235
Schmitz JM, Oswald LM, Jacks SD, Rustin T, Rhoades HM, Grabowski J (1997) Relapse
prevention treatment for cocaine dependence: group vs. individual format. Addict Behav
22:405–418
Schmitz JM, Stotts AL, Mooney ME, Delaune KA, Moeller GF (2007) Bupropion and cognitive-
behavioral therapy for smoking cessation in women. Nicotine Tob Res 9:699–709
Smith SS, Jorenby DE, Fiore MC, Anderson JE, Mielke MM, Beach KE, Piasecki TM, Baker TB
(2001) Strike while the iron is hot: can stepped-care treatments resurrect relapsing smokers?
J Consult Clin Psychol 69:429–439
Sobell LC, Sobell MB, Agrawal S (2009) Randomized controlled trial of a cognitive-behavioral
motivational intervention in a group versus individual format for substance us disorders.
Psychol Addict Behav 23:672–683
Stephens RS, Roffman RA, Curtin L (2000) Comparison of extended versus brief treatments for
marijuana use. J Consult Clin Psychol 68:898–908
Telch MJ, Hannon R, Telch CF (1984) A comparison of cessation strategies for the outpatient
alcoholic. Addict Behav 9:103–109
Tucker T, Ritter A, Maher C, Jackson H (2004) A randomized control trial of group counseling in
a naltrexone treatment program. J Subst Abuse Treat 27:277–288
U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services
Administration, Center for Behavioral Health Statistics and Quality (2010) National survey of
substance abuse treatment services (N-SSATS): 2010. Data on substance abuse treatment facilities.
http://www.samhsa.gov/data/DASIS/2k10nssats/NSSATS2010Index.htm. Accessed 4 Feb 2013
Webb MS, de Ybarra DR, Baker EA, Reis IM, Carey MP (2010) Cognitive-behavioral therapy to
promote smoking cessation among African American smokers: a randomized clinical trial.
J Consult Clin Psychol 78:24–33
Weiss RD, Griffin ML, Greenfield SF, Najavits LM, Wyner D, Soto JA, Hennen JA (2000) Group
therapy for patients with bipolar disorder and substance dependence: results of a pilot study.
J Clin Psychiatry 61:361–367
Weiss RD, Jaffee WB, de Meil VP, Cogley CB (2004) Group therapy for substance use disorders:
what do we know? Harv Rev Psychiatry 12:339–350
Weiss RD, Griffin ML, Jaffee WB, Bender RE, Graff FS, Gallop RJ, Fitzmaurice GM
(2009) A “community-friendly” version of integrated group therapy for patients with bipolar disorder
and substance dependence: a randomized controlled trial. Drug Alcohol Depend 104:212–219
Weiss RD, Griffin ML, Kolodziej ME, Greenfield SF, Najavits LM, Daley DC, Doreau HR,
Hennen JA (2009) A randomized trial of integrated group therapy versus group drug counsel-
ing for patients with bipolar disorder and substance dependence. Am J Psychiatry 164:100–107
Zlotnick C, Johnson J, Najavits LM (2009) Randomized controlled pilot study of cognitive-
behavioral therapy in a sample of incarcerated women with substance use disorder and PTSD.
Behav Ther 40:325–336
From Research to Practice: The
International Implementation of 54
Multidimensional Family Therapy
Contents
54.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 891
54.2 MDFT in Europe: The History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 893
54.3 Facilitating MDFT Acceptance in European Youth Care Practice . . . . . . . . . . . . . . . . . . . . 895
54.3.1 Facilitating Interest Among Therapists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 895
54.3.2 The Treatment Agency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 896
H. Rigter (*)
Curium, Department of Child and Adolescent Psychiatry, Leiden University Medical Center,
Leiden, The Netherlands
e-mail: [email protected]
C. Rowe • H.A. Liddle
Department of Public Health Sciences, and Center for Treatment Research on Adolescent
Substance Abuse, University of Miami Miller School of Medicine, Miami, FL, USA
e-mail: [email protected]; [email protected]
A. Gantner
Therapieladen, Berlin, Germany
e-mail: [email protected]
K. Mos
De Jutters, Palmhuis, The Hague, The Netherlands
e-mail: [email protected]
P. Nielsen
Centre Adolescents et Jeunes Adultes, Fondation Phénix, Geneva, Switzerland
e-mail: [email protected]
O. Phan
Inserm U669, Université Paris-Sud et Paris Descartes, Paris, France
e-mail: [email protected]
P. Spapen
Department of Psychiatry, Brugmann University Hospital, Brussels, Belgium
e-mail: [email protected]
Abstract
To address a growing public health problem with youth cannabis use, five
Western European countries – Belgium, France, Germany, the Netherlands
and Switzerland – collaborated on a cannabis treatment research effort. After
deliberation, the research priority chosen was to implement and rigorously
evaluate a treatment program for adolescents with cannabis use
disorders – virtually unavailable in Western Europe at the time. Adolescent
cannabis use disorders were even denied by some policy makers as bona fide
public health problems. The most promising candidate for the treatment pro-
gram to be studied, based on cross-national expert analyses and an exhaustive
review of research findings to date, was Multidimensional Family Therapy
(MDFT), developed in the USA. When pilot training with candidate clini-
cians began, some claimed it was “too American.” Some did not understand
its innovation at first glance, stating that aspects of MDFT interventions were
already part of daily clinical work. Others worried whether the senior role
of psychiatrists would be jeopardized, and if the approach engaged in
too much outreach, and would be a threat to in-office work. Still others
said the model might be too practical, and ignore the need for depth-oriented,
psychodynamic treatment – still dominant in parts of Europe. While at the
outset MDFT presented as a cultural shock, concerns disappeared when
the approach was taught, attempted and integrated into the regular practice
settings. The multi-country randomized controlled trial was designed
with considerable discussion and collaboration. Referred to as
INCANT (International Cannabis Need of Treatment), this study, the first
independent replication of MDFT, showed that most adolescents with can-
nabis use disorders in these five countries have multiple behavioral problems,
including criminality, truancy and mental co-morbidity. MDFT proved to be
more effective than a high level treatment as usual in reducing cannabis
dependence and on other problem behavior measures as well. Positive out-
comes were seen in all the five countries. And given the clinical outcomes,
the therapist competence and fidelity outcomes, and the capacity of the sites
to absorb this new clinical approach, MDFT was found to be feasible
and adaptable to representative regular clinical care Western Europe settings,
adding expanded treatment alternative to standard care. The challenges
54 From Research to Practice 891
54.1 Introduction
Adolescent health, substance misuse and correlated problem behaviors have become
indisputable priorities on the global public health landscape (The Lancet 2012). But
due to many intersecting issues at multiple influence levels, over two decades of
scientific advances in adolescent intervention specialties have failed to yield wide-
spread dissemination of evidence-based approaches. Standard clinical practice for
drug involved youth around the world remains disconcertingly dissimilar from the
evidence-based interventions reported in research journals, practitioner reviews, pol-
icy recommendations, and science-based intervention registries. Effectiveness studies
and implementation trials in the adolescent treatment specialty are more frequent in
recent years (Becker and Curry 2008). And, cross-national surveys and basic science
research on youth substance misuse have added significantly to a useable knowledge
base. But relative to need, the research-rooted knowledge about effective interventions
remains underdeveloped, and at least in the treatment realm, collaborative transna-
tional controlled trials are rare. The multisite study of Multidimensional Family
Therapy (Multidimensional Family Therapy 2014a; Liddle 2010) is the first indepen-
dent replication of MDFT as well as, to the best of our knowledge, the only study of its
kind to date (Rigter et al. 2010, 2013; Schaub et al. 2014) – a multi-national controlled
trial of an evidence-based therapy for youth substance misuse. Although an instru-
mental part of the contemporary process to be sure, controlled studies cannot guaran-
tee transfer or dissemination of a program past a research project’s endpoint. This
article describes the implementation history, plan and outcomes of MDFT in Western
Europe (Rowe et al. 2013), a research-based treatment with significant dissemination
activity in the United States (Multidimensional Family Therapy 2014a) evolving into
an internationally established treatment program (European Monitoring Centre for
Drugs and Drug Addiction 2014b).
Before addressing implementation, we first outline key features of the clinical
approach. MDFT is a comprehensive, family-centered and developmentally-
oriented intervention for clinically-referred adolescents (Liddle 2010). The inter-
vention has strong outcomes for adolescent substance abuse and delinquency in
892 H. Rigter et al.
Fifteen years ago, EU member states were debating cannabis policy. Cabinet
members from five Western European countries (Netherlands, France, Belgium,
Switzerland and Germany) agreed that the discourse was uninformed due to
insufficient data on the effects of cannabis. A common cannabis research and
development project was commissioned to fill the gaps in knowledge. Rigter was
appointed project leader. A Steering Group was convened between 2000 and 2010
with representatives from the federal Ministries of Health in Belgium, Germany,
the Netherlands, Switzerland, and from the government substance abuse office in
France. Its work began by consulting experts from Australia, Europe, and the USA
to identify cannabis research priorities, which were jointly discussed in
a conference in Brussels (Spruit 2002). Based on expert recommendations,
a literature review, and the Steering Committee’s own deliberations, the evaluation
and implementation of a treatment program for adolescents with cannabis use
disorder was defined as the multi-national group’s principal priority.
This decision was not undisputed. Initially, some reported that in their countries,
adolescent cannabis use disorder was rarely seen, yet these countries lacked treat-
ment services specifically for youth or mechanisms to identify adolescents with
these problems. The Steering Committee opted for the aforementioned priority,
understanding that most adolescents with a cannabis use disorder also manifest
other problem behavior such as criminality and school failure, necessitating
a treatment program to focus not only on cannabis use, but on commonly related
problems as well (Spruit 2002).
Which treatment program was to be chosen? A systematic literature review was
conducted (Rigter et al. 2004), from which MDFT emerged as the superior treatment
candidate on the basis of its research evidence and clinical scope (Brannigan
et al. 2004; Vaughn and Howard 2004). Cannabis was targeted effectively in
MDFT studies in the US, and other elements of adolescent problem behavior were
changed as well (Rowe 2010). The Steering Committee opted for MDFT, and MDFT
developer Liddle agreed to collaborate. The Steering Group organized a meeting in
Zurich in 2004, where Liddle presented MDFT to a critical jury of high ranking
European addiction scientists. MDFT passed the test; the Steering Group decided to
test the effectiveness of MDFT in Western Europe, and if study results warranted,
follow the trial with implementation in practice. This research effort was named
INCANT – International Cannabis Need of Treatment study. Steering Group mem-
bers nominated outpatient clinical sites in their countries for participation in the
study. To assess site interest, and viability in terms of case flow and appropriateness,
clinicians’ background, research capacity, and infrastructure stability, Rigter, the
study Principal Investigator, Liddle and MDFT researcher and trainer Rowe made
screening visits to each prospective clinical center in early Summer 2004. The
selected sites for the multisite research included: Brugmann Hospital (an outpatient
substance abuse treatment department of a university hospital in Brussels, Belgium),
Centre Emergence (substance abuse treatment in Paris, France), Therapieladen
894 H. Rigter et al.
In Berlin, the authorities offered troubled youth a sheltered living arrangement with
pocket money, and some coercion to accept treatment as well (Rigter 2005).
Results of the randomized trial (n ¼ 450) showed that across sites, irrespective of
IP theoretical orientation, MDFT outperformed IP on major outcome measures.
Most prominent was the larger reduction of the rate of cannabis disorder for MDFT
participants compared with IP youth up to the 1 year follow-up (Rigter et al. 2013;
Schaub et al. 2014). Retention rates for MDFT participants were twice as high than
for IP adolescents (Rowe et al. 2013). This effect was consistent across all sites, and
these clinical outcomes and retention rates are consistent with the U.S.-based trials.
INCANT MDFT therapists demonstrated adherence and competence on treatment
fidelity measures, suggesting that MDFT could be adopted with strong adherence in
diverse cultures and systems in Western Europe (Rowe et al. 2013).
For many therapists, MDFT means stretching beyond one’s comfort zone: from
conducting one session once every 2 or 3 weeks to doing several sessions per week;
from scheduling sessions at the office to also seeing the family at their home and in
the community; from a focus on one disorder or problem behavior to
a comprehensive approach; from solely treatment sessions to treatment plus case
management extending to all major domains in the life of an adolescent.
Difficulties in changing practice patterns are always a worry in evidence based
therapy transfer. In the case of the Netherlands, for instance, we met with genuine
interest from therapists all over the country. Some clinicians had their interest piqued
by word-of-mouth, or by video-intensive presentations by INCANT MDFT thera-
pists. Dissatisfaction with the outcomes and limited scope of their own professional
work might have been another reason therapists were curious about and open to
MDFT. The appeal of working in teams – as defined in MDFT – was another
influential factor. Clinicians also learned that they could have a role in expanding
MDFT services, which helped in committing them to the treatment program. Our
subsequent experience with Finland has been similar in these ways.
896 H. Rigter et al.
In discussing the challenges and worries about the transfer potential of North
American based prevention intervention programs in Europe, Burkhart (2013)
sheds considerable light on a still to be fully illuminated process. We have also
concluded that these idiosyncratic responses to an intervention’s philosophy, clin-
ical features, even training requirements and methods are among the probably many
germane intervention characteristics. In France and Switzerland, for instance, we
found psychodynamic traditions to remain influential and that adoption of more
practical, family systems, and outcome-oriented treatment programs such as MDFT
can be a stretch. Initially, concerns were voiced that one’s freedom as a therapist
could be curtailed by following a treatment manual. Clinical presentations by
INCANT MDFT staff emphasized the how-to aspects of the approach. Aspects of
clinicians’ current thinking, practice habits, and previous training were used as
ways to learn about a new approach. But vital to the clinician change process was
a supportive and guiding type of supervision to help therapists with cases in their
own clinical settings. Hardly a simple administrative decision, implementation
involves multiple and intersecting processes within an organization or system of
care. At the therapist level, changing a clinical mind set may involve direct or
indirect challenges to ingrained views, and transforming treatment paradigms by
offering training in and considerable support to learn new methods.
Perhaps there was a time when researchers believed that publication of study
outcomes will yield recommendation adoption. But experience and the burgeoning
literature in specialties such as implementation science demonstrate the complexity
of practice change. Scientific journals do not target clinicians. Therapists need to be
informed in terms relevant for daily practice. We have written MDFT materials in
Dutch, English, German and French. We also produced a DVD with basic facts
about MDFT and with interviews with an adolescent and his mother, therapists, and
a juvenile judge (in Dutch, with English and German subtitling; see video at
Multidimensional Family Therapy 2014d). Country-specific websites offer informa-
tion for therapists and centers (and for teenagers and parents); see for instance
(Multidimensional Family Therapy 2014e). Following a community of practice
model, we update MDFT information through e-mails, e-newsletters, social media,
and face to face substantive clinical meetings for therapists. But as has been the case
in MDFT’s dissemination in North America, materials play only a supporting role in
influencing clinicians. Therapists and managers of treatment agencies experience the
worth of MDFT during on-site visits. Videos demonstrate the approach in action,
and live sessions with local clinicians being coached in the main MDFT methods
seem critical to address their particular realities and questions. As in MDFT itself,
relationships and gaining hands-on experience with the approach are instrumental.
Multiple factors and levels of process interact with therapist variables to create
a context of receptivity and change in adopting an evidence-based program.
54 From Research to Practice 897
The treatment agency, particularly the manager of the department where the MDFT
team will be housed, are key in this regard. Although often interested in MDFT,
managers are challenged to integrate this program, or any program for that matter,
into local routines and financial structures. We facilitate this integration, a systems
intervention in and of itself, in various ways. Implementation staff visit the man-
agement of a treatment center a few times before the contract for training is signed,
and afterwards once every 6 months. In the Netherlands, we also convene regular
meetings with all managers together. Topics of discussion include:
(a) reimbursement of MDFT; (b) where and how to enroll cases to be treated with
MDFT (referral policies, relationships with other treatment sectors); (c) how to
arrange coverage for MDFT therapists to be available after regular working hours
without violating labor regulations; (d) ethical and legal issues, including the
protection of the privacy of clients; and (e) treatment innovation. This is all critical
for implementation success. We are extending this systematic approach of admin-
istrative collaboration to other European countries.
In all Western European countries where MDFT is being implemented, treat-
ment agencies are facing a mix of public and private policies. In the Netherlands, an
agency has some leeway to choose its own course in offering treatments. In
Belgium, MDFT was to be paid through federal or regional government budgets
as long as the treatment was deemed ‘experimental’ – and anything not performed
by a medical doctor will remain experimental for a long time. In Flanders at least,
treatment agencies now have more freedom to opt for MDFT if insurance compa-
nies agree to pay the bill. In Germany in 2012, the federal government opened
positions for treatment centers to take part in an MDFT implementation project.
Major adolescent substance abuse treatment centers did apply (in Cologne, Dres-
den, Hamburg and Munich) and are now part of a four-center implementation
effort. Without the government subsidy, these agencies would not have signed up
for MDFT. Treatment innovation is difficult in Germany, because local, state and
federal authorities and insurance agencies – although all supporting MDFT by
now – are in deadlock about who is to take the initiative to get MDFT established
and financed. An additional complication is that in Germany, therapists are
expected to pay from their own pocket for any training in a new treatment program.
In all other Western European countries, the treatment agency pays to train an entire
MDFT team. Implementation of MDFT in Germany is proceeding, but future
prospects – when the federal subsidy ends – are uncertain. Of note, too, is the
position of national professional organizations, such as in Germany, the German
Association for Systems Therapy and Family Therapy (DGSF). In a systematic
literature review carried out under the umbrella of DGSF (Von Sydow et al. 2007),
MDFT was found to be an effective therapy. DGSF is in favor of giving
MDFT a place within the DGSF framework, but MDFT concepts need to be
harmonized with DGSF concepts first, and this will take time. Terms like ‘super-
visor’ have different meanings in MDFT and DGSF contexts. MDFT accreditation
by DGSFT is necessary to convince therapists to personally pay for training
in MDFT.
898 H. Rigter et al.
In France, the INCANT trial and ongoing liaison efforts of the MDFT team
leader (Phan) combined to convince government services (MILDT; and the Minis-
tries of Health and Justice) to support MDFT after the research study ended.
Adolescent substance abuse centers were willing to meet a call to have teams of
therapists trained in MDFT, with subsidy from MILDT. Teams are in training in
Lille and Dijon. Teams focusing on forensic or residential care will follow in the
suburbs of Paris. The aim of the French government is to have at least one MDFT
team per region (country).
All in all, implementing a treatment program in a country requires adequate
knowledge of national, regional and local policies and politics. Local experts must
be fully on board. For lasting implementation, it does not suffice to have good
research data or to win over therapists; one also needs the enduring support of the
management of treatment centers and of policy makers at all levels of the youth care
sector. One needs to have staff to make this happen, and to pay for that staff, one
needs funding capital. In the Netherlands, we were fortunate to secure charity
funding. All other European MDFT countries, except Finland, rely on government
subsidies so far, which is insecure in times of economic crisis.
Implementing MDFT in Europe was a joint aim of the MDFT experts at CTRADA
and pioneers in Europe, headed by Rigter. MDFT developers saw throughout the
INCANT pilot and trial that MDFT would disseminate throughout Europe only if
the MDFT leaders in each country experienced personal ownership – a sense of
being pioneers themselves. Rigter established “MDFT Academy” in 2008, a Dutch-
based foundation to offer MDFT training to teams of therapists in Europe. Liddle
granted MDFT Academy the free-of-charge right to train MDFT teams in Europe,
provided training principles and procedures would conform to established MDFT
standards developed in research trials and applied in US-based implementation
efforts. MDFT representatives from Western European countries founded “MDFT
Europe” in 2010, a body for agreeing on MDFT (training) practices in Europe in
order to ensure consistency and uniformity.
It is made clear from the outset what it takes for a treatment institute to offer
MDFT. MDFT Academy uses a set of MDFT program requirements as formulated
in the MDFT manual (Liddle 2007). All MDFT supervisors and therapists must
be certified (see below). Candidates for MDFT therapist training must
have a university (usually psychiatrist, psychologist, pedagogue) or college
(social work) degree, with additional education in psychosocial therapy. They
need to have at least 3 years of experience in treating adolescents and have
a basic knowledge of family therapy. An MDFT therapist is pragmatic,
non-judgmental, skilful in communication, willing to work irregular hours, and
receptive to feedback, seeing that there is always more to be learned. He or she is
open to teamwork, intervision and supervision. The same is true of a MDFT
supervisor, who also should have leadership skills.
54 From Research to Practice 899
54.3.4 Training
Important are (a) the course materials, and (b) the training interventions. The key
training document is the MDFT Manual (Liddle 2007) and accompanying pro-
tocols, which have been translated in European languages (Dutch, German, French)
and adapted to local practice (e.g., regulations, referral mechanisms, assessment
tools as used by youth probation officers and other professionals).
American and European trainers use parallel presentation materials, core MDFT
videos, and written case vignettes to cover the introductory didactic training.
Instruction DVDs target the same topics, but key treatment sessions shown for
training purposes are increasingly from local (Dutch, German, etc.) practice.
Training interventions include plenary content and protocol review days (all
trainees come together); the systematic evaluation of treatment session recordings
for MDFT adherence and competence, and of supervision session recordings for
supervision skills; regular site visits by the MDFT trainer to the MDFT team for
on-site case review and other feedback; regular consultation telephone calls
between the trainer and the supervisor and the whole team; annually, fully
documenting 1 case by the trainee (session planning, case assessment, treatment
plan) with feedback from the trainer; an extensive written exam; and booster
training of the team and, separately, of the supervisor.
The full training in MDFT takes 2 years. The Basic Level certificate is issued at the
end of Year 1, the Master Level certificate after Year 2.
In Europe, teams with at least three Master Level certified members receive
a free-of-charge license to practice MDFT. Once every 3 years, teams are required
to refresh their license, allowing MDFT Academy to check if MDFT is still carried
out properly.
54.3.6 Trainers
MDFT trainers achieve their status by developing through the ranks, first as an
MDFT therapist, then supervisor, before being invited for trainership. Trainers are
trained by G. Dakof (Multidimensional Family Therapy 2014b) and by MDFT
Academy. At present, there are 8 Dutch trainers, 1 Flemish and 1 French-speaking
trainer in Belgium, 3 trainers in Germany, 1 in France, and 1 in Switzerland.
Between 2008 and Spring 2013, 35 Dutch teams have been trained in MDFT or are
presently in training. Add to this number 2 teams in Belgium, 5 in Germany,
900 H. Rigter et al.
5 in Finland, 5 in France, and 1 in Sweden, and the European total approximates 60.
There are 50 teams in the United States, yielding 110 MDFT teams worldwide.
As is the case in the U.S. uptake of MDFT, the European teams originate not
only from addiction treatment, but also from youth care, mental health, and forensic
settings. In Europe, MDFT has evolved beyond the narrow connotation of being an
addiction treatment. In accordance with the evidence base, MDFT is seen as
a treatment program for adolescents with diverse, often multiple problem behavior,
regularly including delinquency and substance abuse.
54.3.8 Accreditation
54.3.9 Reimbursement
Accreditation is the green light for funding agencies to pay for a treatment program.
MDFT is now being paid from all relevant reimbursement schemes in the
54 From Research to Practice 901
Netherlands and Finland, including government sources and private health and
social insurance companies. It is being funded by the (federal) governments in
Belgium, Germany and France, yet a challenge here is to convince insurance
companies and local authorities to take over reimbursing MDFT.
54.3.10 Innovation
54.4 Conclusion
One might say that these other European countries could replicate the Dutch
model, but this would be a misapprehension of implementation realities. The exact
path traveled in the Netherlands will not necessarily work in Belgium, Finland,
France, Germany, Switzerland, or any other country. Implementation should
always acknowledge the basic principles of the treatment program but procedures
must and can be adapted to local circumstances.
International collaboration can speed up implementation. There is close working
relationship between European stakeholders in disseminating MDFT and setting
quality standards, and there is tight collaboration between Europe and the source of
MDFT, the USA (www.mdft.org). Important here has been the decision of the
MDFT personnel to consider this treatment program as a public asset rather than
a commercial product.
The implementation outcomes of MDFT in a European context discussed in this
chapter and elsewhere (Rowe et al. 2013) add to published reports of MDFT
implementation in the U.S. (Liddle et al. 2002, 2006). These studies showed that
MDFT can be successfully transported to usual care American juvenile justice,
mental health, and addiction care settings with multi-ethnic youth presenting with
a range of problem behaviors (substance abuse, delinquency, symptoms of other
mental and behavioral disorders), and taught to staff from various professional
backgrounds (psychiatrists, psychologists, social workers, nurses, juvenile justice
court staff, judges, lawyers) (Liddle et al. 2006).
The pursuit of international projects that have included independent replication of
previous outcomes contributes to a treatment system’s development, and offers
another metric by which its usefulness can be assessed. The knowledge base about
how an intervention should and can be adapted, culturally, emerging institutionally
(systems of care), or procedurally (intervention structure, methods), are in an early
developmental stage. Although guidance is emerging about the international transport
of evidence-based interventions, numerous controversies have been specified as well
(Andréasson 2010). International work, like travel in general (De Botton 2002), offers
perspective and insight unavailable at home. In the case of MDFT, the international
implementation described in this chapter offers a case study of the complex and
sensitive intervention adoption process. This effort has enriched our knowledge of the
change principles that guide clinical work with adolescents and families across
cultures and settings, and our dissemination work as well.
References
Andréasson S (2010) Premature adoption and dissemination of prevention programmes. Addiction
105(4):583–584
Becker SJ, Curry JF (2008) Outpatient interventions for adolescent substance abuse: a quality of
evidence review. J Consult Clin Psychol 76(4):531–543
Brannigan R, Schackman BR, Falco M, Millman RB (2004) The quality of highly regarded
adolescent substance abuse treatment programs: results of an in-depth national survey. Arch
Pediatr Adolesc Med 158(9):904–909
54 From Research to Practice 903
Burkhart G (2013) North American drug prevention programmes: are they feasible in European
cultures and contexts? European monitoring centre for drugs and drug addiction. Publications
Office of the European Union, Luxembourg
California Evidence-Based Clearinghouse (2012) Multidimensional Family Therapy (MDFT).
Retrieved from http://www.cebc4cw.org/program/multidimensional-family-therapy/
Center for Treatment Research on Adolescent Substance Abuse (CTRADA) (2014) Center for
treatment research on adolescent substance abuse website. Retrieved from http://www.med.
miami.edu/ctrada/
Crime Solutions: National Institute of Justice- Office of Justice Programs (2012) Multidimensional
Family Therapy. Retrieved from http://www.crimesolutions.gov/ProgramDetails.aspx?ID¼267
De Botton A (2002) The art of travel. Random House, New York
Diamond GS, Liddle HA, Wintersteen MB, Dennis ML, Godley SH, Tims F (2006) Early
therapeutic alliance as a predictor of treatment outcome for adolescent cannabis users in
outpatient treatment. Am J Addict 15:26–33
Division 53 American Psychological Association (2012) Effective child therapy: evidence-based
mental health treatment for children and adolescents. Retrieved from http://effective-
childtherapy.com/content/substance-abuse
European Monitoring Centre for Drugs and Drug Addiction (2014a) Retrieved from http://www.
emcdda.europa.eu/publications/emcdda-papers/multidimensional-family-therapy-review
European Monitoring Centre for Drugs and Drug Addiction (2014b) European monitoring centre
for drugs and drug addiction website. Retrieved from http://www.emcdda.europa.eu/
Fogel A, Thelen E (1987) Development of early expressive and communicative
action: reinterpreting the evidence from a dynamic systems perspective. Dev Psychol
23(6):747–761
Godley SH, Godley MD, Wright KL, Funk RR, Petry NM (2008) Contingent reinforcement of
personal goal activities for adolescents with substance use disorders during post-residential
continuing care. Am J Addict 17(4):278–286
Gottlieb G (1991) Epigenetic systems view of human development. Dev Psychol 27(1):33–34
Granic I, Hollenstein T (2003) Dynamic systems methods and models for developmental
psychopathology. Dev Psychopathol 15(3):641–669
Henderson CE, Rowe CL, Dakof GA, Hawes SW, Liddle HA (2009) Parenting practices as
mediators of treatment effects in an early-intervention trial of Multidimensional Family
Therapy. Am J Drug Alcohol Abuse 35(4):220–226
Henderson CE, Dakof GA, Greenbaum PE, Liddle HA (2010) Effectiveness of Multidimensional
Family Therapy with higher severity substance-abusing adolescents: report from two
randomized controlled trials. J Consult Clin Psychol 78(6):885–897
Henderson CE, Marvel F, Liddle HA (2011) Multidimensional family therapy: an evidence-based
treatment for juvenile justice involved and substance abusing adolescents. In: Jainchill N (ed)
Understanding and treating adolescent substance use disorders. Civic Research Institute,
Kingston, NJ
Hogue A, Liddle HA (2009) Family-based treatment for adolescent substance abuse: controlled
trials and new horizons in services research. J Fam Ther 31(2):126–154
Hogue A, Henderson CE, Dauber S, Barajas PC, Fried A, Liddle HA (2008) Treatment adherence,
competence, and outcome in individual and family therapy for adolescent behavior problems.
J Consult Clin Psychol 76(4):544–555
Hogue A, Dauber S, Henderson CE (2014) Therapist self-report of evidence-based practices in
usual care for adolescent behavior problems: factor and construct validity. Adm Policy Ment
Health Ment Health Serv Res 41(1):126–139
Liddle HA (1999) Theory development in a family-based therapy for adolescent drug abuse. J Clin
Child Psychol 28(4):521–532
Liddle HA (2007) Multidimensional Family Therapy for adolescent substance abuse and
delinquency: treatment manual. University of Miami, Center for Treatment Research on
Adolescent Drug Abuse, Miami
904 H. Rigter et al.
Liddle HA (2010) Treating adolescent substance abuse using Multidimensional Family Therapy.
In: Weisz J, Kazdin A (eds) Evidence-based psychotherapies for children and adolescents.
Guilford Press, New York, pp 416–432
Liddle HA, Rigter H (2013) How developmental research and contextual theory drive clinical
work with drug using adolescents. Harv Rev Psychiatry 21(4):200–204
Liddle HA, Rowe CL, Quille TJ, Dakof GA, Mills DS, Sakran E, Biaggi H (2002)
Transporting a research-based adolescent drug treatment into practice. J Subst Abuse Treat
22:231–243
Liddle HA, Rowe C, Gonzalez A, Henderson C, Dakof GA, Greenbaum PE (2006) Changing
provider practices, program environment, and improving outcomes by transporting
Multidimensional Family Therapy to an adolescent drug treatment setting. Am J Addict
15:102–112
Multidimensional Family Therapy (2014a) MDFT international website. Retrieved from www.
mdft.org
Multidimensional Family Therapy (2014b) MDFT international website. Retrieved from http://
www.mdft.org/About/Leadership-team-of-MDFT-International
Multidimensional Family Therapy (2014c) MDFT international website. Retrieved from http://
www.mdft.org/About/Program-history
Multidimensional Family Therapy (2014d) MDFT international website. Retrieved from http://
www.mdft.org/Resources/Videos
Multidimensional Family Therapy (2014e) MDFT Netherlands website. Retrieved from http://
www.mdft.nl
Phan O, Henderson CE, Angelidis T, Weil P, van Toorn M, Rigter R, Soria C, Rigter H (2011)
European youth care sites serve different populations of adolescents with cannabis use
disorder. Baseline and referral data from the INCANT trial. BMC Psychiatry 11:110
Rigter H (2005) Report on the INCANT pilot study: the feasibility of Multidimensional Family
Therapy in European context as a treatment for troubled adolescents misusing cannabis and
possibly other substances. Erasmus MC, Rotterdam. http://incant.eu
Rigter H, van Gageldonk A, Ketelaars T, van Laar M (2004) Hulp bij probleemgebruik van drugs.
Trimbos-instituut/NDM, Utrecht (Interventions for problematic use of drugs)
Rigter H, Pelc I, Tossmann P, Phan O, Grichting E, Hendriks V, Rowe C (2010) INCANT:
a transnational randomized trial of Multidimensional Family Therapy versus treatment as usual
for adolescents with cannabis use disorder. BMC Psychiatry 10(1):28
Rigter H, Henderson CE, Pelc I, Tossman P, Phan O, Hendriks V, Schaub M, Rowe CL (2013)
Multidimensional Family Therapy lowers the rate of cannabis dependence in adolescents:
a randomised controlled trial in Western European outpatient settings. Drug Alcohol Depend
130(1–3):85–93
Rowe CL (2010) Multidimensional Family Therapy: addressing co-occurring substance abuse and
other problems among adolescents with comprehensive family-based treatment. Child Adolesc
Psychiatr Clin N Am 19(3):563–576
Rowe C, Rigter H, Henderson C, Gantner A, Mos K, Nielsen P, Phan O (2013) Implementation
fidelity of Multidimensional Family Therapy in an international trial. J Subst Abuse Treat
44:391–399
Schaub MP, Henderson CE, Pelc I, Tossmann P, Phan O, Hendriks V, Rowe C, Rigter H (2014)
Multidimensional Family Therapy decreases the rate of externalising behavioural disorder
symptoms in cannabis abusing adolescents: outcomes of the INCANT trial. BMC Psychiatry
14(1):26
Schmidt SE, Liddle HA, Dakof GA (1996) Changes in parenting practices and adolescent drug
abuse during Multidimensional Family Therapy. J Fam Psychol 10(1):12–27. doi:10.1037/
0893-3200.10.1.12
Sherman C (2010) Multidimensional Family Therapy for adolescent drug abuse offers broad,
lasting benefits: an approach that integrates individual, family, and community interventions
outperformed other treatments. NIDA Notes 23(3):13–15
54 From Research to Practice 905
Spruit IP (2002) Cannabis 2002 report. Ministry of Public Health of Belgium, Brussels
Substance Abuse and Mental Health Services Administration (2014) NREPP Substance abuse and
mental health services administration website. Retrieved from http://www.samhsa.gov/
The Lancet (2012) Editorial: putting adolescents at the centre of health and development. Lancet
379(9826):1561
Thelen E, Smith LB (1994) A dynamic systems approach to the development of cognition and
action. Bradford Books/MIT Press, Cambridge, MA
Vaughn MG, Howard MO (2004) Adolescent substance abuse treatment: a synthesis of controlled
evaluations. Res Soc Work Pract 14(5):325–335
Von Sydow K, Beher S, Retzlaff R, Schweitzer J (2007) Die Wirksamkeit der systemischen
Therapie/Familietherapie. Hogrefe, Göttingen
Von Sydow K, Retzlaff R, Beher S, Haun MW, Schweitzer J (2013) The efficacy of systemic
therapy for childhood and adolescent externalizing disorders: a systematic review of 47 RCT.
Fam Process 52(4):576–618
Williams RJ, Chang SY (2000) A comprehensive and comparative review of adolescent substance
abuse treatment outcome. Clin Psychol Sci Pract 7(2):138–166
Zavala SK, French MT, Henderson CE, Alberga L, Rowe C, Liddle HA (2005) Guidelines and
challenges for estimating the economic costs and benefits of adolescent substance abuse
treatments. J Subst Abuse Treat 29(3):191–205
Couples Therapy in Treatment of
Alcoholism and Drug Abuse 55
Timothy J. O’Farrell
Contents
55.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 908
55.2 Behavioral Couples Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 908
55.2.1 Description of the Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 908
55.2.2 Evidence to Support the Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 920
55.2.3 International Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921
55.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 923
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 924
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 925
Abstract
Couples therapy has been developed and studied as an approach to treating
married or cohabiting individuals seeking help for alcoholism or drug abuse,
starting in the 1970s. Behavioral Couples Therapy (BCT) is a specialized form
of couples therapy that has received substantial research support. BCT sees
the substance-abusing patient together with the spouse or live-in partner for
outpatient couple counseling sessions. BCT aims to build support for abstinence
Author Note: This chapter is adapted from a clinical guideline developed for the Behavioral
Health Recovery Management project, a project of Fayette Companies, Peoria, IL, and Chestnut
Health Systems, Bloomington, IL, that was funded by the Illinois Department of Human Services’
Office of Alcoholism and Substance Abuse. This chapter also draws heavily from the book
Behavioral Couples Therapy for Alcoholism and Drug Abuse, copyright 2006 by Guilford Press.
Material is used with permission from Fayette Companies and from Guilford Press. Preparation of
this article also was supported by the US Department of Veterans Affairs.
T.J. O’Farrell
Families and Addiction Program, VA Boston Healthcare System, Harvard Medical School,
Brockton, MA, USA
Department of Psychiatry, VAMC, Harvard Medical School, Brockton, MA, USA
Department of Psychiatry, VA Boston Healthcare System, Harvard Medical School, Brockton,
MA, USA
e-mail: [email protected]
55.1 Introduction
Historically, alcoholism and drug abuse have been viewed as individual problems
best treated on an individual basis. However, over the past 35 years, there has been a
growing recognition that couple and family relationship factors often play a crucial
role in understanding and treating substance abuse. Behavioral Couples Therapy
(i.e., “BCT”) for alcoholism and drug abuse is one approach that has developed out
of this recognition.
Viewed from a couple perspective, there are several antecedent conditions
and reinforcing consequences of substance use. Poor communication and
problem-solving, arguing, lying and distrust, financial stressors, and nagging are
common antecedents to substance abuse. Additionally, caretaking by the
non-substance-abusing spouse following drinking or drug use can inadvertently
reinforce substance use. Further, spouses’ resentments, while understandable, can
lead to ignoring rather than reinforcing abstinence. BCT was designed to address
these couple factors in the recovery process.
a daily trust discussion ritual to reward abstinence. BCT improves the relationship
with techniques for increasing positive activities and improving communication.
BCT also fits well with 12-step or other self-help groups, individual or group
substance abuse counseling, and recovery medications. BCT can be easily inte-
grated into a variety of orientations to addiction treatment, including 12-step and
cognitive-behavioral addiction programs.
BCT is founded on two fundamental assumptions. First, family members can
reward abstinence. Second, relationship distress and conflict are powerful triggers
for substance abuse and reduction of these triggers improves treatment outcomes.
BCT typically consists of 12–20 weekly outpatient couple sessions over a 3–6-
month period. Generally, couples are married or cohabiting for at least a year,
without current psychosis, and one member of the couple has a current problem
with alcoholism and/or drug abuse. The couple starts BCT soon after the substance
abuser seeks help. BCT can start immediately after detoxification or a short-term
intensive rehab program or when the substance abuser seeks outpatient counseling.
The remainder of this section on clinical procedures for BCT is written in the form
of instructions to a counselor who wants to use BCT.
session and agrees to try it each day for the coming week at home. In the next BCT
session, if they did it faithfully at home, the couple signs the contract for a specific
time period. In each subsequent BCT session, the counselor reviews the
contract performance in the past week and the couple does the trust discussion in
session to highlight its importance. Self-help meetings, drug urine screens for
patients with a current drug problem, and recovery-related medication are part of
the contract for many patients – each activity helps the patient stay abstinent and
demonstrates to the spouse the patient’s commitment to abstinence and a changed
lifestyle.
It is important for couples to see that the recovery contract does not conflict with
12-step beliefs. For patients, stating that they do not intend or plan to drink or use
drugs in the next 24 h does not constitute a guarantee or conflict with having
a disease over which they are powerless. For spouses, being part of the trust
discussion or observing the patient take recovery medication in no way makes
them responsible for the patient’s recovery.
Fig. 55.1 Recovery contract and calendar for Mary and Jack (Reprinted from O’Farrell and
Fals-Stewart (2006), p. 48. Used with permission)
55 Couples Therapy in Treatment of Alcoholism and Drug Abuse 913
Both wanted to “quit for good” to get their three school-age children back. Sue’s
parents were given temporary custody when Gene was arrested for drunk-driving.
Sue, also intoxicated, and the kids were in the car. Sue and Gene had 6 months of
weekly BCT. Their “dual recovery contract” shown in Fig. 55.2 had (1) a daily trust
discussion, (2) taking Antabuse daily together, (3) three AA meetings per week, and
(4) weekly urine screens.
About 5 weeks after starting BCT, Sue used cocaine on Friday night when she went
to the local bar with a girlfriend. At the next BCT session, her urine was positive for
Fig. 55.2 Recovery contract and calendar for Sue and Gene, a dual-problem couple (Reprinted
from O’Farrell and Fals-Stewart (2006), p. 201. Used with permission)
55 Couples Therapy in Treatment of Alcoholism and Drug Abuse 915
cocaine. The following Friday, they were both found in the bar. They planned to just
socialize, but when cocaine was offered, they did not refuse, but just did one line of
cocaine each. The next night, they went to the bar again and each used multiple lines
of cocaine. This relapse was a turning point. They got more committed to their
recovery. They planned things to do Friday and Saturday nights, starting with an
AA meeting together on Friday night. Each got a sponsor and some sober friends.
After weekly BCT, they had quarterly checkups for two more years. They
regained custody of their children and stayed abstinent except for a few isolated
days for Gene and a 5-day relapse for Sue, which led to a few crisis sessions with
the BCT counselor to help them get back on track.
Caring Day
In the caring day assignment, each person plans ahead to surprise their partner with
a day when they do some special things to show their caring. This can involve doing
a number of little things throughout the day or a bigger, special gesture of caring.
55 Couples Therapy in Treatment of Alcoholism and Drug Abuse 917
This is important because the stress and unhappiness of living with substance
abuse often causes partners to hold back caring actions and feelings out of anger and
disappointment. Therefore, active efforts like caring day are needed to increase
caring and to help repair the damage done to the relationship by the substance
abuse and other problems. The BCT therapist encourages each partner to take
risks and to act lovingly toward the spouse rather than wait for the other to make
the first move.
Listening Skills
Effective listening helps each spouse to feel understood and supported. It slows
down couple interactions to prevent quick escalation of angry exchanges. The
listener restates and checks the accuracy of the message received from the speaker
(What I heard you say was __________. Did I get that right?). When the listener
has understood the speaker’s message, roles change and the first listener
then speaks. Teaching a partner to communicate support and understanding by
summarizing the spouse’s message and checking the accuracy of the received
message before stating their own position is often a major accomplishment that
has to be achieved gradually.
After presenting the rationale and instructions, the therapist models correct and
incorrect ways of expressing feelings and elicits the couple’s reactions to these
modeled scenes. Then, the couple role-plays a communication session in which
spouses take turns being speaker and listener, with the speaker expressing feelings
directly and the listener using the listening response. During this role-playing, the
therapist coaches the couple as they practice reflecting the direct expressions of
918 T.J. O’Farrell
feelings. Next, the therapist assigns for homework similar communication sessions,
10 to 15 min each three to four times weekly. Subsequent therapy sessions
involve more practice with role-playing, both during the BCT sessions and for
homework.
Communication Sessions
These are planned, structured discussions used for in-session and at-home practice
of communication skills. The couple talks privately, face-to-face, without distrac-
tions. Each spouse takes turns expressing their point of view without interruptions.
The therapist discusses with the couple when and where they plan to have their
assigned communication practice sessions. Assess the success of this plan at the
next session, and suggest any needed changes. Just establishing a communication
session as a method for discussing feelings, events, and problems can be very
helpful for many couples.
Communication training in BCT starts with positive or neutral topics and
then switches to real problems, first on less sensitive issues and finally working
up to major charged issues. Before the couple learns how to negotiate charged
issues “on their own,” the BCT therapist is a very active negotiator, problem-solver,
and guide to help the couple find at least temporary solutions to heated conflicts that
arise.
After weekly BCT ends, couple checkup visits with the counselor every few
months for an extended period can encourage continued progress. These ongoing
contacts can review the couple’s success with continuing activities to promote
recovery and with their action plan to prevent or minimize relapse. These contacts
also help to evaluate whether there is a need for additional BCT sessions.
Couples who have more severe problems or who had trouble during weekly BCT
sessions may benefit from more frequent “booster session” contacts in the year after
weekly BCT ends. Such BCT booster sessions seek to maintain gains achieved
during weekly BCT, deal with problems that are still unresolved or that emerge
later, and prevent or minimize relapse (O’Farrell 1993). Research shows that BCT
with booster sessions produces better drinking outcomes than standard BCT, with
the benefits of BCT booster sessions especially evident for couples with more
severe addiction problems (O’Farrell et al. 1998).
Finally, continued contacts with the couple can address relationship issues still
unresolved or those that emerge later. This is important because many substance
abusers continue to have relationship problems even after a period of stable
abstinence has been established, and couple and family issues often appear after a
period of recovery.
Most of the research on BCT has focused on two primary outcomes, namely,
substance use and relationship functioning. This is understandable, given that
BCT for substance abuse is designed primarily to have a direct effect on these
areas of functioning. However, studies show that BCT has broader effects on
important secondary outcomes, including reduced partner violence and improved
adjustment for children of couples getting BCT. These are called secondary
outcome domains, not to diminish their importance but rather to signify that these
outcomes were not the primary targets of the initial BCT intervention.
reduced in the first and second year after BCT and nearly eliminated with absti-
nence. O’Farrell et al. (2004) found that in the year before BCT, 60 % of alcoholic
patients had been violent toward their female partner, five times the comparison
sample rate of 12 %. In the year after BCT, IPV decreased significantly to 24 % of
the alcoholic sample but remained higher than the comparison group. Among
remitted alcoholics after BCT, IPV prevalence of 12 % was identical to the
comparison sample. Results were similar for the second year after BCT. An earlier
second study of male alcoholics (O’Farrell and Murphy 1995) found nearly iden-
tical results as the first study. A third study (Schumm et al. 2009) found an identical
pattern of reduced IPV after BCT with female alcoholic patients.
These three studies show very substantial reductions in IPV in the first and
second year after BCT. Using structural equation modeling, O’Farrell et al. (2004)
found that these IPV reductions most likely result from BCT primary outcomes of
reduced drinking and improved relationships. In other words, greater sobriety and
better communication after BCT reduce IPV.
Most of the research on BCT has been done in the USA. Four BCT studies have
been done internationally outside the USA, in Canada, India, the Netherlands, and
Australia.
922 T.J. O’Farrell
55.2.3.1 Canada
O’Farrell et al. (2010) successfully transported a BCT program from Boston where
it had been researched to a community clinic in Calgary. On-site BCT training in
Calgary was followed by telephone consultations for 6 months. A quasi-
experimental evaluation compared outcomes of (a) 38 alcoholic patients who
received BCT plus treatment as usual (TAU) with (b) 33 alcoholic patients who
received TAU only. The latter group was referred to the BCT program but did
not enter it due to logistics or refusal. At baseline, the two groups were similar
on demographics, substance use, relationship problems, and comorbid mood or
anxiety diagnoses. At 6-month follow-up, patients treated in BCT, as compared to
patients who got TAU only, were significantly more likely to be abstinent
from alcohol and drugs and together rather than separated and to have higher
relationship adjustment scores. Implementation of BCT was considered successful
because BCT had better outcomes than individual-based TAU as expected
from controlled trials of BCT and because the BCT program in Calgary continues
to operate.
55.2.3.2 India
Nattala et al. (2010) randomized 90 male alcohol-dependent patients admitted for
3 weeks at an inpatient facility in Bangalore to either (a) dyadic relapse prevention
(DRP), (b) individual relapse prevention (IRP), or (c) TAU. In DRP, which was
based on BCT treatment manuals from the USA, both the patient and a family
member (75 % spouses) planned and rehearsed how the dyad could work together to
prevent relapse. IRP also focused on preventing relapse, but only the individual
patient took part. Monthly follow-ups encouraged progress and collected outcome
data for 6 months after leaving the treatment center. Results for this 6-month period
showed that DRP performed better than IRP and TAU on quantity of alcohol
consumed, drinking days, and family problems. The authors concluded that their
study provided evidence for the effectiveness of Western-based family-oriented
intervention for alcohol-dependent patients in India.
BCT sessions used in this study, whereas many other studies have used 50–60-min
BCT sessions (e.g., O’Farrell et al. 1998) the same as used for CBT.
55.2.3.4 Australia
Halford et al. (2001) in Brisbane randomly assigned 61 women whose husbands drank
heavily but were not currently in alcohol treatment to BCT, supportive counseling, or
stress management. All three treatments eased the wife’s emotional distress, but neither
BCT nor the other treatments improved the man’s drinking or the couple’s relationship.
The lack of impact of BCT is not surprising when one considers that BCT has always
been studied when the alcoholic has already sought help, not as a method for engaging
treatment-resistant alcoholics. The 6 of 21 women assigned to BCT who actually
engaged their husband in BCT completed this therapy and benefited from reduced
drinking and happier relationships. This study suggests BCT may have limited useful-
ness when the alcoholic refuses to change or will not enter treatment with the spouse.
55.3 Conclusion
References
Chase K, O’Farrell TJ, Murphy CM, Fals-Stewart W, Murphy M (2003) Factors associated with
partner violence among female alcoholic patients and their male partners. J Stud Alcohol
64:137–149
Halford WK, Price J, Kelly AB, Bouma R, Young RM (2001) Helping the female partners of men
abusing alcohol: a comparison of three treatments. Addiction 96:1497–1508
Kelley ML, Fals-Stewart W (2002) Couples versus individual-based therapy for alcoholism and
drug abuse: effects on children’s psychosocial functioning. J Consult Clin Psychol 70:417–427
Meis LA, Griffin JM, Greer N, Jensen AC, MacDonald R, Carlyle M, Rutks I, Wilt TJ (2013) Cou-
ple and family involvement in adult mental health treatment: a systematic review. Clin Psychol
Rev 33:275–286
Moos RH, Finney JW, Cronkite RC (1990) Alcoholism treatment: context, process, and outcome.
Oxford University Press, New York
Nattala P, Leung KS, Nagarajaiah, Murthy P (2010) Family member involvement in relapse
prevention improves alcohol dependence outcomes: a prospective study at an addiction
treatment center in India. J Stud Alcohol Drugs 71:581–587
O’Farrell TJ (1993) Couples relapse prevention sessions after a behavioral marital therapy couples
group program. In: O’Farrell TJ (ed) Treating alcohol problems: marital and family interven-
tions. Guilford, New York, pp 305–326
O’Farrell TJ, Fals-Stewart W (2006) Behavioral couples therapy for alcoholism and drug abuse.
Guilford, New York
O’Farrell TJ, Murphy CM (1995) Marital violence before and after alcoholism treatment.
J Consult Clin Psychol 63:256–262
O’Farrell TJ, Murphy CM (2002) Behavioral couples therapy for alcoholism and drug abuse:
encountering the problem of domestic violence. In: Wekerle C, Wall AM (eds) The violence
and addiction equation: theoretical and clinical issues in substance abuse and relationship
violence. Brunner-Routledge, New York, pp 293–303
O’Farrell TJ, Choquette KA, Cutter HSG (1998) Couples relapse prevention sessions after
behavioral marital therapy for male alcoholics: outcomes during the three years after starting
treatment. J Stud Alcohol 59:357–370
O’Farrell TJ, Murphy CM, Stephen S, Fals-Stewart W, Murphy M (2004) Partner violence before
and after couples-based alcoholism treatment for male alcoholic patients: the role of treatment
involvement and abstinence. J Consult Clin Psychol 72:202–217
O’Farrell TJ, Richard R, el-Guebaly N (2010) Implementing behavioral couples therapy for
substance abuse patients: an international dissemination project from Boston to Calgary. Poster
presented at the World congress on behavior therapy, Boston, June
Rosenthal R (1991) Meta-analytic procedures for social research, 2nd Edition, Sage Publications,
Newbury Park California
Powers MB, Vedel E, Emmelkamp PMG (2008) Behavioral couples therapy (BCT) for alcohol
and drug use disorders: a meta-analysis. Clin Psychol Rev 28:952–962
Schumm J, O’Farrell TJ, Murphy CM, Fals-Stewart W (2009) Partner violence before and after
couples-based alcoholism treatment for women alcoholic patients and their male partners.
J Consult Clin Psychol 77:1136–1146
Schumm J, O’Farrell TJ, Burdzovic Andreas J (2012) Behavioral couples therapy when both
partners have a current alcohol use disorder. Alcohol Treat Q 30:407–421
Schumm J, O’Farrell TJ, Kahler C, Murphy M, Muchowski PM (2014) A randomized clinical trial
of behavioral couples therapy versus individually-based treatment for women with alcohol
dependence. J Consult Clin Psychol, in press
55 Couples Therapy in Treatment of Alcoholism and Drug Abuse 925
Stuart GL, O’Farrell TJ, Leonard K, Moore TM, Temple JR, Ramsey SE et al (2009) Examining
the interface between substance misuse and intimate partner violence. Subst Abuse Res Treat
3:25–29
Vedel E, Emmelkamp PMG, Schippers GM (2008) Individual cognitive-behavioral therapy and
behavioral couples therapy in alcohol use disorder: a comparative evaluation in community-
based addiction treatment centers. Psychother Psychosom 77:280–288
Further Reading
McCrady BS, Epstein EE (2008) Overcoming alcohol problems: a couples-focused program
therapist guide. Oxford University Press, New York
O’Farrell TJ, Clements K (2012) Review of outcome research on marital and family therapy in
treatment of alcoholism. J Marital Fam Ther 38:122–144
Network Therapy in Addiction Treatment
56
Marc Galanter
Contents
56.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 928
56.2 Facets of Network Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 928
56.2.1 Key Elements of Network Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 928
56.2.2 CBT and Social Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 929
56.2.3 Starting a Network . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 930
56.2.4 Defining the Network’s Membership . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 931
56.2.5 Defining the Network’s Task . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 931
56.2.6 The Use of Twelve-Step Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 932
56.2.7 Use of Pharmacotherapy in the Network Format . . . . . . . . . . . . . . . . . . . . . . . . . . . . 932
56.2.8 Format for Medication Observation by the Network . . . . . . . . . . . . . . . . . . . . . . . . 933
56.2.9 Meeting Arrangements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 933
56.2.10 Adapting Individual Therapy to the Network Treatment . . . . . . . . . . . . . . . . . . . . 934
56.2.11 The Technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 934
56.2.12 Research on Network Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 937
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 939
Abstract
Individual therapists in office practice are often considered to have limited
effectiveness in treating alcohol and drug dependence. In this chapter, the author
describes network therapy, an approach developed to assure greater success in
such treatment. A cognitive-behavioral model of addiction related to securing
abstinence is reviewed by the role of social cohesiveness as a vehicle for
engaging patients in treatment, along with a related technique for enhancing
an addicted patient’s commitment to the therapy. This is done by using the
patient’s family and peers as a therapeutic network to join the patient at intervals
in therapy sessions.
M. Galanter
Division of Alcoholism and Drug Abuse, NYU School of Medicine, New York, NY, USA
e-mail: [email protected]
56.1 Introduction
Three elements are essential to the network therapy technique. The first is a
cognitive-behavioral approach to relapse prevention, independently reported to be
valuable in addiction treatment (Marlatt and Gordon 1985). Emphasis in this
approach is placed on triggers to relapse and behavioral techniques for avoiding
them, rather than on exploring underlying psychodynamic issues.
Second, support of the patient’s natural social network is engaged in treatment.
Peer support in AA has long been shown to be an effective vehicle for promoting
abstinence, and the idea of the therapist’s intervening with family and friends in
starting treatment was employed in one of the early ambulatory techniques
specific to addiction (Johnson 1986). The involvement of spouses (McCrady
et al. 1991) has since been shown to be effective in enhancing the outcome of
professional therapy.
Third, the orchestration of resources to provide community reinforcement sug-
gests a more robust treatment intervention by providing a support for drug-free
rehabilitation (Azrin et al. 1982). In this relation, Khantzian points to the “primary
care therapist” as one who functions in direct coordinating and monitoring roles in
order to combine psychotherapeutic and self-help elements (Khantzian 1988). It is
this overall management role over circumstances outside as well as inside the office
session that is presented to trainees to maximize the effectiveness of the
intervention.
56 Network Therapy in Addiction Treatment 929
Patients should be asked to bring their spouse or a close friend to the first
session. Alcoholic patients often dislike certain things they hear when they first
come for treatment and may deny or rationalize even if they voluntarily sought
help. Because of their denial, a significant other is essential to both history
taking and implementing a viable treatment plan. A close relative or spouse
can often cut through the denial in a way that an unfamiliar therapist cannot
and can therefore be invaluable in setting a standard of realism in dealing with
the addiction.
Once the patient comes for an appointment, establishing a network is a task
undertaken with active collaboration of patient and therapist. The two, aided by
those parties who join the network initially, must search for the right balance
of members. The therapist must carefully promote the choice of appropriate
network members, however, just as the platoon leader selects those who will go
into combat.
56 Network Therapy in Addiction Treatment 931
The network will be crucial in determining the balance of the therapy. This process
is not without problems, and the therapist must think in a strategic fashion of the
interactions that may take place among network members. The following case
illustrates the nature of their task.
A 25-year-old graduate student had been abusing cocaine since high school, in
part drawing from funds from his affluent family, who lived in a remote city. At two
points in the process of establishing his support network, the reactions of his live-in
girlfriend, who worked with us from the outset, were particularly important. Both
he and she agreed to bring in his 19-year-old sister, a freshman at a nearby college.
He then mentioned a “friend” of his, apparently a woman whom he had apparently
found attractive, even though there was no history of an overt romantic involve-
ment. The expression on his girlfriend’s face suggested that she did not like this
idea, although she offered no rationale for excluding this potential rival. However,
the idea of having to rely for assistance solely on two women who might see each
other as competitors was unappealing. The therapist therefore finessed the idea of
the “friend,” and both she and the patient moved on to evaluating the patient’s
uncle, whom he initially preferred to exclude, despite the fact that his girlfriend
thought him appropriate. It later turned out (as expected) that the uncle was
perceived as a potentially disapproving representative of the parental generation.
The therapist encouraged the patient to accept the uncle as a network member
nonetheless, so as to round out the range of relationships within the group, and
did spell out my rationale for his inclusion. The uncle did turn out to be caring
and supportive, particularly after he was helped to understand the nature of the
addictive process.
As conceived here, the therapist’s relationship to the network is like that of a task-
oriented team leader rather than that of a family therapist oriented toward insight.
The network is established to implement a straightforward task: aiding the therapist
in sustaining the patient’s abstinence. It must be directed with the same clarity of
purpose that a task force is directed in any effective organization. Competing and
alternative goals must be suppressed or at least prevented from interfering with the
primary task.
Unlike family members involved in traditional family therapy, network mem-
bers are not led to expect symptom relief for themselves or self-realization. This
lack of expectation prevents the development of competing goals for the network’s
meetings. It also provides the members protection from having their own motives
scrutinized and thereby supports their continuing involvement without the threat
of an assault on their psychological defenses. Because network members
have – kindly – volunteered to participate, their motives must not be impugned.
Their constructive behavior should be commended. It is useful to acknowledge
932 M. Galanter
appreciation for the contribution they are making to the therapy. There is always
a counterproductive tendency on their part to minimize the value of their contribu-
tion. The network must, therefore, be structured as an effective working group with
high morale.
At the outset of therapy, it is important to see the patient with the group on a weekly
basis for at least the first month. Unstable circumstances demand more frequent
contacts with the network. Sessions can be tapered off to biweekly and then to
monthly intervals after a time.
To sustain the continuing commitment of the group, particularly that between
the therapist and the network members, network sessions should be held every
3 months or so for the duration of the individual therapy. Once the patient has
stabilized, the meetings tend less to address day-to-day issues. They may begin with
the patient’s recounting of the drug situation. Reflections on the patient’s progress
and goals, or sometimes on relations among the network members, then may be
discussed. In any case, it is essential that network members contact the therapist if
they are concerned about the patient’s possible use of alcohol or drugs and that the
therapist contact the network members if the therapist becomes concerned about
a potential relapse.
934 M. Galanter
3. In the initial interview, frame the exchange so that a good case is built for the
grave consequences of the patient’s addiction, and do this before the patient can
introduce his or her system of denial. That way you are not putting the spouse or
other network members in the awkward position of having to contradict a close
relation.
4. Then make clear that the patient needs to be abstinent, starting now. (A tapered
detoxification may be necessary sometimes, as with depressant pills.)
5. When seeing an alcoholic patient for the first time, start the patient
on disulfiram treatment as soon as possible, in the office if you can.
Have the patient continue taking disulfiram under observation of
a network member.
6. Start arranging for a network to be assembled at the first session, generally
involving a number of the patient’s family or close friends.
7. From the very first meeting you should consider how to ensure sobriety till
the next meeting, and plan that with the network. Initially, their immediate
company, a plan for daily AA attendance, and planned activities may all be
necessary.
receiving vouchers for each day of abstinence and each pill taken, the network
member was reinforced with a voucher for each pill recorded as monitored. The
primary treatment outcome was retention in treatment. Patients who used metha-
done at baseline did more poorly than those using only heroin as demonstrated in
the retention rates: 39 % versus 65 % and 0 % versus 31 %, respectively, at 1 month
and 6 months.
Copello et al. (2002) combined elements of NT with social aspects of the
community reinforcement approach and relapse prevention referred to as social
behavior and network therapy (SBNT) in the treatment of persons with alcohol-
drinking problems. A number of social skills training strategies are incorporated
into the treatment especially those involving social competence in relation to the
development of positive social support for change in alcohol use. Every individual
involved in treatment is considered a client in his/her own right and the person with
alcohol problems is referred to as the focal client. The core element of the approach
is mobilizing the support of the network even though this may involve network
sessions that are conducted in the absence of the focal client. In their initial
feasibility study with 33 clients, there were two cases in which sessions were
held with network members in the absence of the focal client and in both cases
reengagement of the focal client in treatment was achieved. Out of the 33 clients
enrolled in the study, 23 formed a network with the mean number of network
members ¼ 1.82 and the mean number of network sessions ¼ 5.24. In a multisite,
randomized, controlled trial of 742 clients with alcohol problems, the UKATT
Research Team (2005a) compared SBNT to motivational enhancement therapy
(MET). Both treatment groups exhibited similar reductions in alcohol consumption
and alcohol-related problems and improvement in mental functioning over
a 12-month period. Attending more sessions was associated with a better outcome,
and SBNT patients with greater motivation to change and those with more negative
short-term expectancies were more likely to attend (Dale et al. 2011).
Additional studies involving the UKATT study sample were conducted
assessing (1) cost-effectiveness (UKATT Research Team 2005b), (2) client-
treatment matching effects (UKATT Research Team 2008), (3) clients’ perceptions
of change in alcohol-drinking behaviors (Orford et al. 2009), and drinking goal
preference (Adamson et al. 2010). The UKATT Research Team evaluated the cost-
effectiveness of SBNT relative to motivational enhancement therapy. SBNT
resulted in a fivefold cost savings in health, social, and criminal justice service
expenditures and was similar to cost-effectiveness estimates obtained for motiva-
tional enhancement therapy. The UKATT Research Team (2008) tested a priori
hypotheses concerning client-treatment matching effects similar to those tested in
Project MATCH. The findings were consistent with Project MATCH in that no
hypothesized matching effects were significant. Orford et al. (2009) interviewed
a subset of clients (n ¼ 397) who participated in this trial to assess their views
concerning whether any positive changes in drinking behavior had occurred and to
what they attributed those changes. . . At 3 months after randomization to treatment,
SBNT clients made more social attributions (e.g., involvement of others in
supporting behavior change) and MET clients made more motivational attributions
56 Network Therapy in Addiction Treatment 939
References
Adamson S, Heather N, Morton V, Raistrick D (2010) Initial preference for drinking goal in the
treatment of alcohol problems: II. Treatment Outcomes. Alcohol Alcohol 45:136–142
Azrin NH, Sisson RW, Meyers R, Godley M (1982) Alcoholism treatment by disulfiram and
community reinforcement therapy. J Behav Ther Exp Psychiatry 13:105–112
Beckman LJ, Amaro H (1986) Personal and social difficulties faced by women and men entering
alcoholism treatment. J Stud Alcohol 47:135–145
Carroll KM (1998) A cognitive-behavioral approach. Treating cocaine addiction. National Institute
on Drug Abuse, Rockville
Copello A, Orford J, Hodgson R, Tober G, Barrett C (2002) Social behaviour and network therapy:
basic principles and early experiences. Addict Behav 27:345–366
Copello A, Williamson E, Orford J, Day E (2006) Implementing and evaluating social behaviour
and network therapy in drug treatment practice in the UK: a feasibility study. Addict Behav
31:802–810
Dale V, Coulton S, Godfrey C, Copello A, Hodgson N, Healther J et al (2011) Exploring treatment
attendance and its relationship to outcome in a randomized controlled trial of treatment for
alcohol problems: secondary analysis of the UK alcohol treatment trial (UKATT). Alcohol
Alcohol 46:592–599
Fals-Stewart W, O’Farrell TJ, Feehan M, Birchler GR, Tiller S, McFarlin SK (2000) Behavioral
couples therapy versus individual-based treatment for male substance-abusing patients. JSAT
18:249–254
Fuller R, Branchey L, Brightwell DR et al (1986) Disulfiram treatment of alcoholism. A veterans
administration cooperative study. JAMA 256:1449–1455
Galanter M (1993) Network therapy for addiction: a model for office practice. Am J Psychiatry
150:28–36
Galanter M, Keller D, Dermatis H (1997) Network therapy for addiction: assessment of the clinical
outcome of training. Am J Drug Alcohol Abuse 23:355–367
Galanter M, Dermatis H, Keller D, Trujillo M (2002) Network therapy for cocaine abuse: use of
family and peer supports. Am J Addict 11:161–166
940 M. Galanter
Contents
57.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 942
57.2 Understanding and Using CRA and CRAFT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 942
57.2.1 CRA Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 942
57.2.2 CRA Scientific Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 949
57.2.3 International Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 950
57.2.4 CRAFT Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 951
57.2.5 CRAFT Scientific Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 955
57.2.6 International Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 956
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 957
Abstract
The Community Reinforcement Approach (CRA) is a behavioral treatment for
substance abuse problems which is based on the belief that a nondrinking and
nonusing lifestyle must be accessible and experienced as rewarding in order for
individuals to choose it routinely over substance use. As part of CRA, the
client’s “community” (e.g., family, friends, colleagues, organizations, work) is
explored to find new areas of potential reinforcement that can compete with
substance use. CRA therapists help clients determine which goals they want to
pursue in life, and they then teach clients the skills required to obtain these goals.
Community Reinforcement and Family Training (CRAFT) is a treatment for the
family members or close friends (Concerned Significant Others, CSOs) of
unmotivated, treatment-refusing substance abusers (identified patients, IPs).
CRAFT therapists work with CSOs in an attempt to change the home
environment of the unmotivated IPs such that a healthy and enjoyable lifestyle is
supported over one dominated by substance use. CRAFT goals include getting
IPs to seek treatment but also having CSOs take care of themselves as well. Both
CRA and CRAFT have solid empirical support, and each has been used suc-
cessfully with diverse populations and various drugs of choice.
57.1 Introduction
that sustain the substance use behavior. For example, a client may state that he
enjoys drinking because it allows him to relax and have fun with friends
after a stressful day at work. Once these positive consequences are identified, the
clinician can help the client generate reasonable alternatives for relaxing and
having fun after work: options that do not involve alcohol. The positive
consequences of substance use are referred to as short term, while the negative
consequences are specified as long term. The latter are broken down into multiple
domains: interpersonal, physical, emotional, legal, job, and financial.
The CRA program’s second type of F.A. is for prosocial behaviors (e.g., going
for a bike ride, relaxing at a coffee shop). A better understanding of the antecedents
and consequences surrounding these behaviors helps the clinician see why
a prosocial behavior is sometimes chosen over a substance-using one (and vice
versa) and identify possible mechanisms for getting the client to select the healthy
alternative more often.
similar to: “Mrs. Gray, I can see why you thought I was cheating in class yesterday
when you heard whispering coming from the back of the room during the test,
because I’ve had trouble with cheating in the past (understanding statement).
And I know it didn’t help for me to get all upset as soon as you started talking to
me; I guess it sort of made me seem guilty (partial responsibility statement). What
can I do to convince you that things are different now and that I don’t cheat
anymore?” (offer to help).
Clients report that when they start a conversation with these communication
components they typically are met with less defensiveness from the listener.
The message being conveyed is that more than one person contributes to interper-
sonal problems, and the communicator is willing to take an active role in improving
the situation. Clinicians teach these skills by providing relevant examples and
engaging the client in role plays complete with specific feedback.
Information gathered during the F.A. can be extremely useful when helping the
client identify high-risk situations. Working with personally relevant situations will
make the drink/drug refusal role plays more effective. Oftentimes clients are overly
confident that they will be able to walk into these situations and “simply not drink”
(or use other substances). Despite this confidence, refusal is often much more
difficult than anticipated, and thus, clients are encouraged to practice refusing
offers assertively.
Without this specialized assertiveness training, clients tend to respond either too
passively or too aggressively to substance use offers. Suggested components of an
assertive response include (1) saying “no, thanks” without feeling guilty, (2) using
appropriate body language (good eye contact, a firm stance, etc.), (3) suggesting
alternatives (“No, thanks, but I’ll take a soda”), (4) changing the subject (“Did you
see that game last night? Unbelievable!”), (5) directly addressing the aggressor
about the issue if needed (“I’ve already said more than once that I’m not smoking.
Why is it important to you that I smoke?”), and (6) leaving the situation. Clients are
asked to generate their own assertive response style and are coached in its
implementation.
healthy social activities, including the use of problem solving. Once an activity is
identified, a homework assignment is made to sample the activity, and as usual,
potential barriers (e.g., transportation, money, fear of rejection) are discussed.
Periodically clinicians are doubtful that a client will follow through and sample
a new activity despite being motivated to do so. In these cases clinicians utilize
a technique, systematic encouragement, to increase the likelihood that the client
will successfully complete that homework assignment in the upcoming week.
Systematic encouragement involves helping the client take the first step toward
engaging in the new activity before leaving the session. For example, assume
a client is interested in playing basketball at the local YMCA but appears unlikely
to make any progress toward pursuing that goal without assistance. The clinician
either would help the client search for relevant information on the YMCA website
(e.g., the YMCA’s operation schedule, whether there are “pickup” games on the
basketball court, whether fees are involved) or would conduct a role play in which
the client practiced calling the organization to ask these questions directly. Next,
a specific plan for getting to the YMCA would be created, and obstacles would be
addressed. The clinician would start the next session by reviewing the client’s
experience at the YMCA, in part to determine the reinforcement value.
For the past 40 years, the Community Reinforcement Approach (CRA) has been
accruing evidence of its efficacy and effectiveness in treating alcohol and drug
problems. The earliest CRA studies were conducted with inpatients on alcohol
wards (Azrin 1976; Hunt and Azrin 1973). In both of these small studies, CRA was
shown to be significantly better than standard treatment, which at the time was
participation in a hospital’s Alcoholics Anonymous program. Specifically, at the
6-month follow-up, the participants in the CRA program had fewer days of drinking
and institutionalization and more days working compared to those in standard
treatment. The second of these studies introduced several new procedures to the
original CRA protocol, most notably a disulfiram (Antabuse) compliance monitor-
ing program (Azrin 1976).
The third CRA study was the first to use an outpatient population of problem
drinkers (Azrin et al. 1982). The researchers contrasted three treatments: traditional
(12-step) treatment with a disulfiram prescription, traditional treatment with the
disulfiram compliance program, and CRA with the disulfiram compliance program.
The compliance program included not only monitoring of the daily disulfiram use
by a loved one but training in positive communication skills as well. As expected,
the conditions that included the disulfiram compliance component had the highest
abstinence rates, with the CRA program outperforming the traditional program
overall at 6 months.
A much larger study (N ¼ 237) with an ethnically diverse population was
conducted which extended the design of the first outpatient study by examining
whether one’s willingness to take disulfiram affected the findings
(Miller et al. 2001). Although the study revealed less robust results, CRA
still showed an advantage over traditional treatment on several outcome mea-
sures. The CRA program was modified in another study to make it applicable to
a day treatment program for homeless alcohol-dependent individuals
(Smith et al. 1998). As predicted, CRA (conducted in group format) was proven
950 J.E. Smith et al.
CRA has gained international recognition in more recent years. For instance, CRA
was implemented successfully within Spain’s Public Health System with cocaine-
dependent individuals in an outpatient clinic (Secades-Villa et al. 2011). A later
study added vouchers to the CRA program and improved treatment outcomes
(Garcia-Fernandez et al. 2011). Several Dutch studies and reviews led by Roozen
and colleagues already have been noted (e.g., Roozen et al. 2003, 2004, 2006), and
a pilot study of CRA with substance-abusing individuals in Mexico detected highly
57 CRA and CRAFT 951
promising findings (Torres et al. 2005). Finally, the National Drugs Strategy of
Ireland has acknowledged CRA as an effective evidence-based approach that can
be used as an adjunct to services delivered within the rehabilitation pillar, and
Germany has already sponsored a CRA conference. To date, the CRA trainers’
manual, Clinical Guide to Alcohol Treatment: The Community Reinforcement
Approach (Meyers and Smith 1995), has been translated into German and Dutch.
Alternatively, the CSO could urge the IP to come straight home after work so that the
two of them could go for a relaxing walk in the park. Ideally the exercise and
the conversation would serve as a suitable substitute for the “unwinding” in the bar.
By choosing a substance-free activity, the IP will not only experience positive
consequences but will also experience a reduction in the negative consequences that
typically follow substance use. Using a gentle approach, the CSO can help the IP
recognize that the negative consequences of substance use (e.g., trouble getting up for
work the next day) are eliminated when the IP engages in the substance-free
alternative.
It is important to realize that simply making one change in behavior will not
suddenly solve the IP’s substance use problem. Instead, the CSO typically needs to
introduce a number of changes (as outlined in the remaining CRAFT procedures
below) before the IP decides to seek treatment.
financially damage the entire family if the CSO did not call in sick for a hungover
IP. But if deemed an appropriate behavior to target, a specific plan for changing the
CSO’s behavior would be developed. If the CSO wanted to explain the plan to the
IP, the conversation would be rehearsed.
Prior to the development of CRAFT, a few traditional programs were available for
the loved ones of treatment-refusing individuals with substance use problems:
Al-Anon/Nar-Anon and the Johnson Institute Intervention. Al-Anon (Al-Anon
Family Groups 1984) was shown to provide good emotional support (Barber and
Gilbertson 1996; Dittrich and Trapold 1984), but many CSOs were uncomfortable
with the message to “detach” from their IPs. The Johnson Institute Intervention (JII;
Johnson 1986), in contrast, was specifically geared toward working through CSOs
in order to get a resistant individual into treatment. After several planning sessions
with multiple CSOs, a “surprise party” was scheduled in which the CSOs
confronted the IP with the substance use problem and its ramifications. Studies
showed that when families actually carried out the entire intervention, the treatment
engagement rate was high, but the vast majority of people dropped out of the
program before the final meeting with the IP (Liepman et al. 1989), potentially
due to concerns over the effect of the intervention on the relationship with the IP
(Barber and Gilbertson 1997).
Unilateral Family Therapy (UFT) was introduced in the early 1980s as a type of
family therapy that involved individuals other than the IP. Thomas and colleagues
conducted several studies with UFT and found promising results, but the studies
tended to be small and lacked good experimental controls (e.g., Thomas and Ager
1993; Thomas et al. 1987). Another UFT program with some scientific support was
Pressures to Change (e.g., Barber and Crisp 1994; Barber and Gilbertson 1997).
Finally, ARISE (A Relational Intervention Sequence for Engagement) is an “invi-
tational” intervention that uses different levels of treatment (e.g., starting with
phone conversations with CSOs) and informs the IP about the ongoing meetings
with CSOs throughout. Much of the evidence to date has been promising case
reports and a pilot study (see Landau and Garrett 2008).
CRAFT, a type of UFT, originally was called CRT (Community Reinforcement
Training) when the first small study was conducted by Sisson and Azrin (1986).
Twelve female CSOs were randomly assigned into either CRT (n ¼ 7) or individual
counseling + Al-Anon referrals (n ¼ 5). Six of the seven women in the CRT group
(86 %) were able to get their problem-drinking IPs into treatment compared to none
of the IPs in the comparison group. The second CRAFT study that focused on IPs
with alcohol problems was a large NIAAA-funded project that randomly assigned
130 CSOs into one of the three treatment groups: CRAFT, Al-Anon Facilitation
Therapy (an individual therapy version of Al-Anon; Nowinski et al. 1992), or the
Johnson Institute Intervention. Results indicated that CRAFT-trained CSOs were
significantly more effective in engaging unmotivated problem drinkers in treatment
(64 %) as compared with the CSOs in the more commonly practiced Al-Anon
(13 %) and Johnson interventions (30 %; Miller et al. 1999). Interestingly, CSOs
improved in their own functioning independent of treatment condition and whether
their IP entered treatment. For those IPs who entered treatment, they did so with
their CSOs receiving an average of only 4.7 CRAFT or Al-Anon sessions and 5.7
Johnson Institute sessions.
956 J.E. Smith et al.
The success of CRAFT also has been established for treatment-refusing IPs with
illicit drug problems. In a pilot project, 62 CSOs from diverse ethnic backgrounds
were trained in the CRAFT protocol. As expected, the CSOs were able to get a high
percentage of IPs (74 %) into treatment very quickly (less than five CSO sessions)
while also reducing the CSOs’ own levels of depression, anxiety, and anger
(Meyers et al. 1999). At about the same time, a CRAFT (CRT) study was conducted
by Kirby and colleagues in which 32 CSOs were randomly assigned to either CRT
or 12-step meetings. Engagement rates were 64 % for the CRT-trained CSOs and
17 % for CSOs in the 12-step condition (Kirby et al. 1999).
A large NIDA-funded study was conducted next in which 90 CSOs of illicit drug
using IPs were randomly assigned to CRAFT, CRAFT + Aftercare, or Al-Anon/
Nar-Anon Facilitation Therapy. An aftercare component was added to one of the
CRAFT conditions to mimic the availability of ongoing aftercare groups within the
12-step model. The results demonstrated that the combined CRAFT conditions’
engagement rates (67 %) were significantly higher than the Al-Anon/Nar-Anon
rates (29 %), but there were no significant engagement differences between the two
CRAFT conditions (Meyers et al. 2002). More recently an effectiveness study
demonstrated that CRAFT could be successfully transferred from a controlled
research setting to a community treatment agency, while maintaining levels of
engagement quite similar to previous controlled studies (Dutcher et al. 2009).
CRAFT’s success with adults was tested with adolescents in an uncontrolled trial
that recruited the parents of 42 drug-abusing, treatment-refusing adolescents
(Waldron et al. 2007). A total of 71 % of the parents engaged their adolescents into
treatment using CRAFT, and the parents overall experienced a significant reduction in
negative symptoms. Another unique application of the CRAFT protocol was a study
that delivered CRAFT in a group treatment format (Manuel et al. 2012). Participants
were randomly assigned to a CRAFT group or to self-directed CRAFT, with the latter
receiving the CRAFT self-help book (Meyers and Wolfe 2004). The intent-to-treat
analysis contrasted the CRAFT group engagement rate (60 %) with the self-directed
CRAFT rate (40 %) and detected no statistically significant difference. However, for
those CSOs assigned to the CRAFT group condition who attended at least one session,
71 % engaged their IP into treatment. The implication is that group CRAFT can be
a cost-effective method of getting treatment-refusing IPs into treatment.
CRAFT has been found superior in engaging treatment-refusing substance-
abusing individuals compared with traditional programs. Additionally, CRAFT
has been shown effective across ethnicities, different types of CSO-IP relationships,
and various kinds of drugs of abuse. Furthermore, CRAFT works in less than five
CSO sessions on average, and CSOs report psychological improvement regardless
of the outcome of their engagement efforts.
German, Korean, Finnish, and Japanese to date. The self-help version (Meyers
and Wolfe 2004) is available in Finnish and Spanish. Therapists have been trained
in CRAFT across the world, including Ireland, Wales, Scotland, the Netherlands,
Sweden, Finland, Germany, and Canada.
References
Abbott PJ, Weller SB, Delaney HD, Moore BA (1998) Community reinforcement approach in the
treatment of opiate addicts. Am J Drug Alcohol Abuse 24:17–30
Al-Anon Family Groups (1984) Al-Anon faces alcoholism. Author, New York
Azrin NH (1976) Improvements in the community-reinforcement approach to alcoholism. Behav
Res Ther 14:339–348
Azrin NH, Besalel VA (1980) Job club counselor’s manual. University Press, Baltimore
Azrin NH, Sisson RW, Meyers R, Godley M (1982) Alcoholism treatment by disulfiram and
community reinforcement therapy. J Behav Ther Exp Psychiatry 13:105–112
Azrin NH, Acierno R, Kogan ES, Donohue B, Besalel VA, McMahon PT (1996)
Follow-up results of supportive versus behavioral therapy for illicit drug use. Behav Res
Ther 34:41–46
Barber JG, Gilbertson R (1996) An experimental study of brief unilateral intervention for the
partners of heavy drinkers. Res Soc Work Pract 6:325–336
Barber JG, Gilbertson R (1997) Unilateral interventions for women living with heavy drinkers.
Soc Work 42:69–78
Bickel WK, Amass L, Higgins ST, Badger GJ, Esch RA (1997) Effects of adding behavioral
treatment to opioid detoxification with buprenorphine. J Consult Clin Psychol 65:803–810
Bickel WK, Marsch LA, Buchhalter AR, Badger GJ (2008) Computerized behavior therapy for
opioid-dependent outpatients: a randomized controlled trial. Exp Clin Psychopharmacol
16:132–143
Dennis ML, Godley SH, Diamond G, Tims FM, Babor T, Donaldson J, Liddle H, Titus JC,
Kaminer Y, Webb C, Hamilton N, Funk RR (2004) The Cannabis Youth Treatment (CYT)
study: main findings from two randomized trials. J Subst Abus Treat 27:197–213
Dittrich JE, Trapold MA (1984) A treatment program for the wives of alcoholics: an evaluation.
Bull Soc Psychol Addict Behav 3:91–102
Dutcher LW, Anderson R, Moore M, Luna-Anderson C, Meyers RJ, Delaney HD, Smith JE
(2009) Community reinforcement and family training (CRAFT): an effectiveness study. J
Behav Anal Health Sports Fitness Med 2:80–93
D’Zurilla T, Goldfried M (1971) Problem solving and behavior modification. J Abnorm Psychol
78:107–126
Garcı́a-Fernández G, Secades-Villa R, Garcı́a-Rodrı́guez O, Sánchez-Hervás E,
Fernández-Hermida JR, Higgins ST (2011) Adding voucher-based incentives to community
reinforcement approach improves outcomes during treatment for cocaine dependence. Am
J Addict 20:456–461
Garcia-Rodriguez O, Secades-Villa R, Higgins ST, Fernandez-Hermida JR, Carballo JL, Errasti
Perez JM, Al-halabi Diaz S (2009) Effects of voucher-based intervention on abstinence and
retention in an outpatient treatment for cocaine addiction: a randomized controlled trial. Exp
Clin Psychopharmacol 17:131–138
Godley SH, Meyers RJ, Smith JE, Godley MD, Titus JC, Karvinen T, Dent G, Passetti LL,
Kelberg P (2001) The adolescent community reinforcement approach (A-CRA) for adolescent
cannabis users (DHHS publication no. SMA 01-3489), Cannabis Youth Treatment (CYT)
manual series, vol 4, Center for Substance Abuse Treatment, Substance Abuse and Mental
Health Services Administration, Rockville
958 J.E. Smith et al.
Godley SH, Hedges K, Hunter B (2011) Gender and racial differences in treatment process and
outcome among participants in the adolescent community reinforcement approach. Psychol
Addict Behav 25:143
Higgins ST, Abbott PJ (2001) CRA and treatment of cocaine and opioid dependence. In:
Meyers RJ, Miller WR (eds) A community reinforcement approach to addiction treatment.
Cambridge University Press, Cambridge, pp 123–146
Higgins ST, Sigmon SC, Wong CJ, Heil SH, Badger GJ, Donham R, Dantona RL, Anthony S
(2003) Community reinforcement therapy for cocaine-dependent outpatients. Arch Gen Psy-
chiatry 60:1043–1052
Hunt GM, Azrin NH (1973) A community-reinforcement approach to alcoholism. Behav Res Ther
11:91–104
Johnson VE (1986) Intervention: how to help those who don’t want help. Johnson Institute,
Minneapolis
Kirby KC, Marlowe DB, Festinger DS, Garvey KA, LaMonaca V (1999) Community reinforce-
ment training for family and significant others of drug abusers: a unilateral intervention to
increase treatment entry of drug users. Drug Alcohol Depend 56:85–96
Klostermann K, Kelley ML, Mignone T, Pusateri L, Fals-Stewart W (2010) Partner violence and
substance abuse: treatment interventions. Aggress Violent Behav 15:162–166
Landau J, Garrett J (2008) Invitational intervention: the ARISE model for engaging reluctant
alcohol and other drug abusers in treatment. Alcohol Treat Q 26:147–168
Liepman MR, Nirenberg TD, Begin AM (1989) Evaluation of a program designed to help family
and significant others to motivate resistant alcoholics into recovery. Am J Drug Alcohol Abuse
15:209–221
Manuel JK, Austin JL, Miller WR, McCrady BS, Tonigan JS, Meyers RJ, Smith JE,
Bogenschutz MP (2012) Community reinforcement and family training: a pilot comparison
of group and self-directed delivery. J Subst Abus Treat 43:129–136
Meyers RJ, Smith JE (1995) Clinical guide to alcohol treatment: the community reinforcement
approach. Guilford Press, New York
Meyers RJ, Wolfe BL (2004) Get your loved one sober: alternatives to nagging, pleading, and
threatening. Hazelden, Center City
Meyers RJ, Miller WR, Hill DE, Tonigan JS (1999) Community Reinforcement and Family
Training (CRAFT): engaging unmotivated drug users in treatment. J Subst Abus 10:291–308
Meyers RJ, Miller WR, Smith JE, Tonigan JS (2002) A randomized trial of two methods for
engaging treatment-refusing drug users through concerned significant others. J Consult Clin
Psychol 70:1182–1185
Miller WR, Meyers RJ, Tonigan JS (1999) Engaging the unmotivated in treatment for alcohol
problems: a comparison of three strategies for intervention through family members. J Consult
Clin Psychol 67:688–697
Miller WR, Meyers RJ, Tonigan JS, Grant KA (2001) Community reinforcement and traditional
approaches: findings of a controlled trial. In: Meyers RJ, Miller WR (eds) A community
reinforcement approach to addiction treatment. Cambridge University Press, Cambridge,
pp 79–103
Nowinski J, Baker S, Carroll K (1992) 12-step facilitation therapist manual: a clinical
research guide for therapists treating individuals with alcohol abuse and dependence,
vol 1, Project MATCH monograph series. National Institute on Alcohol Abuse and
Alcoholism, Rockville
Orford J, Natera G, Davies J, Nava A, Mora J, Rigby K, Bradbury C, Copella A, Velleman R
(1998) Stresses and strains for family members living with drinking or drug problems in
England and Mexico. Salud Ment 21:1–13
Roozen HG, Kerkhof AJ, van den Brink W (2003) Experiences with an out-patient relapse
program (community reinforcement approach) combined with naltrexone in the treatment of
opioid-dependence: effect on addictive behaviors and the predictive value of psychiatric
comorbidity. Eur Addict Res 9:53–58
57 CRA and CRAFT 959
Roozen HG, Boulogne JJ, van Tulder MW, van den Brink W, De Jong CA, Kerkhof AJ
(2004) A systematic review of the effectiveness of the community reinforcement approach in
alcohol, cocaine and opioid addiction. Drug Alcohol Depend 74:1–13
Roozen HG, van Beers SE, Weevers HJ, Breteler MH, Willemsen MC, Postmus PE, Kerkhof AJ
(2006) Effects on smoking cessation: naltrexone combined with a cognitive behavioral treat-
ment based on the community reinforcement approach. Subst Use Misuse 41:45–60
Secades-Villa R, Sánchez-Hervás E, Zacarés-Romaguera F, Garcı́a-Rodrı́guez O, Santonja-
Gómez FJ, Garcı́a-Fernández G (2011) Community Reinforcement Approach (CRA) for
cocaine dependence in the Spanish public health system: 1 year outcome. Drug Alcohol Rev
30:606–612
Sisson RW, Azrin NH (1986) The use of systematic encouragement and community access
procedures to increase attendance at Alcoholics Anonymous and Al-Anon meetings. Am J
Drug Alcohol Abuse 8:371–376
Slesnick N, Prestopnik JL, Meyers RJ, Glassman M (2007) Treatment outcome for street-living,
homeless youth. Addict Behav 32:1237–1251
Smith JE, Meyers RJ (2004) Motivating substance abusers to enter treatment: working with family
members. Guilford Press, New York
Smith JE, Meyers RJ, Delaney HD (1998) The community reinforcement approach with homeless
alcohol-dependent individuals. J Consult Clin Psychol 66:541–548
Thomas EJ, Ager RD (1993) Unilateral family therapy with the spouses of uncooperative alcohol
abusers. In: O’Farrwll TJ (ed) Treating alcohol problems: marital and family interventions.
Guilford Press, New York, pp 3–33
Thomas EJ, Santa C, Bronson D, Oyserman D (1987) Unilateral family therapy with spouses of
alcoholics. J Soc Serv Res 10:145–163
Torres LB, Vazquez JG, Medina-Mora ME, Velazquez HA (2005) Adaptation of a model of
cognitive-behavioral intervention for dependent users of alcohol and other drugs in Mexico:
a preliminary study. Salud Ment 28:61–71
Waldron HB, Kern-Jones S, Turner CW, Peterson TR, Ozechowski TJ (2007) Engaging resistant
adolescents in drug abuse treatment. J Subst Abus Treat 32:133–142
Development and Dissemination of the
Matrix Model of Intensive Outpatient 58
Treatment
Contents
58.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 962
58.1.1 Matrix Model Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 962
58.2 Elements of the Matrix Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 963
58.2.1 Description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 963
58.2.2 Matrix Model Randomized Clinical Trial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 967
58.2.3 Dissemination of the Matrix Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 968
58.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 970
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 970
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 971
Abstract
The Matrix Model of intensive outpatient treatment was developed in the 1980s
to address the needs of stimulant users. Over time, a manualized treatment
protocol was developed and published, and the application of the Matrix
Model was extended to other drug and alcohol users. A randomized, controlled,
multisite trial was funded by the Center for Substance Abuse Treatment to
evaluate the Matrix Model compared to “treatment as usual” with 978 metham-
phetamine users at eight sites. The results of this study were the basis for the
Matrix Model achieving the designation as an evidence-based program. In the
late 1990s, the methamphetamine epidemic combined with the funding
58.1 Introduction
The Matrix Model of outpatient treatment was developed at the height of the
stimulant epidemic in Southern California in the 1980s (Obert et al. 2000). In the
urban areas of Los Angeles, crack cocaine was the major drug problem affecting
communities, but 50 miles to the east of downtown Los Angeles, in San Bernardino
County, large numbers of methamphetamine (MA) users began to present at the
Matrix Institute on Addiction clinic in Rancho Cucamonga (one of three Matrix
clinics in the Southern California area) for assistance. At the time, there was no
established approach for structuring outpatient services to meet the needs of these
two groups of stimulant users. Therefore, with funding from the National Institute
on Drug Abuse (NIDA), the authors of the Matrix approach attempted to integrate
existing knowledge and empirically supported techniques into a single,
multielement manual that could serve as an outpatient “protocol” for the treatment
of cocaine and MA users (Rawson et al. 1989, 1995).
The development of the Matrix Model was influenced by an ongoing interaction
between clinicians working with patients and researchers collecting clinical research
data. As clinical experience with stimulant-dependent individuals was amassed,
clinical impressions frequently generated questions that were answered by using
relevant research findings. For example, stimulant users in outpatient treatment
frequently gave the impression of being unmotivated or uncooperative because they
failed to comply with counselors’ directions. At the time (mid-1980s), many treatment
programs considered these patients to be “in denial” and often confronted them
aggressively or discharged them as “not ready for treatment.” New information on
stimulants and the brain provided an alternate view of these patients for Matrix
clinicians. They began to understand that it was not “denial and resistance” but rather
a neurobiological issue involving brain chemistry changes that contributed to patients’
inability to recognize and deal rationally with their self-destructive behavior.
As Matrix staff worked with these stimulant users, they identified specific
clinical issues (e.g., conditioned cues, drug craving, anhedonia) that created chal-
lenges for patients. Materials were adopted from the cognitive behavioral and
58 Development and Dissemination of the Matrix Model 963
58.2.1 Description
58.2.1.4 Psychoeducation
The Matrix Model includes educating patients about conditioning and neurobiology
to help them understand the concept of addiction as a “brain disease” (Obert
et al. 2002). The educational materials used in the Matrix program help
patients recognize the physiology/neurobiology of addiction and remove some of
the confusion they have about their own feelings, thinking, and behavior. This
knowledge is used to empower patients to take steps to actively become
change agents in building a recovery program. While the Family Education com-
ponent of the program is a major forum for presentation of psychoeducational
materials, an educational aspect of the Matrix program is included in all treatment
activities.
for drug and alcohol use during treatment is through the use of urine and breath
alcohol testing. Urine testing is used as a way to reveal continuing drug use, which
is a sign that the treatment plan needs revising. Urine and breath alcohol testings
done in a clinical setting for clinical purposes are quite different from urine testing
that is done for legal monitoring.
Matrix Model training efforts, both within the United States and internationally, began
in the late 1990s, as many areas in the United States and other regions sought direction
on approaches for the treatment of amphetamine-type stimulant (ATS) use disorders.
In order to accommodate these training requests, a model for dissemination of the
Matrix Model was developed that would not be too restrictive (both in terms of cost
and fidelity requirements) but would create local expertise to provide ongoing training
and supervision of clinical staff and ensure fidelity to the main components of the
model. Consultation on the development of a dissemination model was obtained from
Texas Christian University, the University of South Florida, and the National Imple-
mentation Research Network. The Matrix Model training process ideally begins with a
pre-training phone consultation with the organization where staff are to be trained, in
order to review the setting, staff, and population to be treated and explain the overall
training plan. The first training component is a two-day training on the Matrix Model
that is attended by the organizations’ clinical and administrative personnel. The
organization leadership, with input from Matrix trainers, selects the trainee clinicians
to be developed as local Matrix experts. These local experts are referred to as Matrix
Key Supervisors. Key Supervisors should be:
• Respected clinical leaders who are both credible to clinicians and knowledge-
able about organizational dynamics
• People who possess excellent communication and clinical skills
• Leaders who are committed to actively working to implement the Matrix Model
with fidelity and good effect
After attending the core training, Key Supervisors are trained in a two-day training
that includes instructions on how to teach the model and monitor fidelity to it, how to
supervise clinical staff in delivering the model, and how to train new clinical staff who
join the program after the initial training.
58.2.3.2 Certification
The Matrix Institute developed a certification program in response to requests by
state agencies for a way to determine which programs were delivering the Matrix
Model with adequate training and fidelity to the model. The Matrix certification
confirms that the organization has been delivering the model for at least 6 months,
has clinicians who are properly trained, and has Key Supervisors who oversee the
implementation and supervise the clinical staff.
58 Development and Dissemination of the Matrix Model 969
58.2.3.6 Spain
The first Matrix Model training in Spain was sponsored by the government of
Murcia in 2005. Three major training events have been conducted in the region of
Murcia, in which more than 80 professionals and four Key Supervisors have been
trained. Despite severe economic obstacles, efforts are underway to ensure conti-
nuity of implementation, training, monitoring, and evaluation efforts with the
Matrix Model throughout Spain.
970 J. Obert et al.
58.3 Conclusion
References
Carroll KM, Rounsaville BJ, Gawin FH (1991) A comparative trial of psychotherapies for
ambulatory cocaine abusers: relapse prevention and interpersonal psychotherapy. Am J Drug
Alcohol Abuse 17:229–247
Carroll KM, Rounsaville BJ, Gordon LT, Nich C, Jatlow PM, Bisighini RM, Gawin FH (1994a)
Psychotherapy and pharmacotherapy for ambulatory cocaine abusers. Arch Gen Psychiatry
51:177–197
Carroll KM, Rounsaville BJ, Nich C, Gordon LT, Wirtz PW, Gawin FH (1994b) One year follow-
up of psychotherapy and pharmacotherapy for cocaine dependence: delayed emergence of
psychotherapy effects. Arch Gen Psychiatry 51:989–997
58 Development and Dissemination of the Matrix Model 971
Huber A, Ling W, Shoptaw S, Gulati V, Brethen P, Rawson R (1997) Integrating treatments for
methamphetamine abuse: a psychosocial perspective. J Addict Dis 16(4):41–50
Humphreys K, Wing S, McCarty D, Chappel J, Gallant L, Haberle B, Horvath AT, Kaskutas LA,
Kirk T, Kivlahan D, Laudet A, McCrady BS, McLellan AT, Morgenstern J, Townsend M,
Weiss R (2004) Self-help organizations for alcohol and drug problems: toward evidence-based
practice and policy. J Subst Abuse Treat 26(3):151–158
Marlatt GA, Gordon JR (eds) (1985) Relapse prevention: maintenance strategies in the treatment
of addictive behaviors. Guilford Press, New York
Miller WR, Rollnick S (1991) Motivational interviewing: preparing people for change. Guilford
Press, New York
Obert JL, McCann MJ, Brethen P, Marinelli-Casey P, Rawson RA (2000) The Matrix Model of
outpatient substance abuse treatment: history and description. J Psychoactive Drugs 32:157–165
Obert JL, London ED, Rawson RA (2002) Incorporating brain research findings into standard
treatment: an example using the Matrix Model. J Subst Abuse Treat 23:107–114
Petry NM (2000) A comprehensive guide to the application of contingency management pro-
cedures in clinical settings. Drug Alcohol Depend 58:9–25
Rawson RA, Obert JL, McCann MJ, Smith DP, Scheffey EH (1989) The neurobehavioral
treatment manual. Matrix Institute on Addiction, Beverly Hills
Rawson RA, Shoptaw SJ, Obert JL, McCann MJ, Hasson AL, Marinelli-Casey P, Brethen PR,
Ling W (1995) An intensive outpatient approach for cocaine abuse treatment: the Matrix
Model. J Subst Abuse Treat 12(2):117–127
Rawson RA, Marinelli-Casey P, Anglin MD, Dickow A, Frazier Y, Gallagher C, Galloway GP,
Herrell J, Huber A, McCann MJ, Obert J, Pennell S, Reiber C, Vandersloot D, Zweben J,
Methamphetamine Treatment Project Corporate Authors (2004) A multi-site comparison of
psychosocial approaches for the treatment of methamphetamine dependence. Addiction
99(6):708–717
Rawson RA, McCann MJ, Flammino F, Shoptaw S, Miotto K, Reiber C, Ling W (2006)
A comparison of contingency management and cognitive-behavioral approaches for
stimulant-dependent individuals. Addiction 101(2):267–274
Rogers CR (1951) Client-centered therapy. Houghton-Mifflin, Boston
Roll JM, Petry NM, Stitzer ML, Brecht ML, Peirce JM, McCann MJ, Blaine J, MacDonald M,
DiMaria J, Lucero L, Kellogg S (2006) Contingency management for the treatment of
methamphetamine use disorders. Am J Psychiatry 163(11):1993–1999
Further Reading
Carroll KM, Rawson RA (2005) Relapse prevention approaches for stimulant dependent individ-
uals. In: Marlatt GA, Donovan D (eds) Relapse prevention approaches for the treatment of
substance use disorders. Guilford, New York
Obert JL, McCann MJ, Brethen P, Marinelli-Casey P, Rawson RA (2000) The Matrix Model of
outpatient substance abuse treatment: history and description. J Psychoactive Drugs 32:157–165
Rawson RA (2009) Treatments for methamphetamine dependence: contingency management and
the Matrix Model. In: Pates R, Riley D (eds) Interventions for amphetamine misuse. Wiley
Blackwell, Oxford, UK, pp 83–100
Rawson RA, Obert JL, McCann MJ, Smith DP, Scheffey EH (1989) The neurobehavioral
treatment manual. Matrix Institute on Addiction, Beverly Hills
Rawson RA, Marinelli-Casey P, Anglin MD, Dickow A, Frazier Y, Gallagher C, Galloway GP,
Herrell J, Huber A, McCann MJ, Obert J, Pennell S, Reiber C, Vandersloot D, Zweben J,
Methamphetamine Treatment Project Corporate Authors (2004) A multi-site comparison of
psychosocial approaches for the treatment of methamphetamine dependence. Addiction
99(6):708–717
Exercise for Substance Use Disorders
59
Larissa J. Mooney, Christopher B. Cooper, Edythe D. London,
Joy Chudzynski, and Richard A. Rawson
Contents
59.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 974
59.2 Exercise as an Intervention for Health Conditions Associated with Substance
Use Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 975
59.2.1 Exercise Is Effective for Medical Conditions and Symptoms . . . . . . . . . . . . . . . . 975
59.2.2 Exercise Is Effective for Psychiatric Conditions and Symptoms . . . . . . . . . . . . . 975
59.2.3 Exercise Improves Cognition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 976
59.2.4 Exercise for Reducing Substance Use and Preventing Relapse . . . . . . . . . . . . . . 977
Abstract
This chapter provides an overview of the rationale and evidence for exercise as
a treatment intervention for substance use disorders. The benefits of exercise on
physical health, including weight and cardiovascular outcomes, are well known;
emerging literature also supports the use of exercise in reducing depression and
anxiety symptoms. These and other negative affect states are common during
withdrawal and early abstinence from substances and may predispose users to
relapse. Exercise may facilitate abstinence by enhancing positive mood states
via effects on the endogenous opioid system and potentiation of dopaminergic
transmission. Furthermore, cognitive deficits have been observed in long-term
substance users, and exercise has been associated with improvement in cognitive
functioning, particularly executive control tasks. The addition of a new,
non-drug-related activity such as exercise may provide a reinforcing alternative
behavior that may complement relapse prevention skills taught in common
therapy approaches for substance users while promoting health and positive
behavioral changes consistent with treatment goals.
59.1 Introduction
There is clear scientific evidence that physical exercise can have a positive effect as
an intervention for a variety of medical and psychiatric disorders and symptoms.
As noted in the 2008 Physical Activity Guidelines for Americans (Leavitt 2008) and
elsewhere (e.g., Lautenschlager et al. 2008; Palmer et al. 1995), exercise appears to
have generally beneficial effects on mood, cognition, and health. In addition, exercise
has been shown to have positive effects in mediating many of the conditions that are
associated with substance use. Research has shown that individuals addicted to drugs
and alcohol experience high levels of negative affect states including depression and
anxiety, which may be ameliorated by exercise (e.g., Reed and Ones 2006). Cogni-
tive impairment (Kramer and Erickson 2007), fatigue, and low energy (e.g., Häuser
et al. 2010) associated with drug use may also improve as a result of exercise.
Direct experience in treating stimulant users has demonstrated the benefits of
exercise. For example, clinicians at the Matrix network of addiction treatment clinics
in Southern California observed that anhedonia and cognitive disruption that persisted
for months after cessation of use appeared to be significantly less severe among those
individuals who engaged in regular exercise as part of their recovery plan (Rawson
et al. 2002). This observation became the basis for a recommendation appearing in
a clinical guide publication: “the experience at Matrix over the past 20 years has
59 Exercise for Substance Use Disorders 975
suggested that if patients can be engaged in a program of physical exercise, they are
more able to manage difficult emotional states. An exercise program, three to five
times per week, appears to help relieve symptoms” (Rawson 2006). This chapter
recounts the experience of the author and colleagues who have employed exercise in
a clinical research study conducted in a community-based residential treatment
program serving patients with stimulant use disorders; initial discussion provides
a brief rationale for exercise as an intervention for substance use disorders.
Aerobic and resistance exercise interventions are useful for a wide range of
psychiatric conditions, including anxiety and depression (Zschucke et al. 2013).
The majority of studies have demonstrated efficacy of exercise in reducing
symptoms of depression in both inpatient (Martinsen et al. 1985) and outpatient
(e.g., McNeil et al. 1991) settings; favorable results have been highlighted in
several review articles (e.g., Barbour et al. 2007; Martinsen 2008) and meta-
analyses (North et al. 1990; Craft and Landers 1998). Exercise has been shown to
reduce depressive symptoms in medically compromised populations, including
cardiac (Pinto et al. 2013) and cancer (McLellan 2013) patients. The benefits of
exercise relative to psychotropic medication (Blumenthal et al. 1999) and
976 L.J. Mooney et al.
psychotherapy (Greist et al. 1979; Klein et al. 1985; Fremont and Craighead 1987)
have also been investigated; equivalent benefits have been found comparing exer-
cise with medication, time-limited or time-unlimited psychotherapy, group therapy,
and cognitive-behavioral therapy.
State anxiety has been shown to acutely diminish after individual episodes of
exercise (Raglin and Morgan 1987), and aerobic exercise may confer significant
benefit in the treatment of adults with moderate to severe panic disorder (Broocks
et al. 1998; Strӧhle et al. 2009) and obsessive compulsive disorder (Abrantes
et al. 2009). The majority of studies have suggested efficacy of exercise in mitigat-
ing stress-related symptoms across a variety of study populations, including
nonclinical (Lion 1978; Bahrke and Morgan 1978; Blumenthal et al. 1982), clinical
(Abrantes et al. 2009), and medically compromised (Prosser et al. 1981) adults.
In a study of adults with significant anxiety sensitivity, a 2-week exercise
intervention significantly reduced anxiety sensitivity relative to no-treatment
control (Smits et al. 2008), an effect which mediated the benefits of exercise on
negative affect states including anxious and depressed mood.
Substance dependence is associated with elevated rates of comorbid psychiatric
disorders, particularly depressive and anxiety disorders (e.g., Mason et al. 1998;
Glasner-Edwards et al. 2008). Severity of psychiatric symptoms has been associ-
ated with poorer treatment outcomes in multiple prior studies (e.g., Rounsaville
et al. 1986; Cacciola et al. 2001; Glasner-Edwards et al. 2009). Upon cessation of
drug use, abstinence syndromes comprising prominent psychiatric features may
emerge (e.g., McGregor et al. 2005). Syndromes may be characterized by drug
cravings coupled with marked depressive symptoms including anhedonia, dyspho-
ria, irritability, poor concentration, hypersomnia, low energy, and even suicidality
(Meredith et al. 2005). The contribution of emotional stress to drug use and relapse
has been well documented (e.g., Sinha et al. 2006; Fox et al. 2007; Tate et al. 2008),
and considerable evidence is accumulating to suggest that substance abusers exhibit
deficits in their ability to process and regulate such stress.
cocaine seeking relative to those who did not have access to such activity (Lynch
et al. 2010). The majority of clinical research has focused on aerobic exercise as
a potential intervention to aid smoking cessation and has shown mixed effects of
exercise on smoking abstinence; more consistent positive effects on cigarette
cravings, withdrawal symptoms, and smoking-related behaviors after exercise
sessions have been demonstrated (Taylor et al. 2006). In an investigation of
women enrolled in a 12-week cognitive behavioral smoking-cessation program,
subjects were randomized to receive either vigorous aerobic exercise or health
education three times a week (Bock et al. 1999). Those who participated in the
exercise group evidenced significant reductions in cigarette craving, negative
affect, and nicotine withdrawal during most weeks of the program.
More recent observational studies have suggested a preliminary positive effect
of exercise in reducing substance use in both treatment-engaged substance users
(Brown et al. 2010) and in nontreatment-seeking cannabis users (Buchowski
et al. 2011). In the treatment population, it was noted that substance use outcomes
were significantly better among substance users who attended at least 75 % of
exercise sessions (Brown et al. 2010). An 8–9-week structured exercise program
has also demonstrated efficacy in adolescents enrolled in drug treatment programs;
adolescents who improved in self-concept, anxiety, and depression risk factors
reported reduced substance use relative to those who did not improve on similar
measures (Collingwood et al. 1991). Similarly, a prospective investigation of more
than 4,000 twins revealed lower rates of illicit drug use and alcohol use conse-
quences in adulthood among physically active adolescents, supporting prior work
suggesting a relationship between low physical activity in adolescents and drug use
(Korhonen et al. 2009).
In addition to our ongoing study described below, a multisite study is being
conducted in the United States by the Clinical Trials Network (CTN), funded by the
National Institute on Drug Abuse, investigating the benefits of an exercise compo-
nent added to residential programs addressing stimulant use disorders. The
CTN0037 trial, Stimulant Reduction Intervention Using Dosed Exercise
(STRIDE), is a randomized controlled trial to test the effectiveness of the addition
of exercise compared to health education to treatment as usual in improving drug
treatment outcomes in 330 participants with DSM-IV-diagnosed stimulant abuse or
dependence (e.g., cocaine, methamphetamine, amphetamine) and receiving treat-
ment in residential settings; conditions include either Vigorous Intensity High Dose
Exercise Augmentation (VIHD) plus Usual Care or Health Education Intervention
Augmentation (HEI) plus Usual Care.
As indicated in the brief review of the literature, an exercise regime may be useful
in addressing craving, mood states, and resultant drug-seeking behavior that can
lead to relapse. To explore the effectiveness of exercise for stimulant use disorders,
59 Exercise for Substance Use Disorders 979
Dr. Richard Rawson and colleagues at the University of California, Los Angeles,
are conducting an investigation of the utility and efficacy of an 8-week, evidence-
based aerobic and resistance exercise intervention to promote improved treatment
outcomes for a sample of 150 individuals in residential treatment for methamphet-
amine dependence. The study is examining medical, psychiatric, neurocognitive,
and behavioral benefits that may accrue during participation in an 8-week exercise
intervention, as well as possible sustained beneficial impacts on drug use following
completion of the exercise protocol and discharge from the residential treatment
program. The project also includes a brain imaging component to collect data
leading to an improved understanding of the mechanisms that may underlie
observed effects on treatment outcomes and symptom remediation associated
with the exercise intervention.
Methamphetamine-dependent individuals are screened to determine eligibility,
and those randomized to the exercise intervention participate in supervised pro-
gressive endurance and resistance training three times per week for 8 weeks
(24 sessions) consistent with current guidelines for comprehensive exercise pro-
grams (American College of Sports Medicine [ACSM] 2000). Each session consists
of a 5-min warm-up, 30 min of aerobic activity on a treadmill, 15 min of resistance
training, and a 5-min cooldown with stretching and light calisthenics. The goal of
the aerobic training is to accumulate at least 30 min of continuous aerobic exercise
at a target intensity set by data derived from maximal incremental exercise testing
as described below. Information derived from the incremental testing is also used to
define a safe ceiling for exercise intensity for each participant. The goal of the
resistance training is to develop adaptations in muscle strength and body composi-
tion to complement the aerobic training program. A total of nine exercises are
performed each day for major muscle groups.
Participants randomized to the control condition participate in a health and
wellness education session three times a week for 45 min. A counselor provides
informational materials, facilitates discussion of educational content, monitors
attendance, and documents participants’ involvement. Sessions consist of an inte-
grated multimedia educational program addressing a variety of health, wellness,
and lifestyle topics such as nutrition, dental care, acupressure, sleep hygiene, and
health screening, adapted from a previously implemented wellness manual used by
Kinnunen et al. (2008).
All study participants complete a maximal incremental exercise test (XT) on a
treadmill ergometer using a symptom-limited incremental protocol with linear
increases in the work rate with respect to time (Cooper 2001). This test
occurs three times during participation – at baseline, study week 5, and
immediately following the intervention phase or upon intervention termination.
Aerobic capacity VO _ 2 max and the metabolic or lactate threshold VO _ 2 y , which
is the level of oxygen uptake that defines one’s ability to perform prolonged work,
are measured using indirect calorimetry with an automated metabolic measurement
system. The VO _ 2 max and VO _ 2 y are used as baseline markers of aerobic fitness as
well as for objective indices of each individual’s tailored aerobic exercise
intervention.
980 L.J. Mooney et al.
Preliminary data from the study based on the 123 participants randomized by the time
of this writing suggest that methamphetamine users can safely engage in exercise
and can derive significant health benefits over a short period. Data from the
first 29 study completers, randomized to either exercise (EX, n ¼ 15) or health
education (ED, n ¼ 14), were analyzed to evaluate exercise-related physical outcomes,
including aerobic fitness, body composition, and muscle strength. EX subjects
significantly improved maximum oxygen uptake by 0.63 0.22 L/min (21 %),
leg press (LP) strength by 24.4 5.6 kg (40 %), and chest press (CP) strength by
20.6 5.7 kg (49 %). For EX subjects, LP and CP endurance improved by ten
repetitions (120 %) and seven repetitions (96 %), respectively, and these changes
were significantly greater than those seen in ED. Changes in body composition
for EX subjects included significant reductions in body weight (average 1.7
2.4 kg, 2 %), % relative body fat (2.8 1.3 %, 15 %), and fat weight (2.8 1.8 kg,
18 %). None of these variables changed significantly in participants receiving ED
(Dolezal et al. 2013).
Preliminary data collected from 50 participants revealed an increase in heart rate
variability in individuals who participated in the 8-week exercise program, but not
in individuals randomized to the health education control group. Heart rate
59 Exercise for Substance Use Disorders 981
variability reflects the ability of the autonomic nervous system (ANS) to adapt
quickly to stress and changes in the environment and is diminished in stimulant
users (Dolezal et al. 2013). In addition, preliminary results from the PET and MRI
neuroimaging examination of a subset of participants suggest improvement in
dopamine receptor binding after participation in the exercise program. Study
participants in the EX condition demonstrated improvement in D2/D3 binding
after 8 weeks of exercise according to analysis of PET (using18F-fallypride);
matched outpatient controls did not demonstrate increased dopamine receptor
binding after 4 weeks of abstinence only (Robertson et al. 2012).
59.3 Conclusion
Exercise may be a useful approach to aiding individuals with substance use disorders
in their efforts to avoid relapse after they have achieved abstinence via treatment. The
addition of a new, non-drug-related activity may provide a reinforcing alternative
behavior that may be effective in facilitating abstinence by enhancing positive mood
states via effects of exercise on the endogenous opioid system and potentiation of
dopaminergic transmission (Meeusen 2005). Prior literature demonstrates that exer-
cise can improve anxiety and depression, symptoms that are often associated with
initial phases of abstinence after cessation of drug use. Such conditions predispose
individuals to relapse and predict poorer treatment outcomes (e.g., Nunes and Levin
2004; Poling et al. 2007). Exercise also improves sleep (Youngstedt 2005) and
performance on cognitive tasks, which may be impaired in chronic substance users.
In light of the documented associations between stress, negative affect, and
substance relapse in addicted populations (Breslin et al. 2002; Marlatt 1996),
together with evidence demonstrating stress regulation deficits in substance users,
the development of interventions to ameliorate symptoms of depression and
anxiety and improve affect regulation may help to reduce relapse risk in this
population. Relief of distressing psychological symptoms may serve to comple-
ment relapse prevention skills taught in common therapy approaches for sub-
stance users and to promote health and positive behavioral changes consistent
with treatment goals.
References
Abrantes AM, Strong DR, Cohn A, Cameron AY, Greenberg BD, Mancebo MC, Brown RA
(2009) Acute changes in obsessions and compulsions following moderate-intensity
aerobic exercise among patients with obsessive-compulsive disorder. J Anxiety Disord
23(7):923–927
American College of Sports Medicine (2000) ACSM’s guidelines for exercise testing and
prescription, 6th edn. Lippincott Williams & Wilkins, Baltimore
Angelucci F, Ricci V, Pomponi M, Conte G, Mathe AA, Tonali PA, Bria P (2007) Chronic heroin
and cocaine abuse is associated with decreased serum concentrations of the nerve growth factor
and brain-derived neurotrophic factor. J Psychopharmacol 21(8):820–825
982 L.J. Mooney et al.
Angevaren M, Aufdemkampe G, Verhaar HJ, Aleman A, Vanhees L (2008) Physical activity and
enhanced fitness to improve cognitive function in older people without known cognitive
impairment. Cochrane Database Syst Rev 3:CD005381
Bahrke M, Morgan W (1978) Anxiety reduction following exercise and meditation. Cogn Ther
Res 2:323–333
Barbour KA, Edenfield TM, Blumenthal JA (2007) Exercise as a treatment for depression and
other psychiatric disorders: a review. J Cardiopulm Rehabil Prev 27(6):359–367
Bechara A, Damasio H (2002) Decision-making and addiction (part I): impaired activation of
somatic states in substance dependent individuals when pondering decisions with negative
future consequences. Neuropsychologia 40(10):1675–1689
Blumenthal JA, Williams RS, Wallace AG, Williams RB Jr, Needles TL (1982) Physiological and
psychological variables predict compliance to prescribed exercise therapy in patients recover-
ing from myocardial infarction. Psychosom Med 44:519–527
Blumenthal J, Babyak M, Moore K, Craighead WE, Herman S, Khatri P, Waugh R, Napolitano
MA, Forman LM, Appelbaum M, Doraiswamy PM, Krishnan KR (1999) Effects of exercise
training on older patients with major depression. Arch Intern Med 159:2349–2356
Bock BC, Marcus BH, King T, Borrelli B (1999) Exercise reduces withdrawal symptoms and
improves affect among women attempting smoking cessation: results of a randomized con-
trolled clinical trial. Addict Behav 24:399–410
Breslin FC, Zack M, McMain S (2002) An information-processing analysis of mindfulness:
implications for relapse prevention in the treatment of substance abuse. Clin Psychol Sci Pract
9:275–299
Broocks A, Bandelow B, Pekrun G, George A, Meyer T, Bartmann U, Hillmer-Vogel U, R€ uther E
(1998) Comparison of aerobic exercise, clomipramine, and placebo in the treatment of panic
disorder. Am J Psychiatry 155:603–609
Brown RA, Abrantes AM, Read JP, Marcus BH, Jakicic J, Strong DR, Oakley JR, Ramsey SE,
Kahler CW, Stuart GG, Dubreuil ME, Gordon AA (2010) A pilot study of aerobic exercise as
an adjunctive treatment for drug dependence. Ment Health Phys Act 3:27–34
Buchowski MS, Meade NN, Charboneau E, Park S, Dietrich MS, Cowan RL, Martin PR
(2011) Aerobic exercise training reduces cannabis craving and use in nontreatment seeking
cannabis-dependent adults. PLoS ONE 6:e17465
Cacciola JS, Alterman AI, Rutherford MJ, McKay JR, Mulvaney FD (2001) The relationship of
psychiatric comorbidity to treatment outcomes in methadone maintained patients. Drug Alco-
hol Depend 61(3):271–280
Chang YK, Tsai CL, Huang CC, Wang CC, Chu IH (2013) Effects of acute resistance exercise on
cognition in late middle-aged adults: General or specific cognitive improvement? J Sci Med
Sport [Epub ahead of print]
Cipolli C, Galliani I (1987) Addiction time and intellectual impairment in heroin users. Psychol
Rep 60:1099–1105
Colcombe SJ, Kramer AF (2003) Fitness effects on the cognitive function of older adults: a meta-
analytic study. Psychol Sci 14(2):125e–130e
Collingwood TR, Reynolds R, Kohl HW, Smith W, Sloan S (1991) Physical fitness effects on
substance abuse risk factors and use patterns. J Drug Educ 21:73–84
Cooper CB (2001) Exercise in chronic pulmonary disease: aerobic exercise prescription. Med Sci
Sports Exerc 33(7 Suppl):S671–S679
Craft LL, Landers DM (1998) The effects of exercise on clinical depression and de-
pression resulting from mental illness: a metaregression analysis. J Sport Exerc Psychol
20:339–357
Davis PE, Liddiard H, McMillan TM (2002) Neuropsychological deficits and opiate abuse. Drug
Alcohol Depend 67(1):105–108
de Cid R, Fonseca F, Gratacos M, Gutierrez F, Martin-Santos R, Estivill X, Torrens M (2008)
BDNF variability in opioid addicts and response to methadone treatment: preliminary findings.
Genes Brain Behav 7:515–522
59 Exercise for Substance Use Disorders 983
Kramer AF, Erickson KI (2007) Capitalizing on cortical plasticity: influence of physical activity
on cognition and brain function. Trends Cogn Sci 11:342–348
Lautenschlager NT, Cox KL, Flicker L, Foster JK, van Bockxmeer FM, Xiao J, Greenop KR,
Almeida OP (2008) Effect of physical activity on cognitive function in older adults at risk for
Alzheimer disease: a randomized trial. JAMA 300(9):1027–1037
Leavitt MO (2008) 2008 physical activity guidelines for Americans. U.S. Department of Health
and Human Services. http://www.health.gov/paguidelines/pdf/paguide.pdf
Lee RC, Wang Z, Heo M, Ross R, Janssen I, Heymsfield SB (2000) Total-body skeletal muscle
mass: development and cross-validation of anthropometric prediction models1–3. Am J Clin
Nutr 72:796–803
Lion LS (1978) Psychological effects of jogging: a preliminary study. Percept Mot Skills
47:1215–1218
Lohman TG, Roche AF, Martorell R (eds) (1991) Anthropometric standardization reference
manual. Human Kinetics Books, Champaign
Lundqvist T (2005) Cognitive consequences of cannabis use: comparison with abuse of stimulants
and heroin with regard to attention, memory and executive functions. Pharmacol Biochem
Behav 81:319–330
Lynch WJ, Piehl KB, Acosta G, Peterson AB, Hemby SE (2010) Aerobic exercise attenuates
reinstatement of cocaine-seeking behavior and associated neuroadaptations in the prefrontal
cortex. Biol Psychiatry 68:774–777
Marlatt GA (1996) Taxonomy of high-risk situations for alcohol relapse: evolution and develop-
ment of a cognitive-behavioral model. Addiction 91(suppl):37–49
Martinsen EW (2008) Physical activity in the prevention and treatment of anxiety and depression.
Nord J Psychiatry 62(suppl 47):25–29
Martinsen EW, Medhus A, Sandvik L (1985) Effects of aerobic exercise on depression: a
controlled study. Br Med J (Clin Res Ed) 291(6488):109
Mason BJ, Kocsis JH, Melia D, Khuri ET, Sweeney J, Wells A, Borg L, Millman RB, Kreek MJ
(1998) Psychiatric comorbidity in methadone maintained patients. J Addict Dis 17(3):75–89
McDonough SM, Tully MA, O’Connor SR, Boyd A, Kerr DP, O’Neill SM, Delitto A, Bradbury I,
Tudor-Locke C, Baxter DG, Hurley DA (2010) The back 2 activity trial: education and advice
versus education and advice plus a structured walking programme for chronic low back pain.
BMC Musculoskelet Disord 11:163
McGregor C, Srisurapanont M, Jittiwutikarn J, Laobhripatr S, Wongtan T, White JM (2005) The
nature, time course and severity of methamphetamine withdrawal. Addiction 100(9):1320–1329
McLellan R (2013) Exercise programs for patients with cancer improve physical functioning and
quality of life. J Physiother 59(1):57
McNeil JK, LeBlanc EM, Joyner M (1991) The effect of exercise on depressive symptoms in the
moderately depressed elderly. Psychol Aging 6:487–488
Meeusen R (2005) Exercise and the brain: insight in new therapeutic modalities. Ann Transplant
10:49–51
Meredith C, Jaffe C, Ang-Lee K, Saxon A (2005) Implications of chronic methamphetamine use:
a literature review. Harv Rev Psychiatry 13(3):141–154
Mintzer MZ, Stitzer ML (2002) Cognitive impairment in methadone maintenance patients. Drug
Alcohol Depend 67:41–51
National Strength and Conditioning Association (NSCA) (2010) Strength and conditioning pro-
fessional standards and guidelines. NSCA, Colorado Springs. http://www.nsca-lift.org/publi-
cations/SCStandards.pdf
Neeper SA, Gomez-Pinilla F, Choi J, Cotman C (1995) Exercise and brain neurotrophins. Nature
373(6510):109
North TC, McCullagh P, Tran ZV (1990) Effects of exercise on depression. Exerc Sport Sci Rev
18:379–415
Nunes EV, Levin FR (2004) Treatment of depression in patients with alcohol or other drug
dependence: a meta-analysis. JAMA 291:1887–1896
59 Exercise for Substance Use Disorders 985
O’Dell SJ, Galvez BA, Ball AJ, Marshall JF (2012) Running wheel exercise ameliorates
methamphetamine-induced damage to dopamine and serotonin terminals. Synapse 66(1):71–80
Palmer JA, Palmer LK, Michiels K, Thigpen B (1995) Effects of type of exercise on depression in
recovering substance abusers. Percept Mot Skills 80(2):523–530
Paulus MP, Hozack N, Frank L, Brown GG, Schuckit MA (2003) Decision making by
methamphetamine-dependent subjects is associated with error-rate-independent decrease in
prefrontal and parietal activation. Biol Psychiatry 53(1):65–74
Pinto BM, Dunsiger SI, Farrell N, Marcus BH, Todaro JF (2013) Psychosocial outcomes of an
exercise maintenance intervention after phase II cardiac rehabilitation. J Cardiopulm Rehabil
Prev 33(2):91–98
Ploughman M (2008) Exercise is brain food: the effects of physical activity on cognitive function.
Dev Neurorehabil 11:236–240
Poling J, Kosten TR, Sofuoglu M (2007) Treatment outcome predictors for cocaine dependence.
Am J Drug Alcohol Abuse 33:191–206
Prosser G, Carson P, Phillips R, Gelson A, Buch N, Tucker H, Neophytou M, Lloyd M, Simpson
T (1981) Morale in coronary patients following an exercise programme. J Psychosom Res
25:587–593
Raglin JS, Morgan WP (1987) Influence of exercise and quiet rest on state anxiety and blood
pressure. Med Sci Sports Exerc 19:456–463
Rawson RA (2006) Methamphetamine: new knowledge, new treatments. Hazelden, Center City
Rawson RA, McCann MJ, Huber A, Shoptaw S, Farabee D, Reiber C, Ling W (2002)
A comparison of contingency management and cognitive-behavioral approaches for cocaine
dependent methadone-maintained individuals. Arch Gen Psychiatry 59:817–824
Reed J, Ones DS (2006) The effect of acute aerobic exercise on positive activated affect: a meta-
analysis. Psychol Sport Exerc 7:477–514
Robertson CL, Chudzynski J, Rawson R, Cooper C, Mooney L, Brown AK, Mandelkern MA,
Ishibashi K, London ED (2012) Increased caudate dopamine D2/3 receptor binding
after abstinence from chronic methamphetamine in a treatment program including
exercise. Poster presented at college on problems of drug dependence 74th annual meeting,
Palm Desert
Rounsaville BJ, Kosten TR, Weissman MM, Kleber HD (1986) Prognostic significance of
psychopathology in treated opiate addicts. A 2.5-year follow-up study. Arch Gen Psychiatry
43(8):739–745
Russo-Neustadt AA, Beard RC, Huang YM, Cotman CW (2000) Physical activity and antidepres-
sant treatment potentiate the expression of specific brain-derived neurotrophic factor tran-
scripts in the rat hippocampus. Neuroscience 101:305–312
Seifert T, Brassard P, Wissenberg M, Rasmussen P, Nordby P, Stallknecht B, Adser H, Jakobsen
AH, Pilegaard H, Nielsen HB, Secher NH (2010) Endurance training enhances BDNF release
from the human brain. Am J Physiol Regul Integr Comp Physiol 298:R372–R377
Shirado O, Doi T, Akai M, Hoshino Y, Fujino K, Hayashi K, Marui E, Iwaya T (2010) Multicenter
randomized controlled trial to evaluate the effect of home-based exercise on patients with
chronic low back pain: the Japan low back pain exercise therapy study. Spine (Phila Pa 1976)
35(17):E811–E819
Simon SL, Domier CP, Sim T, Richardson K, Rawson RA, Ling W (2002) Cognitive performance
of current methamphetamine and cocaine abusers. J Addict Dis 21:61–74
Sinha R, Garcia M, Paliwal P, Kreek MJ, Rounsaville BJ (2006) Stress-induced cocaine craving
and hypothalamic-pituitary-adrenal responses are predictive of cocaine relapse outcomes. Arch
Gen Psychiatry 63(3):324–331
Smits JA, Berry AC, Rosenfield D, Powers MB, Behar E, Otto MW (2008) Reducing anxiety
sensitivity with exercise. Depress Anxiety 25:689–699
Ströhle A, Graetz B, Scheel M, Wittmann A, Feller C, Heinz A, Dimeo F (2009) The acute
antipanic and anxiolytic activity of aerobic exercise in patients with panic disorder and healthy
control subjects. J Psychiatr Res 43(12):1013–1017
986 L.J. Mooney et al.
Tate SR, Wu J, McQuaid JR, Cummins K, Shriver C, Krenek M, Brown SA (2008) Comorbidity of
substance dependence and depression: role of life stress and self-efficacy in sustaining absti-
nence. Psychol Addict Behav 22(1):47–57
Taylor RS, Unal B, Critchley JA, Capewell S (2006) Mortality reductions in patients receiving
exercise-based cardiac rehabilitation: how much can be attributed to cardiovascular risk factor
improvements? Eur J Cardiovasc Prev Rehabil 13:369–374
Youngstedt SD (2005) Effects of exercise on sleep. Clin J Sport Med 24:355–365
Zschucke E, Gaudlitz K, Strӧhle A (2013) Exercise and physical activity in mental disorders:
clinical and experimental evidence. J Prev Public Health 46:S12–S21
Computerized Therapies: Towards an
Addiction Treatment Technology Test 60
Alan J. Budney, Lisa A. Marsch, and Warren K. Bickel
Contents
60.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 988
60.2 Technology Development, Testing, and Application . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 991
60.2.1 Psychosocial Interventions and Their Translation to Technology-Based
Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 991
60.2.2 Computerized Interventions for Related Problems . . . . . . . . . . . . . . . . . . . . . . . . . . 998
60.2.3 Innovative Technologies to Enhance Effective Psychosocial
Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 998
60.2.4 International Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1001
60.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1002
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1003
Abstract
Information technology is broadly influencing many aspects of modern life,
including the activities of healthcare users and providers. As part of this evolution,
Disclosure: In addition to their academic affiliation, Drs. Bickel and Marsch are affiliated with
HealthSim, LLC, the health-promotion software development organization that developed the
Web-based Therapeutic Education System referenced in this manuscript. They have worked
extensively with their institutions to manage any potential conflict of interest.
A.J. Budney (*)
Dartmouth Psychiatric Research Center, Department of Psychiatry, Geisel School of Medicine at
Dartmouth, Dartmouth College, Lebanon, NH, USA
e-mail: [email protected]
L.A. Marsch
Center for Technology and Behavioral Health, Dartmouth Psychiatric Research Center,
Department of Psychiatry, Geisel School of Medicine at Dartmouth, Dartmouth College, Lebanon,
NH, USA
e-mail: [email protected]
W.K. Bickel
Virginia Tech Carilion Research Institute, Roanoke, VA, USA
e-mail: [email protected]
opportunities for utilizing technology are being realized and evaluated in the field of
addiction. This chapter reviews progress toward achieving the goals of an Addiction
Treatment Technology Test that comprises development of technological applica-
tions that advance the addiction treatment delivery system by facilitating better
access to care, improving efficiency of treatment delivery, enhancing treatment
outcomes, proliferating the translation and implementation of evidence-based inter-
ventions, and fostering implementation of cost-effective care. The chapter provides
an overview of the types of treatments that have been adapted for technology
delivery, a review of studies that have evaluated computer- and Web-based pro-
grams, and examples of innovative technology-based applications designed to
supplement or enhance traditional psychosocial therapies. We synthesize these
findings into general conclusions recognizing the limitations of current knowl-
edge. We additionally discuss the prospects for current use and future possibilities.
Understanding optimal models of deployment of addiction treatment may be
particularly important in light of evolving healthcare systems (such as those
evolving under the Affordable Care Act in the USA). We view the future
optimistically and anticipate that continued research exploring novel aspects of
addiction and its treatment will reveal interventions that can be effectively
deployed using innovative technological approaches. Such technologies can
clearly extend the reach of our interventions, which will contribute to improving
the lives of those suffering from problems related to addiction.
60.1 Introduction
treatment can avoid the challenges of waiting lists and can be used by countless numbers
of individuals concurrently. Second, technology-delivered treatment can be accessed
where the patients live, even if they live in rural or other environments that make the
commute to treatment difficult. Third, this type of treatment needs not be restricted to
office hours or provider availability. Therefore, this treatment is available in principle all
the time and potentially for greater durations of time. Another benefit for patients is that
by not directly interacting with a human change agent, they may find it easier to address
sensitive issues, such as addiction and other related topics like HIV status, as suggested by
several studies (Kobak et al. 1996; Marsch and Bickel 2004).
For the provider of care, there are at least three benefits. First, technology-delivered
treatment has the potential to dramatically lower costs; that is because even in hybrid
models where therapists also participate and monitor the use of technology-based
treatment, less therapist time would be required per case (e.g., Bickel et al. 2008;
Budney et al. 2011). Second, treatments that are delivered via technology will be
conducted with fidelity. One reason for the loss of efficacy of providing evidence-based
treatments in many community-based systems of care is that the treatment is provided
without being faithful to intended procedures, which, in turn, renders the treat-
ment both not evidence based and less likely to be effective. Third, providing
treatment via technologies permits new scientific information to be rapidly and
continuously incorporated into contemporary treatment without the effort and
expensive task of training therapists in each novel innovation. Collectively, these
and other potential benefits provide a strong case for incorporating this novel
approach into routine care.
Fortunately, opportunities for optimally utilizing technology have begun to be
realized and evaluated in the field of addiction. Given this increased activity in the
space of technology-delivered treatment for addiction, we can consider what might
constitute a modern-day Turing test, perhaps labeled the Addiction Treatment Tech-
nology Test. This test would consist of the development of technological applications
that advance the addiction treatment delivery system by facilitating better access to
care, improving efficiency of treatment delivery from both the patient and provider
perspective, enhancing treatment outcomes, proliferating the translation and imple-
mentation of evidence-based interventions, and fostering implementation of cost-
effective care. We hope that the posing of an Addiction Treatment Technology Test,
like the framing of the Turing test, will prompt the development and improvement of
information technology as related to such therapeutic ends.
In this chapter, we review the current status and postulate future directions of
technology-delivered treatments for substance use disorders. In doing so, we first
briefly review and describe the types of treatments that have been adapted for
technology-delivered treatment. Second, we concisely review those studies that
have evaluated computer- and Web-based programs. Third, we provide examples
of innovative technology-based applications designed to supplement or enhance
traditional psychosocial therapies. Finally, we synthesize the findings into general
conclusions with recognition of the limitations of current knowledge, prospects for
current use, future possibilities, as well as assessment of the status of the field with
respect to the Addiction Treatment Technology Test.
60 Computerized Therapies: Towards an Addiction Treatment Technology Test 991
that the positive effects endured over time (Carroll et al. 2009). There were
statistically significant increases in mean ratings of the quality of participants’
coping responses for those assigned to CBT4CBT compared to treatment as
usual, and these differences remained significant 3 months after treatment comple-
tion. Moreover, quality of coping responses mediated the effect of treatment on
participants’ duration of abstinence during the follow-up period (Kiluk et al. 2010).
Last, the clinic cost of adding CBT4CBT approximates just $39 per participant
(Olmstead et al. 2010).
initial findings with 107 postpartum women (Ondersma et al. 2007). More reduction
in self-reported indicators of illicit drug use (nonsignificant effects, but mild to
moderate effect sizes) was observed for the MES participants at a 4-month follow-up.
The MES has been adapted and piloted for alcohol reduction in pregnant women
(Tzilos et al. 2011). This same research group adapted the MES for smoking using
the 5-As brief intervention model for smoking cessation and tested it in combination
with a CM incentive program (also computer assisted: Ondersma et al. 2012). Findings
from this study of 110 pregnant smokers suggested that the computerized 5-As program
improved abstinence and increased discussion with a health professional about smoking
cessation.
The TES program described above was modified to add an MET component
similar to the DCU in an initial study of outpatient treatment for cannabis use
disorders (Budney et al. 2011). Parallel, nine-session MET/CBT therapist- and
computer-delivered programs were compared in an initial quasi-experimental trial
in which both groups also received abstinence-based CM. The computerized
condition also involved three brief supportive therapy sessions. Cannabis use and
abstinence outcomes did not differ between conditions during treatment, and no
differences were observed on other secondary outcomes such as problems related to
marijuana, self-efficacy, or use of coping skills strategies. The mean amount of
therapist time per case was approximately tenfold greater in the therapist-delivered
condition, suggesting substantial cost savings associated with the computerized
MET/CBT. Preliminary findings reported from a second trial replicated and
extended these findings, suggesting that the computer- and therapist-delivered
MET/CBT showed comparable outcomes both during treatment and throughout
a 12-month follow-up period.
A research group from Australia developed a similar computer-delivered
CBT-type program to treat cannabis or alcohol problems and depression
(Kay-Lambkin et al. 2009, 2011). This eight-session program focuses on the usual
CBT skills, using a motivational interviewing (MI) style to interact with the partic-
ipant related to goal setting and change planning. It concurrently provides content
underscoring the relationship between substance misuse and depressive symptoms. In
a randomized trial, 97 adults with major depressive disorder and problems with
alcohol or cannabis use first received a one-session, brief MI interview targeting
depressive symptoms and substance misuse followed by one of three conditions:
(1) no further treatment, (2) nine sessions of CBT/MI delivered by a psychologist, or
(3) nine sessions of CBT/MI delivered by a computer with concomitant 10–15 check-
in sessions with a therapist at the end of each session. Acceptability, treatment
retention, and therapeutic alliance did not differ between the CBT/MI conditions.
The CBT/MI conditions produced better cannabis, alcohol, and depression outcomes
than the brief intervention alone. The computerized intervention showed the largest
effects on substance use outcomes. The therapist-delivered CBT showed better short-
term outcomes on depression, but similar outcomes to the computer condition at
12 months.
A larger replication trial compared the same two CBT/MI conditions and a ten-
session supportive, person-centered therapy (PCT) (Kay-Lambkin et al. 2011).
996 A.J. Budney et al.
cumulative drug testing results, and a place for messages (e.g., social reinforcement
or encouragement). The data needed to provide this information can be either entered
manually by staff or sent directly from a computer integrated with drug testing
analyzers. Although this does not fully automate a CM program, it helps systematize
delivery and eases staff burden associated with administering CM.
The Therapeutic Workplace (TWP) is a novel, employment-based treatment
intervention that has considerable potential for promoting sustained abstinence
from alcohol and drugs while simultaneously addressing some of their interrelated
problems of poverty, unemployment, and homelessness. The TWP integrates an
abstinence-based reinforcement (CM) program (using the Motiv8 platform) with
a CM-based employment program. A sophisticated, Web-based training and
employment system trains, hires, and pays participants to work each day, using
behavior analytic principles of learning and reinforcement (Silverman et al. 2001,
2005). The application operates from a PC server that is networked with staff
and participant workstations. TWP software establishes users with a bar-coded pic-
ture ID card. The program records each trainee’s arrival time and determines whether
the trainee arrived to work on time. On days in which urine collection is required, the
software requests urinalysis results, and if required test results are negative, the
software grants access to the workroom. Drug-positive results deny access. Comput-
erized typing, keypad, and data entry training programs are delivered to all partici-
pants, who take placement tests to determine at which step to begin training. The
software monitors performance and automatically moves participants through each
step of the program as they meet the speed and accuracy requirements.
An Activities and Earnings section of the participant’s home page displays
earnings for the current day, account balance, and key parameters that can affect
earnings. The Base Pay section shows the current day’s base pay hourly rate,
minutes spent out of the workroom, hours worked, hours that earned the base pay
rate, and total base pay earnings. The Administrative section shows additional
administrative pay. The Training section data on training activities, number of
correct and incorrect responses, the amount earned completion bonuses (Bonus),
and the earnings for each program. For participants who advance to paid operators,
the Data Entry section includes information for all work batches completed on the
current day including the pay rate, the number of errors and amount lost for each,
and the total earnings. Each participant has an Inbox to receive files and messages.
Purchases from earnings are requested and tracked through the software.
The TWP has demonstrated effectiveness across multiple controlled studies
in diverse subpopulations of substance abusers including heroin- and cocaine-
using treatment-resistant young mothers (Silverman et al. 2001, 2002) and unem-
ployed injection drug and crack cocaine users (Donlin et al. 2008; DeFulio et al.
2009; Dunn et al. 2013), homeless alcohol dependent (Koffarnus et al. 2011), and
opioid-dependent adults (Everly et al. 2011). Such strong empirical support for the
TWP and its Web-based technology clearly demonstrates how a technology-based
system can produce cost-effective, sustainable effects with great potential for
dissemination.
998 A.J. Budney et al.
regular reminders of specific goals and planned actions. Providers and patients
could together develop and program messages to be sent at specific times and as
often as deemed useful. With cell phone ownership having become the norm,
almost all patients could benefit from this type of intervention if it proves effica-
cious in supplementing CBT/CRA.
Second, smartphones (i.e., cell phones with computing ability), Internet
connectivity, and in some cases global position systems (GPS), offer even more
possibilities than utilization of SMS (Gustafson et al. 2011; Marsch 2012). Access
to the Internet and the ability to run software applications (Apps) translate into
capability for delivering the same types of psychosocial therapy programs
described above for the personal computer, but with the added benefit of access
anywhere at anytime. Capitalizing on the mobile dimension of smartphones and
their GPS capability, researchers have begun to develop and test “warning” systems
that prompt coping responses from the user when she or he goes somewhere
designated as a high-risk environment. Similarly, GPS tracking could be used to
increase monitoring capabilities such that, for example, parents could increase
awareness of their teens’ whereabouts, a common goal in family-based therapies
or prevention programs. Another example under development is smartphone inte-
gration with wireless devices that measure physiological responses (e.g., indicators
of stress or craving). Detection of specific responses would trigger an automatic
communication with the phone that would prompt or deliver a therapeutic coping
intervention (e.g., Boyer et al. 2010). These types of innovative uses of technology
to enhance CBT/CRA interventions are only just beginning to be realized and
tested.
Virtual reality (VR), i.e., computer-simulated experiences that utilize visual,
auditory, tactile, or olfactory sensory features to facilitate active participation in
simulated environments, offers another exciting possible method for augmenting
the learning of behavioral coping responses to high-risk situations. VR can simulate
realistic substance use environments and provide opportunities to practice skills
consistent with successfully negotiating the risk situations without substance
(Bordnick et al. 2011). Exposure therapies for specific phobias and posttraumatic
stress disorder have effectively utilized VR to enhance outcomes (e.g., Gerardi
et al. 2010; Meyerbroker and Emmelkamp 2010). Similar projects are under way in
the substance abuse field that use VR to improve cue exposure therapies targeting
reduction in cravings associated with specific environmental situations.
Last, video game platforms may offer another promising paradigm for
supplementing CBT/CRA interventions (e.g., Raiff et al. 2012). Such games
could provide a medium that includes modeling of coping skills via culture- and
gender-relevant characters and environments and reinforcement of mastery and
effective use of coping skills. The player would be faced with making decisions in
various substance use or related situations that lead to “realistic” consequences.
Advancing to higher levels or winning the game would require effective decision
making and use of coping skills associated with refusal to use or responsible use of
substances. Health behavior video games, including some that target prevention of
substance abuse, are already a reality (Marsch et al. 2007a, b; Schinke et al. 2009).
1000 A.J. Budney et al.
whose family members are struggling with addiction, these networks would
increase access to support, guidance, and skills training related to coping effectively
with their child or spouse.
60.3 Conclusion
The brief review included in this chapter illustrates how the exploration of
technology-delivered or technology-assisted therapies for substance use problems
has been developing for some time, shows great promise, and is gathering momen-
tum. The accumulation of data and knowledge has progressed to the extent that
a “review of reviews” recently appeared in the literature and identified 9 meta-
analytic and 13 qualitative reviews of technology-based interventions for substance
use disorders (Litvin et al. 2013). This review concluded that “technology-based
interventions for substance use problems are efficacious, but effect sizes are
generally small to medium at best and treatment mechanisms remain largely
unknown”; a conclusion that most would agree closely parallels the status of the
majority of traditional therapist-delivered interventions.
Although research to date is promising, we have a long way to go to pass our
Addiction Treatment Technology Test. Multiple studies have demonstrated that
treatment models assisted by computer- or Web-based delivery of evidenced-based
interventions (MET, CBT, CRA, CM) have the potential to improve access to care,
reduce costs, and improve efficiency of treatment delivery. However, in order to
advance the potential public health impact of this research, several areas warrant
further investigation. Among these is the need for an expansion of research that
embraces an implementation science framework in evaluating models for best
integrating evidence-based technology-based innovations in diverse community
settings, bringing value to all relevant stakeholders in a care setting, and promoting
their sustained use. These models may include evaluation of technology-based
therapeutic tools as supplements to standard care models, as tools that can replace
a portion of “treatment as usual,” or as stand-alone tools accessed outside of care
settings. Results of such research offer the potential to generate knowledge regard-
ing models for accelerating the process from research discovery in this arena to
public health benefit.
A related area of inquiry that could greatly benefit the field is an expanded focus
on economic analyses that parallel analyses of clinical effectiveness. An under-
standing of the cost-effectiveness and cost-benefit of technology-based interven-
tions, and the conditions and deployment models under which they do/do not
demonstrate cost-effectiveness and cost-benefit, is critical in efforts to scale up
their deployment. Understanding optimal models of deployment may be particu-
larly important in light of evolving healthcare systems (such as those evolving
under the Affordable Care Act in the USA).
Further, another important area of future efforts is an increased research focus on
the mechanisms of behavior change from technology-based interventions compared
to traditionally delivered approaches. Given their “on-demand” availability and
opportunities for personalization, technology-based interventions may impact the
rate and nature by which health behavior change occurs. An increased understand-
ing of the active ingredients and mediators of outcome from technology-based
therapeutic tools can greatly enhance future efforts to optimize technology devel-
opment efforts. This understanding could additionally aid the research field of
60 Computerized Therapies: Towards an Addiction Treatment Technology Test 1003
References
Acosta MC, Marsch LA et al (2012) A web-based behavior therapy program influences the
association between cognitive functioning and retention and abstinence in clients receiving
methadone maintenance treatment. J Dual Diagn 8(4):283–293
Alfonso JP, Caracuel A et al (2011) Combined goal management training and mindfulness
meditation improve executive functions and decision-making performance in abstinent
polysubstance abusers. Drug Alcohol Depend 117(1):78–81
Bechara A (2005) Decision making, impulse control and loss of willpower to resist drugs:
a neurocognitive perspective. Nat Neurosci 8(11):1458–1463
Bickel WK, Marsch LA et al (2008) Computerized behavior therapy for opioid-dependent out-
patients: a randomized controlled trial. Exp Clin Psychopharmacol 16(2):132–143
Bickel WK, Jarmolowicz DP et al (2011a) The behavioral economics and neuroeconomics of
reinforcer pathologies: implications for etiology and treatment of addiction. Curr Psychiatry
Rep 13(5):406–415
Bickel WK, Yi R et al (2011b) Remember the future: working memory training decreases delay
discounting among stimulant addicts. Biol Psychiatry 69(3):260–265
Bickel WK, Jarmolowicz DP et al (2012) Are executive function and impulsivity antipodes? A
conceptual reconstruction with special reference to addiction. Psychopharmacology
221(3):361–387
Blankers M, Koeter MW et al (2011) Internet therapy versus internet self-help versus no treatment
for problematic alcohol use: a randomized controlled trial. J Consult Clin Psychol 79(3):330–341
1004 A.J. Budney et al.
Boden MA (ed) (1990) The philosophy of artificial intelligence (Oxford Readings in Philosophy).
Oxford University Press, New York
Bordnick PS, Carter BL et al (2011) What virtual reality research in addictions can tell us about the
future of obesity assessment and treatment. J Diabetes Sci Technol 5(2):265–271
Boyer EW, Smelson D et al (2010) Wireless technologies, ubiquitous computing and mobile
health: application to drug abuse treatment and compliance with HIV therapies. J Med Toxicol
6(2):212–216
Budney A, Fearer S et al (2011) An initial trial of a computerized behavioral intervention for
cannabis use disorder. Drug Alcohol Depend 115:74–79
Carroll KM, Ball SA et al (2008) Computer-assisted delivery of cognitive-behavioral therapy for
addiction: a randomized trial of CBT4CBT. Am J Psychiatry 165(7):881–888
Carroll KM, Ball SA et al (2009) Enduring effects of a computer-assisted training program for
cognitive behavioral therapy: a 6-month follow-up of CBT4CBT. Drug Alcohol Depend
100(1–2):178–181
Crick F, Koch C (2003) A framework for consciousness. Nat Neurosci 6(2):119–126
Dallery J, Glenn IM (2005) Effects of an Internet-based voucher reinforcement program for
smoking abstinence: a feasibility study. J Appl Behav Anal 38(3):349–357
Dallery J, Glenn IM et al (2007) An internet-based abstinence reinforcement treatment for
cigarette smoking. Drug Alcohol Depend 86(2–3):230–238
Dallery J, Meredith S et al (2008) A deposit contract method to deliver abstinence reinforcement
for cigarette smoking. J Appl Behav Anal 41(4):609–615
DeFulio A, Donlin WD et al (2009) Employment-based abstinence reinforcement as
a maintenance intervention for the treatment of cocaine dependence: a randomized controlled
trial. Addiction 104(9):1530–1538
Deglise C, Suggs LS et al (2012) SMS for disease control in developing countries: a systematic
review of mobile health applications. J Telemed Telecare 18(5):273–281
Des Jarlais DC, Paone D et al (1999) Audio-computer interviewing to measure risk behaviour for
HIV among injecting drug users: a quasi-randomised trial. Lancet 353(9165):1657–1661
Donlin WD, Knealing TW et al (2008) Attendance rates in a workplace predict subsequent
outcome of employment-based reinforcement of cocaine abstinence in methadone patients.
J Appl Behav Anal 41(4):499–516
Dunn KE, Defulio A et al (2013) Employment-based reinforcement of adherence to oral naltrex-
one treatment in unemployed injection drug users. Exp Clin Psychopharmacol 21(1):74–83
Everly JJ, DeFulio A et al (2011) Employment-based reinforcement of adherence to depot
naltrexone in unemployed opioid-dependent adults: a randomized controlled trial. Addiction
106(7):1309–1318
Gerardi M, Cukor J et al (2010) Virtual reality exposure therapy for post-traumatic stress disorder
and other anxiety disorders. Curr Psychiatry Rep 12(4):298–305
Gibbons MC, Fleisher L et al (2011) Exploring the potential of Web 2.0 to address health
disparities. J Health Commun 16(Suppl 1):77–89
Goldzweig CL, Towfigh A et al (2009) Costs and benefits of health information technology: new
trends from the literature. Health Aff 28(2):w282–w293
Grohman K, Fals-Stewart W (2003) Computer-assisted cognitive rehabilitation with substance
abusing patients; effects on treatment response. J Cogn Rehabil 21:1–9
Grohman K, Fals-Stewart W et al (2006) Improving treatment response of cognitively impaired
veterans with neuropsychological rehabilitation. Brain Cogn 60(2):203–204
Gustafson DH, Boyle MG et al (2011) An e-health solution for people with alcohol problems.
Alcohol Res Health 33(4):327–337
Hester RK, Delaney HD (1997) Behavioral self-control program for windows: results of
a controlled clinical trial. J Consult Clin Psychol 65(4):686–693
Hester RK, Squires DD et al (2005) The drinker’s check-up: 12-month outcomes of a controlled
clinical trial of a stand-alone software program for problem drinkers. J Subst Abuse Treat
28(2):159–169
60 Computerized Therapies: Towards an Addiction Treatment Technology Test 1005
Hester RK, Delaney HD et al (2012) The college drinker’s check-up: outcomes of two randomized
clinical trials of a computer-delivered intervention. Psychol Addict Behav 26(1):1–12
Horvath T, Azman H et al (2012) Mobile phone text messaging for promoting adherence to
antiretroviral therapy in patients with HIV infection. Cochrane Database Syst Rev
3, CD009756
Houben K, Wiers RW et al (2011) Getting a grip on drinking behavior: training working memory
to reduce alcohol abuse. Psychol Sci 22(7):968–975
International Telecommunication Union (2012) ITU world telecommunication/ICT indicators
database. Statistical highlights
ITU (2011) The world in 2011: ICT facts and figures. International Telecommunications Union,
Geneva
Kayingo G (2012) Transforming global health with mobile technologies and social enterprises:
global health and innovation conference. Yale J Biol Med 85(3):425–427
Kay-Lambkin FJ, Baker AL et al (2009) Computer-based psychological treatment for comorbid
depression and problematic alcohol and/or cannabis use: a randomized controlled trial of
clinical efficacy. Addiction 104(3):378–388
Kay-Lambkin FJ, Baker AL et al (2011) Clinician-assisted computerised versus therapist-
delivered treatment for depressive and addictive disorders: a randomised controlled trial.
Med J Aust 195(3):S44–S50
Kiluk BD, Nich C et al (2010) Quality versus quantity: acquisition of coping skills following
computerized cognitive-behavioral therapy for substance use disorders. Addiction
105(12):2120–2127
Kobak KA, Greist JH et al (1996) Computer-administered clinical rating scales. A review.
Psychopharmacology 127(4):291–301
Koffarnus MN, Wong CJ et al (2011) A randomized clinical trial of a therapeutic workplace for
chronically unemployed, homeless, alcohol-dependent adults. Alcohol Alcohol 46(5):561–569
Kurth AE, Martin DP et al (2004) A comparison between audio computer-assisted self-interviews
and clinician interviews for obtaining the sexual history. Sex Transm Dis 31(12):719–726
Kurzweil R (2012) How to create a mind: the secret of human thought revealed. Viking, London
Litvin EB, Abrantes AM et al (2013) Computer and mobile technology-based interventions for
substance use disorders: an organizing framework. Addict Behav 38(3):1747–1756
Marsch LA (2012) Leveraging technology to enhance addiction treatment and recovery. J Addict
Dis 31(3):313–318
Marsch LA, Bickel WK (2004) Efficacy of computer-based HIV/AIDS education for injection
drug users. Am J Health Behav 28(4):316–327
Marsch LA, Bickel WK et al (2007a) Applying computer technology to substance abuse preven-
tion science: results of a preliminary examination. J Child Adolesc Subst Abuse 16(2):69–94
Marsch LA, Bickel WK et al (2007b) Application of interactive, computer technology to adoles-
cent substance abuse prevention and treatment. Adolesc Med State Art Rev 18(2):342–356, xii
Marsch LA, Grabinski MJ et al (2011) Computer-assisted HIV prevention for youth with sub-
stance use disorders. Subst Use Misuse 46(1):46–56
Meredith SE, Grabinski MJ et al (2011) Internet-based group contingency management to promote
abstinence from cigarette smoking: a feasibility study. Drug Alcohol Depend 118(1):23–30
Meyerbroker K, Emmelkamp PM (2010) Virtual reality exposure therapy in anxiety disorders:
a systematic review of process-and-outcome studies. Depress Anxiety 27(10):933–944
Noar SM, Webb EM et al (2011) Using computer technology for HIV prevention among African-
Americans: development of a tailored information program for safer sex (TIPSS). Health Educ
Res 26(3):393–406
Olmstead TA, Ostrow CD et al (2010) Cost-effectiveness of computer-assisted training in
cognitive-behavioral therapy as an adjunct to standard care for addiction. Drug Alcohol
Depend 110(3):200–207
Ondersma SJ, Chase SK et al (2005) Computer-based brief motivational intervention for perinatal
drug use. J Subst Abuse Treat 28(4):305–312
1006 A.J. Budney et al.
Ondersma SJ, Svikis DS et al (2007) Computer-based brief intervention a randomized trial with
postpartum women. Am J Prev Med 32(3):231–238
Ondersma SJ, Svikis DS et al (2012) A randomized trial of computer-delivered brief intervention
and low-intensity contingency management for smoking during pregnancy. Nicotine Tob Res
14(3):351–360
Pedrero-Perez EJ, Rojo-Mota G et al (2011) Cognitive remediation in addictions treatment. Rev
Neurol 52(3):163–172
Pemberton MR, Williams J et al (2011) Evaluation of two web-based alcohol interventions in the
U.S. military. J Stud Alcohol Drugs 72(3):480–489
Raiff BR, Jarvis BP et al (2012) Prevalence of video game use, cigarette smoking, and accept-
ability of a video game-based smoking cessation intervention among online adults. Nicotine
Tob Res 14(12):1453–1457
Reynolds B, Dallery J et al (2008) A web-based contingency management program with adoles-
cent smokers. J Appl Behav Anal 41(4):597–601
Schaub M, Sullivan R et al (2011) Snow control – an RCT protocol for a web-based self-help
therapy to reduce cocaine consumption in problematic cocaine users. BMC Psychiatry 11:153
Schinke SP, Fang L et al (2009) Preventing substance use among adolescent girls: 1-year outcomes
of a computerized, mother-daughter program. Addict Behav 34(12):1060–1064
Schneider SJ, Walter R et al (1990) Computerized communication as a medium for behavioral
smoking cessation treatment: controlled evaluation. Comput Hum Behav 6:141–151
Silverman K, Svikis D et al (2001) A reinforcement-based therapeutic workplace for the treatment
of drug abuse: six-month abstinence outcomes. Exp Clin Psychopharmacol 9:14–23
Silverman K, Svikis D et al (2002) A reinforcement-based therapeutic workplace for the treatment
of drug abuse: three-year abstinence outcomes. Exp Clin Psychopharmacol 10(3):228–240
Silverman K, Wong CJ et al (2005) A web-based therapeutic workplace for the treatment of drug
addiction and chronic unemployment. Behav Modif 29(2):417–463
Stephenson N (1995) The diamond age: or, a young lady’s illustrated primer (Bantam Spectra
Book). Bantam Dell, A Division of Random House, New York
Stoops WW, Dallery J et al (2009) An internet-based abstinence reinforcement smoking cessation
intervention in rural smokers. Drug Alcohol Depend 105(1–2):56–62
Swendeman D, Rotheram-Borus MJ (2010) Innovation in sexually transmitted disease and HIV
prevention: internet and mobile phone delivery vehicles for global diffusion. Curr Opin
Psychiatry 23(2):139–144
Turing AM (1950) Computing machinery and intelligence. Mind 59:433–460
Tzilos GK, Sokol RJ et al (2011) A randomized phase I trial of a brief computer-delivered
intervention for alcohol use during pregnancy. J Womens Health 20(10):1517–1524
United States Census Bureau (2013) U.S. and world population clocks. U.S. Department of
Commerce
Whittaker R, McRobbie H et al (2012) Mobile phone-based interventions for smoking cessation.
Cochrane Database Syst Rev 11, CD006611
Cultural Adaptation of Empirically-
Validated Therapies for Treating Drug 61
Dependence
Contents
61.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1008
61.1.1 The Case for the Cultural Adaptation of Drug Abuse Treatments . . . . . . . . . . 1008
61.1.2 Issues Involving Fidelity and Adaptation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1009
61.2 Intervention Exemplar, Perspectives on Evidence, and International
Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1012
61.2.1 Description of Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1012
61.2.2 Evidence to Support the Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1014
61.2.3 International Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1016
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1025
Abstract
Efficacious drug abuse treatments (empirically validated treatments – EVTs) are
those that have been designed by applying scientific theory and principles of
effective drug abuse treatment. These EVTs are defined as efficacious when
tested in randomized controlled trials that demonstrate that they “work” in
promoting abstinence from drug use, in avoiding relapse, and in attaining
targeted treatment outcomes. In principle, efficacious treatments should be
implemented with fidelity in the delivery of the core elements necessary for
effective treatment. By contrast, the need for local adaptations of these EVTs has
emerged based on the considerable diversity in client needs that exists worldwide,
given considerable variations in local cultural environments that exist within
diverse communities worldwide. Issues of local adaptation are magnified when
an EVT that is designed in one nation, such as the United States, is “exported” for
use in another nation. The present chapter examines and analyzes issues in the local
adaptation of EVTs to render them culturally relevant for treating members of local
subcultural groups, while also maintaining the core elements that from scientific
research must be delivered correctly to promote effective recovery from drug abuse
and addiction. The Matrix Model is presented as an exemplar of an EVT that has
been adapted for delivery within diverse communities worldwide. Also, stage
models of common adaptation approaches and practices are examined. Finally,
some practical approaches and recommendations are presented for conducting
a local adaptation of an EVT within various nations or cultural communities.
61.1 Introduction
English proficiency students, and (c) addressing issues relevant for racial and ethnic
minority students (Ringwald et al. 2004). Although this example relates to
substance use prevention interventions for adolescents within the United States,
these adaptation issues parallel similar concerns in the adaptation of drug abuse
treatments within the United States, as administered to underserved clients from
major racial/ethnic minority populations – African Americans, Hispanics/Latinos,
Asian Americans, and Native Americans.
In principle, each EBI and EVT should be broadly disseminated, thus making
that treatment readily available to many communities and consumers. However, in
practice, such broad-based dissemination and implementation has not been fully
realized (Carroll et al. 2011). A general challenge involves the distinction between
adopting an intervention or treatment “as is” and adapting that intervention with
strategic adjustments to make it truly relevant and responsive to the needs of
a local community and its consumers. Unfortunately, if a treatment lacks genuine
relevance and appeal for local consumers, despite its efficacy rating, if local
consumers dislike it and drop out, that treatment ultimately produces no benefits
for these local consumers.
In the decade since these fidelity-adaptation controversies emerged, efforts
to adapt model treatments have become “the rule rather than the exception”
(Ringwald et al. 2004). One of several reasons for this may be that there exists no
1010 F.G. Castro and M. Barrera
clinical “best practices” and, better yet, from “empirical scientific research” regard-
ing the treatment’s efficacy or effectiveness (Flay et al. 2005), as established from
one or more randomized controlled trials.
This manualized treatment includes patient handouts and a patient workbook that
introduce evidence-based recovery activities as developed from the integration of
five theory-based treatment approaches: cognitive behavioral therapy (CBT),
12-step facilitation, motivational interviewing, contingency management, and fam-
ily therapy (Obert et al. 2000). As developed from these five treatment approaches,
the formal core components of the Matrix Model consist of (a) early recovery phase
treatment activities, (b) relapse prevention, (c) social support groups, (d) family and
conjoint sessions, (e) individual sessions, (f) urine testing, (g) relapse analysis, and
(h) family education groups. The Matrix Model is guided by eight treatment
principles which are conveyed to clients: (a) create explicit structure and expecta-
tions; (b) establish positive, collaborative relationship with the client; (c) teach
information and cognitive behavioral concepts; (d) reinforce positive behavior
change; (e) provide corrective feedback when necessary; (f) educate family regard-
ing stimulant/drug abuse recovery; (g) introduce and encourage self-participation;
and (h) use urinalysis to monitor drug use (Rawson et. al. 1995; J. Obert, 2 Apr
2013, personal communication).
also as measured by staying in treatment for 90 days or more versus less than
90 days; (c) abstinence, as indicated by the average number of drug-free urinalysis
tests collected during treatment and the occurrence of three consecutive drug-free
urine analyses during treatment; and (d) completion, the completion of the 16-week
Matrix Model treatment with no more than two consecutive missed weeks of
treatment versus non-completion of this 16-week program (Hillhouse et. al. 2007).
These indices of client participation are likely correlated, although each provides
slightly different indicators of treatment outcomes. As one example, from the
Matrix Model, significant predictors of abstinence following treatment from meth-
amphetamine abuse were female gender, a high frequency of methamphetamine use
at treatment entry (15 days or more of use), and the client’s route of drug admin-
istration (e.g., injection drug use) (Hillhouse et al. 2007). Also, criteria on route of
administration indicated that the more severe form of self-administration, e.g.,
injection versus snorting, was associated with lower rates of abstinence. Regarding
gender differences, the reason why women exhibited greater difficulties in
maintaining abstinence relative to men was unclear (Hillhouse et al. 2007).
preliminary steps that are summarized in a table and detailed in text (e.g., language
translations, tests of translated materials, focus group checks on the cultural appro-
priateness of intervention materials and activities). These preliminary steps help to
shape the adapted intervention.
In phase 2 of PIA, the authors recommend conducting a three-arm effectiveness
study which would consist of (a) a minimally adapted intervention (solely surface
structure changes such as language translation), (b) a fully adapted intervention
(both surface and deep structure changes), and (c) a control condition. However,
even for this recommendation, given the complexities in conducting conceptually
equivalent linguistic translations, a linguistic translation itself may actually involve
more than just surface changes. The PIA also recommended the inclusion of
appropriate measures and data analytic procedures to identify possible mediators
and moderators of intervention effects (Iacobucci 2008; MacKinnon 2008). Unfor-
tunately, based on Sundell et al. (2013) article, it is not certain that the PIA
framework actually has been used in the international adaptation of an original
EVT intervention.
Undoubtedly, the best examples of international adaptations involve studies of
the Strengthening Families Program (SFP), a family skills intervention for the
prevention of youth substance abuse (Kumpfer et al. 2008). SFP was initially
developed and tested in the United States and subsequently has been adapted for
applications in Australia, Canada, Central America, Europe, South America, and
Southeast Asia. The results of that work have been summarized with the following
statement (Kumpfer et al. 2012, p. 176):
Replications of SFP in non-experimental and quasi-experimental studies in about 17 coun-
tries and randomized control trials (RCTs) in nine countries (United States, Canada,
Australia, UK, Sweden, Netherlands, Spain, Italy, and Thailand) with different cultural
groups by independent evaluators have found SFP to be an effective program in reducing
multiple risk factors for later alcohol and drug abuse, mental health problems and delin-
quency by increasing family strengths, children’s social competencies and improving
parent’s parenting skills.
research staff, the funding and time, and other research or evaluation resources) to
conduct a formalized and months-long randomized controlled clinical trial to test
the efficacy of an EVT adaptation as described by Sundell and colleagues and by
Kumpfer and colleagues.
61 Cultural Adaptation of Empirically-Validated Therapies 1021
This should also take into account the literacy level of members of the targeted
subcultural group.
2. Affective-motivational adaptation involves modifications of program content or
activities that can induce cultural conflict or that prompt reactance (behavioral
resistance). An example might be a Westernized cultural approach that requires
male clients to publically disclose their drug dependence or to discuss sexual
issues in the presence of certain family members. Without understanding its
possible cultural implications, that practice might be perceived by traditional
culture males as culturally inappropriate, whereby they may feel stigmatized and
resist participating in this otherwise important treatment activity. Conversely, as
a culturally modest adaptation, eliminating a discussion of stimulant use as
a trigger for sexual arousal and activity can undermine drug treatment, given
the association between stimulant use and sexual activity, as this can trigger
a relapse episode (J. Obert, 2 Apr 2013, personal communication). Thus,
a discussion of benefits and liabilities from such adaptations is critical for
making sound adaptation decisions that are both culturally sensitive and that
also adhere to scientific principles of effective drug abuse treatment.
3. Environmental adaptation involves therapeutic changes in a client’s family
system, in the client’s home neighborhood, and within the treatment agency,
thus modifying local environment conditions to aid in the client’s recovery. In
this domain, two basic forms of adaptation consist of (a) modifying program
content which relates to the environment and (b) modifying the form of program
delivery. Modification of content would include shallow or deep structure
changes in that content. Changes in form of delivery would involve presenting
the same treatment content, although delivered with changes in
(a) characteristics of delivery personnel, lay health workers rather than health
educators; (b) channel of delivery, Internet delivery rather than a group session;
or (c) location of delivery, improving access by delivering the program within
a church setting rather than within a drug treatment center.
Table 61.1 presents these five stages as described by Barrera and colleagues (2013).
Based in this framework and process, these five stages are:
1. Information gathering – Review relevant drug treatment literature as back-
ground to identify implementation problems and sources of client-treatment
mismatches, as linked to the three major dimensions of cultural adaptation
assessment, along with proposed adaptive changes that consider (a) participant
characteristics, (b) program delivery staff, and (c) administrative/community
factors (see Castro et al. 2004).
2. Preliminary adaptation design – Integrate recommendations from the Cultural
Adaptation Committee which is staffed by (a) various stakeholders,
(b) community experts, (c) developers of the model treatment, and (d) former
clients or representatives from the drug treatment program (treatment insiders)
and, if needed, other important representatives from the local community or
treatment center. Core intervention components would be preserved, unless
there exists convincing evidence that one of these core components is detrimen-
tal to the well-being of clients from the targeted constituency.
3. Preliminary adaptation tests – Design and pilot test a preliminary adapted
version of the original EVT to assess (a) the elimination of prior implementation
difficulties, (b) the emergence of problems with content or activities, (c) client
satisfaction with treatment elements, and (d) suggestions for improvement.
4. Adaptation refinement – Revise the adapted intervention. Then, if viable as
a more formal adaptation activity, proceed to stage 5.
5. The cultural adaptation trial – Formally determine the efficacy of this adapted
version by comparing it to a treatment-as-usual (TAU) control group and ideally
to the original EVT. This adapted EVT’s efficacy can be assessed as it influences
identified psychological and health outcome variables, as well as the assessment
of engagement indicators (e.g., client involvement, client attendance, comple-
tion of the treatment). Although seldom evaluated, within the cultural adaptation
trial stage, intervention evaluators or research investigators should aim to assess
the effects of the adapted EVT on specified mediators and moderators (Iacobucci
2008; MacKinnon 2008). For example, if a culturally adapted EVT adds
a cultural pride component, a mediation analyses could determine whether the
intervention was successful in enhancing cultural pride and then if this cultural
pride enhancement exerts an effect in reducing drug use or in avoiding relapse.
Similarly, moderator analyses could be conducted to determine if the culturally
adapted EVT was differentially effective: (a) for men versus for women, (b) for
clients high versus low in levels of acculturation, (c) among immigrants versus
natives, or (d) for any other potential moderators of intervention efficacy
(Barrera et al. 2012).
In addition, the adaptation team could utilize a rigorous mixed methods research
design (Creswell et al. 2011), one that includes in-depth interviews with partici-
pants and interventionists, to conduct a more in-depth assessment of treatment
outcomes and of the process involved in the implementation of this adapted EVT
(Castro et al. 2014). This approach would allow a deep structure analysis of client
and therapist commentaries on factors that (a) may operate as core treatment
1024 F.G. Castro and M. Barrera
rigorous treatment adaptation possible within the local community and also to
sustain the delivery of that treatment with the requisite fidelity needed to produce
efficacious treatment results.
References
Bandura A (1986) Social foundations of thought and action: a social cognitive theory. Prentice
Hall, Englewood Cliffs
Barrera M Jr, Castro FG (2006) A heuristic framework for the cultural adaptation of interventions.
Clin Psychol Sci Pract 13:311–316
Barrera M Jr, Castro FG, Holleran-Steiker LK (2011) A critical analysis of approaches to the
development of prevention interventions for subcultural groups. Am J Community Psychol
48:439–454
Barrera M Jr, Toobert DJ, Strycker LA, Osuna D (2012) Effects of acculturation on a culturally-
adapted diabetes intervention for Latinas. Health Psychol 31:51–54. doi:10.1037/a0025205
Barrera M Jr, Castro FG, Strycker LA, Toobert DJ (2013) Cultural adaptation of behavioral health
interventions: a progress report. J Consult Clin Psychol 81:196–205. doi:10.1037/a0027085
Bernal G, Jimenez-Chafey MI, Domenech Rodriguez MM (2009) Cultural adaptation of treat-
ments: a resource for considering culture in evidence-based practice. Prof Psychol Res Pract
40:361–368
Camfield L, Ruta D (2007) ‘Translation is not enough’ : using the Global Person Generated Index
(GPGI) to assess individual quality of life in Bangladesh, Thailand, and Ethiopia. Qual of Life
Res 16(6):1039–1051
Carroll KM, Ball SA, Jackson R, Martino S, Petry NM, Stitzer ML, Wells EA, Weiss RD
(2011) Ten take home lessons from the first 10 years of the CTN and 10 recommendations
for the future. Am J Drug Alcohol Abuse 37:275–282
Castro FG, Hernández-Alarcón E (2002) Integrating cultural factors into drug abuse prevention
and treatment with racial/ethnic minorities. J Drug Issues 32:783–810
Castro FG, Barrera M Jr, Martinez CR (2004) The cultural adaptation of prevention interventions:
resolving tensions between fidelity and fit. Prev Sci 5:41–45
Castro FG, Nichols E, Kater K (2007) Relapse prevention with Hispanic and other racial/ethnic
populations: can cultural resilience promote relapse prevention? In: Witkiewitz K, Marlatt GA
(eds) A therapist’s guide to evidence-based relapse prevention. Academic, Boston, pp 259–292
Castro FG, Barrera M Jr, Holleran Steiker LK (2010) Issues and challenges in the design of
culturally-adapted evidence-based interventions. Annu Rev Clin Psychol 6:213–239
Castro FG, Morera OF, Kellison JG, Aguirre KM (2014) Mixed methods research design for
prevention science: methods, critiques and recommendations. In: Sloboda Z, Petras H (eds)
Defining prevention science Springer, New York, pp 453–490
Creswell JW, Klassen AC, Plano Clark VL, Smith KC (2011) Best practices for mixed methods
research in the health sciences. Office of Behavioral and Social Science Research (OBSSR),
Bethesda
Domenech Rodrıguez M, Wieling E (2004) Developing culturally appropriate, evidence-based
treatments for interventions with ethnic minority populations. In: Rastogi M, Wieling E (eds)
Voices of color: first-person accounts of ethnic minority therapists. Sage, Thousand Oaks,
pp 313–333
Donovan DM, Daley DC, Brigham GS, Hodgkins CC, Perl H, Floyd AS (2011) How practice and
science are balanced and blended in the NIDA Clinical Trials Network: the bidirectional
process in the development of the STAGE-12 protocol as an example. Am J Drug Alcohol
Abuse 37:408–416
Elliot DS, Mihalic S (2004) Issues in disseminating and replicating effective prevention programs.
Prev Sci 5:47–53
1026 F.G. Castro and M. Barrera
Flay B, Biglan A, Boruch RF, Castro FG, Gottfriedson D, Kellam EK, Moscicki EK, Schinke S,
Valentine JC, Ji P (2005) Standards of evidence: criteria for efficacy, effectiveness and
dissemination. Prev Sci 6(3):151–175
Geisinger KF (1994) Cross-cultural normative assessment translation and adaptation
issues influencing the normative interpretation of assessment instruments. Psychol Assess
6:304–312
Gonzalez VM, Stewart A, Ritter PL, Lorig K (1995) Translation and validation of arthritis
outcome measures into Spanish. Arthritis Rheum 38:1429–1446
Greenfield SF, Brooks AJ, Gordon SM, Green CA, Kropp F, McHugh RK, Lincoln M, Hien D,
Miele GM (2007) Substance abuse treatment entry, retention, and outcome in women: a review
of the literature. Drug Alcohol Depend 86:1–21
Hillhouse MP, Martinelli-Casey P, Gonzales R, Ang A, Rawson RA (2007) Predicting
in-treatment performance and post-treatment outcomes in methamphetamine users. Addiction
102(Suppl 1):84–95
Iacobucci D (2008) Mediation analysis. Sage, Thousand Oaks
Ja D, Aoki B (1993) Substance use treatment: cultural barriers in the Asian American community.
J Psychoactive Drugs 25:61–71
Kumpfer KL, Alvarado R, Smith P, Bellamy N (2002) Cultural sensitivity in universal family-
based prevention interventions. Prev Sci 3:241–244
Kumpfer KL, Pinyuchon M, de Melo A, Whiteside HO (2008) Cultural adaptation process for
international dissemination of the Strengthening Families Program (SFP). Eval Health Prof
33(2):226–239
Kumpfer KL, Xie J, O’Driscoll R (2012) Effectiveness of a culturally adapted strengthening
families program 12–16 years for high-risk Irish families. Child Youth Care Forum
41:173–195
MacKinnon DP (2008) Introduction to statistical mediation analysis. Lawrence Erlbaum,
New York
McKleroy VS, Galbraith JS, Cummings B, Jones P, Harshbarger C, Collins C et al (2006)
Adapting evidence-based behavioral interventions for new settings and target populations.
AIDS Educ Prev 18:59–73. doi:10.1521/aeap.2006.18.supp.59
Minkler M, Wallerstein N (2003) Community-based participatory research for health. Jossey-
Bass, San Francisco
Minkler M, Wallerstein N, Wilson N (2008) Improving health through community organization
and community building. In: Glanz K, Rimer BK, Viswanath K (eds) Health behavior and
health education: theory, research and practice, 4th edn. Jossey-Bass, San Francisco,
pp 287–312
National Institute on Drug Abuse (1999) Principles of drug addiction treatment: a research-based
guide. NIH publication no 99-4180. National Institute on Drug Abuse, Rockville
Norcross JC, Beutler LE, Levant RF (2006) Evidence-based practice in mental health:
debate and dialogue on the fundamental questions. American Psychological Association,
Washington, DC
Obert JL, McCann MJ, Martinelli-Casey P, Weiner A, Minsky S, Brethen P, Rawson R (2000) The
Matrix Model of outpatient stimulant abuse treatment: history and description. J Psychoactive
Drugs 32:157–164
Orlandi MA, Weston R, Epstein LG (1992) Cultural competence for evaluators. Office of
Substance Abuse Prevention, Rockville
Parsai MB, Castro FG, Marsiglia FF, Harthun M, Valdez H (2011) Using community based
participatory research to create a culturally grounded intervention for parents and youth to
prevent risky behaviors. Prev Sci 12:34–47
Ramirez M (1999) Multicultural psychotherapy: an approach to individual and cultural differ-
ences, 2nd edn. Allyn & Bacon, Boston
61 Cultural Adaptation of Empirically-Validated Therapies 1027
Rawson RA, Shoptaw SJ, Obert JL, McCann MJ, Hasson AL, Martinelli-Casey PJ, Brethen PR,
Ling W (1995) An intensive approach to cocaine abuse treatment. J Subst Abuse Treat
12:117–127
Resnicow K, Soler R, Braithwait RL, Ahluwalia JS, Butler J (2000) Cultural sensitivity in
substance abuse prevention. J Community Psychol 28:271–290
Ringwald CL, Vincus A, Ennett S, Johnson R, Rohrbach LA (2004) Reasons for teachers’
adaptation of substance use prevention curricula in schools with non-white student
populations. Prev Sci 5:61–67
Schwartz A, Domenech Rodriguez MM, Santiago-Rivera AL, Arredondo P, Field LD (2010)
Cultural and linguistic competence: welcome challenges from successful diversification. Prof
Psychol Res Pract 41:210–220
Shiraev EB, Levy DA (2010) Cross-cultural psychology: critical thinking and contemporary
applications. Allyn & Bacon, Boston
Shoptaw S, Rawson RA, McCann MJ, Obert JL (1994) The Matrix model of outpatient stimulant
abuse treatment: evidence of efficacy. J Addict Dis 13(4):129–141
Simpson DD (2004) A conceptual framework for drug treatment process and outcomes. J Subst
Abuse Treat 27(4):99–121
Spoth R, Rohrbach LA, Greenberg M et al (2013) Addressing core challenges for the next
generation of Type 2 translation research and systems: the Translation Science to Population
Impact (TSci Impact) framework. Prev Sci. doi:10.1007/s 11121-012-0362-6
Sue DW, Sue D (1999) Counseling the culturally different: theory and practice, 3rd edn. Wiley,
New York
Sue S, Zane N (2006) Ethnic minority populations have been neglected by evidence-based
practices. In: Norcross JC, Beutler LE, Levant RF (eds) Evidence-based practices in mental
health: debate and dialogue on the fundamental question. American Psychological Association,
Washington, DC, pp 329–337
Sundell K, Ferrer-Wreder L, Fraser MW (2013) Going global: a model for evaluating empirically
supported family-based interventions in new contexts. Eval Health Prof. doi:10.1177/
0163278712469813
Terrell MD (1993) Ethnocultural factors and substance abuse towards culturally sensitive treat-
ment models. Psychol Addict Behav 7:162–167
Trimble JE (1995) Toward an understanding of ethnicity and ethnic identity, and their relationship
with drug abuse research. In: Botvin GJ, Schinke S, Orlando MA (eds) Drug abuse prevention
with multiethnic youth. Sage, Thousand Oaks, pp 3–27
Vandevelde S, Vanderplasschen W, Broekaert E (2003) Cultural responsiveness in substance-
abuse treatment: a qualitative study using professionals and clients perspectives. Int J Soc Welf
12:221–228
Wingood GM, DiClemente RJ (2008) The ADAPT-ITT model: a novel method of adapting
evidence-based HIV interventions. J Acquir Immune Defic Syndr 47:S40–S46. doi:10.1097/
QAI.0b013e3181605df1
Section V
Social Therapies and
Treatment Settings
1
The Definition of Addiction ASAM Public Policy Statement Adoption Date: April 12, 2011
G. Bunt
Daytop Village, Inc., New York, NY, USA
Department of Psychiatry, NYU Langone Medical Center, New York, NY, USA
e-mail: [email protected]
M. Nazar Mohamed (*)
Faculty of Allied Health Sciences, Cyberjaya University College of Medical Sciences (CUCMS),
Cyberjaya, Selangor, Malaysia
e-mail: [email protected]
Therapeutic communities emerging in the 1960s with Daytop Village, Phoenix House,
Odyssey House, and Samaritan Village are multisite programs with Daytop in fact
expanding internationally. These programs are based on the premise that transformation
of pathological character traits can lead to a resolution of drug-seeking behavior. The
noninstitutional peer-based programs exemplified by Alcoholics Anonymous and Nar-
cotics Anonymous, both emerging from centers in the United States altogether with over
150,000 peer-led groups worldwide, are premised on peer support infused with spiritual
renewal. Densingi in Japan is also peer led but does not emphasize spirituality to the
same degree.
Two chapters related to service delivery illustrate the complexity of various
treatment networks constituted of diverse approaches. The policy initiatives and
technology-based approaches are described with an emphasis on specific examples
of innovative service delivery. Additionally, strategies for drug abuse prevention in
the workplace provide another example of the introduction of treatment methods
into a broader social context.
Inevitably, the illness of addiction impacts on both the criminal justice system
and the acute medical emergency services, and in recent years, there has been
considerable progress in moving addiction treatment forward into settings outside
of those directed specifically at treatment, i.e., prison settings; forensic applications
as Drug Courts, or alternatives to incarceration; or legal civil sanctions. Addition-
ally considerable sophistication has been introduced into the Emergency Medical
Services for addicted patients.
We can learn a great deal indeed from examining the diversity of
clinical approaches in differing cultural, regional, and national settings. Whether
in the United States, Japan, Malaysia, Iceland, the United Arab Emirates, Vietnam,
Lebanon, or any other nation delivering addiction treatment services worldwide,
the diversity of options and opportunities for developing and advancing
addiction services remains a vital challenge for the professionally trained addiction
physician today.
Altogether, these diverse but carefully framed aspects of social therapies illus-
trate the many ways in which social support and structure, both in formal treatment
settings and outside of them, have emerged since the twentieth century. The skill,
wisdom, and knowledge with which addiction physicians apply these principles
of social therapies and treatment settings for addictive disorders will have an
enormous impact on the future of our field.
Therapeutic Communities for
Addictions: Essential Elements, Cultural, 63
and Current Issues
Contents
63.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1034
63.2 Essential Elements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1035
63.2.1 The TC Perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1035
63.2.2 The TC Approach: Community as Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1036
63.2.3 TC Program Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1037
63.2.4 The Effectiveness of Therapeutic Communities . . . . . . . . . . . . . . . . . . . . . . . . . . . 1039
63.2.5 Adaptations and Modifications of the TC for Special
Populations and Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1040
63.2.6 TCs Worldwide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1041
63.2.7 TC Outcome Research Worldwide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1041
63.2.8 Cultural Adaptations of the TC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1041
63.2.9 Issues and Challenges to the TC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1042
63.2.10 Funding and Planned Duration of Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1042
63.2.11 Workforce . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1043
63.2.12 Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1044
63.2.13 Treatment Fidelity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1044
G. De Leon (*)
Behavioral Science Training Program at NDRI, New York, NY, USA
Department of Psychiatry, NYU School of Medicine, New York, NY, USA
e-mail: [email protected]
F.B. Perfas
Daytop International Training Academy, New York, NY, USA
e-mail: [email protected]
A. Joseph
Daytop International, Inc., New York, NY, USA
e-mail: [email protected]
G. Bunt
Daytop Village, Inc., New York, NY, USA
Department of Psychiatry, NYU Langone Medical Center, New York, NY, USA
e-mail: [email protected]
Abstract
The therapeutic community (TC) is a major treatment modality serving a wide
spectrum of substance abuse clients worldwide. The weight of the research
evidence developed over some 40 years demonstrates that the TC is an effective
and cost-effective treatment particularly for substance abusers with serious
social and psychological problems in addition to their drug abuse. This chapter
provides an overview of the essential elements of the TC approach: its perspec-
tive, method, program model, and adaptation for special populations, settings,
and different cultures.
TCs have been successfully modified for special populations of substance
users including those with co-occurring disorders, adolescents, women with
children, criminal justice clients in prisons, and community-based settings. TC
programs have been implemented in Europe, Asia, Africa, Latin America, and
the Middle East. And, despite ethnic, social-political, and religious differences,
TCs have retained their essential elements and effectiveness across a variety of
cultures.
Its evolution over some 50 years has surfaced key issues that challenge the TC
to maintain the integrity of its unique social psychological approach – community
as method. Several of these are briefly highlighted including funding, workforce,
research, treatment fidelity, and the diversity of TC programs. In the current
context, the TC is compelled to reassert its place and mission in human
services – that of promoting recovery and right living.
63.1 Introduction
abuse clients. Although the TC approach has been adapted for different populations
and settings, it is the perspective and method of the traditional long-term residential
prototype for adult substance abusers that has documented effectiveness in
rehabilitating substance-abusing individuals.
The TC perspective or theory shapes its program model and its unique approach,
community as method. The perspective consists of four interrelated views of the
substance use disorder, the individual, recovery process, and healthy living.
Table 63.1 Typical behavioral, cognitive, and emotional characteristics of substance abusers in
therapeutic communities
Low tolerance for all forms of discomfort and delay of gratification
Problems with authority
Inability to manage feelings (particularly hostility/anger, guilt, and anxiety)
Poor impulse control (particularly sexual or aggressive impulses)
Poor judgment and reality testing concerning consequences of actions
Unrealistic self-appraisal regarding discrepancies between personal resources and aspirations
Prominence of lying, manipulation, and deception as coping behaviors
Personal and social irresponsibility (e.g., inconsistency or failures in meeting obligations)
Marked deficits in learning and in marketable and communication skills
lifestyle for the first time. Among individuals from more advantaged backgrounds,
the term rehabilitation is more suitable, which emphasizes a return to a lifestyle
previously lived, known, and perhaps rejected.
The key components of the program model are its social organization (structure),
peer and staff roles, groups and individual counseling, community enhancement
meetings, community management elements, and program stages. Each component
reflects an understanding of the TC perspective and each is used to transmit
community teachings, promote affiliation, and self-change.
Thus, they strengthen community as a context for social learning. The main elements
that are staff managed, although with some input from the senior resident social
hierarchy, are privileges, disciplinary sanctions, surveillance, and urine testing. How-
ever, peer confrontation in the form of verbal correctives, affirmations, and feedback
(e.g., reactions, advice, information) are ongoing community management activities.
63.2.3.8 Aftercare
TCs have always acknowledged the patient’s efforts to maintain sobriety and a
positive lifestyle beyond graduation. Until recently, long-term TCs addressed key
clinical and life adjustment issues of aftercare during the reentry stages of the 2-year
program. As noted, funding pressures have resulted in shorter planned durations of
residential treatment and the stages and phases therein. This has underscored the
necessity for aftercare resources to address both primary treatment as well as reentry
issues. Thus, many contemporary TCs offer post residential aftercare treatment and
social services within their systems, such as intensive day treatment and step-down
outpatient ambulatory treatment, or through linkages with outside agencies.
Over the past four decades, a considerable scientific knowledge base has developed
with follow-up studies on thousands of individuals treated in TCs. The most
extensive body of research bearing on the effectiveness of addiction TC programs
has amassed from field outcome studies. These all employed similar longitudinal
designs that follow admissions to TCs during treatment and 1–5 years (and in one
study up to 12 years) after leaving the index treatment.
1040 G. De Leon et al.
These studies show that TC admissions have poor profiles in terms of severity
of substance use, social deviance, and psychological symptoms. The striking
replications across studies leave little doubt as to the reliability of the
main conclusion. Namely, there is a consistent relationship between retention in
treatment and positive posttreatment outcomes in TCs. Replication studies
overseas seem to follow the same trend. This conclusion is supported in the smaller
number of controlled and comparative studies involving TC programs (for
a recent review of the TC outcome literature in North America, see De Leon 2010).
Overall, the weight of the research evidence from multiple sources (multi-program
field effectiveness studies, single-program controlled studies, meta-analytic statisti-
cal surveys, and cost-benefit studies) is compelling in supporting the hypothesis that
the TC is an effective and cost-effective treatment for certain subgroups of substance
abusers, particularly those with serious social and psychological problems in addition
to their drug abuse.
The North American research literature is the most extensive and has been briefly
cited above. There is a modest but developing research literature on TCs worldwide
particularly of European programs. The main conclusion from recent reviews of the
European outcome studies may be briefly summarized.
“Length of stay in treatment and participation in subsequent aftercare were
consistent predictors of recovery status. The authors conclude that TCs can
promote change regarding various outcome categories. Since recovering
addicts often cycle between abstinence and relapse, a continuing care approach is
advisable, including assessment of multiple and subjective outcome indicators”
(Vanderplasschen et al. 2013). Similar conclusions are obtained in outcome studies
of TC programs in Peru and Thailand (Johnson et al. 2007, 2008), Australia, (Pitts
and Yates 2010).
Although treatment process studies are few, emerging research has
supported hypotheses concerning the generality of the perspective, model, and
method of TC. Utilizing a common assessment instrument (the Survey of Essential
Elements Questionnaire SEEQ; Melnick and De Leon 1999), these studies
emphasize that differences exist between standard and modified TCs in
essential elements within cultures but that the similarities in elements outweigh
the differences across cultures (Dye et al. 2009; Goethels et al. 2011; Johnson
et al. 2007, 2008).
Beyond the above studies supporting the generality of the essential elements,
there has been relatively little empirical research that focuses on cultural influences
in the adaptation of the TC. However, a considerable descriptive literature of TCs in
different cultures has unfolded over some four decades. Some reports can be found
in scientific journals but most are contained in the published conference proceed-
ings of international and regional TC associations, e.g., the World Federation of
Therapeutic Communities (WFTC), the European Federation of Therapeutic
Communities (EFTC), the Australasian Therapeutic Communities Association
(ATCA), the Latin American Federation of Therapeutic Communities, and the
Asian Federation of Therapeutic Communities.
These writings, along with the few empirical studies and the years of observa-
tions by trainers, consultants, and others, have indentified various cultural context
influences that are embedded in TC programs (see some examples in Table 63.2).
It is beyond the purview of this chapter to discuss these in detail, but several
working conclusions are offered concerning the TCs adaptation to cultural
influences.
First, the TC perspective (i.e., views of the whole person disorder, recovery,
and right living) and its approach (community as method) can be preserved and
integrated within diverse cultures. Second, empirical research is needed to abstract
a more complete list of cultural influences and to assess their impact on outcomes.
Finally, across all cultures, maintaining fidelity of practice is necessary to assure the
optimal effectiveness of the TC approach, a general issue which is briefly discussed
in the last section of this chapter.
The evolution of the contemporary therapeutic community (TC) for addictions over
the past 45 years may be characterized as a movement from the marginal to the
mainstream of substance abuse treatment and human services. Currently TCs serve
a wide diversity of clients and problems; they have reshaped staffing composition,
reduced the planned duration of residential treatment, reset its treatment goals, and,
to a considerable extent, modified the approach itself. These evolutionary changes
have surfaced key issues that challenge the TC to maintain the integrity of its
unique approach. Several of these are briefly highlighted: funding, workforce,
research, treatment fidelity, and the diversity of TCs. Though interrelated, these
issues are discussed separately.
Issue: The success of the TC approach has been demonstrated primarily for
residential programs with planned durations of treatment of at least 9–12 months.
In recent years, however, fiscal support has been steadily decreasing for long-term
treatment in general and for residential treatment in particular. Thus, for the large
63 Therapeutic Communities for Addictions 1043
Table 63.2 Some examples of cultural elements shaping the unique TC characteristics in
different cultures
Gender. In cultures where there are strict norms regarding the mixing of the sexes, there are
separate TCs for men and women. The segregation is not driven by clinical rationale intended to
better meet the unique needs of a particular gender but more for moral and reasons of propriety.
Religion. In most Eastern TCs, religion and religious practices are integrated into the TC structure.
Those who belong to minority religions are encouraged to practice their faith. Major religious
holidays are observed and program activities are tailored around celebrations of such holidays.
Even dietary practices are observed.
Social organization. The traditional hierarchical structure of the TC is highly compatible with
the formal and often rigid social structure in most conservative cultures. The TC hierarchical
structure lends clarity which is consistent with the formal social structures of most of these
societies. The delineation and lack of ambiguity of job positions and social status in the community
promotes social harmony. It also defines the social roles of and expectations from the community
members.
Role of the recovering addict as therapist. In most Oriental or Eastern cultures, academic
credentials are preferred over experiential training. The contributions of the “recovering” person
as therapist are not greatly appreciated, unless the person has a college degree in addition to
personal experience. It requires a paradigm shift to consider, for example, a recovering addict or
a recovered mentally ill person become therapists themselves.
Time orientation or temporal perception. Eastern culture has a fluid perception of time in contrast
to Western society’s highly structured time perception, “on time” versus “in time” orientation.
Time orientation or how and when activities are implemented has implications in terms of
operational efficiency and outcomes. The result-oriented and purpose-driven structure and
schedule of the TC compel timeliness in order to comply with the demands and expectations of
supporting and maintaining the community. Timeliness is observed across the board out of
necessity, transcending cultural temporal perception.
The professional as TC staff. Many TCs outside the United States were founded by professionals
who employed the services of TC-recovered ex-addicts as clinical staff along with professional
staff. Working as a team, the combination creates a very progressive TC by exploiting the unique
contributions of each.
Family. The importance of the family and their role in treatment in various cultures are evident in
the popularity of family associations (Perfas 2012). Some TCs, such as in the case of Indonesia,
were conceived by parents who originally sent their children to a Malaysian TC for treatment. In
due time, they initiated a TC movement in their own country. Malaysian and Chinese TCs consider
family and religion (spirituality) to be central to treatment (Bunt et al. 2010).
majority of TCs that depend upon public funding, planned duration of treatment has
been reduced often below the threshold of time needed to yield positive outcomes.
This adjustment to funding pressures potentially undermines the viability of the TC
as a cost-effective modality in the health-care system.
63.2.11 Workforce
Issue: The expansion of the TC to serve special populations in special settings has
resulted in a number of problems in the recruitment, retention, and development of
experienced staff. General problems include low salaries, limited career goals, and
difficult working conditions. However, a specific workforce issue arises from the
1044 G. De Leon et al.
63.2.12 Research
Issue: The TC approach and model has been successfully adapted and modified for
various populations and settings. However, within the wide diversity of programs
that represent themselves as TCs, many do not actually implement the TC approach
that has proven successful. This often results in variable treatment outcomes and
fosters misperceptions of the therapeutic community as an effective evidence-based
approach. The credibility of the TC modality in health and human services will
require classification of the diversity of programs as well as the development of
standards of quality assurance.
The range of TC programs for substance abuse and related problems can be
organized into three broad categories. These are based upon the extent to which
a program is guided by the TC perspective (whole person, recovery, and right
living), adheres to the approach (community as method), and retains essential
components of the program model (see Table 63.3).
Thus, not all programs that label themselves as therapeutic communities are
actually TCs. Clarification of differences in programs, the clients they serve, the
goals of treatment, and the fidelity of the particular treatment strategies utilized, is
necessary to preserve the integrity of the TC approach.
Finally, TCs worldwide are also undergoing many of the evolutionary changes
described above, including modifications for special populations and particularly
adapting to fiscal pressures to reduce time in residential treatment. A notable
development is the rapprochement between the addiction TC and the psychiatric
TC pioneered by Maxwell Jones that has been prominent in Europe. Both of
1046 G. De Leon et al.
63.3 Conclusion
Arguably, the therapeutic community for addictions (TC) is the first formal treat-
ment approach that is explicitly recovery oriented. Surely, AA and similar mutual
self-help approaches facilitate recovery but these represent themselves as support,
not treatment. Pharmacological approaches, notably, methadone maintenance, have
as their treatment goal the reduction or elimination of illicit opiate use; and
behavioral approaches, such as cognitive-behavioral therapy (CBT), contingency
contracting, and motivational enhancement (MET), focus upon reduction, and not
necessarily abstinence and recovery, in targeted drug use. In the TC perspective,
however, the primary goal of treatment is recovery which is broadly defined as
changes in lifestyles and identities.
Thus, in the current context of substance abuse policy and issues (e.g., various
treatment options, harm reduction strategies, the economic pressures on health
care), the overarching challenge of the TC is to reassert its unique place and
mission – that of promoting recovery and right living.
References
Bunt GC, Kressel D, Stanick V, Au M (2010) Therapeutic community: a three-country compar-
ison. NIDA Int Prog
De Leon G (ed) (1997) Community as method: therapeutic communities for special populations
and special settings. Greenwood, Westport
De Leon G (2000) The therapeutic community: theory, model, and method. Springer, New York
De Leon G (2010) Is the therapeutic community an evidence based treatment? What the evidence
says. Ther Commun 31(2):104–175
De Leon G, Melnick G, Schoket D, Jainchill N (1993) Is the therapeutic community culturally
relevant? Findings on race/ethnic differences in retention in treatment. J Psychoactive Drugs
25(1):77–86
De Leon G, Sacks S, Staines G, McKendrick K (2000) Modified therapeutic community for
homeless MICAs: treatment outcomes. Am J Drug Alcohol Abuse 26(3): 461–480
Dye M, Ducharme L, Johnson J, Knudsen H, Roman P (2009) Modified therapeutic communities
and adherence to traditional elements. J Psychoactive Drugs 41(3):275–283
Goethels L, Soyez V, De Leon G, Melnick G, Broekert E (2011) Essential elements of Treatment:
a comparative study of European and American therapeutic communities for addiction. Subst
Use Misuse 46(8):1023a–1031a
Jainchill N, Hawke J, Messina M (2005) Post-treatment outcomes among adjudicated adolescent
males and females in modified therapeutic community treatment. Subst Use Misuse
40:975–996
Johnson KW, Young L, Pan T, Zimmerman RS, Vanderhoff KJ (2007) Therapeutic communities
(TC) drug treatment success in Thailand: a follow-up study. In: Research monograph.
63 Therapeutic Communities for Addictions 1047
Further Reading
Bunt GC, Muehlbach B, Moed CO (2008) The therapeutic community: an international perspec-
tive. Subst Abuse 29(3):81–87
Spiritual Aspects of the Twelve
Step-Method in Addiction Treatment 64
Marc Galanter
Contents
64.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1049
64.1.1 AA as a Spiritual Recovery Movement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1049
64.2 Spiritual Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1050
64.2.1 Spirituality as a Psychological Construct . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1050
64.2.2 Spirituality and Religious Experience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1051
64.2.3 Spiritually Grounded Recovery in AA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1052
64.2.4 AA in the Professional Context . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1054
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1055
Abstract
This chapter is directed at defining the nature of spirituality and its relationship
to empirical research and clinical practice. A preliminary understanding of the
spiritual experience can be achieved on the basis of diverse theoretical and
empirically grounded sources, which will be delineated. Furthermore, the impact
of spirituality on addiction in different cultural and clinical settings is explicated
by illustrations of its application with regard to Alcoholics Anonymous.
64.1 Introduction
How does spirituality relate to recovery from addiction? There is a parallel between
the way attitudes are transformed in intensely zealous groups and the way the denial
M. Galanter
Division of Alcoholism and Drug Abuse, NYU School of Medicine, New York, NY, USA
e-mail: [email protected]
of illness and the self-defeating behaviors of alcoholics and drug addicts may be
reversed through induction into Twelve-Step groups like AA.
Members of the lay public may conclude that certain healthcare issues are
inadequately addressed by the medical community, particularly when doctors are
not sufficiently attentive to the emotional burden that an illness produces. When
mutually supportive groups of laymen coalesce to implement a response to this
perceived deficit, they may form a spiritual recovery movement (Galanter 1997),
one premised on achieving remission based on beliefs independent of evidence-
based medicine. Such movements may ascribe their effectiveness to higher meta-
physical or nonmaterial forces and claim to offer relief from illness.
AA can be considered as a highly successful example of a spiritual recovery
movement, as such movements have three primary characteristics. They (a) claim
to provide relief from disease, (b) operate outside the modalities of established
empirical medicine, and (c) ascribe their effectiveness to higher metaphysical
powers. The appeal of such movements in the contemporary period is due in part
to the fact that physicians tend not to attend the spiritual or emotional concerns of
their patients (Galanter 2005).
Clearly, the attitudes and behavioral norms that AA espouses are much more in
conformity with the values of the larger culture than those of zealous religious sects.
The expectation of avoiding drunkenness in AA, normative in our culture, illus-
trates this. People who are highly distressed over the consequences of their addic-
tion are therefore candidates to respond to the strong ideologic orientation of AA
toward recovery and are operantly reinforced by the relief produced by affiliation
with the group’s ideology and behavioral norms, all related to abstinence and
a spiritually grounded lifestyle. Significantly, AA generates distress in its members
by pressing them to give up their addictive behaviors, but the distress associated
with this conflict is relieved if they sustain affiliation and cleave to the group.
Two empirically grounded perspectives have played a material role in framing how
we conceptualize recovery. One derived from a model of psychopathology modeled
on the work of Emil Kraeplin (1902). He framed an approach that now characterizes
the contemporary medical model for mental disorders, categorizing disease entities
diagnosed on the basis of explicit and discrete symptoms. This approach is evident
in the development of criteria for substance use disorders employed in recent
editions of the symptom-based Diagnostic and Statistical Manual of Mental Disor-
ders (American Psychiatric Association 2000). From this perspective, a state of
remission, colloquially called recovery in rehabilitation circles, can take place with
the resolution of the specific symptoms listed as diagnostic criteria. A second
perspective on recovery derives from behavioral psychology, whose model of
stimulus-response sequences has led to the ordering of experience around discrete
64 Spiritual Aspects of the Twelve Step-Method in Addiction Treatment 1051
The relative role of spiritual experience in the Twelve-Step recovery process has
been investigated from a variety of perspectives, generally in relation to patients’
experience in AA. Kelly et al. (2009) reviewed studies that applied mediational
tests to ascertain how AA achieves beneficial outcomes and found little support for
a role of AA’s specific spiritual mechanisms. In fact, with regard to religiosity,
Tonigan et al. (2002) found that, although atheists were less likely to attend
1052 M. Galanter
AA meetings, those who did join derived equal benefit as did spiritually focused
individuals. On the other hand, in one study on persons recovering from cocaine
dependence (Flynn et al. 2003), respondents attributed their positive outcomes to
religion and spirituality. Additionally, Zemore (2007) followed up a large sample
of substance abusers 1 year after inpatient treatment and found that increases in
spirituality contributed to the increment in total abstinence associated with Twelve-
Step involvement.
Our own experience, as well, is compatible with these findings, as we have found
in multiple settings (Galanter et al. 2012, in press a, b) that spirituality is integral to
recovery in Twelve-Step groups. This was particularly evident among long-term
members.
C. Flow: The experience associated with engaging one’s highest strengths and
talents to meet achievable challenges, as measured by Experience Sampling
(Csikszentmihalyi and Larson 1987) or the Flow Scale (Mayers 1978).
D. Spirituality: The Spirituality Self-Rating Scale, which we developed and
applied to both substance-abusing and non-substance-abusing populations
(Galanter et al. 2007), as well as other such scales. By means of our own
scale, we were able to distinguish different populations of substance abusers’
level of spiritual orientation from the of non-substance populations.
E. Personality assessment: The Classification of Strengths (Peterson and Seligman
2004), a series of characteristics based on categories of moral excellence drawn
from observations across different cultures.
F. AA involvement: Measures of the degree of affiliation and commitment to the
AA fellowship (Humphreys et al. 1998).
A methodology for defining recovery based on measurements like these may not
have the same appeal to biomedically oriented clinicians as does the conventional
symptom-based approach, as these measurements are based on self-report of the
person’s subjective state. Furthermore, the enthusiasm of newfound recovery may
yield a Hawthorne effect. The biomedical format currently applied in diagnosis
derives from the school of Kraeplin and subsequent investigators like those who
developed the Feighner criteria (Feighner et al. 1972) in the 1970s and then in the
ensuing DSM system. Spiritual variables, however, have a lineage as well, from
William James, Carl Jung, and Bill W.
The spiritually oriented Twelve-Step approach has been integrated into profes-
sional treatment in some settings where it serves as the overriding philosophy of an
entire program or, in others, where it is one aspect of a multimodal eclectic
approach. The Minnesota Model for treatment, typically located in an isolated
institutional setting, is characterized by an intensive inpatient stay during which
a primary goal of treatment is to acculturate patients to acceptance of the philos-
ophy of AA and to continue with AA attendance after discharge (Cook 1988).
Although a variety of exercises are included during the stay, this approach has been
criticized as dogmatic because of its sole reliance on the Twelve-Step approach.
The outcome of this model, however, has been shown to yield positive results in
a survey of patients discharged from one such setting (Hazelden, in Center City,
MN) (Stinchfield and Owen 1998), but randomization of patients treated in
Minnesota Model facilities with those treated by means of an alternative approach
is needed.
A more eclectic option is illustrated in the integration of Twelve-Step groups
into a general psychiatric facility for the treatment of patients dually diagnosed for
major mental illness and substance abuse. The importance of spirituality in such
a highly compromised population was evidenced in our studies (Galanter
et al. 2007) in which such patients ranked spiritual issues like belief in God and
64 Spiritual Aspects of the Twelve Step-Method in Addiction Treatment 1055
inner peace higher than tangible benefits like social service support and outpatient
treatment. One inherent advantage of this format is that it benefits from the
introduction of an inspirational approach to patients who, as Goffman has pointed
out (1963), have become “degraded” by stigmatization due to their psychiatric
disorders.
In summary, spirituality is a matter of personal meaning that is widely accepted.
It is also central to the recovery process from addiction for many AA members. The
fellowship of AA, in fact, can be considered a movement developed in relation to
people’s spiritual needs. Although spirituality is subjectively experienced, it can be
assessed systematically in given individuals by employing currently available
empirical techniques. By such means, an important aspect of addiction recovery
can be defined and studied.
References
Alcoholics Anonymous World Services (1955) Alcoholics Anonymous: the story of how many
thousands of men and women have recovered from alcoholism. Alcoholics Anonymous
Publishing, New York
American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders,
4th edn, text revision. American Psychiatric Association, Washington, DC
Brown BS, O’Grady K, Battjes RJ et al (2004) Factors associated with treatment outcomes in an
aftercare population. Am J Addict 13:447–460
Campbell A, Converse PE, Rogers WL (1976) The quality of American life. Russell Sage
Foundation, New York
Cheever S (2004) My name is Bill: Bill Wilson – his life and the creation of Alcoholics
Anonymous. Simon & Schuster, New York
Cohen S, Mermelstein R, Kamarck T et al (1985) Measuring the functional components of social
support. In: Sarason IG, Sarason BR (eds) Social support: theory, research and application.
Martinus Nijhoff, The Hague, pp 73–94
Cook CCH (1988) The Minnesota model in the management of drug and alcohol dependency:
miracle, method or myth? Part II: evidence and conclusions. Br J Addict 83:735–748
Crumbaugh JD, Maholick LT (1969) Manual of instructions for the purpose in life test. Psychometric
Affiliates, Munster
Csikszentmihalyi M, Larson R (1987) Validity and reliability of the experience sampling method.
J Nerv Ment Dis 175:526–536
Diener E, Suh EM, Lucas RE et al (1999) Subjective well-being: three decades of progress.
Psychol Bull 125:276–302
Dupuy H (1973) The psychological section of the current health and nutrition examination survey.
In: Proceedings of the public health conference on records and statistics (1972). DHEW
Publication HRA 74–1214. National Center for Health Statistics, Rockville
Feighner JP, Robins E, Guze SB et al (1972) Diagnostic criteria for use in psychiatric research.
Arch Gen Psychiat 26:57–63
Flynn PM, Joe GW, Broome KM, Simpson DD, Brown BS (2003) Looking back on cocaine
dependence: reasons for recovery. Am J Addict 12:398–411
Frankl V (1984) Man’s search for meaning, 3rd edn. Touchstone, Simon & Schuster, New York
Galanter M (1997) Spiritual recovery movements and contemporary medical care. Psychiat
Interpers Biol Proc 60:236–248
Galanter M (2005) Spirituality and the healthy mind: science, therapy and the need for personal
meaning. Oxford University Press, New York
1056 M. Galanter
Contents
65.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1058
65.2 Support Groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1058
65.2.1 Danshukai . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1058
65.2.2 DARC (Drug Addiction Rehabilitation Center) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1061
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1063
Abstract
Japan has rapidly developed in the economic field following World
War II. Simultaneously, alcohol and drug dependence have been serious prob-
lems for several decades. To deal with such problems, indigenous self-help and
mutual-help organizations for alcohol and drug dependence have been founded
and developed.
Danshukai is the most widely spread organization of self-help and mutual
help for alcohol dependence throughout Japan. Its early activities were inspired
by AA (Alcoholics Anonymous) and have been translated into the Japanese
context. The membership of Danshukai has reached double the number of AA
participants in Japan but has gradually tapered off in recent years. The consistent
slogan of Danshukai is “one-day abstinence,” which means that the members
promise themselves that they will not drink alcohol on that day.
The DARC (Drug Addiction Rehabilitation Center) system was developed
originally in Japan. DARC was formed as a rehabilitation facility with
a community of drug-dependent associates in Tokyo. Such communities have
been formed in many cities in Japan. The activities of DARC not only have
extended to the rehabilitation for drug dependence but also encompass the
approach to various drug addiction problems, such as consultation for and
education in drug problems.
65.1 Introduction
Alcohol and drug misuse have created social, medical, and economic problems for
several decades in Japan. Both formal and informal interventions for these prob-
lems have been conducted. Many facilities have developed systems to meet the
therapeutic needs associated with alcohol and other drug misuse.
Japan has a particular language, culture, and tradition. In earlier eras, the
Japanese were gifted at translating various cultures from China or Western coun-
tries into the Japanese context. These trends have been inherited by modern
Japanese society and systems. Rehabilitation programs and organizations aimed
at treating alcohol and drug addiction in Western countries have been modified to
suit the Japanese context. Particular mutual aid support groups for alcohol and drug
addiction also spread throughout Japan. Here, we introduce these distinctive
mutual-help organizations in Japan.
65.2.1 Danshukai
In Japan, there are currently two major self-help groups for alcohol-dependent
individuals. The first is AA (Alcoholics Anonymous), which was introduced from
the United States. The second is the Japan Sobriety Association “Danshukai,”
which is an indigenous and distinctive organization in Japan.
Danshukai was founded in the city of Kochi in November 1958 and has spread
throughout Japan since 1965. Its early activities were inspired by AA and have been
translated into the Japanese context. The number of members reached approximately
10,000 individuals at the beginning of the 2000s, which was double the number of AA
participants in Japan. However, the number of Danshukai participants reached
a plateau and has gradually tapered off in recent years, partly because the number of
medical institutions treating alcohol dependence has increased and an extended
medical support system has been developed for alcohol-dependent patients. In April
2012, the number of Danshukai members decreased to 8,500 (Zendanren 2013). The
members belong to one of the 556 nationwide community-level “Danshukai.” Most
cities and towns have one or more of these community-level Danshukai. Therefore,
knowledge of Danshukai for alcohol-dependent individuals has spread widely among
the general public, although the precise roles and activities are not necessarily known.
Instead of the 12 steps of AA, Danshukai has 7 principles (Zendanren 2012):
1. We should confess that we are helpless against alcohol and that we could not do
anything by ourselves.
65 Danshukai and Other Support Groups in Addiction Treatment 1059
meet the needs of the times. Danshukai has started activities to increase the number
of members. They have held meetings for alcohol-dependent women only.
Recently, they have received alcohol-dependent adolescents with multiple prob-
lems, such as drug dependence or eating disorders. Moreover, Danshukai meetings
have been frequently held in the afternoon for retired members or unemployed
members who are free during the daytime. Those who have physical disabilities or
gait disturbances can also easily attend the daytime meetings (Wake 2013).
One of the most important tasks of members is to attend regular meetings.
Meetings are usually informal and almost all are open (i.e., available to anyone).
Members talk about their stories caused by drinking. While feature discussions are
sometimes held, general discussions account for most of the meeting time. The core
regulation of the meetings is “just speaking and listening.” The members talk about
their present condition or problems with alcohol in turn, and others must not
interrupt their speech. Other members, except for the speaker, just listen. In
principle, they are not allowed to criticize or encourage, even if the speakers
confess their re-drinking or complain of their circumstances. Just talking about
one’s self and just listening to other members’ speech lead to a sense of relief and an
awareness that they have similar alcohol problems. Members can share the recog-
nition that the troubles caused by alcohol are not unique to themselves, helping
them to realize that they are not alone. Members can begin to help each other,
65 Danshukai and Other Support Groups in Addiction Treatment 1061
because they are companions who have undergone similar catastrophes. The sense
of solidarity and responsibility is a motivating power to prevent members from
drinking. AA members are encouraged to find an experienced individual, called
a sponsor, who can help them to understand and follow the AA program. Although
Danshukai members do not have such a sponsor, they receive mutual help as well as
advice and support from other members as needed.
Regular meetings are held once every day, once a week, or once a month. The
frequency of meetings is arbitrarily decided by each community-level Danshukai.
A member is able to join a meeting held by another community apart from their
home-affiliated community. Therefore, members in urban areas can easily attend
meetings held in different spots. Members who have just started abstinence or who
are continuing to drink are recommended to take part in meetings more frequently
to avoid drinking. Through the meetings, members are able to recover their
sensitivity and develop social skills.
The other important task is to maintain “one-day abstinence,” which is
a consistent slogan of Danshukai. Although abstinence should be maintained as
long as possible, it is very difficult for alcohol-dependent individuals to achieve
such a goal. To maintain abstinence, members pledge “one-day abstinence,” which
means that they will not drink alcohol on that day. Maintaining “one-day absti-
nence” can result in lifetime abstinence. Today, Danshukai members are trying to
maintain abstinence by pledging “one-day abstinence.”
Little evidence of the efficacy of Danshukai is available. Since participation in
Danshukai meetings is voluntary and is not randomly allocated, a controlled study
is very difficult to do. Two opposing self-selection biases may exist: (1) participants
in Danshukai might have sufficient motivation to change their drinking habits, and
(2) participants in Danshukai might have severe and refractory alcohol problems.
A longitudinal follow-up study of 133 alcohol-dependent Danshukai members
was previously conducted in a rural area in Japan (Doi 1987). The ratio of
newcomers who attended more than three meetings was 45.6 % during a 10-year
period. More than half the members dropped out after participating in the meetings
only once or twice. Twenty-five of the 133 participants who attended more than
three meetings remained abstinent for over 2 years. The ratios of attendance and
abstinence were relatively high, compared to another longitudinal follow-up study
of AA meetings (Pagano et al. 2013), partly because medical staff played a role in
the study. Eighteen of the 133 attendants died during the 10-year period.
individuals with serious anxiety and depressive moods. Actually, drug dependence
has long been a problem in Japan, dating back to the 1950s.
DARC is an acronym for “Drug Addiction Rehabilitation Center.” DARC consists
of rehabilitation facilities for drug-dependent individuals (Tokyo DARC Support
Center 2010). DARC members can use the facilities to recover from drug dependence
over the course of several months to years. Members are able to receive physical,
mental, and social support from DARC while they learn to live without drugs.
DARC was founded in 1985 by a drug-dependent patient. The patient provided
an old house in Tokyo and formed a community with other drug-dependent
associates (Kondo 2000). They started a rehabilitation program for drug depen-
dence in their community. The program was a modification of the 12 steps of AA
and emphasized group meetings. The goal of the program is not only to stop drug
use but to recover their human nature, such as expressions of sympathy, kindness,
and honesty. As of 2013, about 50 communities exist around Japan. The activities
of DARC are independently practiced in each community. This diversity of activ-
ities among each community is an outstanding characteristic of DARC.
Member candidates of DARC are introduced through many pathways including
lawyers, police officers, welfare, psychiatric hospitals, public health centers, and so
on. Some members voluntarily enter DARC on their own. In many cases, they are
brought to DARC by their families. About 90 % of the members have experienced
medical care for a drug-related problem. About 70 % have been arrested prior to
participating in DARC. Members in their 20s or 30s account for 80 % of DARC
members. Usually, 12–13 years since their first drug use have elapsed at the time of
a member’s first DARC meeting (Nishimura 2004).
DARC members must generally live jointly with other members in a community
house for 3 months to over 1 year and complete the residential program. They can
then attend DARC meetings after they have left the community house. Members
must pay a fee every month. The activities of DARC are administered using the
membership fees. Since anonymity must be maintained within the community,
DARC members use nicknames when speaking with each other. All members
have an equal status in DARC and are free from social positions.
The only rule of DARC is regular participation in the meetings. Members are
obliged to participate in morning meetings, afternoon meetings, and evening NA
(Narcotics Anonymous) meetings. DARC is strongly connected to NA. Members
are recommended to continue attending NA meetings after the completion of the
DARC program. DARC does not necessarily force its members not to use drugs, but
it encourages them to cultivate their independence and responsibility.
Even if members encounter problems, such as the reuse of drugs, they must
participate in the meetings and tell their problems to the other members honestly. In
their relationships with other members, they can share their distress, loneliness, and
emptiness that resulted in their drug use or that were caused by drug use. They are
also able to acquire the ability to communicate with others and to experience
alternative lifestyles without drug use through the DARC program. The slogan of
DARC members is “just for today,” which means not using drugs today and doing
their best today. Today without drugs will certainly lead to a clean future.
65 Danshukai and Other Support Groups in Addiction Treatment 1063
Many members drop out of the program and return to a drug-dependent lifestyle.
However, any member can resume the DARC program whenever they decide to
stop drug use once again. DARC does not exclude those who slip into the reuse of
drugs. Less than 1 % of the members have never resumed drug use after taking part
in DARC. However, 30–35 % of members continue to attend NA meetings, even if
they resume drug use several times along the way (Kondo 2000). Some members
can become staff members who manage the DARC program after the completion of
staff training. The staff and program members are equal and support each other to
prevent drug reuse.
DARC also addresses various addiction problems. Therefore, the role of DARC
has extended into various fields (Table 65.2). Members have spoken about their
experiences with drug use in schools to prevent young people from using drugs.
DARC has trained some members to be addiction counselors who can sympathize
with people who cannot help being addicted to drugs. Through such campaigns, the
activities of DARC have become known among medical, judicial, and educational
staffs. The outlook of DARC emphasizing rehabilitation has spread, and DARC
activities are expected to expand throughout Japan so that many people who suffer
from drug dependence can participate in rehabilitation programs to recover, instead
of being isolated in prisons or hospitals. Such interventions are critical for those
who are afflicted with drug abuse.
References
Doi A (1987) A longitudinal follow-up study of 133 alcoholic members of a Danshukai. Seishin
Shinkeigaku Zasshi 89:407–431, In Japanese
1064 A. Yoshimura and S. Higuchi
Higuchi S, Kono H (1994) Early diagnosis and treatment of alcoholism: the Japanese experience.
Alcohol Alcohol 29:363–373
Kondo T (2000) Beyond drug dependence. Kaitakusha, Tokyo, In Japanese
Nishimura N (2004) About DARC activities. Seisinkachiryougaku 19:1405–1410, In Japanese
Pagano ME, White WL, Kelly JF, Stout RL, Tonigan JS (2013) The 10-year course of alcoholics
anonymous participation and long-term outcomes: a follow-up study of outpatient subjects in
project MATCH. Subst Abus 34:51–59
Tokyo DARC Support Center (2010) Just for today 3. Tokyo DARC Support Center, Tokyo,
In Japanese
Wake K (2013) Regular meeting in the daytime for developing Danshukai. Zendanren, Tokyo,
In Japanese
Zendanren (2012) Shishin to Kihan (principles and rules). Tokyo. In Japanese
Zendanren (2013) Developing Zendanren 2013. Tokyo. In Japanese
Addiction Recovery in Services
and Policy: An International Overview 66
Alexandre Laudet and David Best
Contents
66.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1066
66.2 Recovery Becoming Guiding Vision of a Substance Use Services and Policy . . . . . . 1066
66.3 What Does “Recovery” Mean? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1068
66.4 What Does Adopting a Recovery Orientation Mean for Addiction
Treatment Services? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1069
66.5 What Do Recovery-Oriented Addiction Services Systems Look Like? . . . . . . . . . . . . . . 1070
66.6 Recovery-Oriented Systems of Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1071
66.7 Individual Recovery Support Services Elements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1072
66.8 What Can Medical Professionals Do to Promote Recovery
Among Substance-Using Patients? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1075
66.9 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1077
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1077
Abstract
This chapter provides an overview of the sweeping changes occurring in
the addiction field in the United States and abroad, with special emphasis
on the growing focus on recovery as the goal of services and the
guiding vision of drug policy. “Recovery” goes well beyond substance use
patterns to encompass improved functioning in life areas impaired by active
substance use, as well as improved overall quality of life. Because research
shows that substance use disorders are often chronic, recovery is
A. Laudet (*)
Center for the Study of Addictions and Recovery, National Development and Research Institutes,
Inc., New York, NY, USA
e-mail: [email protected]
D. Best
Turning Point Alcohol and Drug Centre, Fitzroy, VIC, Australia
Monash University, Melbourne, Australia
e-mail: [email protected]
Keywords
Recovery • Peer support • Addiction • Treatment
66.1 Introduction
Treatment systems addressing substance use disorders (SUDs) and the federal
agencies regulating them (e.g., in the United States, SAMHSA – the Substance
Abuse and Mental Health Services Administration) have begun to effect a shift in
their emphasis, with recovery becoming the guiding framework. There are two key,
empirically based elements to this paradigmatic shift: the reconceptualization of
SUD as chronic disorders and the broadening of what “recovery” means. First,
research in the past decade has suggested that addiction is best conceptualized as
a chronic disorder on par with other chronic conditions such as diabetes, asthma, or
hypertension (McLellan et al. 2000). However, unlike these other conditions,
treatment for substance use disorders (SUDs) has historically been delivered and
evaluated using an acute care model: intense episodes of care during which
a person, often in crisis, is assessed, treated, and released – ideally “cured” – all
in a relatively short time (Dennis and Scott 2007). Growing evidence for long
addiction and treatment “careers” consisting of multiple cycles of intensive and
66 Addiction Recovery in Services and Policy: An International Overview 1067
costly treatment episodes (Dennis et al. 2005) followed by return to active addiction
(Scott et al. 2005) has led to the conclusion that the acute care model is ill suited to
address SUD as a chronic condition (Hser et al. 1997; McLellan et al. 2005a;
O’Brien and McLellan 1996). Noting the disappointing outcomes of the current
system and the many similarities between SUD and other chronic illnesses, the
Institute of Medicine and leading addiction researchers have called for SUD
treatment to shift from the acute care model to one of recovery management akin
to the chronic care model used in the treatment of other chronic conditions (Dennis
and Scott 2007; Humphreys 2006; Institute of Medicine 2005; McKay 2005;
McLellan et al. 2000; Miller 2007; White et al. 2002, 2005b). A continuum of
care model consistent with chronic disease is also aligned with the experience of
persons in recovery who overwhelmingly describe recovery as “a process” vs. “an
end point” (Laudet 2007).
The second element of the paradigmatic shift to a recovery orientation is rooted
in the growing recognition that recovery goes well beyond making changes in one’s
substance use patterns (see next section). McLellan and colleagues may have put it
best where stating: “typically, the immediate goal of reducing alcohol and drug use
is necessary but rarely sufficient for the achievement of the longer-term goals of
improved personal health and social function and reduced threats to public health
and safety – i.e., recovery” (McLellan et al. 2005b, p. 448). Thus, the emerging
recovery-oriented model of care provides a continuum of service and support
designed to promote and sustain improvements in substance use (abstinence or
significant reductions) and psychosocial functioning. This recovery framework
reconciles a public health response to chronic care with a strength- and
community-based focus that places the individual at the heart of their own recovery
journey and emphasizes personal empowerment and individual ownership of the
definition of and pathway to recovery. Promoting recovery requires giving individ-
uals the tools and strategies to develop “capital,” a strength-based approach that has
gained prominence in both psychology (Seligman 2003) and criminology (Ronel
and Elisha 2011) and is embodied in the addiction field by the construct of
“recovery capital” (Granfield and Cloud 2001).
The emerging emphasis on recovery in addiction services is paralleled by
a similar shift at the federal policy level. In the United States, the President’s
National Drug Control Strategy emphasizes the importance of promoting recovery,
regardless of pathway (Office of National Drug Control Policy 2011) and calls for
the expansion of recovery support services across community-based settings. The
White House Office of National Drug Control Policy (ONDCP, the so-called drug
tsar office) has also begun several interagency initiatives that emphasize the
centrality of the recovery orientation to addressing SUDs, the need for recovery
support services, and the importance of eliminating legal barriers to recovery
(e.g., restrictions on housing and student loans for persons with a drug-related
criminal history). For example, ONDCP is working in the US Department of
Education that adopted the goal of providing a continuum of recovery supports at
all levels in academic settings (Dickard et al. 2011). ONDCP has created
a Recovery Branch to coordinate these efforts and engage federal partners, state
1068 A. Laudet and D. Best
The term “recovery” has been ubiquitous in the substance abuse field for half a century
if not longer but, until recently, had remained undefined. Researchers typically
operationalized the term in studies by measuring short-term abstinence (typically
a year or less), some from a single substance (e.g., alcohol) and others from all
substances (for a discussion, see Laudet 2007). The field began to delve into the
meaning of “recovery” in 2005 when the Center for Substance Abuse Treatment
(CSAT), a division of the Substance Abuse and Mental Health Services Administration
(SAMHSA), convened a panel of experts representing a number of key stakeholder
66 Addiction Recovery in Services and Policy: An International Overview 1069
groups (Center for Substance Abuse Treatment 2006). The following year, the Betty
Ford Center convened a smaller panel of experts and stakeholders that published the
first consensus definition of “recovery” as “voluntarily maintained lifestyle composed
characterized by sobriety, personal health, and citizenship” (Belleau et al. 2007,
p. 221). Other definitions have since been formulated, but all share the premise that
SUD recovery goes well beyond the reduction of/desistance from substance use and
extends to improved functioning in key life areas typically impaired but active use.
Stated differently, one can regard recovery as currently conceptualized as
non-problematic substance use (or total abstinence) plus improved functioning in
such areas as physical and mental health, employment, economic, family, and social
life, to name only a few. Central to this new model is that recovery is a dynamic and
individual process whereby the combination of factors defining recovery is individually
determined and may well change over time as recovery progresses.
Broadly stated, the two elements of the paradigmatic shift discussed above mean
that SUD services need to be expanded in time, in philosophy, and in scope. In
terms of time, SUDs have thus far been addressed using intensive, short-term
episodes of professionally delivered services in in- and/or outpatient settings.
While the effectiveness of treatment has received support (Waldron and Turner
2008; Weisner et al. 2003b), the rate of return to active use following treatment,
even among those who had achieved abstinence (the goal of treatment in the United
States), is high (Dennis et al. 2005; Laudet et al. 2007; McLellan et al. 2005a). This
typically leads to treatment reentry (be it in the community or in jail settings) as
well as to numerous costs to the individual, to his/her community, and to society.
On the other hand, there is evidence that participation in ongoing recovery
support – typically 12-step fellowship meetings such as Alcoholics Anonymous,
often the only available community-based recovery support resource until very
recently but also less structured forms of community engagement and activities – is
associated with decreased rates of return to active substance use (Fiorentine and
Hillhouse 2000; Kyrouz et al. 2002; Laudet et al. 2007; Tonigan 2008) and with
utilization of costly services (Humphreys and Moos 2001, 1996). Taken in
a broader context, the empirically demonstrated usefulness of mutual aid recovery
support groups emphasizes the importance of peer and most notably the critical role
on ongoing support to sustaining recovery (see later section).
In terms of scope, a recovery orientation requires the provision of comprehen-
sive services designed to address needs in all life areas that are typically impaired
during active addiction and where improvements are considered an inherent part of
recovery – e.g., physical and mental health, employment, economic, family, and
social life (see preceding section). Services addressing these issues have thus far
often been referred to as “ancillary” in status or “aftercare” in the timing of delivery
in spite of their importance to clients, and their evidences impact on the transition to
1070 A. Laudet and D. Best
stable recovery (Laudet et al. 2009; Laudet and White 2010). One study illustrating
the importance of non-addiction-related services to treatment clients interviewed
individuals who had left treatment before completion – in that study, 60 % of the
cohort has left before completion, a finding on par with the national average
(Substance Abuse and Mental Health Services Administration Office of Applied
Studies Treatment Episode Data Set (TEDS) 2005, 2008). We asked clients why
they left the program and whether they felt there was anything the program could
have done differently to keep them engaged in services longer (Laudet et al. 2009).
Answers fell into one of three broad categories, none of which mentioned addiction
treatment services: need for social services (54.2 % – job training, help with
housing, childcare, stable housing), need for more supportive staff (25.8 % – e.g.,
encouraging, trusting, and caring), and need for greater schedule flexibility to
accommodate other responsibilities, including work (20 %). These findings are
consistent with that of another study we conducted examining current challenges
and life priorities in a sample of 356 community-based persons in abstinent
recovery from severe polysubstance dependence (Laudet and White 2010). Partic-
ipants’ responses were examined as a function of how long they had been abstinent:
under 6 months (28 %), 6–18 months (26 %), 18–36 months (20 %), and over
3 years (26 %). Across these stages, working on one’s recovery (e.g., staying sober,
“making recovery a priority”) was consistently cited as the top priority (cited by
34–49 % across stages); notably, employment was the second most frequently
mentioned priority at all stages, cited by the same percentage of persons abstinent
over 3 years as working on one’s recovery (34.1 % each). Taken together, findings
from these studies underline the importance of services designed to foster improve-
ment in non-addiction functioning among both individuals in treatment and those at
various stages of the recovery process.
The comprehensive recovery-oriented service model is significantly different
from the currently prevalent model where services focus, by necessity, on substance
use-related issues and are delivered by trained addiction professionals. Note that
delivering a comprehensive recovery-promoting approach does not require that all
services be delivered in a single setting, nor does it signify the approaching
disappearance of “addiction treatment” as practiced today. In the next section, we
summarize prevalent models of recovery support services.
As clinicians and researchers have come to recognize the chronic nature of SUD, they
have developed and evaluated a growing menu of interventions designed to help
clients sustain and build on their treatment gains – i.e., relapse prevention. Perhaps
the most prevalent form of aftercare consists of a stepped down course of services
typically following intensive inpatient or residential treatment (McKay 2001, 2009;
McKay et al. 2009); in spite of its established existence and intuitive appeal, few
clients access these resources and the evidence for the effectiveness of the approach
66 Addiction Recovery in Services and Policy: An International Overview 1071
remains limited (Godley et al. 2007; McKay 2001). In the past decade, clinicians
have also started to capitalize on health technology such as telephone-based continu-
ing care (McKay et al. 2005), and several large treatment agencies are developing
proprietary web-based online recovery maintenance and support programs for clients
to use after they leave service; one example is Hazelden’s MORE.1
In the United States, the shift to a recovery orientation in SUD services has been
primarily spearheaded by the Substance Abuse and Mental Health Services Admin-
istration (SAMHSA). SAMHSA is advancing the Recovery-Oriented Systems of
Care (ROSC) model that constitutes an organizing framework for recovery support
services. A key premise underlying recovery supports is that addiction is typically
a chronic rather than acute condition. While a chronic condition cannot be “cured,”
the symptoms can be arrested and the condition managed. The need for this new
model was perhaps stated most explicitly by Dr. Clark, a SAMHSA official:
“Recovery is more than abstinence from alcohol and drugs; it’s about building
a full, meaningful, and productive life in the community. Our treatment systems
must reflect and help people achieve this broader understanding of recovery” (Clark
2008b, p. 2). As described in SAMHSA materials,2 ROSC’s goals are to intervene
early with individuals with SUDs, to support sustained SUD recovery, and to
improve the health and wellness of SUD-affected individuals and families. Con-
sistent with the multidimensional and developmental nature of recovery discussed
earlier in this chapter, the ROSC model proposes a multisystem, person-centered
continuum of care in which a comprehensive menu of coordinated services and
supports is tailored to individuals’ recovery stage, needs, and chosen recovery
pathway (Clark 2008a, b). Services and supports are provided in a comprehensive
array of recovery-related domains including education and job training, housing,
childcare, transportation to treatment and work, case management, spiritual sup-
port, as well as SUD-focused services – e.g., relapse prevention, recovery support,
SUD education for family members, peer-to-peer services and coaching, self-help,
and support groups (Kaplan 2008; Sheedy and Whitter 2009).
Services are intended to address the multitude of life areas adversely affected by
active substance use and to respond to clients’ changing needs across their life span.
ROSC is responsive to calls from the Institute of Medicine and leading addiction
researchers for a shift in SUD treatment from the acute care model to one more akin
to the model used in other chronic conditions (Humphreys and Tucker 2002; Institute
of Medicine 2005; McLellan et al. 2000; White et al. 2005a). From a systems
perspective, this means that the case management and care coordination function of
services is conferred a more prominent role in treatment design and delivery.
1
http://www.hazelden.org/web/public/more_demo.page
2
http://partnersforrecovery.samhsa.gov/rosc.html
1072 A. Laudet and D. Best
article (A. Laudet and Humphreys 2013). One model is the sober residence,
a home that offers mutual help-oriented, financially self-sustaining, self-
governed, democratic communal-living environments where individuals in
recovery can reside for as long as they choose after inpatient treatment or
incarceration, during outpatient treatment or as an alternative to treatment
(Polcin 2009). The most prevalent model of sober residences is Oxford House
(OH) with 1,300 houses in the United States (Jason and Ferrari 2010). The
benefits of the model in terms of substance use and related domains (e.g.,
employment, criminal involvement) have been extensively documented in pro-
spective peer-reviewed studies across subpopulations (Alvarez et al. 2006; Jason
et al. 2001, 2009; Majer et al. 2002, 2011; Millar et al. 2011), as has been its
cost-effectiveness (Lo Sasso et al. 2012; Olson et al. 2006). Most recent and
perhaps most innovative is the campus-based Collegiate Recovery Program
(CRP) model that is emerging nationwide. The high prevalence of substance
use on college campus can jeopardize recovery for young people at a time of
their development where fitting in with peers is central to their identity; for
some, that may lead to foregoing or postponing college in the absence of
a readily available sober network (Baker and Harris 2010; Botzet et al. 2007;
Harris et al. 2008; Laitman and Lederman 2007; Smock et al. 2011;
U.S. Department of Education Higher Education Center for Alcohol and Other
Drug Abuse and Violence Prevention 2010; Woodford 2001). The CRC devel-
oped to meet the needs of college students with a history of SUD who have
successfully remitted from the disorder and seek to pursue educational goals.
Central elements of the CRC model include a peer-driven approach informed by
12-step tenets and services such as drug-free housing, on-site peer support, and
counseling provided by a small staff, as well as opportunities for sober recrea-
tional activities, relapse prevention, and life skills workshops. Little documen-
tation is currently available about specific CRC services across programs, but it
is believed that the breadth of service varies (Bell et al. 2009). Common to all are
on-site 12-step and other recovery support meetings, a campus-based location
where students can meet and spend time with sober peers; some offer sober
housing and peer academic support. All function with minimal professional
staff as the emphasis is clearly peer driven. The model seems consistent with
the continuing care paradigm within a “recovery management” system that
experts recommend (Godley et al. 2002). CRCs are also responsive to calls for
appropriate campus-based infrastructure to support recovering students (Misch
2009), with recent shifts in drug (Office of National Drug Control Policy 2010)
and with the US Department of Education’s goal of ensuring a continuity of care
from high school to college to postgraduation (Dickard et al. 2011). The model
is growing in popularity nationwide: in the past decade, growing concerns
about substance use on campus and federal agencies’ focus on building a
community-based continuum of care system for youths have fueled a fivefold
increase in the number of CRPs, from four in 2000 to 32 in 19 states today. No
formal evaluation has been conducted yet, but site-specific reports document
66 Addiction Recovery in Services and Policy: An International Overview 1075
encouraging outcomes – low relapse rates, above school average GPAs, gradua-
tion rates, and perceived helpfulness (Baker et al. 2011; Bell et al. 2009; Cleve-
land et al. 2007; Harris et al. 2008). The first author is currently conducting an
NIH-funded survey of all CRC programs and student participants nationwide to
learn more about the breadth of services offered and the characteristics and needs
of students served; that knowledge will inform a subsequent large-scale evalua-
tion of the model. In the same vein as CRCs though professionally rather than peer
delivered are recovery high schools (Moberg and Finch 2008) that typically
function as charter schools in a public school system and serve students who
recently left SUD treatment. This model is currently undergoing systematic
evaluation.
The three initiatives discussed above – around education, housing, and peer
activities – are all consistent with three core tenets of recovery-oriented services:
a care coordination across a range of service sectors requiring case management
skills and “outward-looking” specialist treatment services, an increased role for
peers and a recognition of the validity of “expertise by experience,”
and a continuity of care model that acknowledges the need for integrating acute
services with those targeting longer-term changes in well-being and social
integration. This grassroots or “bottom-up” approach represents a drastic
departure from the current SUD service model. Moreover and importantly, it
is accessible to individuals who have reservations about the mutual aid movement
(12 steps in particular) and is consistent with an asset-based community
development model (Kretzmann 1993) and with the public health model to
addictions that is gathering momentum in the United Kingdom and elsewhere
in Europe.
Overall, a growing menu of professionally and peer-delivered recovery support
services is being developed and implemented, with the professionally
driven efforts being spearheaded (in the United States) by federal funding agen-
cies, principally SAMHSA. None of the peer-driven strategies have been
formally evaluated though state-level data report encouraging outcomes. These
findings are of course preliminary; the approaches need to be systematically
evaluated, and the stability of the documented improvements over time remains
to be determined.
Given the prevalence of substance use disorders and how frequently medical and
substance use disorders co-occur, medical professionals routinely come into contact
with patients who are or were abusers of/dependent drugs and/or alcohol. This
section briefly outlines suggestions for medical professionals to promote the initi-
ation and maintenance of recovery from substance use disorders.
1076 A. Laudet and D. Best
3
http://www.samhsa.gov/prevention/sbirt/SBIRTwhitepaper.pdf
66 Addiction Recovery in Services and Policy: An International Overview 1077
66.9 Conclusion
References
Agerwala SM, McCance-Katz EF (2012) Integrating Screening, Brief Intervention, and Referral to
Treatment (SBIRT) into clinical practice settings: a brief review. J Psychoactive Drugs
44(4):307–317
Alvarez J, Adebanjo AM, Davidson MK, Jason LA, Davis MI (2006) Oxford House: deaf-
affirmative support for substance abuse recovery. Am Ann Deaf 151(4):418–422
1078 A. Laudet and D. Best
Appel PW, Ellison AA, Jansky HK, Oldak R (2004) Barriers to enrollment in drug abuse treatment
and suggestions for reducing them: opinions of drug injecting street outreach clients and other
system stakeholders. Am J Drug Alcohol Abuse 30(1):129–153
Baker A, Harris K (eds) (2010) Questions. . .more answers: creating effective relapse prevention
strategies for recovering college students. U.S. Department of Health and Human Services:
Substance Abuse and Mental Health Services Administration, Rockville
Baker A, Laudet A, Harris K (2011) Collegiate recovery communities: student membership and
prospective outcomes. Paper presented at the 73rd annual scientific meeting of the College on
Problems of Drug Dependence (CPDD), Hollywood
Bell NJ, Kanitkar K, Kerksiek KA, Watson W, Das A, Kostina-Ritchey E, Harris K (2009) “It has
made college possible for me”: feedback on the impact of a university-based center for students
in recovery. J Am Coll Health 57(6):650–657
Belleau C, DuPont R, Erickson C, Flaherty M, Galanter M, Gold M, White W (2007) What is
recovery? A working definition from the Betty Ford Institute. J Subst Abuse Treat
33(3):221–228
Best D (2012) Addiction recovery: a movement for social change and personal growth in the
UK. Pavilion Publishing, Brighton
Best D, Gow J, Knox T, Taylor A, Groshkova T, White W (2011) Mapping the recovery stories of
drinkers and drug users in Glasgow: quality of life and its associations with measures of
recovery capital. Drug Alcohol Rev 15
Borkman T (1999) Understanding self-help/mutual aid: experiential learning in the commons.
Rutgers University Press, New Brunswick
Botzet A, Winters K, Fahnhorst T (2007) An exploratory assessment of a college substance abuse
recovery program: Augsburg College’s stepUP program. J Groups Addict Recover
2(2–4):257–287
Braithwaite RS, Conigliaro J, Roberts MS, Shechter S, Schaefer A, McGinnis K, Rodriguez MC,
Rabeneck L, Bryant K, Justice AC (2007) Estimating the impact of alcohol consumption on
survival for HIV + individuals. AIDS Care 19(4):459–466
Brown ME, Swiggart WH, Dewey CM, Ghulyan MV (2012) Searching for answers: proper
prescribing of controlled prescription drugs. J Psychoactive Drugs 44(1):79–85
Center for Substance Abuse Treatment (ed) (2006) National summit on recovery: conference
report. Substance Abuse and Mental Health Services Administration, Rockville
Clark W (2008a) Recovery-oriented systems of care: SAMHSA/CSAT’s public health approach to
substance use problems & disorders. Paper presented at the aligning concepts, practice, and
contexts to promote long term recovery: an action plan, Philadelphia. www.ireta.org
Clark W (2008b) Recovery as an organizing concept. http://www.nattc.org/learn/topics/rosc/docs/
drwestleyclarkinterview.pdf. 7 Feb 2008
Cleveland HH, Harris KS, Baker AK, Herbert R, Dean LR (2007) Characteristics of a collegiate
recovery community: maintaining recovery in an abstinence-hostile environment. J Subst
Abuse Treat 33(1):13–23
Compton WM, Thomas YF, Stinson FS, Grant BF (2007) Prevalence, correlates, disability, and
comorbidity of DSM-IV drug abuse and dependence in the United States: results from the
national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry
64(5):566–576. doi:10.1001/archpsyc.64.5.566, 64/5/566 [pii]
Cruciani RA, Esteban S, Seewald RM, Altilio T, Bookbinder M, Sheu R, Portenoy RK
(2008) MMTP patients with chronic pain switching to pain management clinics. A problem
or an acceptable practice? Pain Med 9(3):359–364. doi:10.1111/j.1526-4637.2006.00224.x,
PME224 [pii]
Cunningham JA, Sobell LC, Sobell MB, Agrawal S, Toneatto T (1993) Barriers to treatment: why
alcohol and drug abusers delay or never seek treatment. Addict Behav 18(3):347–353
Dennis M, Scott CK (2007) Managing addiction as a chronic condition. NIDA Addict Sci Clin
Pract Perspect 4(1):45–55
66 Addiction Recovery in Services and Policy: An International Overview 1079
Dennis M, Scott C, Funk R, Foss MA (2005) The duration and correlates of addiction and
treatment careers. J Subst Abuse Treat 28(Suppl 1):S51–S62
Dickard N, Downs T, Cavanaugh D (2011) Recovery/relapse prevention in educational settings for
youth with substance use & co-occurring mental health disorders: 2010 Consultative sessions
report. US Department of Education, Office of Safe and Drug-Free Schools, Washington,
DC. http://www2.ed.gov/about/offices/list/osdfs/recoveryrpt.pdf
Easton M (2008) Drug treatment – success or failure? http://www.bbc.co.uk/blogs/thereporters/
markeaston/2008/10/drug_treatment_officials_were.html
Evans A (2007) The recovery-focused transformation of an urban behavioral health care system.
http://www.attcnetwork.org/learn/topics/rosc/docs/arthurcevensinterview.pdf. Retrieved
7 Feb 2008
Faces and Voices of Recovery (2010) Addiction recovery peer service roles: recovery manage-
ment in health reform. Faces and Voices of Recovery, Washington, DC
Fiorentine R, Hillhouse MP (2000) Drug treatment and 12-step program participation: the additive
effects of integrated recovery activities. J Subst Abuse Treat 18(1):65–74
Godley MD, Godley SH, Dennis ML, Funk R, Passetti LL (2002) Preliminary outcomes from the
assertive continuing care experiment for adolescents discharged from residential treatment.
J Subst Abuse Treat 23(1):21–32
Godley MD, Godley SH, Dennis ML, Funk RR, Passetti LL (2007) The effect of assertive
continuing care on continuing care linkage, adherence and abstinence following residential
treatment for adolescents with substance use disorders. Addiction 102(1):81–93
Gonzales A, Westerberg VS, Peterson TR, Moseley A, Gryczynski J, Mitchell SG, Buff G,
Schwartz RP (2012) Implementing a statewide Screening, Brief Intervention, and Referral to
Treatment (SBIRT) service in rural health settings: New Mexico SBIRT. Subst Abus
33(2):114–123. doi:10.1080/08897077.2011.640215
Granfield R, Cloud W (2001) Social context and “natural recovery”: the role of social capital in the
resolution of drug-associated problems. Subst Use Misuse 36(11):1543–1570
Greenfield TK, Stoneking BC, Humphreys K, Sundby E, Bond J (2008) A randomized trial of
a mental health consumer-managed alternative to civil commitment for acute psychiatric crisis.
Am J Community Psychol 42(1–2):135–144
Gryczynski J, Mitchell SG, Peterson TR, Gonzales A, Moseley A, Schwartz RP (2011) The
relationship between services delivered and substance use outcomes in New Mexico’s Screen-
ing, Brief Intervention, Referral and Treatment (SBIRT) initiative. Drug Alcohol Depend
118(2–3):152–157. doi:10.1016/j.drugalcdep.2011.03.012, S0376-8716(11)00138-4 [pii]
Harris K, Baker A, Kimball T, Shumway S (2008) Achieving systems-based sustained recovery:
a comprehensive model for collegiate recovery communities. J Group Addict Recover
2(2–4):220–237
Hasin DS, Stinson FS, Ogburn E, Grant BF (2007) Prevalence, correlates, disability, and comor-
bidity of DSM-IV alcohol abuse and dependence in the United States: results from the National
Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry
64(7):830–842. doi: 10.1001/archpsyc.64.7.830, 64/7/830 [pii]
HM Government (2010) Drug strategy 2010: reducing demand, restricting supply, building
recovery: supporting people to live a drug free life. HM Government, London
Hser YI, Anglin MD, Grella C, Longshore D, Prendergast ML (1997) Drug treatment careers.
A conceptual framework and existing research findings. J Subst Abuse Treat 14(6):543–558
Humphreys K (2006) Closing remarks: swimming to the horizon–reflections on a special series.
Addiction 101(9):1238–1240
Humphreys K, Moos RH (1996) Reduced substance-abuse-related health care costs among
voluntary participants in Alcoholics Anonymous. Psychiatr Serv 47(7):709–713
Humphreys K, Moos R (2001) Can encouraging substance abuse patients to participate in self-help
groups reduce demand for health care? A quasi-experimental study. Alcohol Clin Exp Res
25(5):711–716
1080 A. Laudet and D. Best
Humphreys K, Tucker J (2002) Toward more responsive and effective intervention systems for
alcohol-related problems. Addiction 97(2):126–132
Humphreys K, Moos RH, Cohen C (1997) Social and community resources and long-term
recovery from treated and untreated alcoholism. J Stud Alcohol 58(3):231–238
Humphreys K, Mankowski E, Moos R, Finney J (1999) Do enhanced friendships networks and
active coping mediate the effect of self help groups on substance use? Ann Behav Med
21(1):54–60
Humphreys K, Macus S, Stewart E, Oliva E (2004) Expanding self-help group participation in
culturally diverse urban areas: media approaches to leveraging referent power. J Community
Psychol 32(4):1–12
Institute of Medicine (2005) Improving the quality of health care for mental and substance use
conditions. National Academy Press, Washington, DC
Jason LA, Ferrari JR (2010) Oxford House recovery homes: characteristics and effectiveness.
Psychol Serv 7(2):92–102
Jason LA, Davis MI, Ferrari JR, Bishop PD (2001) Oxford house: a review of research and
implications for substance abuse recovery and community research. J Drug Educ 31(1):1–27
Jason LA, Aase DM, Mueller DG, Ferrari JR (2009) Current and previous residents of self-
governed recovery homes: characteristics of long-term recovery. Alcohol Treat
Q 27(4):442–452
Kaplan L (2008) The role of recovery support services in recovery-oriented systems of care:
DHHS publication No. (SMA) 08-4315. Center for Substance Abuse Treatment, Substance
Abuse and Mental Health Services Administration, Rockville
Kessler RC, Nelson CB, McGonagle KA, Edlund MJ, Frank RG, Leaf PJ (1996) The epidemiology
of co-occurring addictive and mental disorders: implications for prevention and service
utilization. Am J Orthopsychiatry 66(1):17–31
Kirk T (2008) Creating a recovery-oriented system of care. http://www.facesandvoicesofrecovery.
org/pdf/recovery_symposium/GLATTCInterviewKirk.pdf. Retrieved 7 Feb 2008
Kirk T (2010) Connecticut’s journey to a statewide recovery-oriented health-care system: strate-
gies, successes, and challenges. In: Kelly J, White W (eds) Addiction recovery management.
Springer Humana Press, New York, pp 2009–2235
Kretzmann J (1993) In: McKnight J (ed) Building communities from the inside out: a path towards
finding and mobilising a community’s assets. ABCD Institute, Evanston
Kyrouz E, Humphreys K, Loomis C (2002) A review of research on the effectiveness of self-
help mutual aid groups. In: White B, Madara E (eds) American self-help group clearinghouse
self-help group sourcebook, 7th edn. American Self-Help Group Clearinghouse, Dover,
pp 71–86
Laitman L, Lederman L (2007) The need for a continuum of care: the Rutgers comprehensive
model. J Groups Addict Recover 2(2–4):238–256
Laudet A (2007) What does recovery mean to you? Lessons from the recovery experience for
research and practice. J Subst Abuse Treat 33(3):243–256
Laudet AB (2012) Rate and predictors of employment among formerly polysubstance dependent
urban individuals in recovery. J Addict Dis 31(3):288–302
Laudet A, Humphreys K (2013) Promoting recovery in an evolving context: what do we know and
what do we need to know about recovery support services? J Subst Abus Treat 45(1):126–133
Laudet AB, White W (2010) What are your priorities right now? Identifying service needs across
recovery stages to inform service development. J Subst Abuse Treat 38(1):51–59
Laudet AB, Savage R, Mahmood D (2002) Pathways to long-term recovery: a preliminary
investigation. J Psychoactive Drugs 34(3):305–311
Laudet A, Stanick V, Sands B (2007) The effect of onsite 12-step meetings on post-treatment
outcomes among polysubstance-dependent outpatient clients. Eval Rev 31(6):613–646
Laudet AB, Stanick V, Sands B (2009) What could the program have done differently?
A qualitative examination of reasons for leaving outpatient treatment. J Subst Abuse Treat
37(2):182–190
66 Addiction Recovery in Services and Policy: An International Overview 1081
Lo Sasso AT, Byro E, Jason LA, Ferrari JR, Olson B (2012) Benefits and costs associated with
mutual-help community-based recovery homes: the Oxford House model. Eval Program Plann
35(1):47–53
Lotfipour S, Howard J, Roumani S, Hoonpongsimanont W, Chakravarthy B, Anderson CL, Weiss
JW, Cisneros V, Dykzeul B (2013) Increased detection of alcohol consumption and at-risk
drinking with computerized alcohol screening. J Emerg Med. doi:10.1016/j.
jemermed.2012.09.038, S0736-4679(12)01210-3 [pii]
Madras BK, Compton WM, Avula D, Stegbauer T, Stein JB, Clark HW (2009) Screening, Brief
Interventions, Referral to Treatment (SBIRT) for illicit drug and alcohol use at multiple healthcare
sites: comparison at intake and 6 months later. Drug Alcohol Depend 99(1–3):280–295
Majer JM, Jason LA, Ferrari JR, North CS (2002) Comorbidity among Oxford House residents:
a preliminary outcome study. Addict Behav 27(5):837–845
Majer JM, Angulo RS, Aase DM, Jason LA (2011) Gambling behaviors among Oxford House
residents: a preliminary investigation. J Soc Serv Res 37(4):422–427
Mangrum L (ed) (2008) Final evaluation report: creating access to recovery through drug courts.
Texas Department of State Health Services, Mental Health and Substance Abuse Services
Division: Gulf Coast Addiction Technology Transfer Center, Austin
Margolis R, Kilpatrick A, Mooney B (2000) A retrospective look at long-term adolescent
recovery: clinicians talk to researchers. J Psychoactive Drugs 32(1):117–125
McKay JR (2001) Effectiveness of continuing care interventions for substance abusers. Implica-
tions for the study of long-term treatment effects. Eval Rev 25(2):211–232
McKay JR (2005) Is there a case for extended interventions for alcohol and drug use disorders?
Addiction 100(11):1594–1610
McKay JR (2009) Continuing care research: what we have learned and where we are going. J Subst
Abuse Treat 36(2):131–145
McKay JR, Lynch KG, Shepard DS, Morgenstern J, Forman RF, Pettinati HM (2005) Do patient
characteristics and initial progress in treatment moderate the effectiveness of telephone-based
continuing care for substance use disorders? Addiction 100(2):216–226
McKay JR, Carise D, Dennis ML, Dupont R, Humphreys K, Kemp J, Schwartzlose J (2009)
Extending the benefits of addiction treatment: practical strategies for continuing care and
recovery. J Subst Abuse Treat 36(2):127–130
McKeganey N (2010) Controversies in drug policy and practice. Palgrave Macmillan, Basingstoke
McLellan AT, Lewis DC, O’Brien CP, Kleber HD (2000) Drug dependence, a chronic medical
illness: implications for treatment, insurance, and outcomes evaluation. JAMA
284(13):1689–1695
McLellan AT, McKay JR, Forman R, Cacciola J, Kemp J (2005a) Reconsidering the evaluation of
addiction treatment: from retrospective follow-up to concurrent recovery monitoring. Addic-
tion 100(4):447–458
McLellan AT, Weinstein RL, Shen Q, Kendig C, Levine M (2005b) Improving continuity of care
in a public addiction treatment system with clinical case management. Am J Addict
14(5):426–440
Millar JR, Aase DM, Jason LA, Ferrari JR (2011) Veterans residing in self-governed recovery
homes for substance abuse: sociodemographic and psychiatric characteristics. Psychiatr
Rehabil J 35(2):141–144
Miller WR (2007) Bring addiction treatment out of the closet. Addiction 102(6):863
Miotto K, Kaufman A, Kong A, Jun G, Schwartz J (2012) Managing co-occurring substance use
and pain disorders. Psychiatr Clin North Am 35(2):393–409. doi:10.1016/j.psc.2012.03.006,
S0193-953X(12)00023-8 [pii]
Misch DA (2009) On-campus programs to support college students in recovery. J Am Coll Health
58(3):279–280
Mitchell SG, Gryczynski J, O’Grady KE, Schwartz RP (2013) SBIRT for adolescent drug and
alcohol use: current status and future directions. J Subst Abuse Treat. doi:10.1016/j.
jsat.2012.11.005, S0740-5472(12)00438-2 [pii]
1082 A. Laudet and D. Best
Moberg DP, Finch AJ (2008) Recovery high schools: a descriptive study of school programs and
students. J Groups Addict Recover 2:128–161
Murphy MK, Bijur PE, Rosenbloom D, Bernstein SL, Gallagher EJ (2013) Feasibility of a -
computer-assisted alcohol SBIRT program in an urban emergency department: patient and
research staff perspectives. Addict Sci Clin Pract 8(1):2. doi:10.1186/1940-0640-8-2, 1940-
0640-8-2 [pii]
Nealon-Woods MA, Ferrari JR, Jason LA (1995) Twelve-step program use among Oxford House
residents: spirituality or social support in sobriety? J Subst Abuse 7(3):311–318
O’Brien C, McLellan A (1996) Myths about the treatment of addiction. Lancet
347(8996):237–240
Office of National Drug Control Policy (2010) National drug control strategy. Office of National
Drug Control Policy, Washington, DC
Office of National Drug Control Policy (2011) National drug control strategy. Office of National
Drug Control Policy, Washington, DC
Olson BD, Viola J, Jason LA, Davis MI, Ferrari JR, Rabin-Belyaev O (2006) Economic costs of
Oxford House inpatient treatment and incarceration: a preliminary report. J Prev Interv
Community 31(1–2):63–72
Oyugi JH, Byakika-Tusiime J, Ragland K, Laeyendecker O, Mugerwa R, Kityo C, Bangsberg DR,
Mugyenyi P, Quinn TC (2007) Treatment interruptions predict resistance in HIV-positive
individuals purchasing fixed-dose combination antiretroviral therapy in Kampala, Uganda.
AIDS 21(8):965–971
Polcin DL (2009) A model for sober housing during outpatient treatment. J Psychoactive Drugs
41(2):153–161
Portenoy R, Payne R, Passik D (2005) Acute and chronic pain. In: Lowinson J, Ruiz P, Millman R,
Langrod J (eds) Substance abuse: a comprehensive textbook. Lippincott, Williams and Wil-
kins, Philadelphia, pp 863–904 (Reprinted from: 4th)
Recovery Academy Australia (2012) Recovery academies. http://home.vicnet.net.au/
recoveryacademy/principles/
Ronel N, Elisha E (2011) A different perspective: introducing positive criminology. Int J Offender
Ther Comp Criminol 55(2):305–325. doi:10.1177/0306624X09357772
Rowe M, Bellamy C, Baranoski M, Wieland M, O’Connell MJ, Benedict P, Sells D (2007) A peer-
support, group intervention to reduce substance use and criminality among persons with severe
mental illness. Psychiatr Serv 58(7):955–961
Ryan JP, Marsh JC, Testa MF, Louderman R (2006) Integrating substance abuse treatment and
child welfare services. Soc Work Res 30(2):95–107
Samet JH, Walley AY, Bridden C (2007) Illicit drugs, alcohol, and addiction in human immuno-
deficiency virus. Panminerva Med 49(2):67–77
Scott CK, Foss MA, Dennis ML (2005) Pathways in the relapse–treatment–recovery cycle over
3 years. J Subst Abuse Treat 28(Suppl 1):S63–S72
Scottish Government (2008) The road to recovery: a new approach to Scotland’s drug problem.
Scottish Government, Edinburgh
Seligman M (2003) Authentic happiness. Nicholas Brealey Publishing, Boston
Sheedy CK, Whitter M (eds) (2009) Guiding principles and elements of recovery-oriented systems
of care: what do we know from the research? HHS publication No. (SMA) 09-4439. Center for
Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration,
Rockville
Smock S, Baker A, Harris K, D’sauza C (2011) The role of social support in collegiate recovery
communities: a review of the literature. Alcohol Treat Q 29:35–44
Substance Abuse and Mental Health Services Administration Office of Applied Studies Treatment
Episode Data Set (TEDS) 2005 (2008) Discharges from substance abuse treatment services,
DASIS series. Substance Abuse and Mental Health Services Administration, Rockville
Tondora J, Davidson L (eds) (2006) Practice guidelines for recovery-oriented behavioral health
care. Connecticut Department of Mental Health and Addiction Services, Hartford
66 Addiction Recovery in Services and Policy: An International Overview 1083
Tonigan JS (2008) Alcoholics anonymous outcomes and benefits. Recent Dev Alcohol
18:357–372
U.S. Department of Education Higher Education Center for Alcohol and Other Drug Abuse and
Violence Prevention (2010) Meeting the needs of students in recovery. http://www.
higheredcenter.org/files/prevention_updates/august2010.pdf. Retrieved 26 Oct 2010
United Kingdom Drug Policy Commission Consensus Group (2007) Developing a vision of
recovery: a work in progress. UKDPC, London
Victorian Department of Health (2012) New directions for alcohol and drug treatment services:
a roadmap. Victorian Department of Health, Melbourne
Waldron HB, Turner CW (2008) Evidence-based psychosocial treatments for adolescent sub-
stance abuse. J Clin Child Adolesc Psychol 37(1):238–261
Wang PS, Lane M, Olfson M, Pincus HA, Wells KB, Kessler RC (2005) Twelve-month use of
mental health services in the United States: results from the National Comorbidity Survey
Replication. Arch Gen Psychiatry 62(6):629–640. doi:10.1001/archpsyc.62.6.629, 62/6/629
[pii]
Watson B, Conigrave KM, Wallace C, Whitfield JB, Wurst F, Haber PS (2007) Hazardous alcohol
consumption and other barriers to antiviral treatment among hepatitis C positive people
receiving opioid maintenance treatment. Drug Alcohol Rev 26(3):231–239
Weisner C, Delucchi K, Matzger H, Schmidt L (2003a) The role of community services and
informal support on five-year drinking trajectories of alcohol dependent and problem drinkers.
J Stud Alcohol 64(6):862–873
Weisner C, Matzger H, Kaskutas LA (2003b) How important is treatment? One-year outcomes of
treated and untreated alcohol-dependent individuals. Addiction 98(7):901–911
White W (ed) (2008) Recovery management and recovery-oriented systems of care: scientific
rationale and promising practices. Northeast Addiction Technology Transfer Center, Great
Lakes Addiction Technology Transfer Center, Philadelphia Department of Behavioral Health
& Mental Retardation Services, Pittsburgh
White W (ed) (2009) Peer-based addiction recovery support: history, theory, practice and scientific
evaluation. Great Lakes Addiction Technology Transfer Center, Philadelphia Department of
Behavioral Health & Mental Retardation Services, Philadelphia
White W, Boyle M, Loveland D (2002) Alcoholism/addiction as chronic disease: from rhetoric to
clinical reality. Alcohol Treat Q 20:107–130
White W, Boyle M, Loveland D, Corrington P (2005) What is behavioral health recovery
management? A brief primer. www.addictionmanagement.org/recovery%20management.pdf.
Retrieved 13 Feb 2008
White W, Scott C, Dennis M, Boyle M (2005b) It’s time to stop kicking people out of addiction
treatment. Counselor 6(2):12–25
WHO Brief Intervention Study Group (1996) A cross-national trial of brief interventions for heavy
drinkers. Am J Public Health 86(7):948–955
Woodford M (2001) Recovering college students’ perspectives: investigating the phenomena of
recovery from substance abuse among undergraduate students. Dissertation abstracts interna-
tional section A: humanities & social sciences, 62(7-A), University of Virginia
Young MM, Stevens A, Porath-Waller A, Pirie T, Garritty C, Skidmore B, Moher D (2012)
Effectiveness of brief interventions as part of the screening, brief intervention and referral to
treatment (SBIRT) model for reducing the non-medical use of psychoactive substances:
a systematic review protocol. Syst Rev 1:22. doi:10.1186/2046-4053-1-22, 2046-4053-1-22
[pii]
Zemore SE, Mulia N, Yu Y e, Borges G, Greenfield TK (2009) Gender, acculturation, and other
barriers to alcohol treatment utilization among Latinos in three National Alcohol Surveys.
J Subst Abuse Treat 36(4):446–456
Applying Technology to the Assessment,
Prevention, Treatment, and Recovery 67
Support of Substance Use Disorders
Contents
67.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1086
67.1.1 The Promise of Technology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1086
67.2 Applications of Technology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1087
67.2.1 The Scientific Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1087
67.2.2 The Opportunity for Public Health Impact . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1087
67.2.3 Opportunities for Developing Countries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1088
67.2.4 Research Needs and Opportunities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1089
67.2.5 Best Practice Models for Implementation of Technology-Based Care
Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1089
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1091
Abstract
This chapter summarizes the growing body of research demonstrating that
science-based information and communication technologies (e.g., delivered
via the web and/or on mobile devices) offer great promise in targeting the full
spectrum of substance use disorders, ranging from assessment and prevention to
treatment and recovery support. This chapter provides a summary of the growing
scientific literature showing that these tools (when they are well developed and
in close collaboration with the target audience) may be engaging to the target
Disclosure: Dr. Marsch is affiliated with HealthSim, LLC, a small business that developed
a web-based psychosocial intervention for substance use disorders. This relationship is extensively
managed by Dr. Marsch and her academic institution.
L.A. Marsch (*)
Center for Technology and Behavioral Health, Dartmouth Psychiatric Research Center,
Department of Psychiatry, Geisel School of Medicine at Dartmouth, Dartmouth College, Lebanon,
NH, USA
e-mail: [email protected]
S. Lord
Center for Technology and Behavioral Health, Dartmouth College, Lebanon, NH, USA
e-mail: [email protected]
67.1 Introduction
A growing scientific literature is showing that these tools (when they are well
developed and in close collaboration with the target audience) may be engaging
to the target audience and effective in a number of models of deployment. When
provided as an adjunct to a traditional model of care, these tools may enhance the
quality, reach, and outcomes of care (e.g., enhance outcomes in substance abuse
treatment and/or HIV prevention) (Carroll et al. 2008; Marsch et al. 2011). When
compared to science-based interventions delivered by highly trained educators/
clinicians, some data suggest these tools may be of comparable effectiveness
(Budney et al. 2011; Kay-Lambkin et al. 2009). These findings underscore the
scope of effects that can be achieved with a technology-based model of intervention
delivery. Additionally, technology-based tools may enhance treatment outcomes
and allow for greater capacity for service delivery if they are provided in a model
where they replace a portion of traditional models of care (e.g., a substance abuse
treatment program can care for more clients if a portion of intervention delivery is
provided via a technology-based system of care). Further, a number of scientific
studies have supported the effectiveness of a direct-to-consumer model. There is
additionally evidence that these tools may be cost-effective (Olmstead et al. 2010).
[For a comprehensive review of the state of scientific research developing
and evaluating technology-based therapeutic tools targeting behavioral health,
refer to ▶ Chap. 60, “Computerized Therapies: Towards an Addiction Treatment
Technology Test” by Budney and colleagues in this same volume].
The utility of technology-based therapeutic tools for substance use and other
behavioral health care may become even more pronounced in the USA, given
evolving models of health care (under the Affordable Care Act of 2010) which
will expand federal insurance coverage for the first time to an estimated 32 million
individuals who are currently uninsured. It is expected that many of the uninsured
who will receive insurance for the first time are individuals that are poor and
unemployed, with disproportionately high mental health and substance use
problems (Substance Abuse and Mental Health Services Administration 2010).
Technology may be useful as part of an integrated model of care as the current
health-care workforce seeks to embrace this large influx of new clients.
Technology-based therapeutic tools may also be useful to the majority of
persons with substance use disorders who are not engaged in traditional models
of care for their problematic substance use. For example, in the USA, about one in
ten Americans are estimated to be diagnosable with one or more types of substance
use disorders, and the majority of these individuals (about 90 %) are not engaged in
substance abuse treatment. Technology offers a mechanism for providing access to
effective interventions for these persons who are not in care and may, in some cases,
serve as a conduit to more formal models of care for substance use.
Substance use and mental health disorders are also highly prevalent among
persons with chronic physical health conditions and greatly reduce the effective
management of chronic illness. Co-occurring chronic illness and behavioral health
problems have been associated with lower quality of life, poorer response to
treatment, worse medical and psychiatric outcomes, higher mortality, and higher
costs of care (Cimpean and Drake 2011). Leveraging technology in the integration
of behavioral health and physical health disorders offers great promise in overall
health-care management.
Despite a growing evidence base and enthusiasm for the potential of technology-
based therapeutic tools to broaden and enhance care delivery, adoption has been
slow. There is much research to be done to understand best practice strategies
for disseminating evidence-based technologies to consumers and integrating
1090 L.A. Marsch and S. Lord
References
Budney AJ, Fearer S, Walker DD, Stanger C, Thostenson J, Grabinski M, Bickel WK (2011) An
initial trial of a computerized behavioral intervention for cannabis use disorder. Drug Alcohol
Depend 115(1–2):74–79
Carroll KM, Ball SA, Martino S, Nich C, Babuscio TA, Nuro KF, Gordon MA, Portnoy GA,
Rounsaville BJ (2008) Computer-assisted delivery of cognitive-behavioral therapy for addic-
tion: a randomized trial of CBT4CBT. Am J Psychiatry 165(7):881–888
Cimpean D, Drake RE (2011) Treating co-morbid chronic medical conditions and anxiety/
depression. Epidemiol Psychiatr Sci 20(2):141–150
Damschroder LJ, Aron DC, Keith RE, Kirsh SR, Alexander JA, Lowery JC (2009) Fostering
implementation of health services research findings into practice: a consolidated framework for
advancing implementation science. Implement Sci 4:50
Greenhalgh T, Robert G, Macfarlane F, Bate P, Kyriakidou O (2004) Diffusion of innovations in
service organizations: systematic review and recommendations. Milbank Q 82(4):581–629
Kahn JG, Yang JS, Kahn JS (2010) ‘Mobile’ health needs and opportunities in developing
countries. Health Aff (Millwood) 29(2):252–258
Kay-Lambkin FJ, Baker AL, Lewin TJ, Carr VJ (2009) Computer-based psychological treatment
for comorbid depression and problematic alcohol and/or cannabis use: a randomized controlled
trial of clinical efficacy. Addiction 104(3):378–388
Lester RT, Mills EJ, Kariri A, Ritvo P, Chung M, Jack W, Habyarimana J, Karanja S, Barasa S,
Nguti R, Estambale B, Ngugi E, Ball TB, Thabane L, Kimani J, Gelmon L, Ackers M,
Plummer FA (2009) The HAART cell phone adherence trial (WelTel Kenya1):
a randomized controlled trial protocol. Trials 10:87
Lord S, Lardiere M, Ramsey A, Marsch L, Dallery J (2013) Assessing readiness to implement
technology-based therapeutic tools in community behavioral health agencies. Manuscript
under review
Marsch LA, Grabinski MJ, Bickel WK, Desrosiers A, Guarino H, Muehlbach B, Solhkhah R,
Taufique S, Acosta M (2011) Computer-assisted HIV prevention for youth with substance use
disorders. Subst Use Misuse 46(1):46–56
Olmstead TA, Ostrow CD, Carroll KM (2010) Cost-effectiveness of computer-assisted training in
cognitive-behavioral therapy as an adjunct to standard care for addiction. Drug Alcohol
Depend 110(3):200–207
Proctor E, Silmere H, Raghavan R, Hovmand P, Aarons G, Bunger A, Griffey R, Hensley M
(2011) Outcomes for implementation research: conceptual distinctions, measurement challenges,
and research agenda. Adm Policy Ment Health 38(2):65–76
1092 L.A. Marsch and S. Lord
Rogers EM (1995) Lessons for guidelines from the diffusion of innovations. Jt Comm J Qual
Improv 21(7):324–328
Scheffler RM, Mahoney CB, Fulton BD, Dal Poz MR, Preker AS (2009) Estimates of health
care professional shortages in sub-Saharan Africa by 2015. Health Aff (Millwood) 28(5):
w849–w862
Substance Abuse and Mental Health Services Administration (2010) HealthCare Reform,
Overview of the Affordable Care Act. What are the implications for behavioral health?
SAMHSA News 18(3)
Residential Treatment
68
Donald J. Kurth, Vicki Kalira, and Brian Hurley
Contents
68.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1093
68.2 Residential Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1094
68.2.1 Beginnings of Inpatient Residential Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1094
68.2.2 Residential Treatment in the Early Twentieth Century . . . . . . . . . . . . . . . . . . . . . 1098
68.2.3 Residential Treatment in the Mid-Late Twentieth Century . . . . . . . . . . . . . . . . . 1101
68.2.4 Halfway House Movement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1104
68.2.5 Therapeutic Communities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1105
68.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1107
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1108
68.1 Introduction
Romans were known to recommend both public and private asylums for those
addicted to alcohol. In the early nineteenth century in the United States,
Dr. Benjamin Rush (1746–1813) is often credited with one of the first proposals
to treat the disease of intemperance with medical care and residential treatment. He
has been called the “father of American psychiatry” and wrote what became the first
American medical textbook. Other American physicians followed suit with similar
recommendations in the mid-nineteenth century including Eli Todd, Samuel Wood-
ward, and Joseph Turner.
Rush’s interest in chemical dependency issues seems to have arisen from his
own family experience. His father’s alcoholic drinking contributed to his parents’
divorce. His mother was later remarried to a distiller who abused her.
On a professional level as physician-general of the Continental Army, Rush was
struck by the problems created by inebriation in the Army. In 1777 his essay
condemning the use of distilled liquor was distributed to all soldiers. In his 1782
newspaper article “Against spirituous liquors,” Rush recommended that farmers
stop providing laborers with daily allocations of liquor. In 1784 he published
a 36-page pamphlet, An Enquiry into the Effects of Spirituous Liquors on the
Body, and Their Influence Upon the Happiness of Society.
Rush first promoted the chronicity and progression of alcoholism as a medical
ailment, opening the door to addiction to alcohol as a treatable condition.
He attributed this progression to a “disease of will” and recognized the frequent
familial expression of alcoholism. Although his ideas were not readily accepted by
the general public at the time, his writings and teaching of scores of young physicians
at the Philadelphia School of Medicine laid the foundations for the temperance
movement which followed. Working independently, Rush’s international contempo-
rary in England, Dr. Thomas Trotter, wrote, “Essay, Medical, Philosophical and
Chemical, on Drunkenness,” also attributing to alcoholism the status of a medical
illness. The “disease concept” of alcoholism as a medical malady was born.
Let the experiment be fairly tried; let an institution be founded; let the means of cure be
provided; let the principles on which it is to be founded be extensively promulgated and
I doubt not, all intelligent people will be satisfied of its feasibility. . .. At the head of this
institution place a physician of zeal, medical skill and enlarged benevolence; let the
principle of total abstinence be rigorously adopted and enforced. . ..let the appropriate
medication be afforded; let the mind be soothed. . ..let the certainty of success be clearly
delineated to the mind of the sufferer. . .. Let good nutrition be enjoined while the prostra-
tion of strength and energy continue. . ..this course, rigorously adopted and pursued, will
restore none out of ten in all cases. (White)
Finally, in the later nineteenth century specific institutions for the treatment of
addiction began to spring up. By 1870 six such inebriate asylums were in operation.
Their managers soon got together to create the American Association for the Cure
of Inebriates. The association included 32 members by 1878 and more than
100 institution members by 1902. Some of the first members included the Wash-
ingtonian Homes in Boston and Chicago, the New York State Inebriate Asylum, the
Pennsylvania Sanitarium for Inebriates, the Kings County Inebriates’ Home, and
Walnut Lodge.
Many different monikers were attached to these sorts of institutions: inebriate
asylums, inebriate homes, inebriate colonies, inebriate farms, lodging homes,
reformatories, retreats, and sanitaria. Some provided room and board with minimal
additional treatment. Others provided a sober place to stay while the residents
attended temperance movement meetings. Some were established as medical facil-
ities both privately and publically funded. Public funding, unfortunately, was often
inconsistent. The goal of all of these institutions was the treatment of the alcohol
dependence, although other chemical addictions were treated as well. Brooklyn
Home for Habitues, founded by Dr. Jansen B. Mattison in 1891, was one of the first
to focus exclusively on nonalcohol chemical addiction.
Medical treatment was often quite variable at this time with physicians caring for
various medical problems and assisting in ambulatory detoxification. Some patients
visited the physician 3–4 times a day while living at home or staying in a hotel.
1096 D.J. Kurth et al.
From the earliest days, conflicts arose between the administrators of the inebriate
treatment institutions and the administrators of the psychiatric institutions. Inebriate
patients were categorically excluded from the state psychiatric institutions. Where
to place patients suffering from a combination of inebriety and psychiatric illness
became a bone of contention.
Psychiatric asylums often admitted their inability to deal effectively with inebri-
ates and even judged them contrary to the welfare of their psychiatric patients.
In addition, there were conflicts inherent in using the psychiatric treatments of the
time. Whisky and opium were liberally used as psychiatric medications at that time
and drinking and drug problems were apparently not uncommon among the psy-
chiatric hospitals’ staff (Geller and Harris 1994).
As early as 1875, Dr. Henry Bowditch in Massachusetts began to advocate for
patient-helpers in the inebriate home treatment model. In addition to those former
patients who were required to “work off” the cost of their treatment, Dr. Bowditch
believed that recovering inebriates who possessed the education and intelligence
had a moral duty to help those less fortunate patients. Some contributed in the
clinical setting and others in the administrative or maintenance areas. Paid jobs for
these individuals soon evolved and at times the line between patient and paid staff
was muddled.
Wives and family members were often viewed as a nuisance by treatment staff.
All too often the patients’ spouses either interfered with treatment or acceded to the
patients’ wishes and pulled them out of treatment prematurely. The results, of
course, were inevitable. Aftercare was spotty or nonexistent by the standards
of today. Following residential treatment, the patient was often placed in the
home of nondrinking friends. Involvement with a religious or fraternal temperance
organization was encouraged.
In 1870, the American Association for the Cure of Inebriates was founded in
New York City by a group of physicians, lay people, and inebriate asylums. The
American Association for the Study and Cure of Inebriety statement of principles
and purpose included the following (Crothers 1893):
• Intemperance is a disease.
• It is curable in the same sense that other diseases are.
• Its primary cause is a constitutional susceptibility to the alcoholic impression.
• This constitutional tendency may be inherited or acquired.
The statement further recommended that scientifically based residential treat-
ment replaces the penal approach in fashion at the time for the treatment of
addiction. The association also lobbied for state financial support for residential
treatment and for laws which would mandate residential treatment for those
suffering from inebriety. They were concerned with the spread of quack
addiction cures and sought stronger regulation of addiction treatment medications,
physicians, and institutions. Not everyone agreed with this approach; some
even recommended that those suffering from the “hereditary weakness” of
alcoholism be allowed to die, thereby cleansing society forever of alcoholism
(Crothers 1893).
1098 D.J. Kurth et al.
During this period the idea of individualized treatment was further developed.
Treatment philosophies fell within two broad arenas. Asylums viewed the goal of
recovery as physical regeneration resulting from the scientific treatments provided.
Washingtonian homes understood recovery as a moral regeneration resulting from
healthy, courteous, and respectful environment. Many questions were posed, some
perhaps still unanswered. Should treatment be physical or moral? Should facilities
be large or small? Should coercion be used or should treatment be purely voluntary?
Superimposed on all this was the question of length of stay. Hopeful cases were
treated for 6 months or less while more advanced cases of addiction were thought to
require a minimum of 1–5 years of treatment. Mandated treatment was
experimented with in some areas but the public looked disparagingly at these
practices due to the conflict of interest apparent in this model.
Residential treatment came to a conceptual fork in the road at the end of this
period. The young specialty of psychiatry described addiction as a symptom of
a subconscious emotional pathology. Another view evolved that substance abuse
reflected a willful misbehavior which must be criminally punished to be corrected.
However, more so than by any other criteria, it appears that patients were segre-
gated by social class and financial means. Those with social standing and financial
means were treated by psychiatrists in private sanitaria. Those who lacked these
assets were more likely treated in publicly funded asylums or made their way into
the criminal justice system. These nineteenth-century ideas survive today and still
influence the treatment of addiction. Well-to-do prescription addicts with good
medical insurance are often said to be “chronic pain patients” suffering from
“pseudo addiction,” while those without financial means are more likely to be
punished for their addiction within the criminal justice system or redirected to
publicly funded methadone maintenance programs.
were, in fact, merely placebo concoctions designed to keep the patients in residen-
tial treatment for 4 weeks. Leslie Keeley went to his grave without ever revealing
the secret formula for his highly touted cure. The Keeley empire began to
decline with the death of Leslie Keeley in 1900 but continued in operation for
many years thereafter. In the 1940s, Alcoholics Anonymous arranged a loose
affiliation with Keeley, and AA meetings were sometimes organized at Keeley
facilities. The last patients were admitted to the original Keeley facility in Dwight,
Illinois, in 1966.
Notwithstanding the many critics of Dr. Keeley’s concoctions and marketing
techniques, the Keeley phenomenon did advance the evolution of addiction treat-
ment in many positive ways. First, Dr. Keeley’s aggressive marketing campaigns
helped to educate the public about the disease nature of alcoholism and addiction
and its potentially successful treatment. Second, through this public education
process, the stigma of alcoholism and addiction was reduced. Third, regardless of
the actual physiological effects of the Double Chloride of Gold concoction, many
addiction recoveries were initiated through its use. Fourth, many of those were attracted
to treatment by the public’s awareness of the large number of successfully treated
patients coming out of the Keeley Institutes. Fifth, while the focus of the Keeley
Institutes was residential treatment, the widespread mutual help network established by
the Keeley League bridged the gap between the Washingtonians and the inception of
Alcoholics Anonymous in 1935. Sixth, the Keeley philosophy of hiring recovered
alcoholics and addicts laid the groundwork for many of the treatment philosophies of
today. Seventh, more recovered physicians were employed by the Keeley Institutes
than by any treatment provider either before or since. Eighth, the Keeley philosophy
promoted an enthusiasm for sobriety for recovering patients, replacing the pall of
punishment seen in some institutions of the day. And lastly, many permanent recov-
eries resulted from the healing environment established and promoted by the Keeley
system of medically supervised detoxification, mutual support among residential
patients, graduated renewal of both emotional and physical health, and engagement
of patients in early sobriety in the miracle and magic of recovery.
As the twentieth century drew near, optimism reigned among those who envisioned
the upcoming widespread availability of residential treatment for addictive disorders.
Unfortunately, political and economic forces of the day were not aligned with the
enthusiasm of treatment center founders. A look at the early decades of the twentieth
century revealed a dramatic decline in residential treatment in the United States.
For example, the Southern California State Asylum was founded but was neither
opened nor built. Others were opened briefly but soon closed or were used for other
purposes. Even the institutions that remained open experienced a tenuous existence
(White). Crothers noted that only 30 of the first 50 inebriate asylums remained open
and that many of those remaining drifted from their scientific orientation.
The Scientific Temperance Federation studied prohibition’s effect on residential
treatment in 1922. Of the 275 residential treatment facilities identified prior to
prohibition, they were able to collect information on only 184. Of those, only
51 were still open for business. Most had closed their doors or redefined their
1100 D.J. Kurth et al.
Even those that remained open experienced a dramatic drop in admissions. For
instance, between 1919 and 1921 male admissions to the Chicago Washingtonian
Home dropped from 1,114 to 171 (Stoddard 1922).
Residential treatment for addiction all but disappeared. Facilities were either
closed altogether or became prisons, private hospitals, or asylums for the insane.
The only remaining treatment centers were very expensive private hospitals or
public insane asylums. Professional interest in the treatment of addiction withered
and the American Medical Association for the Study of Alcohol and Other
Narcotics dissolved in the 1920s (Cherrington 1925).
White identifies eight external and internal causative factors to explain the rapid
decline in residential inebriate treatment: economic forces, social and political
forces, poorly developed clinical technology, patient selectivity, modality/environ-
mental bias, conflict within the field and with allied fields, ethical abuse, and the
problem of leadership succession (White 1998). A brief expansion of each of these
factors follows:
• Economic forces: The failure of government to provide structure or support to
residential addiction treatment funding left the movement to the whim of the
capricious economic marketplace.
• Social and political forces: The attitudinal trend toward criminalization of
addiction disorders marginalized and ultimately almost eliminated residential
addiction treatment.
• Poorly developed clinical technology: The scientific foundations of residential
addiction treatment never gained the respect of either the scientific community
or the public at large.
• Patient selectivity: While publicly funded establishments were often burdened
with disruptive court-mandated clients, private institutions became adept at
accepting only those wealthiest clients with a high probability of success,
often engendering public scorn through this process.
• Modality/environment bias: While residential treatment costs more than outpa-
tient treatment, at the same time it self-selects for those later-stage patients who
have burned through their resources and thus restricted their ability to afford the
treatment they need.
• Conflict within the field and with allied fields: Conflicts within individual
institutions, within the field of addiction treatment, and between the field of
addiction and that of mental health treatment created an environment in which
sustained growth became impossible.
68 Residential Treatment 1101
• Ethical abuses: Perhaps even more striking than the abuses themselves, which
were significant, was the treatment professionals’ refusal to recognize the
concerns and complaints of the patients.
• The problem of leadership succession: The visionary and often charismatic
founders of the residential treatment movement seemed particularly inept at
recruiting and training the new generation of leaders in the field, and many
residential addiction treatment programs simply died with their founders.
Over the course of the residential chemical dependency treatments, however, the
inebriate homes and asylums did make substantial contributions. These contributions
included support for those suffering from chemical dependence, the first professional
medicalization of drug and alcohol excess consumption, biological explanations of
drug dependence, and recommendations for physical treatment methods. Discussions
of the biology and heredity of inebriety helped move treatment from moral instruc-
tion to medical treatment. And doctors who treated drunks began to gain legitimacy
as physicians who attended to legitimate patients suffering from a real disease.
The period between 1948 and 1950 saw the development of the “Minnesota
Model” developing from the influence of three separate institutions: Pioneer
Hospital, Hazelden, and Willmar State Hospital. This model went on to influence
alcoholism and addiction treatment for the next 65 years, and there seems to be no
indication that this influence will diminish into the foreseeable future.
In the late 1940s, the welfare department of the city of Minneapolis, Minnesota,
became increasingly aware of the rising successes of those residents who became
engaged in the fledgling Alcoholics Anonymous. Funding was identified and
a new treatment facility was created under the direction of a local sober member
of AA. Named Pioneer House, the new treatment program was described
as neo-Washingtonian. Patients were given a copy of Alcoholics Anonymous
(The Big Book) and Twelve Steps and Twelve Traditions upon admission and the
treatment philosophy was based on flexibility and spirituality.
As Pioneer House was just getting underway, Hazelden began to come together
as a “sanitorium for curable alcoholics of the professional class” (White). Again,
the treatment philosophy was to be founded in AA and the early staff was led by
a sober AA alcoholic. Detoxification was generally “cold turkey” but medications
were prescribed at times for severe situations. Treatment consisted of lectures,
mutual support, improved nutrition, and occasional recreational activities. The
facility had four requirements of their patients:
1. “Practice responsible behavior.”
2. “Attend the lectures on the Steps.”
3. “Associate and talk with the other patients.”
4. “Make their beds.”
With the exception of only minor creative flexibility in those earliest days, the
treatment was simply pure AA.
The 28-day inpatient, abstinence-based, program of treatment was initially
developed over a period of 3 years, from 1952 to 1955, by junior clinicians at
Willmar State Hospital in Minnesota. Their work would evolve to become known
as the Minnesota Model of addiction treatment, which arose from the co-integration
of a state hospital program and a nonprofit AA recovery program. The Minnesota
Model gained widespread acceptance in the 1970s and became the standard for
rehabilitation treatment through the 1970s and 1980s.
As described by William White, there were several components that contributed
to the “Minnesota Model” formula (White):
• Alcoholism is an involuntary, primary disease that is describable and diagnosable.
• Alcoholism is a chronic and progressive disease; Barring intervention, the signs
and symptoms of alcoholism self-accelerate.
• Alcoholism is not curable, but the disease may be arrested.
• The nature of the alcoholic’s initial motivation for treatment – its presence or
absence – is not a predictor of treatment.
• The treatment of alcoholism includes physical, psychological, social, and spir-
itual dimensions.
• The successful treatment of alcoholism requires an environment in which the
alcoholic is treated with dignity and respect.
68 Residential Treatment 1103
By 1960 the Unites States was home to approximately 200 alcoholism treatment
centers, some of longstanding presence and others founded within the preceding
2 decades. Some of the long established programs included the Washingtonian
Homes, the Keeley Institute, the Keswick Colony, the Menninger Foundation, the
Shadel Sanitarium, and the Blythewood Sanitarium. Some of the newer residential
treatment facilities included Mrs. Pink’s Place, the Bridge House, Beech Hill
Farms, Alina Lodge, Portal House, Brighton Hospital for Alcoholism, the Georgian
Clinic and Rehabilitation Center for Alcoholism, the Salvation Army, and the Chit
Chat Foundation.
In the 1970s, Minnesota Model proponents were successful in some jurisdictions
at requiring insurance payers to include 28-day inpatient stays for substance use
disorders as a requirement to sell insurance. The late 1980s and early 1990s saw the
emergence of managed care, which sought to aggressively control costs through
limiting benefits for behavioral health treatments and particularly substance use
disorder treatment.
In 1986, President Reagan signed an executive order mandating the federal
Drug-Free Workplace program and the Anti-Drug Abuse Act passed, authorizing
$4 billion to support law enforcement approaches to fight drugs. The very next year,
1987, saw the United States launch its War on Drugs, signaling a shift away from
treatment and toward law enforcement and incarceration approaches to manage
drug and alcohol problems.
These led to changes in payer approaches that effectively eliminated 28-day
inpatient treatment programs as first-line insurance-financed treatment for
substance use disorders (White 1998). The burden of paying for these programs
shifted to state Medicaid programs, and by the mid-1990s, many 28-day free-
standing centers had closed. Hospital-based treatment units, once focused entirely
on the treatment of substance use disorders, consolidated with other forms of
psychiatric treatment under the umbrella of mental health or behavioral health.
Additionally, programs began to focus services on partial hospital or intensive
outpatient levels of care (White 1998).
Despite these changes, 28-day residential inpatient programs remain colloqui-
ally synonymous with the term “rehab.” Many well-known addiction treatment
centers continue to maintain treatment programs organized in the 28-day
residential model of treatment, typically on an out-of-pocket fee basis. In contrast,
for indigent patients, there remain residential or inpatient 28-day programs
for those program meeting criteria for this level of care. These programs are
typically funded by state Medicaid programs in combination with local
fundraising.
and “country farms” had been established places where alcoholics could be sent
to sober up. “Temperance hotels” and “lodging rooms” were used similarly. Begin-
ning in the 1930s, however, it appears that after sober Alcoholics Anonymous
members began to take in newcomers to establish their own sober foundation, the
halfway house concept really began to take hold. Some appeared to focus on
alcoholics who might be on their way into a more structured treatment facility. Others
seemed to be organized in a way to help alcoholics who were on their way from
a structured treatment environment on their way back to society.
While halfway houses differed widely, there were some general commonalities:
structured living, peer support, and lifestyle reconstruction (White). Earl Rubington
noted “four structured principles” (White):
• Small size
• Simple rules
• Reduction of status differences between residents and staff
• Informality
In 1974 the International Halfway House Association boasted 1,300 members.
In 1975 the Oxford House model arose as an interesting subset of the halfway
house concept. Newly sober congressional attorney Paul Malloy was about to be
evicted from the halfway house in which he lived. Rather than go back to the street,
he and the other residents got together and created the first resident-administered
Oxford model halfway house. They took the concept of recovering staff perhaps
one step further. Oxford House has no staff whatsoever, only recovering alcoholics
and addicts. Average length of stay is 15 months but residents can actually stay
indefinitely. All the residents are expected to hold down a job as well as do their
share of the chores. Officers are democratically elected in each house. Every new
resident is interviewed and must be voted in by the current residents. Relapses are
dealt with by a vote of the residents of each house, usually with immediate eviction.
Sobriety is of paramount importance, and if a resident is not willing to maintain
their own sobriety, they must find another place to live. Within 15 years there were
over 200 homes and by 2013 Oxford House could boast 1,600+ homes around the
country, each one run by the residents who supported their own house with their
own contributions.
The middle of the twentieth century saw other experiments in residential treat-
ment. Teen Challenge was founded in 1961 by the clergy of the Assembly of God
Church and operated 40 residential programs around the country.
The concept of the therapeutic community (TC) first appeared in the Dead Sea
Scrolls at Qumron with discussions of the rules of community. Adherents to this
concept were expected to follow the ways of the community and live righteously
and healthfully. Similar ideas were applied in the inebriate asylums of the
nineteenth century and further developed by Dr. Maxwell Jones in the 1950s.
The first broad application of the “community as treatment” was developed as
1106 D.J. Kurth et al.
68.3 Conclusion
Despite a history beginning several centuries ago, the future of residential care in
the treatment of substance use disorders remains uncertain. During the 1970s, there
was an expansion of residential treatment centers particularly with the advent of the
Minnesota Model. However, this eventually contracted due to a lack of support and
recognition. The overall decline of such programs has left a huge treatment void in
Europe, and the United States seems not to be learning from their experience. It is
worrisome to consider the defunding of public treatment programs, drying up of
insurance funding as health care becomes nationalized, and the fact that private
programs are becoming exorbitantly expensive for the common man. Sadly, we
may be seeing the next pendulum swing away from addiction treatment and back
toward incarceration and this at a time when the world’s economies are least able
to squander resources on such wasteful and unsuccessful practices. The future
of addiction treatment worldwide may well be correlated with appreciating that
access to residential treatment is the key in the continuity of care of persons with
addiction.
1108 D.J. Kurth et al.
References
Agnew R (1991) The interactive effect of peer variables on delinquency. Criminology 29:47–72
Anderson DJ, McGovern JP, DuPont RL (1999) The origins of the Minnesota model of addiction
treatment – a first person account. J Addict Dis 18(1):107–14
Anglin MD, Hser Y (1990a) Legal coercion and drug abuse treatment: research findings and social
policy implications. In: Inciardi JA, Biden JR (eds) Handbook of drug control in the United
States. Greenwood Publishing, New York, pp 151–176
Anglin MD, Hser Y (1990b) Treatment of drug abuse. In: Tonry M, Wilson JQ (eds) Crime and
justice: an annual review of research, vol 13. University of Chicago Press, Chicago,
pp 393–460
Anglin MD, Nugent JF, Ng LKY (1976) Synanon and Alcoholics Anonymous: is there really
a difference? Addict Ther 1(4):6–9
Bandura A (1977) Social learning theory. Prentice-Hall, Englewood Cliffs
Barr H (1986) Outcome of drug abuse treatment on two modalities. In: DeLeon G, Ziegenfuss JI
(eds) Therapeutic communities for addictions. Charles C Thomas, Springfield, pp 97–108
Barton E (1994) The adaptation of the therapeutic community to HIV/AIDS. In: Proceedings of the
Therapeutic Communities of America, 1992 planning conference: paradigms – past, present
and future. Chantilly, 6–9 Dec 1994
Batiste CG, Yablonsky L (1979) Synanon: a therapeutic life style. California Med 114(5):90–94
Bell DC (1994) Connection in therapeutic communities. Int J Addict 29:525–543
Brown BS (1998) Towards the year 2000. Drug use – chronic and relapsing or a treatable
condition? Subst Use Misuse 33(12):2515–2520
California Penal Code 1210 PC – Definitions of terms included in Proposition 36
Carroll JFX, McGinley I (1998) Managing MICA clients in a modified therapeutic community
with enhanced staffing. J Subst Abuse Treat 15(6):565–577
Cherrington (1925) Vol I, pp 155–156
Condelli WS Hubbard RL (1994) Client outcomes from therapeutic communities. In: Tims FM,
DeLeon G, Jainchill N (eds) Therapeutic community: advances in research and application,
vol 144, NIDA research monograph. National Institute on Drug Abuse, Rockville, pp 80–98
Crothers TD (1893) The disease of inebriety form alcohol, opium and other narcotic drugs: its
etiology, pathology, treatment and medico-legal relations. EB Treat Publisher, New York
DeLeon G (1988) Legal pressure in therapeutic communities. In: Leukefeld CG, Tims FM (eds)
Compulsory treatment of drug abuse: research and clinical practice, vol 86, NIDA research
monograph. National Institute on Drug Abuse, Rockville
DeLeon G (1995) Therapeutic communities for addictions: a theoretical framework. Int J Addict
30(12):1603–1645
DeLeon G (2000) The therapeutic community: theory, model, and method. Springer, New York
Geller J, Harris M (1994) Women of the Asylum: voices from behind the walls, 1840–1945.
Princeton University Press
Glaser FB (1974) Some historical and theoretical background of a selfhelp addiction treatment
program. Am J Drug Alcohol Abuse 1:37–52
Hubbard RL, Craddock SG, Flynn PM et al (1997) Overview of 1-year follow-up outcomes in the
drug abuse treatment outcome study (DATOS). Psychol Addict Behav Spec Issue
11(4):261–278
Jainchill N (1994) Co-morbidity and therapeutic community treatment. In: Tims FM, DeLeon G,
Jainchill N (eds) Therapeutic community: advances in research and application, vol 144, NIDA
research monograph. National Institute on Drug Abuse, Rockville, pp 209–231
Jainchill N, Battacharya G, Yagelka J (1995) Therapeutic communities for adolescents. In: Rahdert E,
Czechowicz D (eds) Adolescent drug use: clinical assessment and therapeutic interventions,
vol 156, NIDA research monograph. National Institute on Drug Abuse, Rockville, pp 190–217
Kennard D (1983) An Introduction to therapeutic communities. Rutledge and Kegan Paul, London
68 Residential Treatment 1109
Kerr DH (1986) The therapeutic community: a codified concept for training and upgrading staff
members working in a residential setting. In: DeLeon G, Ziegenfuss JI (eds) Therapeutic
communities for addictions. Charles C Thomas, Springfield, pp 55–63
Kooyman M (1993) The therapeutic community for addicts: intimacy, parent involvement and
treatment outcome. Swets and Zeitlinger, Amsterdam
Liberty HI, Johnson BD, Jainchill N et al (1998) Dynamic recovery: comparative study of
therapeutic communities in homeless shelters for men. J Subst Abuse Treat 15(5):401–423
Lipton DS (1999) Therapeutic community treatment programming in corrections. In: Hollin CR
(ed) Handbook of offender assessment and treatment. Wiley, London
Longshore D, Urada D, Evans E, Hser YI, Prendergast M, Hawken A (2005) Evaluation of the
substance abuse and crime prevention act: 2004 report. UCLA integrated substance abuse
program, July 2005
Messina NR, Wish ED, Nemes S (1999) Therapeutic community treatment for substance abusers
with anti-social personality disorder. J Subst Abuse Treat 17(1–2):121–128
National Institute on Drug Abuse. What is a therapeutic community? NIDA Research
Report Series – Therapeutic Community. NIH Publication No. 02-4877. Retrieved from the
Internet on 5 July 2008. http://www.drugabuse.gov/ResearchReports/Therapeutic/Therapeu-
tic2.html.2002
Nielsen A, Scarpitti F (1997) Changing the behavior of substance abusers: Factors influencing the
effectiveness of therapeutic communities. J Drug Issues 27(2):279–298
Nuttbrock LA, Rahav M, Rivera I et al (1998) Outcomes of homeless mentally ill chemical abusers
in community residences and a therapeutic community. Psychiatr Serv 49:68–76
Perfas FB (2012) Deconstructing the therapeutic community: a practice guide for addiction
professionals. Hexagram Publishing, New York
Preston CA, Viney LL (1984) Self- and ideal self-perception of drug addicts in therapeutic
communities. Int J Addict 19(7):805–818
Ray R, The Oxford Group Connection (1999) Retrieved from the Internet on January 6, 2009 from
http://www.winternet.com/terrym/oxford.html
Sacks S, DeLeon G, Bernhardt AI et al (1997) A modified therapeutic community for homeless
mentally ill chemical abusers. In: DeLeon G (ed) Community as method: therapeutic commu-
nities for special populations and special settings. Greenwood Publishing, Westport, pp 19–37
Silberstein CH, Metzger EI, Galanter M (1997) The Greenhouse: a modified therapeutic commu-
nity for mentally ill homeless addicts at New York University. In: DeLeon G (ed) Community
as method: therapeutic communities for special populations and special settings. Greenwood
Publishing, Westport, pp 53–65
Simpson DD, Joe GW, Rowan-Szal GA et al (1997) Treatment retention and follow-up outcomes
in the Drug Abuse Treatment Outcome Study (DATOS). Psychol Addict Behav 11:294–307
Slater MR (1984) An historical perspective of therapeutic communities (Thesis proposal to the
MSS program, University of Colorado, Denver)
Stevens SJ, Arbiter N, McGrath R (1997) Women and children: therapeutic community substance
abuse treatment. In: DeLeon G (ed) Community as method: therapeutic communities for
special populations and special settings. Greenwood Publishing, Westport, pp 129–142
Stoddard (1922) What of the drink cures? STJ September 1933, pp 55–64
Talbot ES (1998) Therapeutic community experiential training: facilitator’s guide. University of
Missouri-Kansas City, Mid-America Technology Transfer Center, Kansas City
University of Utah (2013) Addiction treatment past and present. Resource document. http://learn.
genetics.utah.edu/content/addiction/issues/treatments.html. Accessed 3 April 2013
Westreich L, Galanter M, Lifshutz H, Metzger EJ, Silberstein C (1996) A modified therapeutic
community for the dually diagnosed Greenhouse program at Bellevue Hospital. J Subst Abuse
Treat 13(6):533–536
White WL (1998) Slaying the dragon: the history of addiction treatment and recovery in America,
1st edn. Chestnut Health System/Lighthouse Institute, Bloomington
1110 D.J. Kurth et al.
Wilson B (1957) Alcoholics Anonymous comes of age: a brief history of AA. Alcoholics
Anonymous World Services, New York
Winick C, Evans JT (1997) A therapeutic community program for mothers and their children. In:
DeLeon G (ed) Community as method: therapeutic communities for special populations and
special settings. Greenwood Publishing, Westport, pp 143–160
Yablonsky L (1989) The therapeutic community. Gardner Press, New York
Zweben JE, Smith DE (1986) Changing attitudes and policies toward alcohol use in the therapeutic
community. J Psychoactive Drugs 18(3):253–260
Strategies of Drug Prevention in the
Workplace: An International Perspective 69
of Drug Testing and Employee Assistance
Programs (EAPs)
Contents
69.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1112
69.2 Drug Prevention in the Workplace . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1112
69.2.1 Drug Testing in the US Workplace . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1114
69.2.2 Drug Testing in Europe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1120
69.2.3 Employee Assistance Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1124
69.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1126
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1127
Abstract
Drug testing in the workplace is not universal and is regulated by various
governmental agencies at the federal, state, and municipal levels, as well as by
various industries. Safety-sensitive occupations are typically targeted, and var-
ious industries and agencies have differing drug testing protocols. In the United
States, drug testing is highly structured, and much of it falls under the purview of
a Presidential Executive Order issued in 1986 and subsequent legislation,
establishing a drug-free workplace. A medical review officer (MRO) resolves
questionable false-negative and false-positive tests. In European Union coun-
tries, drug testing is much less uniform, as attitudes to workplace drug problems
are quite variable with no standard approach. While illicit drug use spurred
widespread drug testing in the United States, legitimately prescribed medica-
tions that may impact safety in the workplace are a growing issue that has not yet
been fully addressed. Many companies establish employee assistance programs
(EAPs), which are designed to help businesses address productivity issues by
providing various services to behaviorally affected employees to alleviate and
resolve issues, including substance abuse, with their job performance. It is easier
to evaluate the effectiveness of the US method, due to its structure, than to assess
the varied European approach.
Abbreviations
AA Alcoholics Anonymous
ASAM American Society of Addiction Medicine
CSAT Center for Substance Abuse Treatment, SAMHSA (U.S.)
DAWN Drug Abuse Warning Network (U.S.)
DOT Department of Transportation (U.S.)
EAPA Employee Assistance Professionals Association
EMCDDA European Monitoring Centre for Drugs and Drug Addiction
EAP Employee assistance program
MRO Medical review officer
NCADD National Council on Alcoholism and Drug Dependence (U.S.)
NIDA National Institute on Drug Abuse (U.S.)
NSDUH National Survey on Drug Use and Health (U.S.)
OTC Over the counter, i.e., medications available without
a prescription
SAMHSA Substance Abuse and Mental Health Services Administration
(U.S.)
SAP Substance Abuse Professional
69.1 Introduction
The modern era of drug use prevention – other than alcohol – in the workplace
began in the 1980s in the United States with the establishment of the Drug-Free
Federal Workplace Program (Executive Order 12564 1986), which paralleled
69 Strategies of Drug Prevention in the Workplace 1113
the drug epidemic permeating industrial settings in the United States and
contributed to a number of highly publicized major, multiple-fatality accidents,
in which several of the workers involved tested positive for marijuana. As
a result, the US Federal Government issued Executive Order # 12564 in
September of 1986:
The Federal Government, as the largest employer in the nation, can and should show the
way towards achieving drug-free workplaces through a program designed to offer drug
users a helping hand and, at the same time, demonstrating to drug users and potential drug
users that drugs will not be tolerated in the Federal workplace . . ..
The executive order mandated that most of the federal agencies under the
purview of the Executive Department require their employees to refrain from the
use of illicit drugs, that the agencies implement and develop employee assis-
tance programs, and that they implement drug testing programs and procedures.
The focus of the drug-free workplace was to eliminate illicit drug use such as
heroin, cocaine, amphetamine, marijuana, and 1-(1-phenylcyclohexyl)piperi-
dine (PCP), known as the “NIDA-5” (“NIDA” being the National Institute on
Drug Abuse). However, because alcohol was and is the primary drug problem in
industry in both the United States and worldwide, the Omnibus Transportation
Employee Testing Act of 1991 included alcohol. As determined by the Division
of Workplace Programs of the Substance Abuse and Mental Health Services
Administration (SAMHSA) in the United States, the majority of current illicit
drug users are employees, as full-time workers constitute about two-thirds of the
adult population (unemployed individuals have a higher rate of substance use
behaviors and disorders) (Larson et al. 2007).
While illicit drugs were the main impetus for the establishment of the drug-free
workplace regulation in the 1980s in the United States, legitimately prescribed med-
ications, primarily opiates, are a growing issue that has not yet been fully addressed.
The components of a comprehensive Drug-Free Workplace Program in the
United States include a formal written policy, an employee assistance program,
supervisor training, employee education, and methods for detecting illicit drug
users (i.e., drug testing). Not all companies in the United States have comprehen-
sive workplace programs.
In addition, US legislation established the designation of “medical review
officer” (MRO) for the evaluation of questionable drug test results. Organizations
such as the American Society of Addiction Medicine (ASAM) offer regularly
scheduled courses to provide clinical training in the review and analysis of drug
test results and certification of qualified MROs (ASAM 2005/2009).
Many companies internationally have established employee assistance programs
(EAPs), which are designed to help businesses address productivity issues by
providing various services to behaviorally affected employees to alleviate
and resolve issues interfering with their job performance (Office of Disability
Employment Policy 2009). The Employee Assistance Professionals Association
lists several national and regional EAP associations and organizations at
www.EAPASSN.org.
1114 D.E. Smith and L.D. Davidson
Workplace drug testing in the United States is highly structured and intended to
foster workplace safety standards. Tests are generally administered in a nonmedical
setting, where body fluids, most commonly urine, are collected and analyzed,
passing through a rigorous and well-documented “chain of custody” process
(ASAM 2002/2012). The frequency, type, and drugs tested for typically depend
on the industry and various governmental regulatory bodies involved. Companies
and organizations with US government contracts must be compliant with govern-
mental regulations regarding drug use in the workplace.
Drug testing is most common in settings where employees perform hazardous
tasks such as operating heavy equipment and where they could place other persons
at risk, as in transporting passengers or performing medical and surgical proce-
dures, in the operation of nuclear power facilities, and in public safety positions
such as police and fire. Each branch of the military has a program for drug testing of
its service members.
Several types of drug testing exist: applicant, accident/unsafe practice, reason-
able suspicion, follow-up to treatment, random, and voluntary. Many employers
require drug testing of potential employees; all require drug testing of employees
involved in accidents (accident/unsafe practice). Drug testing may also be ordered
if an employee’s performance is impaired (reasonable suspicion) and/or the
employee has been observed using alcohol and/or other proscribed substances.
Follow-up drug testing is often instituted as part of an individual’s plan for
recovery after intensive treatment. Ideally the tests are random. Voluntary tests
might be characterized by an individual desiring to know his own level of substance
levels, perhaps in anticipation of an employer test.
Interpreting drug test results is more nuanced than a simple “positive” or
“negative” if a valid result is to be obtained. Individuals may test positive if they
are taking a prescribed pain reliever, for example. They may test negative if a test is
compromised or adulterated either intentionally or inadvertently. For this reason, it
is advisable that a qualified medical review officer (MRO) be available to certify the
results obtained. It must be noted that while MRO protocols, supplies, and equip-
ment are quite rigorous to prevent adulteration of samples, the Internet and human
initiative offer an ever-growing fount of information for bypassing the procedures.
Medically prescribed drugs and dental procedures can skew results, and the new
synthetic drugs that are continually emerging typically do not even show up in the
standard assays (ASAM 2002/2012).
Use of a drug is not associated with impairment and risk of accident. Therefore,
in the United States, the focus has been on total drug use prevention, rather than
impairment and accident risk.
Random drug testing is mandated by many regulatory agencies to more accu-
rately gauge whether the employees they are regulating are using illicit substances.
Employee identifications are usually generated in a random fashion, and the
employee must report for a drug test typically within 24 h at a location determined
by the employer. A specimen is collected and, depending on the technology
69 Strategies of Drug Prevention in the Workplace 1115
Drug Test
Negative Result Laboratory
Positive Result
Unemployed
18.5%
Employed Users
Fig. 69.3 The majority of 74.9%
current drug users are
employed (current users of
illicit drugs, ages 18 and over)
(Source: National Survey on
Drug Use and Health:
National Findings 2006)
The drugs most often used in the United States are pain relievers. As these drugs
are often opioids, they can compromise NIDA-5 results, requiring further validation
of the drug test by a medical review officer (MRO).
Companies involved with transportation and use of motor vehicles are usually
governed in the United States by the Department of Transportation (DOT) regula-
tions, which specify testing for five illicit drugs: marijuana, cocaine, amphetamine,
69 Strategies of Drug Prevention in the Workplace 1117
4
Millions
0
Sedatives - 0.4 Stimulants - 1.2 Tranquilizers - 1.8 Pain Relievers - 5.2
Fig. 69.4 Current use of psychotherapeutic drugs (Source: National Survey on Drug Use and
Health: National Findings 2006)
20
17.4 2003
18 16.5 16.3 2004
16 15
14
Percent Increase
12
10.1
10 8.7 8.9
7.8
8
6
4.3
3.6
4
0
Vicodin, Lortab, Percocet, Hydrocodone OxyContin Oxycodone
Lorcet Percodan, Tylox Products Products
Fig. 69.5 Increase in prescription drug use (Source: National Survey on Drug Use and Health:
National Findings 2006)
Alcohol only 7%
Fig. 69.6 Drug-related ER visits, by type of case: 2005 (Source: SAMHSA, ED Trends from the
DAWN Final Estimates 2009)
Since many workers use narcotic pain medication appropriately with physician
prescriptions, differentiating between appropriate use, misuse, abuse, addiction,
and drug diversion in the workplace is crucial so legitimate pain management is not
confused with inappropriate use that produces health consequences and safety risk.
When an employee’s tests results indicate a positive, the medical review officer
(MRO) notifies the employee about his positive test result and requests a copy of the
prescription (which should be of recent origin). The MRO instructs the employee to
stop work immediately and report to his supervisor. If the employee has no
prescription to explain the positive result, the MRO then notifies the employer
that the employee is not medically cleared to return to work.
Opioids, unless carefully monitored, even when used for appropriate pain
management, can lead to workplace accidents and a variety of related medical,
psychological, and behavioral problems. Problems with opioids include side effects
such as drowsiness, inattentiveness, impaired judgment, and poor hand/eye coor-
dination; tolerance and physical dependence; loss of function; perception of emo-
tional pain as physical pain (chemical copers); and hyperalgesia.
An issue that has not yet been satisfactorily addressed is establishing protocols
for appropriate use of prescription medications that can affect workplace perfor-
mance. Among the factors involved in the United States is the role of the Americans
with Disabilities Act (ADA), which prohibits discrimination against those with
disabilities. That is, if an individual requires a medication to maintain a certain
quality of life, will denying that person employment due to his medication impair
his quality of life?
The medical review officer (MRO) course presented by the American Society
of Addiction Medicine (ASAM) provides clinical training on intoxication, over-
dose, and addiction for the opioid and opioid class of drugs. The course also
provides training on the stimulant class of drugs such as amphetamines, metham-
phetamine, and cocaine, which are widely misused and abused in the workplace
(ASAM 2005/2009).
69 Strategies of Drug Prevention in the Workplace 1119
80
70.6
70
61.6
60
Percentage
50
44.1 42.6
40.2
40
33.7 32.4
30 26.2
20 19
14.5
10
0
Tests for Drug and Alcohol Test for Drugs and Alcohol
during hiring randomly
Fig. 69.7 Type of drug and alcohol testing program, aged 18–64 (Source: Worker Substance Use
and Workplace Policies and Programs 2007 NSDUH)
safety concerns are high, such as construction, yet workers’ concerns can outweigh
the implementation of critical elements of the US testing model. National legisla-
tion varies widely in terms of rights and obligations for testing, allowable intake and
use of alcohol or other drugs, acceptance of testing, the conditions under which
testing can take place, monitoring of tests, and access to the results. Such deviation
in policy makes standardized workplace programs associated with testing very
difficult across the European Union. Some countries have no specialized programs,
and most have limited programs, with the United Kingdom having the most
comprehensive program.
Corral et al. (2012) examine in great detail the types of regulation in place
across a wide swath of the European countries in their report Use of alcohol and
drugs at the workplace for the European Foundation for the Improvement of
Living and Working Conditions (Eurofound). As in the United States, drug testing
is mandated (or not) by a variety of regulating governmental bodies and indus-
tries, and in some countries employees have a much louder voice than allowed in
the United States. A sampling of study results cited in the Eurofound document
follows.
Another major factor is the cultural tolerance, particularly toward alcohol in the
workplace, which varies from country to country in contrast to the United States
where the model is zero tolerance.
A majority of employers and employees in Europe reject the use of alcohol and
drugs in the workplace, but the procedures for implementing this policy are quite
varied and strongly influenced by the cultural views of the host country. Further-
more, the cultural stance toward alcohol and drugs in the workplace has grown
more conservative based on a variety of studies. The Swedish Construction Feder-
ation reported that it was no longer socially acceptable to use drugs in the work-
place in contrast to attitudes in the construction industry 30–40 years ago. However,
as reported on a presentation of illegal drugs, the topic of drugs in the workplace is
still a taboo subject in many member European states.
There is growing awareness of the consequences of alcohol and drugs in the
workplace. Ninety percent of Portuguese enterprises had concerns relating to health
problems, higher instances of sick leave/short-term absenteeism, reduced perfor-
mance levels, labor conflicts and an unsettled work environment, and a greater
number of work-related accidents. In an Italian study, absenteeism was found to be
more than double in Italian employees addicted to drugs than in nonaddicted
employees (Mariotti 2004). Alcohol-dependent workers in Austria were on sick
leave 16 times more often and were sick 2.5 times more often than those who were
not dependent.
Other European studies on drugs and the workplace also demonstrated that
alcohol and drug abuse can negatively impact work performance and contribute
to workplace accidents. One of the most important negative consequences of
alcohol and drug use at work is the increased risk of accidents and potential harm
to fellow employees. A 2008 Latvian report indicated that there was substantial
economic loss and a damaged public image where the affected employee interacted
with the public.
1122 D.E. Smith and L.D. Davidson
European studies have also documented the large economic costs of substance
abuse in the workplace. In Norway, alcohol-related illness represents an economic
loss in millions of euros. In Austria, alcohol use accounts for 1.25–2.5 % of the total
payroll cost. The Austrian Chamber of Commerce (WKO) € (p. 35) states that a worker
with alcohol and drug problems only performs 75 % of his/her potential output.
Given these significant economic effects, European enterprises are increasing their
response to unhealthy alcohol and/or drug involvement in the workplace.
However, it is often some time before a worker’s alcohol or drug problem is
recognized. A German study indicated that it was 8–10 years for men and 3–5 years
for women. The typical response is to dismiss the employee. The workplace
strategy of intervention and rehabilitation for first-time offenders widely used in
the United States is much less common in Europe.
In contrast with the United States, European countries put more emphasis on
workplace conditions that contribute to substance abuse, including work-related
and social/personal reasons in which alcohol and illicit drugs are used for coping
with their problems.
Work-related reasons include arduous working conditions, irregular work
practices, and psychological stress at work.
The European Workplace Drug Testing Society (www.EWDTS.org) is organized
to examine issues relating to workplace drug testing and presents annual conferences
on the topic, bringing together various stakeholders: employees, employers, human
resources, occupational health, compliance officers, attorneys, drug counselors, and
treatment providers. EWDTS’ stated goal is to ensure that drug testing in Europe is
performed in a standard and legal manner. Their website also offers brief summaries
of the status of workplace drug testing in various countries.
There is no centralized statistical information source for Europe. However, the
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA 2013)
reports that cocaine is the second leading drug used after cannabis, with amphet-
amines and ecstasy a growing problem. If workplace programs exist, they are
incorporated into an overall national strategy, with a few exceptions.
In France, the National Research and Safety Institute for the prevention of
accidents at work has a program to train employers and managers to identify
employees of concern and address their problems. In Germany, the German Centre
for Addiction Issues commissioned an expert report on the practice of company-
based drug prevention, which in 2006 was debuted by policy makers, health
insurers, and social partners.
Various European states have found that alcohol and drugs represent a severe
problem for a significant percentage of the working population. National estimates
indicate that 5–20 % of workers are impaired by alcohol or other drugs, a problem
that is particularly relevant in sectors such as construction, transportation, and
farming. Alcohol and drug consumption at work often results in negative workplace
consequences in terms of higher incidence of sick leave and reduced performance
and productivity, as well as a negative economic impact. However, the United
States has more comprehensive data on intervention and rehabilitation of the
addicted employee, again highlighting major policy differences.
69 Strategies of Drug Prevention in the Workplace 1123
Cannabis 1.93%
Opiates 1.87%
Cocaine 0.59%
Drug
Benzodiazepines 0.20%
Amphetamines 0.11%
Methadone 0.06%
Heroin 0.02%
0.00% 0.50% 1.00% 1.50% 2.00% 2.50%
Positive
6.00%
5.08% 2011
5.00%
4.00%
3.42% 3.56%
3.15%
3.00%
2.00%
1.47%
1.18%
1.00% 0.66%
0.00%
Female Male Under 25 25-34 35-44 45-54 55 +
whereas the UK rate has increased. However, the equivalent rates in the overall
populations are approximately the same. The question arises, does variation in
workplace strategies between the two countries account for various outcomes?
(Fig. 69.9).
The Concateno report further reveals that patterns of drug use change with age.
Cannabis use decreases, while use of opiates increases.
A number of European studies have defined patterns of drug abuse in different
countries and regions of the world. However, there are far fewer studies of work-
place programs, and those that exist focus on the concepts of medical review,
addiction medicine, and rehabilitation for the employee. Other countries and
continents, particularly in the developing countries, have no studies or uniform
policies for alcohol and drugs in the workplace.
As the economy globalizes, much more study is required to determine the most
effective workplace programs in order to reduce workplace accidents while pro-
viding for the health and safety of the employee as well as increased productivity,
which is often the main concern for the employer.
among the guiding forces behind the formation of the American Society of Addic-
tion Medicine (ASAM).
ASAM now recognizes addiction as a disease and has developed a clinical
definition for addiction:
Addiction is a primary, chronic disease of brain reward, motivation, memory and related
circuitry. Dysfunction in these circuits leads to characteristic biological, psychological,
social and spiritual manifestations. This is reflected in an individual pathologically pursu-
ing reward and/or relief by substance use and other behaviors.
Addiction is characterized by inability to consistently abstain, impairment in behavioral
control, craving, diminished recognition of significant problems with one’s behaviors and
interpersonal relationships, and a dysfunctional emotional response. Like other chronic
diseases, addiction often involves cycles of relapse and remission. Without treatment or
engagement in recovery activities, addiction is progressive and can result in disability or
premature death. (ASAM 2011)
Fig. 69.10 Percentage of full-time workers, aged 18–64, reporting workplace-provided informa-
tion (Source: 2002–2004 NSDUH, Division of Workplace Programs SAMHSA)
69.3 Conclusion
The United States has the most well defined and structured approach, with
elements of strict discipline, mandates, treatment, and rehabilitation with drug
test monitoring before reentry into the workplace. In the European Union, there is
a much broader approach that includes workplace conditions and reasons for
alcohol/drug use with a focus on prevention but relying on rehabilitation.
Employee assistance programs offer benefits to both employers and employees.
For the employer, they provide an avenue for maintaining productivity, reducing
absenteeism and workplace accidents, and retaining skilled employees. For the
employee, an EAP provides a lifeline to the recognition of and referral to treatment
for debilitating substance abuse.
References
ASAM (2002/2012) Drug testing in workplace settings. American Society of Addiction Medicine,
Chevy Chase MD. http://www.asam.org/advocacy/find-a-policy-statement/view-policy-
statement/public-policy-statements/2011/12/15/drug-testing-in-workplace-settings. Accessed
7 Jun 2013
ASAM (2005/2009) The medical review officer. American Society of Addiction Medicine, Chevy
Chase
ASAM (2011) Public policy statement: definition of addiction. American Society of Addiction
Medicine, Chevy Chase, http://www.asam.org/for-the-public/definition-of-addiction.
Accessed 13 June 2013
Concateno (2012) High society: drug prevalence in the UK workplace, 1st edn. Concateno Global
Drug Testing Services, Abingdon, http://www.scribd.com/doc/98867797/High-Society-drug-
prevalence-in-the-UK-workplace-Concateno. Accessed 3 July 2013
Corral A, Durán J, Isusi I (2012) Use of alcohol and drugs at the workplace. European
Foundation for the Improvement of Living and Working Conditions (Eurofound), Dublin/
Brussels, http://www.eurofound.europa.eu/publications/htmlfiles/ef12231.htm. Accessed
10 June 2013)
EMCDDA (2013) European Drug Report 2013: trends and developments. European Monitoring
Centre for Drugs and Drug Addiction, Lisbon, http://www.emcdda.europa.eu/attachements.
cfm/att_212374_EN_TDAT13001ENN.pdf. Accessed 10 June 2013, 80p
Executive Order 12564 1986 Drug-free federal workplace. Federal Register 51 FR 32889, 3 CFR,
1986 Comp., p 224. http://www.archives.gov/federal-register/codification/executive-order/
12564.html Accessed 13 June 2013
Larson SL, Eyerman J, Foster MS, Gfroerer JC (2007) Worker substance use and workplace
policies and programs (DHHS Publication No. SMA 07-4273, Analytic Series A-29).
Substance Abuse and Mental Health Services Administration, Office of Applied Studies,
Rockville, http://samhsa.gov/data/work2k7/Work.htm. Accessed 13 June 2013
Mariotti O (2004) Droghe e lavoro. Giornale Italiano di Medicina del Lavoro ed Ergonomia
26(3):1–21
Office of Disability Employment Policy (2009) Employee assistance programs for a new gener-
ation of employees. U.S. Department of Labor, Washington, DC, http://www.dol.gov/odep/
documents/employeeassistance.pdf. Accessed 7 June 2013
Substance Abuse and Mental Health Services Administration (SAMHSA), Office of Applied
Studies (2009) Drug Abuse Warning Network, 2005: Selected Tables of National Estimates
of Drug-Related Emergency Department Visits, Rockville, MD, http://www.samhsa.gov/data/
2k9/DAWN/ED2005/2k5EDTables.html#Tab1. Accessed 7 June 2014
Treatment in Criminal Justice Settings
70
David Farabee, Richard A. Rawson, and Tarek A. Gawad
Contents
70.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1130
70.2 The Evidence for Causes, Consequences, Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1131
70.2.1 Causal Effects of Illicit Drugs on Criminal Behavior . . . . . . . . . . . . . . . . . . . . . . . 1131
70.2.2 Drug Use Behind Bars . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1132
70.2.3 Mortality Rates Among Just-Released Offenders . . . . . . . . . . . . . . . . . . . . . . . . . . . 1132
70.2.4 Intervention Settings for Drug-Involved Offenders . . . . . . . . . . . . . . . . . . . . . . . . . 1133
70.2.5 Intervention Models for Drug-Involved Offenders . . . . . . . . . . . . . . . . . . . . . . . . . . 1134
70.2.6 Medication-Assisted Treatments (MAT) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1136
70.2.7 Managing Offenders Under Community Supervision . . . . . . . . . . . . . . . . . . . . . . . 1138
70.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1139
70.3.1 Focus on Implementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1139
70.3.2 Need for More Randomized Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1140
70.3.3 Clarify the Role of Coercion: When It Helps, When It Hurts . . . . . . . . . . . . . . . 1140
D. Farabee (*)
Integrated Substance Abuse Programs, Department of Psychiatry and Biobehavioral Sciences,
UCLA, Los Angeles, CA, USA
e-mail: [email protected]
R.A. Rawson
Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, USA
Integrated Substance Abuse Programs, Semel Institute for Neuroscience and Human Behavior,
David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
e-mail: [email protected]
T.A. Gawad
Faculty of Medicine, Cairo University, Cairo, Egypt
National Rehabilitation Center, Abu Dhabi, UAE
e-mail: [email protected]; [email protected]; [email protected]
Abstract
The high prevalence of use among offenders is a consistent trend that tran-
scends international boundaries. Chronic drug users in the criminal justice
system pose risks to themselves and the general population through their
commission of drug-related property and violent crime, as well as through
the spread of infectious diseases, such as HIV and HCV. In this chapter, we
review multinational evidence concerning the drug/crime relationship, the use
of drugs within correctional settings, the consequences of drug use among
offenders, and the intervention approaches for drug-involved offenders in
custodial settings as well as those under community supervision. We conclude
with several recommendations for practice and research that we consider to be
important next steps in advancing this literature: (1) focus on implementation;
(2) need for more randomized trials; (3) clarification of the role of
coercion – when it helps, when it hurts; (4) distinguish “addicted offenders”
from “offender addicts”; and (5) examine the use of depot medications for
opiate-dependent offenders.
70.1 Introduction
The prevalence of substance use and substance use disorders among criminal
justice populations has remained consistently high for decades – and in some places
it continues to increase. It is estimated that half of prisoners in the European Union
have lifetime histories of heavy drug or alcohol use (Zurhold et al. 2004). In the
United States, the prevalence is estimated at nearly 85 % (Center on Addiction and
Substance Abuse [CASA] 2010). Even as US incarceration rates are on the decline,
the percentage of offenders incarcerated for drug charges has increased by nearly
20 % (CASA 2010).
The high rates of substance use among criminal offenders are the result of a host
of demographic, psychological, sociological, and legal factors that vary across
cultures. But despite these variations, one overall trend is clear: In most countries,
substance-involved offenders account for a substantial share of criminal activity
and criminal justice costs. According to one review, drug offenders account for
3–29 % of those incarcerated in the European Union (EU), 4–29 % of inmates in
non-EU European countries, 5–53 % of inmates in the Americas, and 10–58 % of
inmates in Asia/Oceania (Bewley-Taylor et al. 2009).
In this chapter, we review multinational evidence concerning the drug/crime
relationship, the use of drugs within correctional settings, the consequences of drug
use among offenders, and intervention approaches for drug-involved offenders in
custodial settings as well as those under community supervision.
70 Treatment in Criminal Justice Settings 1131
Because the association between drug use and crime is complex, Goldstein’s (1985)
conceptual framework for the various types of drug/crime relationships is widely
accepted and deserves some discussion here. Although originally proposed to
explain the relationships between drug use, the drug trade, and violence, this
framework can be applied more generally to include property offenses as well.
Goldstein argues that drug use can be associated with other forms of criminality
because of economic-compulsive, pharmacological, and systemic models of use
and/or distribution. These are briefly summarized below:
• Economic-compulsive – resorting to criminal behavior to support one’s drug
use. Crimes in this category include property crimes to obtain money for drugs,
selling drugs to support one’s own habit, or having sex with someone in
exchange for drugs or money for drugs.
• Pharmacological – engaging in irrational or violent behavior as a result of the
acute and/or chronic psychological or physiological effects of a drug. For
example, certain offenders might use, or threaten to use, violence because they
were intoxicated and were not aware of what they were doing; or in some cases,
an offender might use drugs or alcohol expressly to reduce the fear of danger
prior to engaging in a criminal act.
• Systemic – engaging in crimes ranging from selling drugs to using violence, or
the threat of violence, to protect a drug operation.
Subsequent research testing these relationships has shown that the systemic
factors offer the strongest link – particularly for violent crimes (Tardiff
et al. 1986). Evidence for the pharmacological link to violence among humans is
often confounded by the poor specification of what drugs were used and in what
quantity. Cartier and colleagues (2006) examined data from over 600 prison parolees
to explore the associations between methamphetamine use and recidivism and found
that methamphetamine use was significantly predictive of self-reported violent
criminal behavior and general recidivism (i.e., a return to custody for any reason).
This analysis controlled for background differences in demographic and criminal
history, but was limited to the narrow range of variables available. More controlled
animal studies have examined aggressive behaviors (number of initiated bite attacks
and latency before attacks) between mice that had received a single injection of
methamphetamine versus chronic injections over 8 weeks. The authors found that the
single injection did not increase fighting, but chronic injections were associated with
increased attacks and decreased latencies in attack behaviors (Sokolov et al. 2004).
Another method to assess the relationship between substance use and crime is to
directly ask arrestees whether their drug or alcohol use was a factor in their
commission of the arresting offense. Using data from the Drug Use Monitoring in
Australia (DUMA) database, Payne and Gaffney (2012) found that 45 % attributed
their current offense to either alcohol or drug use. The highest attribution rate was
found among heroin users (54 %), followed by alcohol users (41 %).
1132 D. Farabee et al.
The research base on drug use in prison is limited. Most of the studies on this topic
have been conducted in the United States, Great Britain, and Canada. In the United
States, estimates of in-prison drug use based on random drug tests have ranged from
1 % to 27 % (Vigdal and Stadler 1989; Inciardi et al. 1993). Using a combination of
convenience and random sampling to survey 1,054 prisoners in 30 prisons in
Kentucky, Tennessee, and Ohio in 2001, Gillespie (2005) found that 35 % reported
some behavior in the past 12 months related to drug and alcohol use (use and
possession, but also manufacture and sale).
Studies in the United Kingdom have revealed even higher prevalence of use in
prison. According to Shewan et al. (1994), 74 % of inmates surveyed in four
Scottish prisons reported using marijuana while in prison. Using a sample of
offenders who had used drugs prior to prison, Bullock (2003) found that 56 % of
inmates reported using any illicit drug in prison, with marijuana being the most
common drug, followed by heroin. This study also queried inmates about their
frequency of use while in prison, finding that 14 % of inmates interviewed reported
using marijuana daily or near daily; the figure for daily heroin use was 3 %.
In an interview study (Pernanen et al. 2002) of Canadian prisons, 29 % of the
sample reported using any illicit drug in the 3 months prior to the interview, with the
most popular drug being marijuana. Alcohol use was reported by 16 %. Nearly 90 %
of those interviewed said that their behavior in the past 3 months was typical of their
behavior over the past year or since their arrival in prison. Random drug testing
results have also been used to develop estimates for drug use. Kendall and Pearce
(2000) reported that the percentage of any positive test across Canadian prisons
ranged from 10 % and 13 % between 1994 and 1998, most commonly for marijuana.
Although prison and jail can be effective at reducing levels of crime and drug use
during the period of incarceration, resumption of these behaviors upon release is the
norm. In the United States, nearly 7 in 10 released offenders are rearrested within
3 years (Bureau of Justice Statistics 2002). Data regarding drug use are even more
disquieting, indicating that in many cases, offenders are re-addicted within 1 month
of release from incarceration and their drug use and/or crime levels following
prison can even exceed those reported prior to incarceration (Hough 2002).
The risk of death among parolees is particularly high – nearly 13 times greater
than those of similar demographic background – during the first 2 weeks following
release from prison, with drug overdose being the leading cause (Binswanger
et al. 2007). As dire as this finding is, it may be an underestimate of the problem.
A study of newly released prisoners in England and Wales found that the mortality
rate among males was 29 times higher than that of the general population during the
first 2 weeks of release. The mortality rate for female offenders was 69 times higher
(Farrell and Marsden 2007). These studies are included in a recent meta-analysis of
70 Treatment in Criminal Justice Settings 1133
In most countries, the criminal justice system encompasses offenders who are
incarcerated in jail or prison and those under supervision in the community. The
latter group – those on probation or parole – constitutes the vast majority of the
criminal justice population. Although the treatments described below can be
implemented in custody or in the community, both settings have advantages and
disadvantages that merit consideration.
The associations between substance misuse and crime, and the public health and
safety risks posed by ongoing drug use behind bars, underscore the need for
prevention and intervention. What is less clear is how to prevent drug use and
provide interventions. In this section, we summarize common approaches to reduc-
ing drug use (and its attendant problems, such as recidivism and the spread of
infectious diseases) among convicted drug-misusing offenders.
in these settings. In the United States, for example, more than a quarter of state
prison inmates and about one in five federal inmates meeting criteria for substance
misuse participate in such groups (Mumola and Karberg 2006).
70.2.6.2 Methadone
Methadone is a synthetic opioid used to reduce craving and block the euphoric
effects of heroin, morphine, and other non-prescribed opioids. It is also used for
opiate detoxification. Since the 1990s, following the development of maintenance
programs in the community, programs have also been introduced in prisons.
In-prison methadone provision is now available in Canada, Australia, Poland,
Indonesia, Iran, New Zealand, Puerto Rico, and the majority of Western Europe
(Betteridge and Jurgens 2008). After researchers in Tehran found that a history of
shared injection equipment in prison was the main predictor of HIV infection in
the general population, the Iranian government launched a pilot program to
provide methadone to 50 opiate-dependent prisoners. The results were promising
enough that over 6 years the program was expanded to 142 institutions – offering
MMT to more than 25,000 inmates in 2009 (Farnia et al. 2010). At the present
time almost every large- and middle-sized prison in Iran provides methadone
treatment to injection heroin users, and as of 2011, there were over 38,000
prisoners in Iranian prisons in treatment with methadone (Momtazi et al. 2012).
Iran has developed one of the largest systems of methadone treatment in prisons,
supported by a clinical trial in an Iranian prison that demonstrated methadone
treatment is associated with a significant reduction in injection drug use
(Bayanzadeh et al. 2007; cited in Momtazi and Noroozi (this volume)). During
that same year, more than 19,000 MMT treatments were provided to inmates in
the United Kingdom (Stover and Michels 2010). A key finding regarding meth-
adone induction for this population is that initiation of MMT prior to release
produces significantly better outcomes than offering MMT upon release to the
community (Gordon et al. 2008).
70 Treatment in Criminal Justice Settings 1137
70.2.6.3 Buprenorphine
A substantial body of research supports the safety and efficacy of buprenorphine
and the buprenorphine-naloxone combination (e.g., Ling and Wesson 2003).
A recent review of 24 randomized trials revealed that buprenorphine (at medium
to high doses) was significantly superior to placebo medication in reducing heroin
use (Mattick et al. 2008). Several properties of buprenorphine may make it poten-
tially less objectionable than methadone to criminal justice personnel as a treatment
for opiate dependence. First, the agonist activity of buprenorphine has a ceiling
effect that decreases the danger of overdose and limits its abuse liability. Second,
buprenorphine produces sufficient tolerance to block the effects of heroin and other
opiates, thus reducing illicit opiate use. Third, buprenorphine exhibits a slow
dissociation from m-opiate receptors, which results in a long duration of action
and a reduced dosing schedule compared with methadone. Fourth, the combination
tablet of buprenorphine and naloxone (as Suboxone) reduces the risk of illicit
injection – along with injection-related HIV/HCV risk (a common problem in
correctional settings where injection equipment is scarce and sharing is common).
In spite of the substantial literature that has accumulated over the past decade
supporting the use of buprenorphine, it has not been readily adopted in correctional
settings. A recent survey of the US state and federal prison systems showed that
only 15 states (29 %) provide any referrals to community buprenorphine providers
(Nunn et al. 2009). Although the use of MAT is more common in jails than in
prisons (used primarily to manage opiate withdrawal), it is important to note that it
remains unavailable in two thirds of US jails (Oser et al. 2009).
70.2.6.4 Naltrexone
Naltrexone is an opioid receptor antagonist that blocks the euphoric effects of
heroin and other opioids. This characteristic has fostered growing acceptance of
naltrexone by correctional authorities who wish to avoid the perception that they
are merely replacing one drug with another. However, it must be taken orally on
a daily basis, making adherence a problem among all but the most committed
patients. Cornish et al. (1997) randomly assigned federal probationers to a 6-month
program of probation plus naltrexone and brief drug counseling or to probation plus
counseling alone and found that opioid use was significantly lower in the naltrexone
group, with the mean percent of opioid-positive urine tests among the naltrexone
subjects at 8 % versus 30 % for control subjects (p < 0.05). Likewise 56 % of the
controls and 26 % of the naltrexone group (p < 0.05) had their probation status
revoked within the 6-month study period and were returned to prison. But treatment
compliance was a problem, with only 52 % of subjects in the naltrexone group
continuing for the 6-month duration of the study.
A depot formulation of naltrexone (e.g., Vivitrol ®; approved in 2010 by the
U.S. FDA for opioid addiction) addresses the problem of noncompliance with
medication dosing, eliminates concerns about potential diversion (an issue with
oral buprenorphine and take-home doses of methadone), and lessens the need
for frequent patient presentation in the clinic or physician’s office. Naltrexone
injections reliably prevented relapse within 1 month after detoxification
1138 D. Farabee et al.
(Foster et al. 2003), and multi-site research in Russia found Vivitrol effective for
treating heroin addiction over 6 months (Krupitsky et al. 2011).
70.3 Conclusion
This chapter highlights the importance of capitalizing on the criminal justice system
to identify and intervene with substance-misusing offenders. The high prevalence
of use among offenders is a consistent international trend. Moreover, drug users in
the criminal justice system pose risks to themselves and the general population
through their commission of drug-related property and violent crime, as well as
through the spread of infectious diseases, such as HIV and HCV.
Although the need for some level of intervention is clear, our review of existing
treatment options and their supporting research underscores the fact that appropri-
ate solutions are still not well established. Nor can we be certain of the extent to
which reductions in substance use will produce commensurate reductions in crim-
inal activity (aside from that inherent to illicit drug use itself).
We conclude this chapter with several recommendations for practice and
research that we consider to be important next steps in advancing this literature.
Over a decade ago, Gendreau and colleagues wrote that “of all the issues critical to
the development of effective correctional treatment programs, program implemen-
tation has been relatively ignored” (Gendreau et al. 1999, p. 180). This observation
is no less relevant today. Implementation fidelity is a challenge in any setting, but
even more so under the auspices of a correctional system. This is because correc-
tional administrators understandably focus their attention on the primary goals of
keeping the general public safe from offenders and incarcerated offenders safe from
each other. Successfully carrying out a rehabilitative agenda within these settings
requires not only a knowledge of implementation science but also a practical
understanding of how the criminal justice system works and why. Identifying
effective practices that can be implemented for offenders – whether in custody or
under community supervision – is only a first step that must be followed by research
on how to encourage other correctional organizations to adopt such practices and
how to ensure that the key elements in the original intervention are not lost or
diluted in the process.
1140 D. Farabee et al.
In most countries, the capacity for providing substance abuse treatment services in
prison falls well short of the estimated need (Dolan et al. 2007). Absent a dramatic
reversal of this trend, it is critical that researchers and practitioners develop criteria
for determining which substance misusers are most likely to benefit from treatment
and, among these, for whom reduced drug use will produce reduced criminal
behavior.
Distinguishing offenders whose drug use impels criminal behavior from those
whose drug use is merely coincidental has proven an elusive goal among addiction
researchers and criminologists, but there is some evidence that such a distinction
70 Treatment in Criminal Justice Settings 1141
can be made. For example, Nurco and colleagues (1988) classified 214 narcotic
addicts according to their criminal involvement during a 2-year pre-addiction
period and then compared rates of criminality during addiction periods for those
who had engaged in crime prior to becoming addicted (approximately one half of
the sample) and those who had not. As hypothesized, both groups increased their
rates of criminality during high-addiction periods. However, during subsequent
periods of low use, 78 % of the high-crime subjects (based on criminal activity
during their pre-addiction period) continued to engage in criminal activity versus
only 40 % of those in the low-crime group. Between-group differences were
particularly disparate for drug dealing, with the high-crime group being responsible
for 91 % of the drug-dealing crimes during the nonaddiction periods.
The high risk of death among offenders during the first 2 weeks following release
from prison – and the fact that drug overdose is the leading cause (Binswanger
et al. 2007) – suggests that drug use treatment might be considered effective even if
it only reduced use or prevented relapse during the initial post-release phase. Newly
approved depot formulations of naltrexone (e.g., Vivitrol ®) and buprenorphine
(e.g., Probuphine ®) offer promise for overcoming poor medication adherence and
eliminate the risk of these substances being diverted for recreational use. Moreover,
even a single administration of these medications immediately prior to release from
custody can reduce the threat of fatal opiate-related overdoses during the initial
reentry period, when risks are at their highest. Given their promise, more evalua-
tions of depot pharmacotherapies for released offenders are strongly recommended,
particularly concerning strategies to encourage initial interest in these medications
and to increase the percentage of offenders who return for subsequent doses.
References
Asscher JJ, Deković M, van der Laan PH, Prins P, van Arum S (2007) Implementing randomized
experiments in criminal justice settings: an evaluation of multi-systemic therapy in the
Netherlands. J Exp Criminol 3:113–129
Bahr SJ, Masters AL, Taylor BM (2012) What works in substance abuse treatment programs for
offenders? Prison J 92(2):155–174
Baillargeon J, Giordano TP, Rich J, Wu Z, Wells K, Pollack BH, Paar DP (2009) Accessing
antiretroviral therapy following release from prison. JAMA 301(8):848–857
Bayanzadeh SA, Bolhari J, Noori R, Lavasani F, Karimi E (2007) The role of pharmacotherapeutic
and psychosocial interventions in reducing drug related harm among addict prisoners. J Iran
Univ Med Sci 14(55):47–55, [In Farsi] Cited in Momtazi S and Noroozi A (this volume)
Belenko S (1998) Research on drug courts: a critical review. Natl Drug Court Inst Rev 1(1):1–42
Betteridge G, Jurgens R (2008) Opioid substitution therapy in prisons: reviewing the evidence.
Canadian HIV/AIDS Legal Network, Canada, http://www.aidslaw.ca/publications/interfaces/
downloadFile.php?ref¼1293. Accessed 1 May 2013
1142 D. Farabee et al.
Inciardi JA, Lockwood D, Quinlan JA (1993) Drug use in prison: patterns, processes, and
implications for treatment. J Drug Issues 23(1):119–130
Kendall PRW, Pearce M (2000) Drug testing in Canadian jails: to what end? Can J Public Health
91(1):26–28
Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL (2011) Injectable
extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled,
multicentre randomised trial. Lancet 377:1506–1513
Landenberger NA, Lipsey MW (2005) The positive effects of cognitive-behavioral programs for
offenders: a meta-analysis of factors associated with effective treatment. J Exp Criminol
1:451–476
Ling W, Wesson DR (2003) Clinical efficacy of buprenorphine: comparisons to methadone and
placebo. Drug Alcohol Depend 70(2):S49–S58
Magill M, Ray L (2009) Cognitive-behavioral treatment with adult alcohol and illicit drug users:
a meta-analysis of randomized controlled trials. J Stud Alcohol Drugs 70:516–527
Mattick RP, Kimber J, Breen C, Davoli M (2008) Buprenorphine maintenance versus
placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2:
CD002207
Merrall LC, Kariminia A, Binswanger IA, Hobbs MS, Farrell M, Marsden J, Hutchinson SJ, Bird
SM (2010) Meta-analysis of drug-related deaths soon after release from prison. Addiction
105:1545–1554
Momtazi S, Rawson R, Musavinasab N, Hamzehlu MB (2012) Methadone maintenance treatment
program for drug abuse prisoners in Iran. Abstract book of the National Institute on Drug
Abuse international forum. Palm Springs, California
Mumola CJ, Karberg JC (2006) Drug use and dependence: state and federal prisoners, 2004. Office
of Justice Programs, Bureau of Justice Statistics, Washington, DC
Nunn A, Zaller N, Dickman S, Trimbur C, Nijhawan A, Rich JD (2009) Methadone and
buprenorphine prescribing and referral practices in US prison systems: results from
a nationwide survey. Drug Alcohol Depend 105:83–88
Nurco DN, Hanlon TE, Kinlock TW, Duszynski KR (1988) Differential criminal patterns of
narcotic addicts over an addiction career. Criminology 26:407–423
Oser CB, Knudsen HK, Staton-Tindall M, Taxman F, Leukefeld C (2009) Organizational-level
correlates of the provision of detoxification services and medication-based treatment for
substance abuse in correctional institutions. Drug Alcohol Depend 103(Suppl 1):S73–S81
Payne J, Gaffney A (2012) How much crime is drug or alcohol related? Self reported attributions
of police detainees. Trends & issues in crime and criminal justice 439 http://www.aic.gov.au/
publications/current%20series/tandi/421-440/tandi439.html. Accessed 1 May 2013
Pearson FS, Lipton DS (1999) A meta-analytic review of the effectiveness of corrections-based
treatments for drug abuse. Prison J 79(4):384–410
Pernanen K, Cousineau M, Brochu S, Sun F (2002) Proportions of crimes associated with alcohol
and other drugs in Canada. Canadian Centre on Substance Abuse, Ottawa
Phipps P, Korinek K, Aos S, Lieb R (1999) Research findings on adult corrections programs:
a review. Washington State Institute for Public Policy, Olympia
Shewan D, Gemmell M, Davies JB (1994) Prison as a modifier of drug using behavior. Addict Res
Theory 2(2):203–215
Sokolov BP, Schindler CW, Cadet JL (2004) Chronic methamphetamine increases fighting in
mice. Pharmacol Biochem Behav 77:319–326
Stephenson BL, Wohl DA, Golin CE, Tien HC, Stewart P, Kaplan AH (2005) Effect of release
from prison and re-incarceration on the viral loads of HIV-infected individuals. Public Health
Rep 120(1):84–88
Stover H, Michels II (2010) Drug use and opioid substitution treatment for prisoners. Harm
Reduction J 7:17–24
Tardiff K, Gross E, Messner S (1986) A study of homicide in Manhattan, 1081. Am J Public
Health 76:139–143
1144 D. Farabee et al.
Taxman F, Perdoni ML, Harrison L (2007) Drug treatment services for adult offenders: the state of
the state. J Subst Abuse Treat 32:239–254
Vigdal GL, Stadler DW (1989) Controlling inmate drug use: cut consumption by reducing
demand. Correct Today 51(3):96–97
Wild TC, Roberts AB, Cooper EL (2002) Compulsory substance abuse treatment: an overview of
recent findings and issues. Eur Addict Res 8:84–93
Zurhold H, Stöver H, Haasen C (2004) Female drug users in European prisons – best practice for
relapse prevention and reintegration. Centre for Interdisciplinary Addiction Research, Univer-
sity of Hamburg, Hamburg
A Case Study from Egypt
71
Tarek A. Gawad
Contents
71.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1145
71.2 The Survey . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1146
71.2.1 Survey of Drug Use in a Cairo Prison (From Ali Kabbash 2009) . . . . . . . . . . 1146
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1148
71.1 Introduction
The Middle East and North Africa (MENA) continues to be a region with limited
data on the extent of the HIV problem. A 2010 review of evidence on HIV in the
MENA region concluded that, while there was no evidence of an HIV epidemic,
without an aggressive program of HIV prevention among high-risk groups, this
situation could rapidly change for the worse (Abu-Radda et al. 2010). According to
the Joint United Nations Programme on HIV/AIDS (UNAIDS 2012), the number of
people newly infected with HIV in the MENA region increased by 35 % between
2001 and 2011. Consequently, efforts to identify high-risk groups and initiate HIV
prevention methods are a priority in the region.
Egypt launched two national strategies in 2008, one on drug use and the other on
HIV. Both strategies address the importance of prison inmates as a target popula-
tion for intervention. In collaboration with the United Nations Office on Drugs and
Crime (UNODC) Regional Office of the Middle East and North Africa (ROMENA)
regional project on increasing access to drug use and HIV prevention and care
services in prison settings, an interministerial national prison task force was
T.A. Gawad
Faculty of Medicine, Cairo University, Cairo, Egypt
National Rehabilitation Center, Abu Dhabi, UAE
e-mail: [email protected]; [email protected]; [email protected]
formulated to coordinate activities aimed at reducing the negative social and health
consequences of drug use in prisons. Accordingly, the prison task force has
facilitated the implementation of an assessment of drug use and the HIV status of
prisoners in six facilities in Egypt. These assessments are used to describe the need
for HIV prevention in prison settings and, accordingly, provide the technical
expertise and resources required to provide such.
The Egyptian Prison Authority called for a consultation meeting on October
2008 to present the concept of establishment of drug treatment facilities, rehabil-
itation programs, social reintegration, and vocational training for inmates within the
prison premises. The main outcome of this consultation meeting was to conceptu-
alize the prison initiative described below. Besides the prison authorities and
UNODC ROMENA representatives, the steering committee permanent members
were the Anti-Narcotics General Administration, the National Fund on Drug Use
and Addiction, the Ministry of Health (General Secretariat for Mental Health and
National AIDS Programme), the International Society of Addiction Medicine
(ISAM), UNAIDS Country Office, and Egyptian academic institutions.
Upon recommendation from the members of the steering committee, a baseline
study funded through UNODC ROMENA to assess the situation related to drug
addiction and HIV infection in prisons and to provide necessary information for
planning the best possible intervention was undertaken in 2009. This project aimed
to provide specialized treatment and rehabilitation services to drug-dependent
prison inmates while minimizing the negative health consequences of drug use
within prison settings in Egypt. The project also sought to provide job opportunities
for the targeted group of inmates during imprisonment and after release through the
establishment of vocational workshops as part of rehabilitation and social
reintegration.
71.2.1 Survey of Drug Use in a Cairo Prison (From Ali Kabbash 2009)
One prison in the Cairo area was chosen to conduct a survey on drug use and HIV
risk behavior. Individual interviews were conducted by experienced interviewers in
a private setting. Participants were assured that their results would not be shared
with the prison authorities. In addition to the individual interviews, focus groups
of six to eight individuals were conducted. These focus groups included groups of
inmates, guards, health-care workers, and social workers (different groups for each
category). Data from the focus groups presented a consistent picture across cate-
gories. There was general agreement that there is a considerable amount of drugs in
the prison and that they come into the prison in a variety of ways: family visits,
prisoner trips outside the prison, and with food brought in by prison suppliers.
The quantitative survey study consisted of 1,926 participants, randomly selected,
which represented 10 % of the prison population. The mean age of participants was
35 years, and 50 % were married; 36 % were illiterate, and 78 % were manual
71 A Case Study from Egypt 1147
laborers. The majority were imprisoned for drug and theft crimes (67.5 %), with
sentences ranging from 1 to 10 years (69.9 %). Knowledge about HIV was variable,
with 88 % and 82 % reporting that they knew that sexual behavior and sharing
injection equipment were methods of HIV transmission, respectively, but only 59 %
knew of mother-child transmission and 40 % thought HIV could be transmitted by
insect bites. Eighty-nine percent (1,541) agreed to be tested for HIV, although only
43 % were aware there was treatment for HIV.
Fifty-three percent of participants reported that they knew of drug use in the
prison, and 49.7 % of participants reported taking drugs in the prison. The majority
of prisoners had a history of drug dependence before prison admission, with an
average onset age of use of 18.6 (SD ¼ 5.37) years. Drug injection had been
practiced by 22 % of drug-dependent participants before prison, and 6.7 % reported
injecting drugs in prison. The same syringe was generally shared by a group of
persons and reused for several days. The common drugs are parkinol, other
psychoactive pills, and hashish/bango. Sixty-five percent do not consider them-
selves to be dependent upon drugs, and 88 % reported they had never experienced
withdrawal symptoms. Five percent of participants reported that they had
overdosed from drugs, and 3.7 % reported more than one overdose episode.
Fewer than 5 % had ever participated in treatment, and only 2.5 % felt they needed
treatment in prison.
The combined efforts of the prison officials, the other Egyptian governmental
and academic leaders, and the representatives of the UNODC ROMENA program
have revealed evidence indicating considerable drug use in Egyptian prisons. The
drug use and related behaviors (e.g., needle sharing and sex while under
the influence of drugs) are reasons for concern about high-risk behaviors for HIV
transmission within Egyptian prisons. According to UNAIDS (2012), new cases of
HIV in Egypt are being reported at an increasing rate, and there are few HIV
prevention activities in Egypt to address this public health problem. Although rates
of HIV are believed to be low in Egypt, relative to other parts of the world, this
situation could change rapidly if high-risk groups and high-risk settings are ignored.
Clearly the prisons in Egypt are settings where the rates of HIV and the transmis-
sion of HIV are seriously elevated as compared to the general society.
Following the collection of the survey data presented above, there were discus-
sions among Egyptian prison, health, and academic leaders about the most effective
strategies for addressing the concerns about HIV transmission and drug use in
Egyptian prisons. A plan was drafted to consider the development of addiction
treatment and HIV prevention programs within Egyptian prison settings, combined
with community aftercare to prevent relapse to drug use once individuals are
released from prisons into the community. There was an extensive review of prison
treatment and aftercare options from the literature around the world. Extensive
discussions occurred regarding the possibility that this demonstrated need to
address the Egyptian prison situation could be an excellent opportunity to conduct
pilot programs in Egypt with addiction medications, including Suboxone ® for
opioid dependence. Further information is needed on the extent of opioid use in
Egyptian prisons. If significant levels of opioid use are found, the induction and
1148 T.A. Gawad
References
Abu-Radda LJ, Hilmi N, Mumtaz G, Benkirane M, Akala FA, Riedner G, Tawil O, Wilson
D (2010) Epidemiology of HIV infection in the Middle East and North Africa. AIDS
24(Suppl 2):S5–S23
Ali Kabbash I (2009) Building a comprehensive program for drug rehabilitation and social
re-integration for drug dependent prison inmates in Egypt. Unpublished report for the United
Nations Office on Drugs and Crime, Cairo
UNAIDS (2012) Global report: UNAIDS report on the global epidemic, 2012. UNAIDS, Geneva.
http://www.unaids.org.br/documentos/UNAIDS_GR2012_em_en.pdf. Accessed 19 Feb 2014
Drug Courts
72
Douglas B. Marlowe
Contents
72.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1150
72.2 Effectiveness of Drug Courts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1152
72.2.1 Criminal Recidivism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1152
72.2.2 Cost-Effectiveness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1152
72.2.3 Psychosocial Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1153
72.2.4 International Perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1153
72.3 Effective vs. Ineffective Drug Courts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1154
72.3.1 Target Population . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1154
72.3.2 Best Practices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1155
72.3.3 International Perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1161
72.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1161
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1162
Abstract
Drug courts provide judicially supervised substance abuse treatment in lieu of
criminal prosecution or incarceration. Substantial research demonstrates that drug
courts reduce crime, incarceration rates, and substance abuse, improve the psycho-
social functioning of offenders, and produce positive cost benefits for taxpayers.
Evidence has identified the optimal target population for drug courts and many of
the best practices that are associated with improved outcomes in these programs.
Although most of the research on drug courts has been conducted in the USA,
emerging evidence is beginning to reveal positive benefits in European, Austral-
asian, South American, and Caribbean countries as well. The challenge now is to
extend the reach of drug courts without sacrificing their efficacy or safety.
D.B. Marlowe
National Association of Drug Court Professionals, Alexandria, VA, USA
e-mail: [email protected]
72.1 Introduction
Over 80 % of adult offenders in the USA misuse drugs or alcohol, meaning they
were arrested for a drug- or alcohol-related offense, were intoxicated at the time of
their offense, reported committing their offense to support a drug or alcohol
problem or they have a significant history of substance abuse or substance abuse
treatment (National Center on Addiction and Substance Abuse [NCASA] 2012).
Approximately one quarter to one half of offenders are estimated to misuse drugs or
alcohol in European, Australasian, South American, and Caribbean nations (Cooper
et al. 2013). Providing substance abuse treatment can reduce recidivism rates
substantially (Chandler et al. 2009); however less than one quarter of drug-involved
offenders will complete a substance abuse treatment episode (Marlowe 2002).
Drug courts were created to improve offenders’ compliance with substance
abuse treatment. The drug court judge leads a multidisciplinary team of
professionals that commonly includes representatives from the prosecution, defense
bar, treatment agencies, case-management agency, probation department, and law
enforcement. These team members meet frequently in staff meetings to review
participants’ progress in treatment and offer recommendations to the judge about
potential consequences to impose (National Association of Drug Court Profes-
sionals [NADCP] 1997). The consequences may include rewards such as verbal
praise, reduced supervision requirements, or small gifts; punitive sanctions such as
verbal reprimands, writing assignments, community service, or brief intervals of
jail detention; or adjustments to the participant’s treatment regimen. The conse-
quences are administered during regularly scheduled status hearings at which the
judge discusses the matter with the participant in court. In pre-adjudication
drug courts, the ultimate legal incentive is to have the criminal charge(s) dropped
or withdrawn, and in post-adjudication drug courts, the legal incentive is to avoid
a sentence of incarceration or reduce the length or conditions of probation.
The first drug court was founded in Miami/Dade County, Florida, in the USA in
1989. Currently, there are more than 2,700 drug courts in the USA (Huddleston and
Marlowe 2011). Nearly 30 countries other than the USA have also established or
are planning to establish drug courts, including Argentina, Australia, the Bahamas,
Barbados, Belgium, Bermuda, Brazil, Canada, Cayman Islands, Chile, Columbia,
Costa Rica, the Dominican Republic, El Salvador, England, Grenada, Ireland,
Jamaica, Mexico, Norway, Panama, Peru, Scotland, Suriname, and Trinidad and
Tobago (Cooper et al. in press).
In 1997, the National Association of Drug Court Professionals in
the USA promulgated what are commonly referred to as the “10 Key
Components” of drug courts (NADCP 1997). A few years later, the International
Association of Drug Treatment Courts (IADTC) adopted the 10 Key Components
but added three more components focusing on the social reintegration
of participants, ensuring flexible treatment for indigenous populations and ethnic
minorities, and planning for aftercare recovery services. The IADTC principles are
embodied in a document entitled the 13 Key Principles for Court-Directed Treat-
ment and Rehabilitation Programmes (“13 Key Principles”) [see Text Box].
72 Drug Courts 1151
The success of adult drug courts (described below) has spawned an array of
other types of problem-solving courts or treatment courts, including juvenile
drug courts, family drug courts (for guardians in child abuse and neglect cases),
driving while impaired (DWI) courts, mental health courts, and veterans treat-
ment courts (for impaired military veterans). Considerably less research has
been conducted on these newer models than on the original adult criminal
model; however, emerging evidence suggests some of the newer programs are
beginning to show favorable results. This chapter reviews the large body of
research on adult criminal drug courts. The reader is referred to other sources for
information on newer variants of the drug court model (Huddleston and
Marlowe 2011; Marlowe 2011).
1152 D.B. Marlowe
Meta-analyses are advanced statistical procedures that calculate the average effects
of an intervention across numerous research studies. Several meta-analyses
performed in the USA and Canada (Aos et al. 2006; Bhati et al. 2008; Downey
and Roman 2010; Latimer et al. 2006; Lowenkamp et al. 2005; Mitchell et al. 2012;
Shaffer 2010; Wilson et al. 2006) and a national multisite study in the USA
(Rossman et al. 2011) concluded that drug courts significantly reduced criminal
recidivism – typically measured by rearrest rates within 2 years of entry into the
drug court – by an average of 8–14 %. In randomized controlled experiments, the
reductions in recidivism were found to have lasted for at least 3 years postentry
(Gottfredson et al. 2005; Mitchell et al. 2012; Turner et al. 1999), and in one study
the effects lasted 14 years (Finigan et al. 2007).
A recent meta-analysis in the USA concluded that drug courts also significantly
reduced incarceration rates by an average of 8–12 % (Sevigny et al. 2013). Notably,
however, this impact did not translate into lesser use of jail or prison beds. Although
the drug court participants were less likely to be incarcerated than comparable
offenders charged with the same crimes, participants who were unsuccessfully
terminated from the drug courts ultimately served more jail or prison time. In
other words, the drug courts reduced the number of offenders who were sent to
jail or prison but increased the length of the jail or prison sentences for the
unsuccessfully terminated cases. The net result was that the unsuccessful cases
washed out the effects of the successful cases, thus leading to a negligible impact on
jail and prison resources.
This finding could be interpreted as an indictment of drug courts because they
may not reduce jail or prison overcrowding or overreliance on the most expensive
correctional resources. An alternative interpretation, however, is that drug courts
reduce crime rates while having no impact on correctional populations or taxpayer
expenditures. In other words, they achieve larger crime reductions than other
correctional programs without increasing jail or prison censuses. Research does
not, as yet, shed light on this debate. It is unknown whether crime rates would
increase if drug courts reduced the consequences for unsuccessful termination.
Some participants might be less likely to apply themselves in treatment if the
consequences for failure were less severe, thus leading to higher termination rates
or crime rates. Future research needs to address this important and policy-relevant
question.
72.2.2 Cost-Effectiveness
In line with their positive effects on crime reduction, drug courts have also proven
to be cost-effective. Meta-analyses of cost-effectiveness studies concluded that
drug courts produced an average of approximately $2–2.25 in direct benefits to
72 Drug Courts 1153
the criminal justice system for every $1 invested (Bhati et al. 2008; Downey and
Roman 2010; Rossman et al. 2011). These savings reflected measurable cost-offsets
to the criminal justice system stemming from reduced rearrests, law enforcement
contacts, court hearings, the use of jail or prison beds, and the tangible impacts of
crime victimization. When more distal cost-offsets were also taken into account,
such as savings from reduced child foster care placements and healthcare service
utilization, studies have reported economic benefits ranging from approximately $4
to 27 for every $1 invested, resulting in savings to local communities of roughly
$3,000–22,000 per participant (e.g., Aos et al. 2006; Finigan et al. 2007; Mayfield
et al. 2013).
Rigorous studies in Australia (Jones 2013) and Canada (Somers et al. 2011) have
demonstrated that drug courts can significantly reduce crime and produce cost
benefits in those countries as well. In other nations, most drug courts are still in
1154 D.B. Marlowe
the formative stages and efforts to evaluate their outcomes have only recently been
initiated.
A 2010 survey conducted by American University on behalf of the Organization
of American States (OAS) analyzed responses from drug court officials in several
South American, Central American, and Caribbean nations (Cooper et al. 2010).
The majority of the respondents reported that drug courts in their countries
appeared to be reducing crime better than traditional correctional dispositions and
approximately half of the respondents reported notable cost savings. Brazil, for
example, reported 12 % recidivism for participants in its drug court in Rio de
Janeiro as compared to a general recidivism rate of 80 % for nontreatment-oriented
criminal dispositions. These figures are merely estimates but they do suggest that
drug courts are feasible and potentially desirable to implement in South American
and Caribbean nations.
A growing body of research indicates which types of offenders are most in need of
the full range of interventions embodied in drug courts. These are the offenders who
are (1) addicted to or dependent on illicit drugs or alcohol and (2) at substantial risk
for criminal recidivism or failure in less intensive rehabilitative dispositions. Drug
courts that focus their efforts on these individuals – commonly referred to as high-
need and high-risk offenders – reduce crime approximately twice as much as those
serving less serious offenders and return approximately 50 % greater cost savings to
72 Drug Courts 1155
their communities (Bhati et al. 2008; Carey et al. 2012; Downey and Roman 2010;
Lowenkamp et al. 2005).
These findings are consistent with a well-validated criminological theory called
Risk-Needs-Responsivity (RNR). According to RNR, intensive programs such as
drug courts offer the greatest benefits for high-risk offenders who have more severe
antisocial propensities or treatment-refractory histories; however, such programs
are often unnecessary or counterproductive for low-risk offenders (Andrews and
Bonta 2010). High-risk offenders have a generally poor prognosis for success in
standard treatment and often require intensive and sustained interventions to
dislodge their entrenched, negative behavioral patterns. Low-risk offenders, in
contrast, are less likely to be on a fixed antisocial trajectory and are apt to improve
their conduct following a run-in with the law. Therefore, intensive interventions
may offer small benefits for low-risk individuals but at a substantial cost (DeMatteo
et al. 2006). Worse still, low-risk offenders may learn antisocial attitudes and
behaviors from associating with high-risk offenders, which can make their out-
comes worse. It has been found that providing formal substance abuse treatment for
nonaddicted substance abusers can lead to higher rates of reoffending and a greater
likelihood of those individuals becoming addicted (Lowenkamp and Latessa 2005;
Wexler et al. 2004). This might be an unintended effect of exposing them to
antisocial peers or interfering with their engagement in productive activities, such
as work or school.
In fiscally challenging times, there is always the pressure to do more with less. This
raises the question of whether certain components of the drug court model can be
dropped or the dosage decreased without eroding the effects. The key components
of drug courts are hypothesized to include an ongoing schedule of judicial status
hearings, a multidisciplinary team approach to managing cases, a standardized
regimen of evidence-based substance abuse treatment, frequent drug and alcohol
testing, and contingent sanctions and incentives (NADCP 1997). Each of these
hypothesized key components has been examined by researchers to determine
whether it is required for effective results.
in several research studies (Finigan et al. 2007; NIJ 2006). Participants in drug
courts often lead chaotic lives and require substantial structure and consistency to
change their maladaptive behaviors. Unstable staffing patterns, particularly when
they involve the central figure of the judge, are apt to exacerbate rather than
ameliorate the disorganization in participants’ lives.
and delivered by inadequately trained staff. The services also tended to be indis-
tinguishable from those routinely offered to noncriminal justice populations and
thus might not have adequately addressed the unique needs and risk factors
presented by offenders.
Recent studies provide a more informative and sanguine picture of the impact of
substance abuse treatment on drug court outcomes. The success of drug courts
appears to be attributable, at least in part, to the fact that they significantly increased
participants’ exposure to substance abuse treatment. The longer drug court partic-
ipants remained in treatment and the more sessions they attended, the better were
their outcomes (Gottfredson et al. 2007; Peters et al. 2002; Shaffer 2010).
Outcomes are also significantly better in drug courts that offer a continuum of
care for substance abuse treatment which includes residential treatment and
recovery housing in addition to outpatient services (Carey et al. 2012;
Koob et al. 2011). The best results are achieved when participants are required
to meet with a treatment provider or clinical case manager for at least one
individual session per week during the first phase of the program
(Carey et al. 2012; Rossman et al. 2011). Many participants are unstable
clinically and in a state of crisis when they first enter a drug court, and group
sessions might not provide adequate time or opportunities to address each
participant’s clinical and social service needs. Individual sessions may reduce
the likelihood that participants will fall through the cracks during the early
stages of treatment when they are most vulnerable to cravings, withdrawal
symptoms, and relapse.
Better results have been reported in drug courts that developed specialized
therapy groups for participants with specific clinical needs or demographic charac-
teristics, such as women with trauma histories (Messina et al. 2012) and young
African-American male participants (Vito and Tewksbury 1998). Young African-
American males have commonly expressed dissatisfaction with group-based ser-
vices in drug courts; therefore, it may be especially important to develop effective
and culturally tailored services for this demographic group.
A substantial body of research spanning several decades reveals that outcomes
from correctional rehabilitation are significantly better when (1) the offenders
received behavioral or cognitive-behavioral treatment (CBT) interventions,
(2) the interventions were carefully documented in treatment manuals, (3) the
treatment providers were trained to deliver the interventions reliably according to
the manual, and (4) fidelity to the treatment model was maintained through contin-
uous supervision of the treatment providers (Andrews and Bonta 2010). Adherence
to these same principles has been associated with significantly better outcomes in
drug courts (Gutierrez and Bourgon 2012). Examples of manualized CBT curricula
that have been shown to reduce criminal recidivism in adult drug courts include
Moral Reconation Therapy (MRT) (Cheesman and Kunkel 2012) and the MATRIX
Model (Marinelli-Casey et al. 2008).
Finally, research reveals outcomes were better for drug courts that
contracted with a single coordinating agency to serve as the primary case manager
for treatment services (Carey et al. 2012). The coordinating agencies did not
72 Drug Courts 1159
necessarily provide all of the clinical services, but they were responsible
for assessing the participants, referring them to the appropriate treatment
programs, and providing routine progress reports to the judge and drug
court team. It can be exceedingly difficult to stay abreast of participants’
progress when they have been referred to numerous treatment providers.
Designating a primary case manager to coordinate the referrals appears to be
essential for maintaining an accurate flow of up-to-date information and
administering consistent and timely consequences for participants’ performance
in treatment.
drug courts (Marlowe et al. 2008; Prendergast et al. 2008). The rewards were
delivered in the form of payment vouchers or gift certificates for negative urine
tests and other desired accomplishments. Neither study found improved outcomes
apparently due to a statistical ceiling effect. The outcomes were so favorable in both
of the drug courts that it was difficult to improve any further upon those outcomes.
In one of the studies, however, a preplanned interaction analysis revealed
a nonsignificant trend (p ¼ .08) in which high-risk offenders with more serious
criminal histories performed relatively better in the enhanced reward conditions
(Marlowe et al. 2008). This preliminary finding might suggest that when drug
courts treat the most incorrigible drug offenders, tangible rewards may make
additive contributions to outcomes. More research is needed to confirm and explain
this interaction effect.
72.4 Conclusion
Despite their unquestionable efficacy, drug courts in the USA serve only a small
fraction (about 5–10 %) of the roughly 1.5 million adults arrested each year who
meet criteria for substance abuse or dependence (Bhati et al. 2008). The primary
obstacle to expanding the reach of drug courts in the USA is a lack of funding and
not an absence of judicial interest or public support (Huddleston and Marlowe
2011). Convincing lawmakers that they will recoup their investments and reap
1162 D.B. Marlowe
References
Andrews DA, Bonta J (2010) The psychology of criminal conduct, 5th edn. Anderson, New
Providence
Aos S, Miller M, Drake E (2006) Evidence-based public policy options to reduce future prison
construction, criminal justice costs, and crime rates. Washington State Institute for Public
Policy, Olympia
Bhati AS, Roman JK, Chalfin A (2008) To treat or not to treat: evidence on the prospects of
expanding treatment to drug-involved offenders. The Urban Institute, Washington, DC
Carey SM, Pukstas K, Waller MS, Mackin RJ, Finigan MW (2008) Drug courts and state mandated
drug treatment programs: outcomes, costs and consequences. NPC Research, Portland, www.
npcresearch.com
72 Drug Courts 1163
Carey SM, Mackin JR, Finigan MW (2012) What works? The ten key components of drug court:
research-based best practices. Drug Court Rev 7(1):6–42
Chandler RK, Fletcher BW, Volkow ND (2009) Treating drug abuse and addiction in the criminal
justice system: improving public health and safety. J Am Med Assoc 301(2):183–190
Cheesman FL, Kunkel TL (2012) Virginia adult drug treatment courts: cost benefit analysis.
National Center for State Courts, Williamsburg
Cooper CS, Franklin B, Mease T (2010) Establishing drug treatment courts: strategies, experiences
and preliminary outcomes. Justice Programs Office, School of Public Affairs, American
University, Washington, DC, http://www.cicad.oas.org/fortalecimiento_institucional/dtca/
files/Establishing_DTC_%20Strategies_Experiences_Preliminary_Outcomes_volume%201.pdf
Cooper CS, Chisman AM, Maurandi AL (eds) (2013) Drug treatment courts: an international
response to drug-dependent offenders. Inter-American Drug Abuse Control Commission,
Organization of American States, and American University, Washington DC
DeMatteo DS, Marlowe DB, Festinger DS (2006) Secondary prevention services for clients who
are low risk in drug court: a conceptual model. Crime Delinq 52:114–134
Downey PM, Roman JK (2010) A Bayesian meta-analysis of drug court cost-effectiveness. Urban
Institute, Washington, DC
Farole DJ, Cissner AB (2007) Seeing eye to eye: participant and staff perspectives on drug courts.
In: Berman G, Rempel M, Wolf RV (eds) Documenting results: research on problem-solving
justice. Center for Court Innovation, New York, pp 51–73
Festinger DS, Marlowe DB, Lee PA, Kirby KC, Bovasso G, McLellan AT (2002) Status hearings
in drug court: when more is less and less is more. Drug Alcohol Depend 68:151–157
Finigan M, Carey SM, Cox A (2007) The impact of a mature drug court over 10 years of operation:
recidivism and costs. NPC Research, Portland, www.npcresearch.com
Finigan MW, Perkins T, Zold-Kilbourn P, Parks J, Stringer M (2011) Preliminary evaluation of
extended-release naltrexone in Michigan and Missouri drug courts. J Subst Abus Treat
41(3):288–293
Flango VE, Cheesman FL (2009) The effectiveness of the SCRAM alcohol monitoring device:
a preliminary test. Drug Court Rev 6:109–134
Gibbs B, Wakefield W (2014) The efficacy of enhanced alcohol use monitoring: An examination of the
effects of EtG/EtS screening on participant performance in drug courts. Drug Court Rev 9:1–22
Goldkamp JS, White MD, Robinson JB (2002) An honest chance: perspectives on drug courts. Fed
Sentencing Report 6:369–372
Gottfredson DC, Kearley BW, Najaka SS, Rocha CM (2005) The Baltimore City drug treatment
court: 3-year outcome study. Eval Rev 29:42–64
Gottfredson DC, Kearley BW, Najaka SS, Rocha CM (2007) How drug treatment courts work: an
analysis of mediators. J Res Crime Delinq 44:3–35
Government Accountability Office (2005) Adult drug courts: evidence indicates recidivism
reductions and mixed results for other outcomes [No. GAO-05-219]. Government Account-
ability Office, Washington, DC
Gutierrez L, Bourgon G (2012) Drug treatment courts: a quantitative review of study and treatment
quality. Justice Res Policy 14(2):47–77
Harrell A, Cavanagh S, Roman J (1999) Final report: findings from the evaluation of the
D.C. Superior Court Drug Intervention Program. The Urban Institute, Washington, DC
Hawken A, Kleiman M (2009) Managing drug involved probationers with swift and certain
sanctions: evaluating Hawaii’s HOPE [NCJRS No. 229023]. National Institute of Justice,
Washington, DC, http://www.ncjrs.gov/pdffiles1/nij/grants/229023.pdf
Hepburn JR, Harvey AN (2007) The effect of the threat of legal sanction on program retention and
completion: is that why they stay in drug court? Crime Delinq 53:255–280
Huddleston W, Marlowe DB (2011) Painting the current picture: a national report on drug courts and
other problem solving court programs in the United States. National Drug Court Institute, Alexandria
Jones CG (2013) Early-phase outcomes from a randomized trial of intensive judicial supervision in
an Australian drug court. Crim Justice Behav 40:453–468
1164 D.B. Marlowe
Koob J, Brocato J, Kleinpeter C (2011) Enhancing residential treatment for drug court participants.
J Offender Rehabil 50(5):252–271
Latimer J, Morton-Bourgon K, Chretien J (2006) A meta-analytic examination of drug treatment courts:
do they reduce recidivism? Department of Justice, Research & Statistics Division, Ottawa
Lindquist CH, Krebs CP, Lattimore PK (2006) Sanctions and rewards in drug court programs:
implementation, perceived efficacy, and decision making. J Drug Issues 36:119–146
Lowenkamp CT, Latessa EJ (2005) Increasing the effectiveness of correctional programming
through the risk principle: identifying offenders for residential placement. Crim Public Policy
4(2):263–290
Lowenkamp CT, Holsinger AM, Latessa EJ (2005) Are drug courts effective? A meta-analytic
review. J Community Correct 15(1):5–28
Marinelli-Casey P, Gonzales R, Hillhouse M et al (2008) Drug court treatment for methamphetamine
dependence: treatment response and post-treatment outcomes. J Subst Abus Treat 34:242–248
Marlowe DB (2002) Effective strategies for intervening with drug abusing offenders. Villanova
Law Rev 47:989–1025
Marlowe DB (2011) The verdict on drug courts and other problem-solving courts. Chapman
J Crim Justice 2:53–92
Marlowe DB, Festinger DS, Dugosh KL, Lee PA, Benasutti KM (2007) Adapting judicial
supervision to the risk level of drug offenders: discharge and six-month outcomes from
a prospective matching study. Drug Alcohol Depend 88S:4–13
Marlowe DB, Festinger DS, Dugosh KL, Arabia PL, Kirby KC (2008) An effectiveness trial of
contingency management in a felony pre-adjudication drug court. J Appl Behav Anal 41:565–577
Matusow H, Dickman SL, Rich JD, Fong C, Dumont DM, Hardin C, Marlowe D, Rosenblum A
(2013) Medication assisted treatment in U.S. drug courts: results from a nationwide survey of
availability, barriers and attitudes. J Subst Abus Treat 44(5):473–480
Mayfield J, Estee S, Black C, Felver BEM (2013) Drug court outcomes: outcomes of adult
defendants admitted to drug courts funded by the Washington State Criminal Justice Treatment
Account. Research & Analysis Division, Department of Social & Health Services, Olympia
Messina N, Calhoun S, Warda U (2012) Gender-responsive drug court treatment: a randomized
controlled trial. Crim Justice Behav 39(12):1539–1558
Mitchell O, Wilson DB, Eggers A, MacKenzie DL (2012) Assessing the effectiveness of drug
courts on recidivism: a meta-analytic review of traditional and nontraditional drug courts.
J Crim Justice 40(1):60–71
National Association of Drug Court Professionals (1997) Defining drug courts: the key compo-
nents. Office of Justice Programs, U.S. Department of Justice, Washington, DC
National Center on Addiction and Substance Abuse (2012) Addiction medicine: closing the gap
between science and practice. Columbia University, New York
National Institute of Justice (2006) Drug courts: the second decade [NCJ 211081]. Office of Justice
Programs, U.S. Department of Justice, Washington, DC
Peters RH, Haas AL, Hunt WM (2002) Treatment “dosage” effects in drug court programs.
J Offender Rehabil 33(4):63–72
Portillo S, Rudes DS, Viglione J, Nelson M (2013) Front-stage stars and backstage producers: the
role of judges in problem-solving courts. Vict Offenders 8:1–22
Prendergast ML, Hall EA, Roll J, Warda U (2008) Use of vouchers to reinforce abstinence and positive
behaviors among clients in a drug court treatment program. J Subst Abus Treat 35:125–136
Rossman SB, Rempel M, Roman JK, Zweig JM, Lindquist CH, Green M, Downey PM, Yahner J,
Bhati AS, Farole DJ (2011) The multisite adult drug court evaluation: the impact of drug
courts, vol 4. Urban Institute Justice Policy Center, Washington, DC, https://www.ncjrs.gov/
pdffiles1/nij/grants/237112.pdf
Sevigny EL, Fuleihan BK, Ferdik FV (2013) Do drug courts reduce the use of incarceration?
A meta-analysis. J Crim Justice 41:416–425
Shaffer DK (2006) Reconsidering drug court effectiveness: a meta-analytic review [Doctoral
dissertation, University of Cincinnati]. Diss Abstr Int 67:09A, AAT No. 3231113
72 Drug Courts 1165
Shaffer DK (2010) Looking inside the black box of drug courts: a meta-analytic review. Justice
Q 28(3):493–521
Somers JM, Currie L, Moniruzzaman A, Eiboff F, Patterson M (2011) Drug Treatment Court of
Vancouver (DTCV): an empirical evaluation of recidivism. Addict Res Ther 2:1–7, http://dx.
doi.org/10.4172/2155-6105.1000117
Turner S, Greenwood P, Fain T, Deschenes E (1999) Perceptions of drug court: how offenders
view ease of program completion, strengths and weaknesses, and the impact on their lives. Nat
Drug Court Inst Rev 2:61–85
Vito GF, Tewksbury RA (1998) The impact of treatment: the Jefferson county (Kentucky) drug
court program. Fed Probat 62:46–51
Wexler HK, Melnick G, Cao Y (2004) Risk and prison substance abuse treatment outcomes:
a replication and challenge. Prison J 84(1):106–120
Wilson DB, Mitchell O, MacKenzie DL (2006) A systematic review of drug court effects on
recidivism. J Exp Criminol 2:459–487
Trauma and Addiction Medicine
73
Michael Dinh and Matthew Oliver
Contents
73.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1168
73.1.1 Injury Profiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1170
73.2 Clinical Aspects of Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1171
73.2.1 Clinical Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1171
73.2.2 Emergency Department Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1174
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1176
Abstract
Injuries represent a major burden of illness across the world, and injuries are
disproportionately represented amongst those with concurrent addiction dis-
orders. In this patient population, various behavioral, mental state, social, and
clinical factors conspire to increase the risk of injury-related harms, ranging
from road crashes due to drink driving to interpersonal violence and self-harm
behaviors as a result of acute behavioral disturbance. Trauma-related
presentations to the emergency department in drug-affected patients therefore
represent some of the most dramatic clinical scenarios in acute medicine.
Not only are there injury-related management issues, but also clinical concerns
related to drug intoxication and the possibility of withdrawal syndromes
masking serious injury. This brief chapter highlights these considerations
in this complex group of patients and outlines a structured clinical approach
in the emergency department.
M. Dinh (*)
Emergency Medicine, Central Clinical School, The University of Sydney, Sydney, NSW, Australia
e-mail: [email protected]
M. Oliver
Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
Sydney Medical School, University of Sydney, New South Wales, Australia
e-mail: [email protected]
73.1 Introduction
Injuries remain the leading cause of death around the world in people under
45 years of age (Krug et al. 2000). It is estimated that over 16,000 people die
every day from injuries and many more are left with permanent disabilities. As
a result of increased urbanization and road transportation in developing countries
over the past 20 years, road trauma is projected to rise to the fifth most common
cause of death by 2020 (WHO 2013). In recognition of this, the World Health
Organization set out to reverse this trend by supporting a global decade of action on
improving road safety from 2011 to 2020. Disturbingly, intentional or self-inflicted
injuries follow closely behind road trauma as a cause of death in these age groups
and, as the population ages, particularly in developed nations, falls have become an
increasingly common cause of morbidity in the elderly (Stevens et al. 2006).
Substance abuse, particularly alcohol, has long been recognized as a risk factor
for injury (Cherpitel et al. 2005; WHO Department of Mental Health and Substance
Abuse 2004). Causal associations exist on a number of levels. Firstly, there are
dose-related effects of certain drugs ranging from disinhibition and impaired
concentration to aggression and impaired level of consciousness that increase the
risk of road crashes, falls, and assaults (Australian Institute of Health and Welfare
2011). Secondly, social factors related to the acquisition and distribution of illicit
drug use increase exposure to violent crime and penetrating trauma. Thirdly,
substance abuse often coexists with or results in psychiatric disorders, increasing
the risk of self-inflicted harm and harm to others (Cunningham et al. 2003). Finally,
major trauma is a well-described risk factor for the development of post-traumatic
stress disorder, which itself leads to substance abuse and a vicious cycle of further
injury (Yehuda 2002). For these reasons and more, substance abuse exacts an
enormous cost to society. In Australia in 2009, the costs of alcohol abuse alone
were estimated to be over $15 billion dollars, which include tangible costs such as
costs of road trauma, hospital treatment, and crime and intangible costs such as lost
productivity and emotional distress (Laslett et al. 2010).
Emergency departments (ED) function within health systems to triage, identify
and stabilize acute undifferentiated health problems (Schuur and Venkatesh 2012).
This paradigm is exemplified by the modern trauma system, where the trauma team
assesses and manages patients with life-threatening injuries with the ED and pre-
pares the patient for definitive surgical treatment. EDs are also an important point of
episodic health care for many people through unplanned admissions and exacerba-
tions of chronic conditions. In most societies EDs also provide access to basic level
care and a safety net for socially disadvantaged and isolated populations. Therefore,
EDs commonly identify and treat patients with substance abuse disorders ranging
from simple to complex conditions (McGeary and French 2000).
As such patients present to ED with a wide spectrum of problems, some of which
are listed in Table 73.1. The effect of alcohol and drugs of addiction on a patient’s
cognition and physical abilities means that these patients are at a higher likelihood
73 Trauma and Addiction Medicine 1169
Table 73.1 Common emergency presentations for patients with substance abuse
Drug intoxication or overdose
Drug withdrawal syndromes
Seeking help or counseling regarding substance abuse
Injuries
Blunt and penetrating assault
Road traumas (including motor vehicle, pedestrian, cyclist)
Falls
Domestic violence
Self-inflicted harm
Behavioral and mental state disturbance
Aggression and violence
Psychosis
Depression
Confusion
Medical conditions
Liver failure
Hyponatremia
Renal failure
Cardiac failure
Atrial fibrillation
Stroke
Aortic dissection
Sepsis
Pneumonia
Infective endocarditis
Table 73.2 Risk behaviors found of acute and chronic alcohol users
Behavior Percentage of patients (n ¼ 145)
Driving
Do not always wear seat belt 37.9 %
Do not always obey speed limit 71.1 %
Ridden with driver under the influence 41.1 %
Driving under the influence 33.8 %
Additional driving
Recent citation/arrest/license suspension 44.1 %
Prior DWI/DUI arrest 17.2 %
Violence
Carried a weapon 10.3 %
Recent physical altercation 35.2 %
Prior assault with weapon 30.3 %
Suicide
Suicidal ideation in last year 26.9 %
Prior suicide attempt 13.8 %
Additional risk factors
Lifetime drug use 57.9 %
Current drug use 32.5 %
Prior alcohol/drug treatment 20.0 %
Table adapted from Field et al. (2001)
DWI driving while intoxicated, DUI driving under the influence
A variety of injury profiles are found in drug and alcohol users ranging from minor
to major injuries depending on the mechanism. Minor injuries may include
73 Trauma and Addiction Medicine 1171
orthopedic injuries such as ankle sprains or rib fractures, minor burns, or soft tissue
injuries. Although not requiring operative intervention in the majority of cases,
minor injuries still account for a large burden on emergency department resources
(London et al. 2009; Tominaga et al. 2004). Conversely major injuries, such as
severe head injuries, and multisystem trauma require intensive care, operating
rooms, and rehabilitation care which explains the high cost of these patients to
the healthcare system (Moore 2005; Lucas 2005).
Case Scenario
A 24-year-old male presents to an inner city emergency department with head
and chest injuries following an assault in which he was beaten about the head
with a baseball bat and stabbed with a small knife. He has a history of alcohol
and cannabis use. He admits to injecting “ice” prior to the incident. He does not
have family and frequently presents to this emergency department where he is
well known for being disruptive and aggressive towards the nursing staff. On
presentation he is sweaty and agitated and has a Glasgow Coma Score of 13, a
heart rate of 130, and a blood pressure of 90/50. He has multiple facial
abrasions, a large occipital scalp hematoma, and a small 2 cm penetrating wound
to his left upper chest. The patient becomes violent and demands to leave the
emergency department stating that there are people out to “get him.”
Hemodynamic Status
Nearly all drug and alcohol use can affect blood pressure or pulse as shown in
Table 73.3. The most concerning presentation to any physician managing trauma
Neurological Status
Most drug abuse syndromes have potentially significant effects on cognitive
function. The primary difficulty with any drug-intoxicated patient therefore is
the assessment of the cognitive state and whether this is due to the intoxication or
traumatic brain injury (TBI). Any unconscious patient (GCS < 9) requires urgent
airway intubation and mechanical ventilation to prevent the occurrence of gastric
aspiration and prevent secondary brain injury. Previous evidence has demon-
strated that alcohol-intoxicated patients are more than twice as likely to require
airway intubation compared to nonintoxicated patients with head injury (Gurney
et al. 1992). Due to the alteration in cognitive level including aggression,
agitation, and sedation, intoxicated patients with evidence of head injury or
involved in serious mechanisms of injury are more likely to undergo CT scanning
(Moore 2005). Also due to the inability to perform an adequate physical exam,
patients are more likely to require imaging of multiple body areas for evaluation
(Roudsari et al. 2012). Part of this imaging will frequently require not only
cranial CT but also CT scans of the cervical spine. Well-described criteria are
used in trauma patients to evaluate for cervical spine injury; however, patients
must be alert and nonintoxicated to meet criteria for cervical spine clearance
(Hoffman et al. 1998; Mower et al. 2004). Patients failing the criteria typically
require CT cervical spine imaging with evidence of head injury or concerning
mechanism of injury.
1174 M. Dinh and M. Oliver
73.2.2.4 Security
Security personnel are often available in EDs to assist in the management of violent
behavior. Additional staff are often required to ensure patient safety by preventing
them from absconding or to monitor and prevent harmful behaviors such as further
self-inflicted harm while in ED. Patients presenting with gun-related injuries,
particularly gang-related crime, should be managed as a potential security threat,
and patients and visitors should be searched for potential weapons. The police
should be notified if the clinician has reason to believe that a patient is in possession
of a firearm and poses an ongoing risk to self or others.
References
ATLS Subcommittee, American College of Surgeons’ Committee on Trauma, and the Interna-
tional ATLS Working Group (2013) Advanced trauma life support (ATLS(R)): the ninth
edition. J Trauma Acute Care Surg 74(5):1363–1366
Australian Institute of Health and Welfare (2011) Drugs in Australia 2010. Tobacco alcohol and
other drugs. Drug statistics series no. 27. Cat no. PHE 154. Canberra
Blomqvist S, Thorne J, Elmer O, Jonsson BA, Strand SE, Lindahl SG (1987) Early post-traumatic
changes in hemodynamics and pulmonary ventilation in alcohol-pretreated pigs. J Trauma
27(1):40–44
Brackett DJ, Gauvin DV, Lerner MR, Holloway FA, Wilson MF (1994) Dose- and time-dependent
cardiovascular responses induced by ethanol. J Pharmacol Exp Ther 268(1):78–84
Brohi K, Singh J, Heron M, Coats T (2003) Acute traumatic coagulopathy. J Trauma
54(6):1127–1130
Chen SC, Lin FY, Chang KJ (1999) Body region prevalence of injury in alcohol- and non-alcohol-
related traffic injuries. J Trauma 47(5):881–884
Cherpitel CJ, Ye Y, Bond J (2005) Attributable risk of injury associated with alcohol use: cross
national data from the emergency room collaborative alcohol analysis project. Am J Public
Health 95:266–272
Cunningham R, Walton WA, Maio RF, Blow FC, Weber JE, Mirel L (2003) Violence and
substance abuse amongst injured emergency department population. Acad Emerg Med
10:764–775
73 Trauma and Addiction Medicine 1177
Roudsari B, Psoter KJ, Mack C, Vavilala MS, Jarvik JG (2012) Burden of alcohol-related injuries
on radiology services at a level I trauma center. AJR Am J Roentgenol 199(4):W444–W448
Savola O, Niemela O, Hillbom M (2005) Alcohol intake and the pattern of trauma in young adults
and working aged people admitted after trauma. Alcohol Alcohol 40(4):269–273
Schuur JD, Venkatesh AK (2012) The growing role of emergency departments in hospital
admissions. NEJM 367(5):391–394
Soderstrom CA, Smith G, Dischinger PC, McDuff DR, Hebel RJ, Gorelick DA, Kerns TJ, Ho S,
Read KM (1997) Psychoactive substance use disorders among seriously injured trauma centre
patients. JAMA 277(22):1769–1774
Stevens JA, Corso PS, Finkelstein EA, Miller TR (2006) The costs of fatal and nonfatal falls
among older adults. Inj Prev 12:290–295
Swanson SM, Sise CB, Sise MJ, Sack DI, Holbrook TL, Paci GM (2007) The scourge of
methamphetamine: impact on a level I trauma center. J Trauma 63(3):531–537
Tominaga GT, Garcia G, Dzierba A, Wong J (2004) Toll of methamphetamine on the trauma
system. Arch Surg 139(8):844–847
Tulloh BR, Collopy BT (1994) Positive correlation between blood alcohol level and ISS in road
trauma. Injury 25(8):539–543
Van der Swan R, Davies L, Andrews D, Brooks A (2011) Aggression and violence in the ED:
issues associated with the implementation of restraint and seclusion. Health Promot J Aust
22:124–127
Waller PF, Stewart JR, Hansen AR, Stutts JC, Popkin CL, Rodgman EA (1986) The potentiating
effects of alcohol on driver injury. JAMA 256(11):1461–1466
Wand A, Wand T (2013) Admit voluntary, schedule if tries to leave. Placing mental health acts in
the context of mental health law and human rights. Australas Psychiatry. doi:10.1177/
1039856212466923
WHO (2013) Global status report on road safety 2013: supporting a decade of action. WHO press,
Geneva. ISBN 978 92 4 156456 4
WHO Department of Mental Health and Substance Abuse (2004) Global status on alcohol 2004.
World Health Organisation, Geneva. ISBN 92 4 156272 2
Yehuda R (2002) Post traumatic stress disorder. NEJM 346(2):108–114
Zink BJ, Stern SA, Wang X, Chudnofsky CC (1998) Effects of ethanol in an experimental model
of combined traumatic brain injury and hemorrhagic shock. Acad Emerg Med 5(1):9–17
Mandatory Versus Voluntary Treatment
and Rehabilitation of People Abusing 74
Drugs: Initiatives from Malaysia
Contents
74.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1180
74.2 Drug Use, Treatment and Rehabilitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1181
74.2.1 The Extent of Drug Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1181
74.2.2 Compulsory Center for Drug Users (CCDU) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1182
74.2.3 Human Rights and Alternatives to Drug Treatment . . . . . . . . . . . . . . . . . . . . . . . . . 1184
74.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1186
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1186
Abstract
Compulsory Centers for Drug Users (CCDU) were established in many countries
to address the issue of drugaddiction such as drug treatment and rehabilitation
center, drug detention center, drug prison, and others. Here, drug users were
called inmates, were sent for mandatory treatment, and were subjected to “boot
camp” approach with emphasis on discipline, religious values, social acceptable
behavior, and punishment like canning. Little medical attention was given to
these inmates and many contracted communicable diseases such as hepatitis,
STIs, HIV, and tuberculosis while in mandated detention. Living conditions in
very tight living quarters in these detention centers were very poor. As an
74.1 Introduction
Drug treatment and rehabilitation is one of the major inputs to the demand
reduction strategy which is endorsed by the United Nations Office of Drug
and Crime (UNODC) to reduce the burden of drug on its users and the society
at large. The nature of the addiction disease requires people dependent to drugs to
be treated and rehabilitated and later to be reintegrated back into society
(Mahmood 2005). However, often enough as observed in the Asian countries,
the method of drug treatment do not follow the science of what is evidenced and
what is not. Many operate on the assumption that any treatment for drug addiction
is better than no treatment, which is not true at all (Simpson et al. 1997). Many
treatment programs in Asian countries prescribed to local norms, religious,
spiritual, and the punitive discipline-based methodologies to “treat” drug addicts
(Mahmood et al. 2006). Drug laws were enacted to contain the epidemic of drug
addiction in their countries. People tested for drugs and found positive are taken
in for mandatory treatment in government-operated treatment facilities. As
such, human rights issues are often infringed (Tongue and Turner 1988;
UNODC 2010c). This chapter looks at the shift from the mandatory
to voluntary treatment of drug dependents and how innovative projects
undertaken in the Asian countries have been made models for other countries to
replicate.
74 Mandatory Versus Voluntary Treatment 1181
The United Nations Office on Drug and Crime (UNODC) reported that in the year
2011, between 167 and 315 million people aged between 15 and 64 were estimated to
have used an illicit substance in the preceding year, which is between 3.6 % and
6.9 % of the global adult population. Since 2008, there has been an overall 18 %
increase in the estimated total number of people who had used an illicit substance in
the preceding year, which to some extent reflects both an increase in the global
population and a slight increase in the prevalence of illicit drug use. This implies that
there is now more need, if not demand, for drug and substance addiction treatment
and rehabilitation globally (WDR 2013).
Asia is one region that has been hardest hit by problematic drug use
(APAIC 2013). There is an estimated of 25–40 % of all illicit drug users worldwide,
as well as 60 % of opiate users and between 30 % and 60 % of ATS users coming
from this region (WDR 2013). Data from Pakistan and China indicated an increase
in the use of all types of drugs.
In 2012, Pakistan reported cannabis as the most commonly used drug, with an
annual prevalence of 3.6 %, followed by prescription opioids (1.5 %) and tranquil-
izers and sedatives (1.4 %). Use of ATS (0.1 %) and cocaine (0.01 %) appeared
to be low but emerging in this country (WDR 2013). The number of people addicted
to drugs is also on the rise. At present, 5.8 % of the adult population, which is
approximately 6.4 million persons or one in every 27 persons in Pakistan, is using
drugs, while nearly 25 % of the youth population is involved in some form of drug
abuse (Muhammad Qasim 2013).
In China, opioid use remains high. The number of registered heroin users is
increasing each year. There were 1.24 million in 2011, compared with 1.06 million
in 2010 (WDR 2013). There is a wide difference between the country’s number of
registered addicts (e.g., 900,000 in 2007) with an estimate of 12 million drug
addicts (Michels et al. 2007). The number and proportion of registered users
of ATS are also increasing (38 % of all registered users in 2012, compared with
28 % in 2010). In addition, there has been a major increase in the number of drug
users registered for use of other substances, such as ketamine. In 2012, more than
7 % of registered drug users were using ketamine.
There are various forms of drug treatment facilities that have been reported for
China. For example, in 2000, there were 717 compulsory detoxification units
(CDU) with 105,529 beds, 69 work education units (WEU) with 52,598 beds, and
119 voluntary units with 7,020 beds. In 2006, a total of 377,000 drug addicts were
detoxified and treated in these facilities, and only 9.5 % of this number is receiving
MMT, while 4.3 % are from voluntary units (Michels et al. 2007).
Data from East and Southeast Asia reported higher levels of ATS use in 2011.
DAINAP reports ATS use, in particular methamphetamine, continues to increase in
most countries in East and Southeast Asia (APAIC 2013). The illicit manufacture of
1182 M. Nazar Mohamed and S. Marican
The existence of CCDU has been observed in many countries since the onset of
drug problem in this region. In the 1970s, CCDU is probably the only available
facility used under the demand reduction strategy in the Asian countries albeit some
treatment conducted in hospitals and medical clinics. In Southeast Asia countries,
various forms of CCDU take place such as drug treatment and rehabilitation center,
drug detention center, drug prison, and many more. Frequently, “boot camp”
modality is used with emphasis on discipline, religious values, social acceptable
behavior, and punishment like canning and chaining. Drug users mandated for drug
treatment were often labeled as inmates. Little medical attention was given to these
“inmates,” and many contracted communicable diseases such as hepatitis, STIs,
HIV, tuberculosis, and others as a result of their drug use, injecting drugs, multiple
sexual partners, and, on top of that, poor living condition and very tight living
quarters in the detention centers (Fu et al. 2012).
At present, over 300,000 men, women, and children suspected of using drugs are
detained in some 1,000 compulsory centers for drug users (CCDUs) in East and
Southeast Asia alone (UNODC 2012b). A large number of drug dependents were
registered at CCDU because most often they were legally mandated by drug
74 Mandatory Versus Voluntary Treatment 1183
(or antidrug) laws in their country to undergo treatment here. Almost all of these
CCDUs are free or the parents have to pay a minimal fee for treatment and
rehabilitation as compared to receiving treatment in hospitals and voluntary units
or private treatment centers. As a point of comparison, in Malaysia, private treat-
ment at private centers costs between 300 and 3,000 USD dollars; in Indonesia, it is
between 250 and 5,000 USD; in the Philippines, it costs between 600 and 8,000
USD; and in Thailand, it is between 500 and 5,000 USD as compared to govern-
ment CCDU which is generally free of charge (Mahmood et al. 2006). However,
many drug dependents receiving treatment at CCDU reported being beaten, abused,
raped, locked, chained, and treated like criminals. Followings are some testimonies
by former detainees of drug treatment centers in China, Vietnam, Lao PDR, and
Cambodia:
If we opposed the staff they beat us with a one-meter, six-sided wooden truncheon.
Detainees had the bones in their arms and legs broken. This was normal life
inside. – Former detainee, Ho Chi Minh City, Vietnam, 2010 (UNODC 2011a).
They try to teach not to use drugs, that it isn’t good to use [drugs], while showing that
normal people have a good future. I don’t think the classes helped me stop using drugs. . .
Some people use more drugs when they come out of Somsanga. – Former detainee,
Vientiane, Lao PDR, late 2010 (UNODC 2012a).
There are lots of people and not enough food. It was hard to sleep there because in my
room there were 60 people. There was not enough water for the showers, only a few
minutes to shower every day. – Former detainee, Vientiane, Lao PDR, late 2010 (UNODC
2011b).
I tried to run away, and in the process, I broke both feet. When I went to the hospital for
treatment, I was arrested and sent back to the drug addiction center. . . Inside I was given
very little food, and they never gave me any medicine at all to treat my feet. I was locked up
for about half a year and my feet became crippled. – Written account from former detainee,
Yunnan, China, 2009 (UNODC 2012a).
All drug detention must work. We get up at five in the morning to make shoes. We work
all day and into the night. That’s all it is. – Former detainee, Yunnan, China, 2009 (UNODC
2010a).
There were about seven children in my room but maybe about 100 children altogether.
The youngest was about 7 years old. The children are not drug users but homeless, like
beggars on the street. – Former detainee, Vientiane, Lao PDR, late 2010 (UNODC 2011b).
[A staff member] would use the cable to beat people. . .On each whip the person’s skin
would come off and stick on the cable. . . – Former detainee, age 16, describing whippings
he witnessed in the Social Affairs Youth Rehabilitation Center in Choam Chao, Cambodia
(UNODC 2010b).
The situation of CCDU in East and Southeast Asia was reviewed at the first
Regional Consultation for Drug Users, organized by UNODC Regional Centre for
East Asia and the Pacific, ESCAP, and UNAIDS Regional Support Team in
December 2010 in Thailand. On March 9, 2012, a Joint Statement was issued by
12 United Nations agencies, including the UN Office on Drugs and Crime
(UNODC), the World Health Organization (WHO), the UN Children’s Fund
(UNICEF), and UNAIDS, calling for the closure of drug detention centers and
the release of the people detained there “without delay” (UNOCD 2012b).
This UN Joint Statement highlights the concerns associated with the CCDUs,
including increased vulnerability to HIV and tuberculosis infection as well as
1184 M. Nazar Mohamed and S. Marican
Throughout the Asian region, there are a plethora of concerns about human rights
violations; forced labor; physical and sexual violence; substandard living condi-
tions; a lack of access to health care (Fu et al. 2012); ineffective, nonevidence-based
treatment modalities (Noor Zurina et al. 2012); and an increasing awareness that
CCDUs fail to address drug use as a chronic relapsing health disorder (Mahmood
and Dzahir 2007; UNODC 2010c). Relapse rates among these “inmates” are high,
and drug use occurs as immediately as they were released from the detention
centers. At this juncture, many treatment experts want the government to make it
a priority to end these abuses and redirect their support to voluntary, community-
based treatment and other programs that truly respect drug users’ human rights.
This has led many governments to look at evidence- and rights-based alternatives to
CCDUs (UNODC 2012b).
Harm reduction was introduced in the Asian countries before the turn of the
millennium when a number of countries are facing epidemic numbers of HIV
infections (Mahmood 2005). Many opposed the idea of substitution therapy and
needle exchange because of religious values and beliefs that giving needles and
syringes will not help drug addicts to stay off drugs (Mahmood and Dzahir 2007). In
Malaysia, harm reduction strategies were endorsed by the government in 2001, and
by 2005, many of the strategies has been implemented with good success. These set
of strategies were also widespread in other Asian and ASEAN countries with
strong support from UNODC (Mahmood and Dzahir 2007; Mahmood 2010;
UNODC 2013).
Other pertinent issues faced by Asian countries are the well-established drug
control and fast emerging drug laws for mandatory treatment and rehabilitation. In
Malaysia, the government set up an innovative project to harmonize between the
country’s drug laws, addressing the CCDUs and human rights issue (Mahmood
2011). The Cure and Care project was established in 2010 in response to low
treatment outcome such as high-relapse rates, poor reemployment capacities, and
74 Mandatory Versus Voluntary Treatment 1185
74.3 Conclusion
In conclusion, UNODC has reported some positive efforts taken by many countries
in the Asian region to depart from the traditional boot camp drug treatment
modality to a more evidence-based substance abuse treatment. Countries like
Malaysia, Thailand, and the Philippines have made tremendous effort to introduce
MMT and other opiate substitution available for heroin abusers; however, no
substitution is currently available for the ever popular ATS in the region. Many
Asian countries like Afghanistan, Brunei, Cambodia, China, Iran, Laos, Pakistan,
and Vietnam are studying efforts taken by Malaysia to harmonize between its strict
drug laws and the humane, voluntary-based drug treatment program for drug users
(NADA 2013). Positive responses and outcome of the C&C projects are being
documented for the benefit of countries who wish to replicate the project for its own
high-risk population.
References
APAIC (2013) Asia & Pacific Amphetamine-Type Stimulants Information Centre. http://www.
apaic.org/
Fu JJ, Bazazi AR, Altice FL, Mohamed MN, Kamarulzaman A (2012) Absence of antiretroviral
therapy and other risk factors for morbidity and mortality in Malaysian compulsory drug
detention and rehabilitation centers. PLoS ONE 7(9):e44249. doi:10.1371/journal.
pone.0044249
Mahmood NM (2005) Risk factors among injecting drug users and PLWHAs in East Asia with
specific reference to Malaysia: implication for harm reduction practices. In: Proceedings of the
1st East Asia International Conference on Human and Social Development (EAIC-HSD 2005),
Kuala Lumpur, Malaysia
Mahmood NM (2010) MMT and psychosocial intervention program among drug dependents
undergoing mandatory community supervision: a 12-months pilot project, Paper presented at
2010 ISAM Conference, Milan, 4–7 Oct 2010
Mahmood NM (2011) Community-based DST for opioid addiction – formulating treatment
program in face of existing laws, changing paradigms and new policies, Paper presented at
the 2nd international conference on addiction medicine, Kuching Sarawak, 17–20 Nov 2011
Mahmood NM (2012) Drug situation in Malaysia: trends, incidences and anti-drug strategies.
Indian J Psychol (special issue), 71–82
Mahmood NM, Dzahir K (2007) Drug substitution therapy: success and limitations of the
methadone and buprenorphine maintenance program. Malays Anti Drug J 1:25–72
Mahmood NM, Yahya D, Muhamad Dzahir K (2006) The practice of TC in 5 ASEAN countries,
Paper presented at the XXIII World Federation of Therapeutic Community conference, New
York, 1–5 Sept
Michels II, Zhao M, Lu L (2007) Drug abuse and its treatment in China. http://www.ahrm.net/
library_uploan/uploadfile/file2934.pdf
74 Mandatory Versus Voluntary Treatment 1187
Contents
75.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1190
75.2 The Changing Face of Substance Abuse Treatment in Vietnam, Lebanon,
and United Arab Emirates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1191
75.2.1 Case Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1191
75.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1196
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1197
Abstract
In the twenty-first century, the development of addiction treatment services around
the world has been increasingly guided by science and the use of evidence-based
practices. This advancement can be seen in the three very different examples of
Vietnam, Lebanon, and Abu Dhabi. Since 2008, the government of Vietnam,
together with substantial support from international donors and technical experts,
has established a network of over 60 methadone treatment programs, distributed
around the country, to reduce the use of injected heroin and the related transmission
of HIV. In Lebanon, a group of clinicians, with support from international orga-
nizations and a receptive government, have introduced buprenorphine into use for
the treatment of opioid dependence. In Abu Dhabi, a concerted effort has been
undertaken by the national government to build a comprehensive continuum of
services, including addiction medications and evidence-based behavioral services,
resulting in a fivefold increase in patients treated from 2009 to 2012. Despite
substantial differences in the circumstances that generated these initiatives and
their varying scope of services, the common theme across these efforts has been the
implementation of science-based approaches with demonstrated effectiveness. The
application of these effective strategies will provide a strong rationale and increase
support for a public health approach to addressing drug abuse and addiction.
75.1 Introduction
Drug abuse and addiction “treatment” services began in many societies as part of their
criminal justice system, social services system, community-based self-help efforts, or
some combination of all three. The initial efforts to develop “treatments” for addicted
individuals were frequently unclear about what they were treating. Was drug addiction
a moral problem or a medical problem? Were addicted individuals bad people, weak in
character, or sick people, with a medical/psychiatric condition? Among the factors that
have spurred societies to develop drug treatment services are concerns about the
following: drug-related crime, drug injection-related infectious diseases (e.g., HIV,
hepatitis C), loss of work productivity, and the disruption caused to family members
and communities (National Center on Addiction and Substance Abuse [NCASA] 2005;
National Drug Intelligence Center [NDIC] 2011; UNDCP 1995). In many societies, the
first response to drug use has been a public safety response addressing drug-related
crime, including criminal penalties for drug possession and use (Chandler et al. 2009).
A variation of incarceration in some societies is mandatory commitment in psychiatric
institutions. Initial treatment alternatives to incarceration or commitment have typically
been a patchwork of storefront counseling centers, therapeutic communities, sober
living houses, self-help programs, and medical treatments for overdose and withdrawal.
Part of the reason for this haphazard societal response has been that the fundamental
nature of addiction was poorly understood, and even if it was viewed as a health
problem or disease, there were no identified medical paradigms to treat this disease.
One thing was consistent across all parts of the world – until the late twentieth
century, the initial treatment services for drug abuse and addiction had very little
foundation in scientific research about addiction or evidence-based medicine. By
the late twentieth century, the role of injection drug use in the AIDS pandemic
stimulated, in some parts of the world, the interest of global public health leaders in
efficient and effective evidence-based treatments for heroin use. The documented
efficacy of methadone in decreasing injection drug use and reducing transmission
of HIV has clearly been a major factor endorsing the implementation of methadone
treatment services. To a lesser extent, the widespread increase in use of cocaine and
75 Opportunities for Addiction Service System Development 1191
amphetamine-type stimulants (ATS) in many parts of the world has also increased
interest in behavioral treatment approaches for individuals with psychostimulant
disorders, whose psychotic and violent behavior can cause a serious detrimental
effect on individuals and communities (UNODC 2013).
To further the global awareness of addiction science, the US National Institute
on Drug Abuse (NIDA) initiated an international program in the early 1990s that
has played a major role in engaging international investigators and institutions in
addiction research and has served as a vehicle for the dissemination of addiction
science. NIDA has sponsored and cosponsored dozens of international conferences
and training events over the past 20 years to increase awareness of addiction science
and its application. In addition, from 1990 through July 2013, NIDA has sponsored
408 international fellows from 103 countries for training fellowships via the NIH
Humphrey program, the NIDA INVEST program, and other such programs (NIDA
2013). Further, NIDA has established seven binational agreements with other
countries to promote co-funding of research and has added an international satellite
meeting to its annual College on Problems of Drug Dependence (CPDD) meeting.
This CPDD international satellite meeting has shown tremendous growth from
a meeting of 20–25 participants at the first meeting in 2000, to a meeting of
300 enrollees from over 40 countries in 2013 (S.W. Gust, personal communication).
Another contributing factor to dissemination of addiction science is the establish-
ment of the International Society of Addiction Medicine (ISAM), which developed
from a small forum of MDs interested in addiction, to a large annual meeting of
400–500 participants. The latest developments in the field, with an emphasis on
clinical applications of addiction medicine, are reflected in the annual ISAM meeting
agenda. Finally, the World Health Organization (WHO) and United Nations Office on
Drugs and Crime (UNODC) have been active contributors to the dissemination of
addiction science. The UNODC Treatnet Program, initiated in 2007, has been
incorporated into a joint WHO-UNODC effort to provide training and technical
assistance internationally to regions developing treatment and harm reduction
services. The Treatnet curriculum was created with an emphasis on science-based
knowledge and evidence-based practices at its core (Tomás-Rosselló et al. 2010).
As of 2013, over 1,200 individuals have been trained as trainers and 9,000 clinicians
have received training via Treatnet (Saenz et al. 2015; UNODC 2007).
The following international case studies provide examples of successful and diverse
advancements in addiction treatment and public health service that were driven by
the best scientific evidence, multiagency international collaborative efforts, and the
influence of public health leaders and committed service providers with a vision for
the future.
1192 R.A. Rawson et al.
75.2.1.1 Vietnam
Vietnam, a country of 90 million people, has a significant prevalence of drug use
and HIV. Injected heroin became a significant public health problem from the time
of the war with the United States in the 1970s. In 1993, the government of Vietnam
opened compulsory centers (06 centers), where drug users were reeducated,
punished, and rehabilitated, since addicts were viewed as a “social evil.” The
06 centers were part of a policy toward drug users in which drug users could be
arrested and, without due process, immediately transported to the 06 centers, where
they were routinely held involuntarily for 2 years; repeat offenders were held for
even longer periods. While in the 06 centers, there was no identifiable drug
treatment, and the primary activity was long hours of tedious manual labor.
Although the 06 centers were not called jails, they were far more oriented to
punishment and control than to medical or psychiatric treatment.
The first case of HIV infection was detected in Vietnam in 1990; by 1999, there
were 17,046 diagnosed cases of HIV infection. By 2012, the estimated number of
HIV-infected individuals was estimated at 206,887. Studies over this time period
suggest that injection drug use (IDU) was the likely route of HIV transmission in
85–90 % of HIV-positive individuals. As of 2012, there were an estimated 220,000
injection drug users in Vietnam (Vietnam Ministry of Health 2012). Following
passage in 2006 of the Law on HIV/AIDS Prevention and Control (known as the
“HIV law”), the Vietnamese government, led by the Deputy Prime Minister, initiated
a plan to change the focus of the response to the IDU/heroin problem in Vietnam.
The Ministry of Health, with support from UNODC, WHO, Global Fund, USAID,
Family Health International, and the United States President’s Emergency Plan for
AIDS Relief (PEPFAR), began plans to introduce methadone into Vietnam.
Methadone treatment programs were piloted in 2008 in Hai Phong and Ho Chi
Minh City as a result of the 2006 HIV law. These pilot programs operated under
guidelines developed by Vietnamese leaders and with extensive consultation from
international experts. The guidelines were grounded in the best scientific evidence,
and an extensive training program was implemented by local and international
clinical experts to promote development of a methadone treatment system based on
best practices. With the success of the pilot programs, the government decided to
scale-up methadone programs in other provinces (Vuong et al. 2011). By July,
2013, 14,000 patients were in methadone treatment in 62 clinics in 20 Vietnamese
provinces. The Ministry of Health (MOH) has projected that methadone treatment
will be provided to about 80,000 drug users in 2015.
Studies on the outcomes of the methadone implementation in Vietnam have
demonstrated promising results. In a four-site cohort study of 965 heroin users who
started treatment in 2009, 88.3 % were retained in methadone treatment for 12 months
(U.S. Agency for International Development 2011). Heroin use, as measured by
urinalyses, was reduced from 100 % positive at admission to 21 % positive at
60 days in treatment; and over the subsequent 10 months, rates varied from 17 % to
10 % positive. Other study results indicated substantial reductions in injection drug
use and crime, as well as improvements in mental health and quality of life.
75 Opportunities for Addiction Service System Development 1193
If the Ministry of Health succeeds in its planned service development, Vietnam will
have gone from two pilot project clinics in 2008 to treating over 80,000 patients with
methadone in 2015 (Nguyen et al. 2012). This extraordinary expansion of treatment
capacity brings with it huge challenges of service funding and workforce develop-
ment. In 2011, Hanoi Medical University, in collaboration with UCLA, established an
Addiction Technology Transfer Center to lead efforts to train clinical staff for the
clinics being developed. Compounding the challenges, amphetamine-type stimulants
(ATS) consumption has rapidly increased in Vietnam – 1.5 % of drug users in
Vietnam in 2001 used ATS, whereas 6.5 % did in 2012 (Department for Social
Evils Prevention [DSEP] 1995–2012). In order to address this emerging problem,
training programs in motivational interviewing and the Matrix Model of treatment
have been initiated to provide services to address the needs of treatment-seeking ATS
users. In less than a decade, Vietnam has mounted a major public health effort to
address the problems of drug use and HIV, and the policies that have guided this
system development have been firmly grounded in addiction science.
The development of the Vietnamese treatment system and capacity-building
effort has been the result of well-informed and responsive public health officials in
the Vietnamese government, in cooperation with international funding organiza-
tions and technical assistance. The urgency for developing these services has been
accomplished in parallel with an equally impressive HIV testing and treatment
program. The challenge for the next decade will be to continue the expansion of the
services to provide treatment access for all individuals who need them, to maintain
the quality of the services, and to better integrate addiction services with HIV
services and the larger health-care system. The development of addiction services
in Vietnam over the past decade was an impressive exercise in public health service
development, guided by the best scientific evidence and implemented by
a multiagency international collaborative effort.
75.2.1.2 Lebanon
At the start of the twenty-first century, services for the treatment of substance use
disorders in Lebanon were a collection of faith-based therapeutic communities and
a limited set of treatment services from psychiatrists and psychiatric hospitals.
Although these resources were helpful to patients and communities, there was no
organized outpatient treatment and no use of addiction medications. In 2003, an
organization named Skoun was created to deliver high-quality, evidence-based
outpatient addiction services. Heroin addiction was the primary drug problem that
was not being effectively addressed by existing treatment services. Skoun initiated
their treatment services using a combination of harm reduction strategies, together
with cognitive behavioral therapy (CBT), motivational interviewing, and psychiat-
ric treatment. It was clear to Skoun staff from the beginning that to effectively
engage and treat individuals addicted to opiates using a harm reduction philosophy,
they would need addiction medications as part of their services. Therefore, an initial
question was whether to introduce methadone or buprenorphine into Lebanon,
where, to date, no medication-assisted treatment had been available. As they
1194 R.A. Rawson et al.
reviewed practices associated with methadone and buprenorphine in Europe and the
United States, they decided that the clinical data on the efficacy of buprenorphine
and flexibility in its dosing and service delivery logistics made buprenorphine the
preferable agonist medication to bring to Lebanon. Furthermore, in their initial
discussions with the Ministry of Health, there were some concerns about metha-
done diversion, but there was general support for the idea of buprenorphine.
However, because rates of HIV are low in Lebanon, there was no perceived public
health urgency for addressing the injection drug use problem as there was in
Vietnam, China, and countries in Eastern Europe.
Because there are close historical and cultural ties between Lebanon and France, it
was not uncommon for opiate-addicted individuals from Lebanon to go to France to
receive buprenorphine and return to Lebanon to participate in counseling treatment
services at Skoun. As this practice developed and some pharmacies in Beirut
established relationships with French pharmacies, buprenorphine became available,
in a limited manner, for patients at Skoun. From 2005 to 2011, several hundred
patients were treated with buprenorphine in Lebanon. During this period, discussions
continued with government officials about the clinical effectiveness of buprenorphine
and its value in improving the lives of addicted individuals. The Pompidou Group,
UNODC, and the WHO Eastern Mediterranean office (EMRO) played important
roles in hosting meetings to promote discussions of the use of buprenorphine in
Lebanon and arranging visits for Ministry of Health officials to France and Iran to
visit treatment centers using medications to treat opiate addiction. The persistent
advocacy and encouragement by individuals at Skoun, along with other addiction and
public health leaders in Lebanon and representatives of international organizations,
resulted in official governmental approval for the importation and use of
buprenorphine for the treatment of opiate addiction in February 2012.
During the first year since the passage of the approval of buprenorphine in
Lebanon, 690 cumulative patients have been treated with buprenorphine, with the
majority being in Beirut. Skoun has expanded services from its original clinic in
Eastern Beirut to a second clinic in South Beirut, sponsored by the Drosos Foun-
dation, a Swiss organization. This clinic, which was projected to enroll 75 individ-
uals on buprenorphine in its first year, was met with tremendous demand for
services and enrolled double that number (150) in its first 9 months of operation.
In addition to the buprenorphine services provided at Skoun, a total of 45 psychia-
trists have been registered by the Ministry of Health to prescribe buprenorphine.
The use of buprenorphine in Lebanon is currently limited by a somewhat restricted
distribution system (all medication has to be dispensed from two government
hospitals in Beirut), and all buprenorphine is available only through patient fees,
which are several hundred US dollars per month. Currently there are efforts to work
with the government to promote treatment (including treatment with
buprenorphine) in place of incarceration for drug offenders. Although the law to
allow treatment rather than incarceration has been in place for almost a decade, it
has not been implemented. The availability and effectiveness of buprenorphine has
made it possible to convince judges to implement this law, and so this practice is
currently expanding.
75 Opportunities for Addiction Service System Development 1195
evidence-based medicine. The NRC recruited a medical director from Cairo Univer-
sity, Egypt, who was then the president of the International Society of Addiction
Medicine, and two other Egyptian psychiatrists who had extensive expertise and
specialized training in addiction. The NRC appointed a training director who,
together with a training expert from Kings College in London, implemented
a comprehensive program of staff training in evidence-based practices with quality
clinical supervision. A team of clinicians received extensive training in the Matrix
Model of outpatient treatment to address the substantial problem of ATS use and
dependence, and the NRC arranged for the importation of Suboxone to treat opioid
dependence. A research director, who had previously held a senior position at NIDA,
was hired to develop a program of clinical and services research. In 2013, an
electronic medical record (EMR) system was implemented, and, at present, the entire
clinical record-keeping system at the NRC is incorporated into this EMR system.
The NRC has moved from the 18-bed residential facility in the city of Abu Dhabi
to a much larger set of offices and villas in the suburbs of Abu Dhabi. The
residential capacity has been expanded to 110 beds for men and a separate facility
for women. Outpatient services (medical services, psychiatric services, addiction
medications, and behavioral treatments) are integrated with the residential
programs into a connected continuum of care. The treatment capacity has increased
fivefold, from 67 patients treated in 2009 to 338 in 2012. Plans are underway for the
development of a satellite facility in a northern sector of the Emirates to make
services more geographically accessible, and ground has been broken for
a comprehensive treatment center that will provide an even greater treatment
capacity. The service development at the NRC over the past 5 years has been
extensive, and a foundational part of the service philosophy is the use of good
science and treatments with a strong evidence base.
75.3 Conclusion
The early twenty-first century has seen an expansion of addiction treatment services
throughout the world, with evidence-based treatments applied as core features of
the service continuum. This application of medical and behavioral health research
findings to addiction service system development is a welcome step toward the
establishment of drug treatment as a public health domain. As these services evolve
and demonstrate effectiveness in reducing drug use and related infectious disease
and drug-related crime, a significant challenge will be to find and mount the
political will to redirect investments from incarceration/public safety interests to
addiction treatment/public health interests that require preventative and clinical
skills, medication, and coordination with related health conditions services.
Disclosures and Acknowledgements The authors have no conflicts of interest. Dr. Rawson is the
Principal Investigator for the Cooperative Agreement for Workforce Development in Vietnam:
HIV-Addiction Technology Transfer Center (2011–2014) and has served as a training consultant
to the Substance Abuse and Mental Health Services Administration (SAMHSA) on addiction
treatment in Vietnam. Dr. Rawson was a member of the ISAM site visit team to the Abu Dhabi
75 Opportunities for Addiction Service System Development 1197
National Rehabilitation Center in 2009 and provided consultation to the NRC on outpatient services.
Dr. Rawson and Dr. Rieckmann are Co-Principal Investigators on an evaluation of the Skoun
Program in Beirut, under contract to the Drosos Foundation. Victor Capoccia was supported by
UNODC to describe the development of community-based care in Vietnam in June and July 2012.
The authors would like to thank Le Minh Giang, MD, PhD, Hanoi Medical University; Nguyen
To Nhu, MD, PhD, Family Health International, Hanoi, Vietnam; Nadya Mikdashi, PhD; Ramzi
Haddad, MD, Skoun, Beirut Lebanon; Hamad Al Ghafri, MD, PhD; and Tarek Abdul Gawad, MD,
Abu Dhabi, UAE. This chapter was supported by the SAMHSA agreement listed above to
Dr. Rawson and the Drosos Foundation contract for the evaluation of the Skoun Chiyah Clinic
to Drs. Rawson and Rieckmann. In addition, support was provided via D43TW009120,
UCLA-Cairo University Training Grant, funded by the NIH Fogarty Center, Richard Rawson, PI.
References
Chandler RK, Fletcher BW, Volkow ND (2009) Treating drug abuse and addiction in the criminal
justice system: improving public health and safety. JAMA 301(2):183–190. doi:10.1001/
jama.2008.976
Department for Social Evils Prevention (DSEP), Ministry of Labor – Invalid and Social Affairs
(MoLISA), National Commission on AIDS, Drugs and Prostitution (NCADP), Vietnam
Administration for HIV/AIDS Control (VAAC). (1995–2012). Annual reports from NCADP
(2012); DSEP/MoLISA (1995, 1999, 2001, 2005); and VAAC (2012)
National Institute on Drug Abuse (NIDA) International Program (2013) Fellows world map, Text-
only version. http://international.drugabuse.gov/fellowships/fellows-world-map-accessible
National Center on Addiction and Substance Abuse (NCASA) (2005) Family matters: substance
abuse and the American family: a CASA White Paper. NCASA, Columbia University, New York
National Drug Intelligence Center (2011) The economic impact of illicit drug use on American
society. United States Department of Justice, Washington DC, http://www.justice.gov/archive/
ndic/pubs44/44731/44731p.pdf
Nguyen T, Nguyen LT, Pham MD, Vu HH, Mulvey KP (2012) Methadone maintenance therapy in
Vietnam: an overview and scaling-up plan. Adv Prev Med 2012:732484
Saenz E, Busse A, Tomas-Rosello J, Clark N (2015) Major international challenges in addiction
treatment: the experience of Treatnet and beyond. In: el-Guebaly N, Galanter M, Carra G (eds)
Textbook of addiction treatment: international perspectives. Springer, Heidelberg
Tomás-Rosselló J, Rawson RA, Zarza MJ, Bellows A, Busse A, Saenz E, Freese T, Shawkey M,
Carise D, Ali R, Ling W (2010) United Nations Office on Drugs and Crime international
network of drug dependence treatment and rehabilitation resources centres: Treatnet. Subst
Abus 31:251–263
United Nations International Drug Control Programme (UNDCP) (1995) The social impact of
drug abuse. World Summit for Social Development, Copenhagen
United Nations Office on Drugs and Crime (UNODC) (2007) Drug dependence treatment: training
package. UNODC, Vienna, http://www.unodc.org/ddt-training/treatment/general.htm
United Nations Office on Drugs and Crime (UNODC) (2013) World drug report. UNODC,
Vienna, http://www.unodc.org/wdr/
United States Agency for International Development (2011) Effectiveness evaluation of the pilot
program for treatment of opioid dependence with methadone in Hai Phong and Ho Chi Minh
Cities (After 12 month treatment), Component II: impact on physical health, mental health,
society and quality of life. Hanoi, Vietnam
Vietnam Ministry of Health (VMH) (2012) Report on HIV/AIDS situation and prevention and
control HIV/AIDS in 2011. Direction and major tasks in 2012
Vuong T, Ali R, Baldwin S, Mills S (2011) Drug policy in Vietnam: a decade of change? Int J Drug
Policy 23:319–326
Addiction Treatment in Iceland
76
Ingunn Hansdóttir, Valgerður Á. Rúnarsdóttir, and
Thorarinn Tyrfingsson
Contents
76.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1200
76.2 Treatment in Iceland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1200
76.2.1 Services at SAA’s Facilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1203
76.2.2 Treatment Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1205
76.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1205
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1206
Abstract
This chapter aims to present various facets of addiction-related problems in
Iceland and the unique features of Icelandic society that have molded the
attitudes and ways of dealing with these problems. Although Iceland is
geographically isolated, it has seen changes in drug use following international
trends. Due to the small size of the population and its centralized health care,
Iceland is in a unique position to follow such trends and monitor the course of
those treated for addiction. These trends in drug use as well as epidemiological
information and social policy issues are discussed. The development of addic-
tion treatment services in Iceland is also reviewed with special emphasis on
social aspects of treatment, such as high availability of treatment and the
equality of access to health care. These aspects have yielded a smaller
treatment gap in Iceland than in many other countries. In addition inpatient
I. Hansdóttir (*)
Department of Psychology, University of Iceland, Reykjavı́k, Iceland
e-mail: [email protected]
V.Á. Rúnarsdóttir • T. Tyrfingsson
Vogur Hospital, Reykjavik, Iceland
e-mail: [email protected]; [email protected]
treatment services in follow-up care have been preserved within the addiction
treatment system, complementing a comprehensive treatment model of addic-
tion with a view of addiction as a chronic disease. These features are discussed
in order to highlight their importance and contribution to effective clinical
practices.
76.1 Introduction
Substance use disorder treatment in Iceland has a history spanning more than
50 years, during which treatment approaches and the general understanding of
substance use disorder have changed dramatically. The development of treatments
has been influenced both by general advancement in medicine and psychosocial
treatments and by unique factors of the Icelandic society. This chapter reviews
these cultural aspects of addiction-related attitudes and describes addiction treatment
in Iceland with the aim of highlighting factors important in understanding how
different societal factors may impact addiction treatment in an international context.
Iceland is a small island country in the North Atlantic Sea with a homogenous
population of 321,857 (Statistics Iceland 2013). It is sparsely populated, with more
than two-thirds of the population living in the capital of Reykjavik or its neighboring
towns. Icelandic society upholds a Nordic social welfare system providing universal
health care, including substance use treatment, and tertiary education for all. Equality
is greatly valued and Iceland has been rated the country with the world’s smallest
gender gap 5 years in a row by the World Economic Forum (2013) reflecting equal
access to education and health care. The standard of living is high and Iceland has
been ranked as the 13th most-developed country in the world by the United Nations’
Human Development Index (2013).
These unique features frame the substance disorder treatment system and high
accessibility to treatment resulting in a smaller treatment gap than in most other
countries. It has been estimated that in the United States, only one in ten in need of
addiction treatment receives it (NDSUH 2010), compared to estimates of 50 %
receiving treatment needed in Iceland (Tyrfingsson et al. 2010).
In addition to accessibility to services being high, another important aspect of
the treatment milieu is that addiction has been seen as a biological disorder needing
professional treatment. Treatment has thus been part of mainstream health care with
treatment being provided by health-care professionals such as physicians, nurses,
addiction counselors, psychologists alongside social workers, and other health-care
professions. Thus, the emphasis has been on the disease model of addiction.
This view of addiction among professionals is disseminated to the mainstream,
making it easier for people to address their addiction problems, and this is reflected,
e.g., in the lenient outlook of most employers who grant sick leave on pay for those
76 Addiction Treatment in Iceland 1201
Treatment of alcohol and drug use disorders in Iceland has involved different
treatment settings with mental health services and specialized alcohol and drug
services as the main providers of treatment for people with alcohol and drug use
disorders. Services for this population began with the foundation of a rehabilitation
home (Bláa bandið) based on AA principles in 1955, following the foundation of
AA in Iceland 1954, with two meetings per week. Icelanders embraced the AA
tradition from the start and today it is thriving, with about 300 meetings per week
(see Olafsdottir 2000 for the history of AA in Iceland). Substance use disorder
treatment has emphasized the AA approach and encouraged patients to engage in
the AA community. The rehabilitation home was shortly subsumed into the mental
health-care system.
The next significant development in addiction treatment in Iceland was during the
1970s. A number of people went to the United States for treatment and were exposed
to what is called the Minnesota Model, consisting of intensive treatment for
4–6 weeks based on the 12-step approach of AA. Those that came back energized
the AA society and decided to form a nonprofit layman’s association for the advance-
ment of alcohol treatment in Iceland. This association, Society of Alcoholism and
other Addictions (SAA), was founded in 1977 and had as its goal to inform and
influence the general public on the nature of the disease of alcoholism and to establish
treatment and counseling services. Thus, the emphasis was placed on the disease
concept, and the treatment of alcoholism was seen as a health-care issue as opposed to
a social problem. SAA’s treatment for addiction was started that same year, 1977.
SAA built Vogur Hospital, the National Center of Addiction Medicine, in 1980 with
donations from the Icelandic people to serve as a national center for addiction
treatment. Vogur Hospital thus gained the recognition of the nation as the main
addiction treatment facility, a welcome addition to the services provided by the
National Hospital. The availability and salience of treatment options grew dramati-
cally and high rates of available treatments have been maintained ever since
(Olafsdottir and Helgason 1988). This high rate of available treatment is also unique
to Iceland. The WHO has estimated worldwide that there are 1.7 beds per 100,000
population available for the treatment of drug and alcohol use disorders, with Iceland
ranking the highest, with 52.4 beds according to the report on Resources for the
Prevention and Treatment of Substance Use Disorders (WHO 2012).
Since its establishment SAA has become the leading treatment facility of alcohol
and drug dependence in Iceland providing treatment at Vogur Hospital to more than
22000 patients (15.880 males (70.9%) and 6.522 females (29.1%)) or a significant
proportion of the nation (10.5 % males over 15 years of age and 4.4 % of women of
the same age). Approximately 1,800 individuals are admitted each year to Vogur
Hospital, with about 600 newcomers annually with roughly 2,400 admissions
yearly or 6–7 patients daily. This accounts for a large proportion of the treatment
addiction services in Iceland. At the University Hospital Psychiatric Ward, about
500–600 patients are admitted yearly, mostly patients with concomitant mental
(50 %) or other physical disorders (38 %) (Birgisdottir 2013). Other facilities that
provide rehabilitation services are outside of mainstream health care.
76 Addiction Treatment in Iceland 1203
Most patients start their treatment in detoxification at Vogur Hospital. They are mostly
self-referred. During the average stay of 7–10 days, patients are detoxified, mental and
physical diseases are stabilized, and psychoeducation is started and the process of
motivation for change begins. Personnel consist of health-care professionals working
full time, most are certified, as well as students in training. These include medical
doctors, registered nurses and nurses’ aids, and certified addiction counselors. In
addition to Vogur Hospital with its 60 beds for adults and 11 beds for adolescents,
SAA runs two inpatient rehabilitation centers, each with 30 beds with services tailored
to specific groups (women, older men, younger men); three outpatient units, two in the
capital Reykjavik and one in a town on the north coast, Akureyri; a recovery house
with 20 beds for IV users without a home; and a social center.
After detoxification at Vogur Hospital, a majority of patients or two-thirds
continue treatment and rehabilitation. One-third goes for further therapy in
a residential setting (4 weeks) and one-third to intensive outpatient (4 weeks)
after detoxification. Recognizing that better outcomes are related to adequate
treatment length (NIDA 2009), residential treatment is the treatment of choice
and treatment providers collaborate with the patient and aim for intense treatment
options when possible and appropriate. Residential treatments are delivered in
nonhospital settings outside of the city. Residential treatment consists of daily
group therapy sessions and psychoeducation as well as individual counseling if
needed (total of 60 h of treatment). Self-help meetings are facilitated in order to
help patients gain community-level support to support recovery and maintain
abstinence after formal treatment ends, with an additional 3 months of weekly
sessions (additional 12 h treatment). The follow-up phase of the inpatient option
consists of biweekly sessions for 3 months (24 h total) followed by weekly sessions
for up to 9 months (36 h total). Group therapy and individual counseling sessions
are guided by principles and techniques of cognitive behavioral therapy and
motivational interviewing and are delivered by certified addiction counselors.
Treatment protocols and staff training follow the NIDA recommendations (2012)
of an evidence-based approach to treatment and training. Recognizing that addic-
tion is a chronic disease, readmissions are not uncommon and are welcomed. About
half of the patients that have come for treatment over the past three decades have
been admitted only once to the hospital, and the majority, 78 %, three or fewer
times. A subgroup of patients need additional assistance and about 4 % have been
admitted more than 10 times.
Another important aspect emphasized in SAA treatment services is relapse
prevention, and follow-up treatment is provided for up to 1 year as described
above, with less intense outpatient services following the more intense options to
closely monitor progress and support relapse prevention.
SAA offers a wide range of treatment options tailored to various levels of disease
severity and different needs of patients based on factors such as gender and age. These
specialized treatment options range from opioid maintenance therapy to adolescent
1204 I. Hansdóttir et al.
treatment; in addition there is specialized treatment for women, for men over 55 years
of age, and for relapse-prone men; treatment is offered for gambling and to families
dealing with addiction. Treatment modality also varies, with counseling, education,
and group therapy provided within both inpatient and outpatient rehabilitation
settings, with long-term treatment available for the most severely affected patients
and an intensive outpatient therapy with assisted housing. Particular emphasis during
the last decade has been placed on counseling one of the high-risk groups in
a preventive effort, i.e., the children of patients growing up with the addiction.
infections are rare in Iceland as is HIV, though the situation could change rapidly if
injecting use continues and spreads. Currently the abuse of methylphenidate, mainly
provided by medical subscription, has rapidly risen the past years, and Iceland is
second only to the United States in the medical consumption per capita of methyl-
phenidate from 2004 to 2009 (Kaye and Drake 2012). Other IV substances used in
Iceland are also prescription drugs, mainly opioids.
The use of amphetamines by adolescents is another area of great concern as use
in this age group has steadily grown over the past 15 years. For example, among
those 19 years old and younger and seeking treatment at SAA, over 92 % have tried
amphetamines and over 60 % reported using amphetamines weekly for six or more
months (SAA 2010). Previously, regular users in this age group entering treatment
at SAA were few (less than 30 per year before 1995) but the numbers recently
doubled, and sometimes tripled, with admissions ranging between 100 and
150 regular teenaged users annually, mostly 18 or 19 years of age.
Looking at all diagnoses, primary and otherwise, the proportion with cannabis
addiction has doubled over the past 20 years, and now about 35 % of the overall
patient population in treatment meet diagnostic criteria for cannabis dependence.
Among those younger than 25 years, cannabis is the main substance of abuse
although multiple drug use is most common. Two-thirds (76 %) of young people
19 years old and younger meet criteria for cannabis dependence and 62 % meet
criteria for amphetamine dependence (SAA 2010). Thus, international trends are
reflected in the patient population.
76.3 Conclusion
References
Birgisdottir K (2013) Gender differences in rates of concurrent alcoholism with major depression
generalized anxiety. (In Icelandic). Kynjamunur samsláttar alkóhólisma við þunglyndi og
almenna kvı́ðaröskun. Unpublished BS thesis, University of Iceland
Directorate of Health (2003) Alcohol and other substances of abuse: various statistics. (Áfengi og
önnur vı́muefni: ýmsar tölulegar upplýsingar). Report of the council on the prevention of
alcohol and drug abuse (Áfengis og vı́muefnaráð). Reykjavı́k, Iceland
Directorate of Health (2012) Smoking among Icelanders 1989–2012 electronic version.
(In Icelandic: Reykingar Íslendinga 1989–2012 [Rafræn útgáfa]. http://www.landlaeknir.is/
Hasin DS, Stinson FS, Elizabeth Ogburn E, Bridget F, Grant BF (2007) Prevalence, correlates,
disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States:
results from the national epidemiologic survey on alcohol and related conditions. Arch Gen
Psychiatry 64(7):830–842. doi:10.1001/archpsyc.64.7.830
Kaye S, Darke S (2012) The diversion and misuse of pharmaceutical stimulants: what do we know
and why should we care? Addiction 107:467–477
Makela K (1981) Scandinavian drinking survey: construction of composite indices of drinking
attitudes and personal experiences related to drinking. National Institute for Alcohol Research,
Oslo
76 Addiction Treatment in Iceland 1207
Makela K (1986) Attitudes towards drinking and drunkenness in four Scandinavian Countries.
Ann N Y Acad Sci 472(1):21–32
NIDA (2012) Principles of drug addiction treatment, a research-based guide, third edition, revised
2012, NIH Publication NO.12-4180. http://www.drugabuse.gov/publications/principles-drug-
addiction-treatment
NSDUH (2010) Results from the 2010 national survey on drug use and health: summary of
national findings. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, Substance
Abuse and Mental Health Services Administration Center for Behavioral Health Statistics and
Quality. http://www.samhsa.gov/data/nsduh/2k10nsduh/2k10results.htm#7.3
Olafsdottir H (1998) The dynamics in shifts in alcoholic beverage preference: effects of the
legalization of beer in Iceland. J Stud Alcohol 59:107–114
Olafsdottir H (2002) Legalizing beer in Iceland. In: Room R (ed) The effects of Nordic alcohol
policies: analyses of changes in control systems. Nordic Council for Alcohol and Drug
Research, Helsinki, pp 95–116
Olafsdottir H, Helgason T (1988) Admissions for treatment of alcohol and drug abuse 1975–1985.
Icel Med J 74:165–167
SAA (2010) Annual report (2007–2010). SAA, Reykajvı́k
Statistics Iceland (2013) Iceland in figures 2013 (Landshagir). http://www.statice.is/pages/916
Stefansson JG, Lindal E (2009) The prevalence of mental disorders in the Greater-Reykjavik area.
Icel Med J 95:559–564
Tyrfingsson T, Thorgeirsson TE, Geller F, Runarsdottir V, Hansdottir I, Bjornsdottir G, Stefansson
K (2010) Addictions and their familiarity in Iceland. Ann N Y Acad Sci 1187:208–217
United Nations’ Human Development Index (2013) Human development report 2013: the rise of
the south – human progress in a diverse world. United Nations Development Programme.
http://hdr.undp.org/en/media/HDR2013_EN_Summary.pdf
WHO (2012) Alcohol in the European Union: consumption, harm and policy approaches. WHO
Regional Office for Europe. http://www.euro.who.int/__data/assets/pdf_file/0003/160680/
e96457.pdf
WHO (2013) Status report on alcohol and health in 35 European Countries 2013. http://www.
euro.who.int/__data/assets/pdf_file/0017/190430/Status-Report-on-Alcohol-and-Health-in-35-
European-Countries.pdf
World Economic Forum (WEF) (2013) The global gender gap report 2013: insight report. http://
reports.weforum.org/global-gender-gap-report-2013/
Section VI
Main Elements of a Systems
Approach to Addiction Treatment
Abstract
This section is dedicated to a range of issues which go beyond the clinical
practice in providing specific treatment options to specific populations, in
specific services by specialists or in primary health care. The focus here is on
the treatment system in the community, at a regional or national level, as a
comprehensive network integrating different approaches, services and actors,
including harm reduction interventions. The various aspects of building up such
a network and of improving an existing system are discussed, legal and ethical
frameworks and rules are described, as well as the evidence base for good quality
interventions and ways how to monitor and evaluate their outcomes.
A. Uchtenhagen (*)
Research Foundation for Public Health and Addiction, Zurich University, Zurich, Switzerland
e-mail: [email protected]
G. Carrà
UCL Division of Psychiatry, Faculty of Brain Sciences, University College London, London, UK
e-mail: [email protected]
Thomas F. Babor
Contents
78.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1214
78.2 Concepts, Requirements, Priorities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1214
78.2.1 Definitions and Rationale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1214
78.2.2 History and Conceptual Developments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1215
78.2.3 Requirements of an Optimal Treatment System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1217
78.2.4 Priorities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1222
78.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1226
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1227
Abstract
This chapter describes the requirements and priorities of service systems
designed to treat persons with substance use disorders. Research and theory
are reviewed to inform policymakers, program administrators, and treatment
providers about the best ways to organize or to expand treatment services using
a public health systems perspective, which is concerned primarily with how
services contribute to the health and welfare of a population. The requirements
of a service system include sound policies (especially stable financing); appro-
priate structural features, such as facilities and trained personnel; and services
that are accessible, affordable, and integrated. The priorities for establishing
such a system will depend on the assessment of population needs, as well as
needs-based planning and the support of mutual help organizations. It is con-
cluded that a public health approach to the development of treatment systems
provides a useful way of responding to the changing needs of the population in
relation to substance use disorders.
T.F. Babor
Department of Community Medicine, University of Connecticut School of Medicine, Farmington,
CT, USA
e-mail: [email protected]
78.1 Introduction
At a time when health-care delivery is changing rapidly throughout the world and
new substance abuse treatment services are being developed and evaluated, it is
critical that services for persons with alcohol and drug problems be delivered in the
most effective as well as in the most efficient manner. The focus on
treatment system issues represented in the title of this chapter is designed to direct
attention at the growing body of research and theory that can be used to inform
treatment planning and quality improvement at the community and national levels.
The development of an effective treatment system is a crucial part of a country’s
public health response to the problems associated with substance use disorders.
Although a great amount of research has been conducted on treatment of substance
use disorders, most of it deals with clinical issues, such as the efficacy of different
psychotherapies or pharmacotherapies, rather than the larger treatment policy
issues that often result from tradition, budget constraints, or political decisions.
As described in a conceptual paper by Babor et al. (2008), what is now needed is
a comparable effort to use systems-level research to inform policymakers and
program administrators about the best ways to configure or to expand their treat-
ment services in order to maximize the impact of treatment services at the popu-
lation level.
This chapter deals with the requirements and priorities of the treatment system,
which are approached from a public health perspective. The requirements of
a service system include sound policies (especially stable financing); appropriate
structural features, such as facilities and trained personnel; and services that are
accessible, affordable, and integrated. The priorities of such a system include the
accurate estimation of population needs through service mapping and needs assess-
ment, as well as rational service planning that includes an emphasis on community
support networks such as mutual help organizations.
current array of services? Are services being distributed and accessed appropri-
ately? Are screening and referral conducted at gateway institutions, such as primary
health care, schools, and employment settings? Are there appropriate diagnostic
capabilities? What are the most effective administrative linkages between sub-
stance abuse services and criminal justice, mental health, general medicine, primary
care, and other human services? Are they coordinated with other specialized
services in a continuum of care? Are evidence-based services available and rele-
vant? What is the policy support for integrated structures? What can be done to
build stronger community support networks (e.g., AA, family social clubs)?
To what extent can mental health and general medical services be better integrated
with addiction treatment? Are there advantages to having separate systems for
substance abuse, or should they be integrated administratively with services for
other health conditions or social problems?
These questions define issues that can be addressed by a public health systems
perspective, which is concerned primarily with how services contribute to the
health and welfare of a population. Services for substance use disorders expanded
dramatically in developed countries in the 1970s but often in a fragmented and
arbitrary way. Resource allocation decisions and treatment policies have
a major effect on the development of services for persons with substance
use disorders, but there is little knowledge to guide service planning or to indicate
whether services achieve their public health objectives. Low- and middle-income
countries are now investing in services as substance use prevalence rates increase
with rising incomes, but there is little systematic knowledge to guide
the development of service systems that would best address the needs of their
populations.
The continuum of care concept, as described by Rush et al. (2013), refers to the
mix of services available to patients and the way patients are expected to pass
through it. The services are generally arranged sequentially beginning with screen-
ing and diagnostic assessment and then assignment to different settings and services
depending on acuity, severity, and complexity. The main services that have been
incorporated into the systems framework in most countries are withdrawal man-
agement and detoxification, residential rehabilitation, outpatient counseling, con-
tinuing care, and community support networks such as Alcoholics Anonymous.
Variations of the continuum of care concept are the core-shell model and the
stepped-care approach. In the core-shell model, core functions, such as intake
assessment and treatment assignment to the most appropriate type of care (the
shell), are facilitated by case management (Glaser et al. 1978). In the stepped-care
approach, patients are assigned to the least intensive level of care initially.
If outcomes are not optimal, they can be “stepped up” to a more intensive level,
and if outcomes are positive, they can be “stepped down” to appropriate continuing
services.
Another innovation that has contributed to the systems concept is SBIRT, which
refers to screening, brief intervention, and referral to treatment, typically in the
context of early intervention in primary health-care settings (Babor et al. 2007). The
SBIRT model grew out of a seminal report issued by the US Institute of Medicine
(1990), called Broadening the Base of Treatment for Alcohol Problems. SBIRT is
a comprehensive and integrated approach to the delivery of early intervention and
treatment services through universal screening for persons with substance use
disorders and those at risk. Beginning in the 1980s, concerted efforts were made
by the World Health Organization (WHO) to provide an evidence base for alcohol
screening and brief intervention in primary health-care settings, in order to broaden
the base of treatment in countries where specialized services were unavailable.
With the development of reliable and accurate screening tests for alcohol, more
than a hundred clinical trials were conducted to evaluate the efficacy and cost-
effectiveness of alcohol screening and brief intervention in primary care, emer-
gency departments, and trauma centers (Babor et al. 2007).
Just as SBIRT attempts to integrate specialized substance abuse treatment
services with outreach to the general health-care system, the chronic care model
addresses the needs of more serious cases of substance dependence by coordinating
specialized services over time under the assumption that once substance depen-
dence has developed, there is a need for continuing care and management, as is
done with chronic conditions like diabetes and hypertension. The chronic care
model has been adapted to substance abuse by Rush (2010, 2013) who has defined
a series of “tiers” that constitute the most important elements of a continuum of
services for the management of chronic substance users. Five tiers are defined on
the basis of their functions, which are higher-order groupings of similar services or
interventions.
Tier 1 refers to health promotion and prevention functions targeted at the general
population. This tier recognizes the likelihood that public policies, the regulatory
environment, and lifestyle factors contribute to the risk of substance abuse and the
78 Treatment Systems for Population Management of Substance Use Disorders 1217
Babor et al. (2008, 2010) have described the components and dynamics of an
optimal treatment system from a public health perspective. These are what have
been referred to as the basic “building blocks” of a service system (Huntington
et al. 2012). As described in Fig. 78.1, the first requirement is a set of policies that
make the governance of the service system and its constituent parts possible.
The second component is the system’s structural resources, including infrastruc-
ture, technologies, personnel, programs, and facilities. The third component
consists of system qualities, such as accessibility, economy, and efficiency, which
contribute to the smooth functioning of the service system. According to this model,
the policies, resources, and qualities of the system should not only translate into the
effectiveness of services on individuals exposed to them, it should also contribute
to population health through reductions in death, disease, and disability.
1218 T.F. Babor
National
Health and Structural
Welfare Resources
Policies Facilities
Programs
Personnel
Substance Abuse Effects on
Treatment Service service users Impact on
Policies population
Financing
Monitoring
Quality control
Licensing System qualities Drug-using
Involuntary Accessibility Population
commitment Economy Characteristics
Integration Case mix
Social capital
Drinking/drug use
subcultures
Fig. 78.1 Conceptual model of service system policies, resources, and qualities and their
potential impact on population health (SOURCE: Adapted from Babor et al. (2008))
The components of this model and the research supporting it are discussed in the
remainder of this section in order to indicate how a systems model might best
contribute to population health.
78.2.3.1 Policies
The first requirement of an effective treatment system is appropriate treatment
policies that provide a statutory basis for designing treatment programs, licensing
treatment providers, and providing funding for programs and personnel. Policies
determine the size, the administrative location, and the organization of the treat-
ment system. They provide a framework for the allocation of resources.
According to Room (2010), there is a great deal of legislation for the treatment
and rehabilitation of persons with substance use disorders, but much of the legis-
lation is concerned with provisions for compulsory treatment or for treatment in lieu
of jail. Other kinds of policy include national standards for clinical practices and
licensing requirements for treatment personnel.
According to a survey conducted by the World Health Organization (2010),
66.2 % of the 145 countries surveyed have a government unit or government official
responsible for treatment services for substance use disorders, but fewer than half of
these countries have a specific budget line for these services. Financing mecha-
nisms vary but most countries use tax revenues, user fees, and private insurance to
pay for alcohol and drug services.
Resource allocation decisions have had a major effect on the development of
these services. For example, the number and variety of services increased dramat-
ically in the United States when the US Public Health Service invested in treatment
78 Treatment Systems for Population Management of Substance Use Disorders 1219
services as part of a broader public health approach to reduce the burden of disease,
disability, and social problems that accompany substance use (White 1998).
The rapid development of federally supported residential and outpatient treatment
programs, along with an expansion of insurance coverage for private programs,
established the feasibility of serving large numbers of alcohol- and drug-dependent
patients within a specialized set of services.
Treatment policies and financing mechanisms affect the degree of centralized
management of treatment services and their incorporation into other human service
areas, such as social welfare, mental health, general medicine, and criminal justice. In
Denmark, policies were used to decentralize treatment services, whereas in Norway,
they moved the system toward a more centralized, medically oriented structure
(Stenius et al. 2010). In Canada and the Netherlands, mental health and substance
abuse treatment systems have been integrated (Rush 2010). In Finland, services are
being reformed by merging mental health and addiction outpatient services and by
emphasizing the management of patients in primary care (Kuussaari and Partanen
2010). Although policy changes designed to reform the organization of treatment
services may have sound assumptions and a good rationale, they are rarely accompa-
nied by systematic evaluation research to inform future decisions.
32.4
39.8
14.3 7.4
SOURCE: WHO ATLAS on Substance Abuse SOURCE: WHO ATLAS on Substance Abuse
Other
Fig. 78.2 Most common settings for treatment of alcohol and drug disorders in WHO member
states
(Babor and Del Boca 2003). Thus, the value of different types of treatment may be
to convince clients that treatment is going to help them. Research (Cooney
et al. 2003) suggests that the key ingredient of the success of any therapy may
be its ability to attract clients and generate enthusiasm among therapists. Instead
of distinct nonoverlapping elements, therapy may work through common
mechanisms, such as empathy, an effective therapist-client alliance, a desire to
change, inner resources, a supportive social network, and the provision of
a culturally appropriate solution to a socially defined problem. Thus, the more
that treatment services are made available to all population segments, the greater
the system’s effectiveness is likely to be, regardless of the specific type of
services.
Some therapeutic interventions are more cost-effective than others, suggesting
that resources could be allocated more efficiently and economically without
compromising effectiveness. One way to improve the efficiency of treatment is
to organize treatment teams or sites to work together for a 12- to 24-month period
with the aim of improving a specific area of care. This “improvement collabora-
tive” approach combines traditional quality improvement methods of teamwork,
process analysis, adoption of standards, training, and coaching. In a study by
Gustafson and colleagues (2013), the use of collaborative methods, especially
coaching, was found to decrease waiting time, improve treatment retention, and
increase recruitment of new patients. Humphreys and McLellan (2011) found that
process improvements can change the efficiency of treatment programs, but the
link to better outcomes is weak, in part because outcomes are mainly influenced
by environmental factors and life events outside of formal treatment.
System integration means the amount of interconnectedness among the organi-
zations in a network. Research suggests several ways to improve system integra-
tion: drug courts, SBIRT, integrated treatment programs for pregnant drug users,
managed care, and case management. There is some evidence to suggest that drug
courts can increase social controls, lengthen the duration of treatment, reduce
criminal behavior, and lower rates of recidivism (Eibner et al. 2006).
The elements of SBIRT have been evaluated in clinical trials and found to be
effective (Babor et al. 2007) to such an extent that demonstration programs have
been conducted in large population areas of several countries, including Finland
(Seppä and Kuokkanen 2008), Norway (Aasland and Johannesen 2008), Denmark
(Barfod 2008), South Africa (Seale and Monteiro 2008), Brazil (Souza-Formigoni
et al. 2008), and the United States (Madras et al. 2009). Despite some successes in
primary health care (Souza-Formigoni et al. 2008), the results of programs relying
on the training of physicians and other health personnel without adequate logistical
support have not been encouraging.
In the United States, a large-scale demonstration of programs operating in
27 states since 2005 has been found (McRee et al. in press) to enhance the states’
continuum of care to include universal, adult SBIRT services in primary care and
other community settings (e.g., health centers, nursing homes, university health
centers, hospitals, emergency departments, and military). In an evaluation of
SBIRT’s system effects, McRee et al. (in press) found that the program filled
1222 T.F. Babor
gaps in services for substance users in both the medical and specialty treatment
systems of care. It was also associated with improved system equity (i.e., equal
access to all population groups) and efficiency by extending services to underserved
populations, expanding services within facilities and across tasks, and improving
system linkages.
Another way to improve the integration of treatment is through integrated treat-
ment programs. Examples include treatment of pregnant women who have substance
use disorders and the delivery of mental health services to patients with co-occurring
mental disorders. Integrated women’s programs providing pregnancy and parenting
services have been associated with improvements in child development (Niccols
et al. 2012). But the results of integrating care for clients with co-occurring mental
health and substance use disorders have been equivocal (Donald et al. 2005).
78.2.4 Priorities
Substance use services have traditionally been established without the benefit of
a comprehensive, quantitative planning process that is closely aligned with
78 Treatment Systems for Population Management of Substance Use Disorders 1223
population needs. Priorities for developing an optimal treatment service system will
vary according to a country’s current level of services, as well as the nature of their
alcohol and drug problems. Among the highest priorities are service mapping,
needs assessment, and service planning. Another priority that is often neglected
despite its recognized effectiveness is the establishment and support of mutual help
organizations that provide a critical community resource for the maintenance of
recovery.
Table 78.1 Scope and configuration of the World Health Organization’s Substance Abuse
Instrument for Mapping Services (WHO-SAIMS)
Policy and legislative domain: includes items about national alcohol and drug policies; legislation
governing drug control, prevention, and treatment; strategic plans that address substance use
disorders, workforce development for substance abuse professionals, and resource allocation to
and the financing of alcohol and drug services
The substance abuse situation and current alcohol and drug service needs: this section is designed
to (i) help identify whether current services match needs and (ii) estimate service coverage
Current alcohol and drug treatment system. This domain describes the type and mix of services
provided, service integration, and system complexity
The alcohol and drug services domain. This section covers (1) other residential services for alcohol
and drug problems such as halfway houses and sober living environments; (2) alcohol and drug
services provided by other sectors such as mental health facilities, primary health-care services,
and the criminal justice sector; (3) the linkages between these services; (4) the availability of
psychosocial treatments and psychotropic medications; and (5) drug substitution therapies and
harm reduction services for opioid users
The primary care domain. Items in this category refer to interventions used in primary care settings
The human resource domain. This describes the quantity of human resources as well as human
resource development, including mutual help organizations and recovering communities such as
AA and NA
Source: Babor and Poznyak (2010)
harmful use are used, these can translate into the potential demand for specialized
services (residential and outpatient) as well as early intervention services in other
health-care settings. These services can be directed at patients with dependence and
harmful use, respectively. Population survey data can be supplemented by
obtaining prevalence estimates from settings where substance users are likely to
be encountered, such as prisons, emergency departments, HIV clinics, etc. The need
for substance abuse services among the general population can also be estimated
through the use of health and social indicators, such as substance-related mortality,
morbidity, social problem statistics, and expert opinion on treatment needs.
Regarding the latter, the SAIMS includes a qualitative module that provides
a way to rapidly collect descriptive information that should be useful to supplement
the quantitative data collected in the core instrument or to provide a minimum of
information to begin the planning process. The qualitative module requires key
informants to collect the information.
mobile technology. The resulting capacity projection for each heath planning area
in the country can be contrasted with current treatment capacity to yield an estimate
of the treatment gap.
78.3 Conclusion
Treatment systems for substance use disorders are a significant part of national
responses to the burden of disease and disability resulting from substance abuse.
In well-resourced countries, a relatively integrated system of services has been
developed in response to population needs. In less-resourced countries, treatment
services are often inadequate and fragmentary. Regardless of development level,
appropriate population health-care management requires the allocation of resources
to preventive, curative, restorative, and rehabilitative services, using the most
effective and efficient evidence-based practices. By organizing service providers
78 Treatment Systems for Population Management of Substance Use Disorders 1227
into networks, it should be possible to shift utilization to lower cost settings or the
most appropriate level of care.
A system-wide holistic approach to the planning and coordination of services for
substance use disorders is more than the mere sum of gains attributable to discrete
interventions and technologies, such as new screening tools, better diagnostic
instruments, improved intervention techniques, and more numerous services. The
systems approach goes beyond capacity building and technical innovation. It is
designed to coordinate services so that they are capable of responding to the
changing needs of the population.
References
Aasland OG, Johannesen A (2008) Screening and brief intervention for alcohol problems in
Norway. Not a big hit among general practitioners. Nordic Stud Alcohol Drugs 25:515–522
Babor TF, Del Boca FK (eds) (2003) Treatment matching in alcoholism. Cambridge University
Press, Cambridge, UK
Babor TF, Poznyak V (2010) The World Health Organization substance abuse instrument for
mapping services. Rationale, structure and functions. Nordic Stud Alcohol Drugs 27:703–711
Babor T, Caulkins J, Edwards G, Fischer B, Foxcroft D, Humphreys K, Obot I, Rehm J, Reuter P,
Room R, Rossow I, Strang J (2010) Drug policy and the public good. Oxford University Press,
Oxford
Babor TF, McRee B, Kassebaum P, Grimaldi P, Ahmed K, Bray J (2007) Screening, Brief
Intervention, and Referral to Treatment (SBIRT): toward a public health approach to the
management of substance abuse. Subst Abus 28:7–30
Babor TF, Stenius K, Romelsjo A (2008) Alcohol and drug treatment systems in public health
perspective: mediators and moderators of population effects. Int J Methods Psychiatr Res
17(S1):S50–S59
Barfod S (2008) A GP’s reflections on brief intervention in primary health care in Denmark.
Nordic Stud Alcohol Drugs 25:523–528
Bray J, Hayashi S, Babor T, Clark W (in press) Screening, Brief Intervention, and Referral to
Treatment (SBIRT): rationale, program overview and cross-site evaluation. Addiction
Bukten A, Skurtveit S, Gossop M et al (2012) Engagement with opioid maintenance treatment and
reductions in crime: a longitudinal national cohort study. Addiction 107:393–399
Cooney NL, Babor TF, DiClemente CC, Del Boca FK (2003) Clinical and scientific implications
of project MATCH. In: Babor TF, Del Boca FK (eds) Treatment matching in alcoholism.
Cambridge University Press, Cambridge, UK, pp 222–237
Donald M, Dower J, Kavanagh D (2005) Integrated versus non-integrated management and care
for clients with co-occurring mental health and substance use disorders: a qualitative system-
atic review of randomized controlled trials. Soc Sci Med 60:1371–1383
Eibner C, Morral A, Pacula RL, MacDonald J (2006) Is the drug court model exportable? An
examination of the cost-effectiveness of a Los Angeles-based DUI court. J Subst Abus Treat
31(1):75–85
Glaser FB, Greenberg SW, Barrett M (1978) A systems approach to alcohol treatment. Alcohol
Research Foundation, Toronto
Gustafson DH, Quanbeck AR, Robinson JM et al (2013) Which elements of improvement
collaboratives are most effective? A cluster-randomized trial. Addiction 108:1145–1157
Holder H, Parker RN (1992) Effect of alcoholism treatment on cirrhosis mortality: a 20-year
multivariate time series analysis. Br J Addict 87:1263–1274
Humphreys K (2004) Circles of recovery: self-help organizations for addictions. Cambridge
University Press, Cambridge, UK
1228 T.F. Babor
Seppä K, Kuokkanen M (2008) Implementing brief alcohol intervention in primary and occupa-
tional health care. Reflections on two Finnish projects. Nordic Stud Alcohol Drugs 25:505–514
Smart RG, Mann RE (2000) The impact of programs for high-risk drinkers on population levels of
alcohol problems. Addiction 95:37–52
Souria JC (1990) A history of alcoholism. Basil Blackwell, Oxford
Souza-Formigoni M, Boerngen-Lacerda R, Vianna VP (2008) Implementing screening and brief
intervention in primary care units in two Brazilian states: a case study. Nordic Stud Alcohol
Drugs 25:553–564
Stenius K, Witbrodt J, Engdahl B, Weisner C (2010) For the marginalized, or for the integrated?
A comparative study of the treatment systems in Sweden and the US. Contemp Drug Probl
37:417–448
Timko C, Moos RH, Finney JW, Lesar MD (2000) Long-term outcomes of alcohol use disorders:
comparing untreated individuals with those in alcoholics anonymous and formal treatment.
J Stud Alcohol 61:529–538
Ungemack J, Babor TF, Bidiorini A (2001) Connecticut compendium on substance abuse treat-
ment need. Department of Mental Health and Addiction Services, Hartford
Walsh DC, Hingson RW, Merrigan DM, Levenson SM, Cupples LA, Heeren T, Coffman GA,
Becker CA, Barker TA, Hamilton SK, McGuire TG, Kelly CA (1991) A randomized trial of
treatment options for alcohol-abusing workers. N Engl J Med 325:775–781
White W (1998) Slaying the dragon: the history of addiction treatment and recovery in America.
Chestnut Health Systems, Bloomington
World Health Organization (2010) ATLAS on substance use: resources for the prevention and
treatment of substance use disorders. WHO, France
An Integrated Approach to the Treatment
of Drug Dependence: The English 79
Experience
Alex Stevens
Contents
79.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1232
79.1.1 The Need for Integration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1232
79.2 The Integrated Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1232
79.2.1 Evidence-Based Services for Dependent Drug Users . . . . . . . . . . . . . . . . . . . . . . . 1232
79.2.2 The Normative Basis for Service Integration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1233
79.2.3 Overcoming the Challenge of Integration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1234
79.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1236
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1237
Abstract
This chapter focuses on the English experience of developing integrated drug
treatment services. It discusses the principles that underlie an integrated
approach to the treatment of drug dependence, presents possible methods for
integration, and argues that there is no inherent conflict between providing
services that both keep people alive through harm reduction and help them to
overcome dependence. Treatment services can maximize the benefits that they
offer by providing a coordinated continuum of care that ranges from
low-threshold harm reduction services to higher-threshold services that give
service users the help they may need to make lasting changes to their patterns
of dependence and to achieve abstinence. Evidence-based principles that may
help people move along this continuum are presented.
A. Stevens
School of Social Policy, Sociology and Social Research, University of Kent, Medway, UK
e-mail: [email protected]
79.1 Introduction
At the birth of the current international regime for the control and regulation of
illicit drugs, in Article 38 of the 1961 Single Convention on Narcotic Drugs, states
committed themselves to the creation of a system for the “identification, treatment,
education, aftercare, rehabilitation and social reintegration” of drug users. More
than 50 years later, we have much more knowledge about what the elements of such
a system should be. But debate continues on the best way to coordinate such
services. Specifically, it is often suggested that there is an inherent conflict between
providing low-threshold, harm reduction services and high-threshold, abstinence-
based treatment. This debate has been long running in the UK, but pragmatic
solutions have been found to integrate services. These solutions are varied across
the countries of the UK. This chapter will focus on the English experience.
It will discuss the principles that underlie an integrated approach to the treatment
of drug dependence, will present possible methods for integration, and will argue
that there is no inherent conflict between providing services that both keep people
alive and help them to overcome dependence. This discussion has two starting
points. One, which is often debated, is the evidence that is available to inform the
development of treatment systems. The other, which is more rarely discussed in the
academic literature, is the normative basis for decisions on treatment provision.
Both will be discussed here. This chapter draws on earlier work completed for the
Beckley Foundation (Stevens et al. 2006) and more recent research.
The evidence in this area has been repeatedly distilled by distinguished agencies
and researchers, including the World Health Organization (WHO), the US National
Institute on Drug Abuse (NIDA), the UK National Institute for Health and Clinical
Excellence (NICE), the European Monitoring Centre for Drugs and Drug Addiction
(EMCDDA), and the United Nations Office on Drugs and Crime (UNODC).
A useful summary of this evidence base has been provided by Babor
et al. (2010). The interventions that they list as being supported by the evidence
can be split into two categories, depending on how much commitment to change
they require from the drug user. Effective low-threshold services, which tolerate
continued drug use, include opiate substitution treatment (with substitution by
methadone, buprenorphine, or heroin), needle exchange programs, naloxone distri-
bution for the prevention of fatalities in overdose, and brief interventions in medical
settings. Higher-threshold services, which require more commitment to change,
include various forms of psychosocial treatment (including outpatient and residen-
tial services) and involvement in peer self-help organizations, which often demand
79 An Integrated Approach to the Treatment of Drug Dependence 1233
Beyond debates around the evidence base and ethics for integrating services, there
are also practical and logistic challenges. These include financial, systemic, and
political barriers. Financially, it is likely that different services will be competitors
with each other for a slice of the limited budget that is available for the treatment of
drug dependence. Money spent on one service is not available to be spent on another.
Systemically, it may be very difficult to coordinate services that are managed
by different organizations. There may be gaps between services that are run by
ministries of health and the criminal justice agencies (e.g., police and prisons) which
have most contact with people who are affected by drug dependence. There may be
fragmentation and gaps in communication between providers of different services,
even when the same individuals are accessing those services simultaneously.
Politically, it may be very difficult to generate the support necessary to provide
high-quality, integrated services to a group of people who are often marginalized and
stigmatized.
Treatment agencies in the UK and elsewhere have increasingly responded to this
challenge by pointing to the excellent financial return that drug treatment provides
to public investment. Estimates of this vary, and are based on less-than-perfect
methodologies, but consistently suggest that treatment provides benefits to society
that are of greater monetary value than its costs (e.g., Doran 2008). This enables
supporters of treatment provision to argue that investment should be increased, at
least until the point where the marginal cost of increasing treatment exceeds
the marginal benefit to be gained from it. But there are problems with this
approach, besides the need to test these estimates with improved methodologies.
One is that the benefits of drug treatment do not always return to the agency that
pays for it. For example, much of the benefit of drug treatment is estimated to come
in the form of reductions in criminal victimization. The National Treatment Agency
for Substance Misuse (NTA, the agency that coordinated drug treatment in
England from 2001 to 2013) estimated that £1 million invested annually in
drug treatment prevents 9,860 drug-related crimes, with an associated benefit of
£1.8 million (NTA 2012). But half of these benefits accrue to potential victims
of crime rather than to the state system that pays for the treatment. On the other
hand, reduced crime is not the only benefit to arise from drug treatment. An as
yet unpublished report by Public Health England (PHE, which took over responsi-
bility for drug treatment from the NTA in 2013) has estimated that the cost of drug
treatment per quality-adjusted life year is well above the threshold that is usually
used to judge whether investment in a health intervention is worthwhile. However,
politicians, despite the desires of many policy analysts, do not make decisions
solely on the basis of cost-benefit studies. They have electorates and other parties
to satisfy, as well as their own normative preferences to express. Investing
money and political capital in the issue of drug dependence may not meet these
needs. Perhaps a more politically palatable argument in financially straightened
times is that service integration offers ways to save money within the budget
that is currently devoted to drug treatment. By reducing duplication of effort,
79 An Integrated Approach to the Treatment of Drug Dependence 1235
drug-related deaths, BBV transmission and relapse, integrated services can save
money as well as lives.
During years of economic growth, England saw a huge expansion in drug
treatment provision between 1998 and 2008. This was delivered through partner-
ship boards, known as Drug Action Teams. These included a range of agencies,
such as local authorities (especially housing, youth and social service departments),
police, education, and health services. The aim was to develop a more coordinated
approach to drug treatment provision. Initially, Drug Action Teams focused on
increasing the capacity of methadone maintenance services. But attention has more
recently turned to assisting people to leave treatment with their dependency behind
them. The current UK drug strategy, published in 2010, recognizes the importance
of opiate substitution treatment (including heroin-assisted treatment) but also
acknowledges the importance of psychosocial therapy, as well as support for stable
housing and employment, in order to help people achieve their aims to live free of
dependence.
Another feature of the English system in recent years has been integration
between health and criminal justice services for problematic drug users.
The government has introduced a growing range of measures to encourage people
who have committed crimes and who have problems with drugs to enter treat-
ment. These have ranged from the arrest referral schemes of the 1990s, through
the 1998 Drug Treatment and Testing Order (DTTO, a court order which
required offenders to enter treatment on a quasi-compulsory basis; the alternative
being the usual punishment for the crime), the replacement of the DTTO in 2005
by the Drug Rehabilitation Requirement (DRR), drug testing on arrest, required
treatment assessments for those who test positive, and, more recently, alcohol
treatment requirements. These have been coordinated through the Drug Interven-
tions Programme (DIP), a centrally funded system of case management
that funded workers to build links between criminal justice and treatment agen-
cies. In prisons, the Integrated Drug Treatment Programme has led to a significant
expansion of opiate substitution programs, with the aim of reducing the very
high rates of death from overdose that have been observed among opiate users in
the first few days and weeks after release (Farrell and Marsden 2008).
The integration of services has been assisted by the National Health Service
taking responsibility for health services in prison (away from the Prison Service
itself) in 2003.
When Public Health England replaced the National Treatment Agency in 2013
as the organization responsible for the coordination and integration of drug treat-
ment, the scope for partnership widened. Drug Action Teams have been subsumed
into local Health and Wellbeing Boards. The budget for drug treatment has been
given to local Directors of Public Health, who are expected to commission services
for drug dependence alongside other public health priorities, including alcohol,
smoking, violence, communicable diseases, sexual health, and child poverty. This
offers the prospect of deeper integration between services but also threatens the
budget for drug treatment, which is currently bigger than that for other public health
services and may be shifted to these other issues.
1236 A. Stevens
England is also moving toward an untested model for the financing of integrated,
outcome-focused services for problematic drug users. The idea of the “Payment by
Results” approach is that the state will pay service providers for the outcomes that
are achieved by the drug users with whom they work. The intention is to create
incentives for service providers to deliver outcomes that are both valued by
service users and cost-effective for the government. As Humphreys and McLellan
(2011) have noted, this strategy is ambitious but untested. Other systems that have
attempted to reward service providers principally on the basis of outcomes have
been plagued by perverse incentives. One example is the practice of “cherry
picking.” This happens where the service provider chooses to focus efforts only
on those clients who already have the best possibility of achieving outcomes
which trigger payments. This creates profit for the service provider but no
commensurate benefit to the state or to more problematic clients who may be
“parked” and receive little support. Current pilots in England will give more
information on the effectiveness of Payment by Results in drug treatment. How-
ever, the emerging indications from the application of similar models to services
for both unemployed persons and people with criminal convictions are not
encouraging.
There is an emerging literature on methods that may help people enter, stay in,
and depart from treatment successfully. These include assertive outreach (borrowed
from the field of mental health), contingency management (using financial and
other incentives to reward retention and progress in treatment), and various forms
of case management. However, none has so far proved that it offers a consistently
effective approach across different places and target groups. We perhaps have
a clearer idea of what does not work. We know that the public stigmatization of
drug users does not support abstinence or treatment entry (Palamar et al. 2013;
Radcliffe and Stevens 2008). We know that ending treatment prematurely increases
risks of death (Hickman et al. 2011). We know that the absence of “recovery
capital” (including stable relationships, housing, and employment) is associated
with worse outcomes (Laudet and White 2008). Taken together, the evidence
suggests that – despite some gaps that need to be filled by more research – we do
already have knowledge that we can use to provide integrated services that are able
to attract, retain and assist people who have problems with drugs.
79.3 Conclusion
The increasingly integrated English system – at least by the account of the agencies
which coordinate it – has been successful in producing health and crime reduction
benefits through increased investment in drug treatment; benefits that far outweigh
the cost of this investment. There have been encouraging reductions in the estimate
of people who have problems with opiates and/or crack cocaine (Hay et al. 2011).
But the provision of treatment alone is not sufficient for all treatment entrants to
achieve good outcomes. Social dislocation, unemployment, and a lack of stable
housing present barriers to the achievement of independent, crime-free lives.
79 An Integrated Approach to the Treatment of Drug Dependence 1237
Treatment services can maximize the benefits that they offer by providing
a coordinated continuum of care that ranges from low-threshold services – which
help to keep people alive while they attain stability – to higher-threshold services
that give them the help they may need to make lasting changes to their patterns of
dependence. There are evidence-based principles that may help people move along
this continuum. These include optimal, sufficient doses for those in medically
assisted treatment, as well as the provision of “phased, layered” treatment that
supports optimism that people can achieve abstinence (Recovery Orientated Drug
Treatment Expert Group 2012). This British report also notes that it is normal for
dependent drug users to go through several cycles of drug treatment before they
achieve abstinence. Coordinated systems should therefore not disadvantage drug
users who have previously “failed” in treatment but should instead offer supportive
routes back into treatment. They should recognize that some drug users may not
wish or be able to achieve abstinence from their drug of dependence and should
provide medical assistance to all categories of drug user. A successful coordinated
system is likely to be one that provides a range of points of entry to treatment,
a range of options and modalities of treatment and clear pathways between treat-
ment types (e.g., from criminal justice to community services, from detoxification
to aftercare, from harm reduction to abstinence – and back again if necessary).
Finally, they should provide support for integration into the kind of stable housing
and employment which we all need to make good lives.
References
Babor T, Caulkins J, Edwards G, Fischer B, Foxcroft D, Humphreys K, Obot I, Rehm J, Reuter P,
Room R, Rossow I, Strang J (2010) Drug policy and the public good. Oxford University Press,
Oxford
Doran CM (2008) Economic evaluation of interventions to treat opiate dependence - a review of
the evidence. Pharmacoeconomics 26(5):371–393
Farrell M, Marsden J (2008) Acute risk of drug-related death among newly released prisoners in
England and Wales. Addiction 103(2):251–255
Hay G, Gannon M, CaseyJ MT (2011) National and regional estimates of the prevalence of opiate
use and/or crack cocaine use 2009/10: a summary of key findings. National Treatment Agency
for Substance Misuse, London
Hickman M, Vickerman P, Robertson R, Macleod J, Strang J (2011) Promoting recovery and
preventing drug-related mortality: competing risks? J Public Health 33(3):332–334
Humphreys K, McLellan AT (2011) A policy-oriented review of strategies for improving the
outcomes of services for substance use disorder patients. Addiction 106(12):2058–2066
Laudet AB, White WL (2008) Recovery capital as prospective predictor of sustained recovery, life
satisfaction, and stress among former poly-substance users. Subst Use Misuse 43(1):27–54
NIDA (2012) Principles of drug addiction treatment: a research-based guide, 3rd edn. National
Institute on Drug Abuse, National Institute on Health, Washington, DC
NTA (2012) Estimating the crime reduction benefits of drug treatment. National Treatment
Agency for Substance Misuse, London
Palamar JJ, Halkitis PN, Kiang MV (2013) Perceived public stigma and stigmatization in
explaining lifetime illicit drug use among emerging adults. Addict Res Theory
21(6):516–525. doi:10.3109/16066359.2012.762508, Early online
1238 A. Stevens
Pearson FS, Prendergast ML, Podus D, Vazan P, Greenwell L, Hamilton Z (2012) Meta-analyses
of seven of the National Institute on Drug Abuse’s principles of drug addiction treatment.
J Subst Abuse Treat 43(1):1–11
Radcliffe P, Stevens A (2008) Are drug treatment services only for ‘thieving junkie scumbags’?
Drug users and the management of stigmatised identities. Soc Sci Med 67(7):1065–1073
Recovery Orientated Drug Treatment Expert Group (2012) Medications in recovery: re-orienting
drug dependence treatment. National Treatment Agency for Substance Misuse, London
Stevens A (2011) Drug policy, harm and human rights: a rationalist approach. Int J Drug Policy
22(3):233–238
Stevens A, Hallam C, Trace M (2006) Treatment for dependent drug use: a guide for
policymakers. Beckley Foundation, Oxford
Addiction Assessment and Treatment
Planning: Developing Countries 80
Nicolas Clark and Ambros Uchtenhagen
Contents
80.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1240
80.2 Planning Steps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1240
80.2.1 Step 1: Defining the Problem (Treatment Need) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1240
80.2.2 Step 2: Look at the Available Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1242
80.2.3 Step 3: Assess the Functioning of the System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1243
80.2.4 Example from WHO Experience: The SAIMS
(Substance Abuse Instrument for Mapping Services) . . . . . . . . . . . . . . . . . . . . . . . 1248
80.2.5 Planning for Treatment Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1249
Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1250
Tools for Treatment Planning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1250
Checklist on Standards of Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1253
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1255
Abstract
Lower-income countries sometimes have difficulties assessing the nature and
scope of addiction problems in their countries and in planning the treatment
system accordingly. Adapting existing services to changing patterns of substance
use disorders and related problems can also be a challenge. This chapter provides
a public health approach to the development of a health-care response to drug
problems, mainly based on the experience of the World Health Organization
working with lower-income countries to assess and develop their drug treatment
systems. Options for assessing the need for substance abuse treatment, the nature
and extent of available resources, and the functioning of existing services are
N. Clark (*)
Management of Substance Abuse, World Health Organisation, Geneva, Switzerland
e-mail: [email protected]
A. Uchtenhagen
Research Foundation for Public Health and Addiction, Zurich University, Zurich, Switzerland
e-mail: [email protected]
80.1 Introduction
The addiction medicine specialist is often called upon to advice on the development
of treatment systems. While Chap. 81, “Screening and Assessment for People with
Substance Use Disorders: A Focus on Developed Countries” in this section advises
on the issues in higher-income countries, this chapter gives a guide to the develop-
ment and organization of services in lower-income countries.
According to the WHO ATLAS survey (WHO 2011), lower-income countries
typically have less medical staff, less services, less funding reserved for addiction care,
and less care provided for special populations like adolescents or prison inmates. Some
countries may find themselves with few addiction medical specialists, or in some cases
none. Few staff will likely have training in structured psychological techniques.
Funding for health services may be from specific donors such as The Global Fund
to Fight AIDS, Tuberculosis and Malaria (GFATM), or may require out-of-pocket
contributions which put it beyond the reach of most of those who needs them.
The last 50 years have seen some dramatic changes in the patterns of substance use
and related health and social problems, and in many countries, the health-care
systems, which often predate these changes, struggle to respond. This is particularly
the case in lower-income country settings. Growing wealth and development leads in
many cases to a rapidly developing health-care system and brings with it the chance
for significant rethinking and reorganization of the health-care system response to
substance use and related problems such as HIV, TB, and hepatitis and social
problems such as poverty, malnutrition, unemployment, homelessness, and crime.
This chapter is an outline of a public health approach to the development of
a health-care response to substance use disorders and related health and social
problems, with a particular focus on lower-income countries, based largely on the
experience of the World Health Organization work in such countries.
It may be the case that there is no good data on the local epidemiology of substance
use disorders and the corresponding demand for treatment. In this case a stepwise
approach to understanding the problem is proposed. While data on substance use is
an important consideration, it is the prevalence of substance use disorders, in
particular substance dependence and associated physical and psychiatric disorders,
which is the better guide to treatment need.
80 Addiction Assessment and Treatment Planning: Developing Countries 1241
problem in a community. The type and amount of drugs seized by customs may
be publically available in a report. The prison may collect data on what drugs
people are using when they come into prison. The police may keep records on
what drug-related arrests are made, or the number of people charged for driving
while over the legal limit for alcohol.
The second step is to conduct an inventory of the resources that are currently being
used and which could be recruited to tackle the problem of substance use disorders
in the country.
This might involve putting together a list of the treatment facilities in the
country, including specialized treatment centers and psychiatric facilities with
how many staff they have and with what skills.
80 Addiction Assessment and Treatment Planning: Developing Countries 1243
– The role of primary health care. Almost certainly, it will soon be clear that there
are not enough specialist staff to treat all the patients with substance use
disorders in the country. The addiction medicine specialist then needs to decide
whether or not to allocate some of his or her time to building the capacity of
primary care services to manage people with substance use disorders. Most
people with substance use disorders already are engaged with a primary care
service. Discharge from hospital, detoxification, or other substance misuse
service can be an occasion to contact that primary care service and encourage
them to continue the care that has been started, particularly if there is a clear role
such as the prescription of relapse prevention medication. Primary care services
are often happy to collaborate with specialist care services, as long as those
specialist services will be able to support them with a difficult patient when the
time comes.
– The lack of key pharmacological responses. Despite being around for many
years, many services do not provide methadone or buprenorphine treatment.
Medication for relapse prevention from alcohol dependence is also often not
available. The use of such medication greatly enhances the effectiveness of the
service and is a must for any addiction service.
– Competing models of care in the criminal justice sector including compulsory
treatment. Despite substance dependence being a health condition, some-
times treatment is provided by services under the responsibility of the
police or justice ministries. Even when the person is in prison, the health-
care treatment should be provided under the auspices of the ministry of
health.
substance abuse problems with the documented number and type of treatment
populations. A simple method is a routine documentation of waiting lists and
waiting time, although those also depend on the quality and acceptability of
services. If there is no formal waiting list, new patients can be asked how easy it
was to access the service. In addition, satisfaction of treatment populations and
other stakeholders is a good indicator for satisfactory outcomes.
Once the assessment of the gaps between the current treatment system and the
treatment need, a plan for sustainable development of the treatment system should
be developed. The nature of this development depends to a large extent on the
funding available.
In the absence of further funding, it may still be possible to reorient the treatment
system to the areas of unmet treatment need. Further development, even if tempo-
rarily funded by foundations such as The Global Fund, will ultimately need sources of
funding found within the country, either from government or insurance mechanisms.
Since this process can take a long time, it is important to start these discussions early.
Any treatment development will need an increased workforce. Inclusion of
elements of substance abuse treatment into the major health curricula in the country
will increase the capacity across the whole treatment system. In the meanwhile,
many existing practitioners can be assisted to provide substance abuse treatment
with mentoring and support, even telephone support, and first-hand exposure to
substance abuse treatment, either within the country or abroad.
1250 N. Clark and A. Uchtenhagen
For rapid expansion in treatment capacity, it may be useful to work with NGOs
which focus on substance misuse treatment. In the longer term, for substance abuse
treatment to be brought to scale, it will probably be necessary to develop such
treatment within the public treatment system.
The addiction medicine physician is often in a unique position to contribute to
treatment system development: understanding the nature of substance misuse
treatment (including the gaps in current treatment), having the skills to train and
mentor the next generation of treatment providers, and also having the capacity to
influence funders and decision makers about the structure of the treatment system.
When there is a shortage of expertise in a country, the addiction medicine physician
will inevitably feel torn between providing patient care and nonclinical activities;
however there are many opportunities for a public health impact by supporting the
development and orientation of treatment systems for substance use disorders
towards public health goals.
Appendix
– General psychiatrists
– Internal medicine specialists
– Other specialist staff (specify)
– Primary care physician
– Nursing staff
– Addiction nurses
– Psychiatric nurses
– General nurses
– Pharmacists
– Psychologists trained in substance use disorders
– Social workers trained in substance use disorders
– Occupational therapists trained in substance use disorders
– Ex patients – trained in substance use disorders
– Other (specify)
5. Services provided (approximate number of patients in each category at any
given time – choose the one category that best fits each patient):
– Assessment/diagnosis
– Outpatient management of withdrawal
– Inpatient management of withdrawal
– Individual counseling
– Group counseling
– Opioid maintenance treatment
– Relapse prevention medication
– Treatment of comorbidity
– Mental health problems
– Wound problems
– HIV/AIDS
– Hepatitis/liver disease
– TB
– Sexually transmitted infections
– Sterile injecting equipment
6. Does the service have programs specifically for different populations?
– Pregnant women
– Adolescents
– People with mental health and substance use problems
– People with physical health and substance use problems
– Men
– Women
7. Who is responsible for the treatment center?
– Ministry of health
– Other government ministry (specify)
– NGO/FBO (specify)
– Private company or individual (specify)
– Academic institution (specify)
1252 N. Clark and A. Uchtenhagen
3.Source of referral:
3.1 self or individual 3.2 health system referral 3.3 criminal jusce system
3.4 other1 1.
please specify: _______________________________________________________
4. Type of substance (s) Specify the name 5. Route of the administraon of Please
Primary
primary
Non
4.9 Other
4.10 Number of days the primary substance was used in 6.2 Is this the first ever treatment episode:
the last 28 days: ____________ Yes no
7. Paern of use (injecon and sharing equipment):
7.1 History of injecng over the lifeme: Yes no
7.2 History of Injecng equipment shared over the lifeme: Yes no
7.3 Any sharing of injecng equipment during the last 28 days: Yes no
8. Treatment seng planned for the current treatment 9.1 Opioid maintenance treatment planned for the
episode: current treatment episode: Yes no
8.1 Inpaent 9.2 Type of medicaon to be used for maintenance
treatment:
8.2 Outpaent
Methadone: Buprenorphine:
8.3 Residenal
Standards on Assessment
B1 An initial assessment is made in order to prioritize interventions in a coordinated treatment plan
B2 An assessment is made to detect complicating physical and neurological disorders
B3 A psychiatric/psychological assessment is made to detect complicating disorders (e.g., depression)
B4 An assessment is made of the social circumstances (e.g., family, employment, housing,
financial, and legal position)
B5 Methods for the rapid identification of substances used are available through laboratory tests
(e.g., urine or blood) or other procedures
B6 Laboratory facilities are available to assist in the assessment of physical and psychiatric/
psychological disorders
B7 Standardized instruments for diagnosis are used (e.g., ICD-10)
B8 Detailed records are kept on assessment results at entry
C3 Treatments are chosen on the basis of somatic and psychiatric disorders and the social
situation of patients
C4 Defined protocols exist for prescribing and other interventions appropriate to the specific
needs of patients
C5 The protocols are based in research evidence wherever possible
C6 Patients are informed on the range of available treatment options
C7 Whether or not the treatment goal is abstinence, measures are taken to reduce the harm from
continued drug use
C8 The least risk-producing treatments are chosen on the basis of a careful risk-benefit assessment
C9 Home-based treatment is available with regular visits by trained staff
C10 Access to self-help and other support groups is available
C11 Information about 24 h emergency facilities is provided
C12 Patients with overdose receive immediate care in-house or through referral to a
well-equipped other service
C13 Continuity of care is assured
C14 There is regular evaluation of the service/program
C15 There are links to other services for the care of children or other family members in need of
care and support
References
EMCDDA (2007) Guidelines for the evaluation of treatment in the field of problem drug use.
European Monitoring Centre on Drugs and Drug Addiction, Lisbon
EMCDDA (2008) Assessing illicit drugs in wastewater. Potential and limitations of a new
monitoring approach. Insights 9. European Monitoring Centre on Drugs and Drug Addiction,
Lisbon
EMCDDA. Evaluation Instrument Bank EIB. www.emcdda.europa.eu/eib
Ford JH II, Green CA, Hoffman KA, Wisdom JP, Riley KJ, Bergmann L, Molfenter T (2007)
Process improvement needs in substance abuse treatment: admissions walk-through results.
J Subst Abuse Treat 33(4):379–389
Hedrich D, Alves P, Farrell M et al (2012) The effectiveness of opioid maintenance treatment in
prison settings: a systematic review. Addiction 107:501–517
Hiller ML, Knight K, Leukefeld C, Simpson DD (2002) Motivation as a predictor of therapeutic
engagement in mandated residential substance abuse treatment. Crim Justice Behav 29:56–75
Mitchell O, Wilson DB, McKenzie DL (2006) The effectiveness of incarceration-based drug
treatment on criminal behaviour. Campbell Syst Rev 2006:11
Mitchell O, Wilson DB, Eggers A et al (2012) Assessing the effectiveness of drug courts on
recidivism: a meta-analytical review of traditional and non-traditional drug courts. J Crim
Justice 40:60–71
NHS (2012) Estimating the crime reduction benefits of drug treatment and recovery. NHS,
National Treatment Agency for Substance Misuse, London
Perry A, Coulton S, Glanville J, Godfrey C, Lunn J, McDougal C, Neale Z (2008) Interventions for
drug-using offenders in the courts, secure establishments and the community. (Review).
Cochrane Libr 19(3):CD005193
Quanbeck AR, Madden L, Edmundson E, Ford JH 2nd, McConnell KJ, McCarty D, Gustafson DH
(2012) A business case for quality improvement in addiction treatment: evidence from the
NIATx collaborative. J Behav Health Serv Res 39(1):91–100
Stevens A, Berto D, Heckmann W, Kerschl V, Oeuvray K, van Ooyen M et al (2005) Quasi-
compulsory treatment of drug dependent offenders: an international literature review. Subst
Use Misuse 40:269–283
UNODC (2003) Investing in drug abuse treatment. A discussion paper for policy makers. United
National Office on Drugs and Crime, Vienna
WHO (1993) Assessing the standards of care in substance abuse treatment. World Health Orga-
nisation, Geneva
WHO (2009a) Guidelines for the psychosocially assisted pharmacological treatment of opioid
dependence. World Health Organisation, Geneva
WHO (2009b) Assessment of compulsory treatment of people who use drugs in Cambodia, China,
Malaysia and Viet Nam. World Health Organisation, Western Pacific Region
WHO (2011) Atlas report on substance abuse. World Health Organisation, Geneva
WHO/UNODC/EMCDDA (2000) Evaluation of psychoactive substance use disorder treatment,
workbook series. World Health Organisation, Geneva
Screening and Assessment for People with
Substance Use Disorders: A Focus on 81
Developed Countries
Brian Rush
Contents
81.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1258
81.2 Core Principles and Practices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1259
81.2.1 Rationale for Screening and Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1259
81.2.2 Collaborative Models for Screening and Assessment . . . . . . . . . . . . . . . . . . . . . . . 1261
81.2.3 Best Practices for Screening and Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1262
81.2.4 Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1269
81.2.5 Treatment and Support and Outcome Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . 1272
81.2.6 Is Screening for Mental Health and Addictions Effective? . . . . . . . . . . . . . . . . . 1273
81.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1275
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1276
Abstract
This chapter outlines the rationale for a more proactive concerted effort to screen
for and assess mental health problems and at-risk consumption of alcohol and
other drugs and related addictions problems given the evidence concerning the
level of under-detection in routine practice and the excellent performance of
a host of screening tools and processes. When used for clinical decision-making,
best practice calls for a staged approach to maximize efficiency of the overall
screening and assessment process and ensure a link to subsequent outcome
monitoring. While several specific tools are highlighted, the essential principle
for service and system planning is that they must be tailored to the setting and
target population for which they are being implemented. Whether working in
generic settings such as primary care or specialized settings, a collaborative
approach, drawing upon multidisciplinary, multi-provider, and multi-sectoral
expertise, is needed across the stages of screening and assessment, along with
B. Rush
Health Systems and Health Equity Research Group, Centre for Addiction and Mental Health and
Department of Psychiatry, University of Toronto, Toronto, ON, Canada
e-mail: [email protected]
81.1 Introduction
It is widely recognized that only a small minority of people with mental health and
addiction-related concerns seek help from either community professionals or less
formal services (Urbanoski et al. 2007; Kohn et al. 2004). Reasons behind this are
many and varied across communities, including limited access to services or just not
knowing how/where to seek help; stigma and discrimination that challenge people to
seek help or that impact the attitudes and behavior of the helping agents they
encounter; feeling able to manage on their own; and personal challenges related to
such responsibilities as work, school, and childcare (Sareen et al. 2007; Urbanoski
et al. 2008). Considerable research has also informed us for some time that, among
those who seek help, the largest proportion will access a primary health-care provider
or other health and social service professional (Shapiro et al. 1984; Kessler et al. 1996;
Urbanoski et al. 2007). Although many people with mental health and addiction-
related problems, or who are at risk of such problems, are in contact with various
service providers, these risks or problems are often not identified (Barnaby et al. 2003;
Weaver et al. 2003; Mitchell et al. 2012). These contacts are “teachable moments” and
as such are missed opportunities for offering advice, more extended consultation, or
referral for additional support.
1260 B. Rush
it is axiomatic that no approach will meet their needs. This calls for a thorough
investigation of needs and strengths and a co-constructed matching of this profile to
available service options across a continuum of care. The focus on screening and
assessment is intended to increase the efficiency of client intake and engagement,
improve individual treatment outcomes, and minimize service delivery costs across
the system as a whole (Hilton 2011).
Best practices for treatment and support of people with co-occurring disorders
who are already engaged with specialized services also call for more proactive
screening of these co-occurring problem areas (Rush and Nadeau 2011). This
includes screening for mental health problems among people seeking addiction
treatment as well as screening for high-risk/hazardous substance use and addiction-
related problems among people seeking mental health treatment and support
(Health Canada 2001; Rush and Castel 2011). Proactive, systematic screening can
identify a wide range of unidentified problems that may impact treatment engage-
ment and outcome among people with co-occurring disorders (e.g., health risks,
suicide ideation, chronic health problems, psychosocial challenges). As noted, the
screening process must be followed up with more comprehensive assessment,
appropriate interventions, and outcome monitoring. A conceptual framework is
presented below to help guide tool selection and service planning across this
trajectory. Different screening and assessment tools and processes align with the
full spectrum of mental health and addiction-related risks and harms and must “fit”
with the varied service delivery settings where people are presenting for assistance.
Ideally, screening should occur at the point of first contact with the treatment
system, which could be a provider at any level of care, and in one of multiple
sectors. As such, it is important that providers across sectors have the knowledge
and skill to implement appropriate screening processes and tools that are feasible in
their context and useful in identifying the person’s needs and determining recom-
mendations for further screening, assessment, treatment, and support. Depending
on the results of screening and initial assessment, people need to be connected to the
level and type of service most suited to their needs, including health promotion and
preventive services. In fragmented systems, where collaboration between services
and sectors is not well developed, individuals may not get the services they require
in a timely manner, if at all, and systematic screening and assessment may facilitate
increased access to services.
Many service providers external to the specialized mental health and addiction
treatment sector do not have the expertise and resources to identify mental health,
addiction, and co-occurring concerns. Further, most specialist service providers do
not have the resources to respond to the breadth of complex issues and problems
that are identified through many screening tools. Collaborative care models provide
the opportunity for various providers to bring together their collective strengths and
capabilities to construct a system whereby individuals are screened and can receive
1262 B. Rush
Through a treatment system lens, there are many disciplines and service delivery
settings potentially involved in the screening and assessment process. An individual
situation may require input from a medical, psychiatric, nursing, psychological,
psychosocial rehabilitation, social work, and/or spiritual perspective. A collaborative
approach to screening and assessment requires mutual interprofessional respect for the
unique contributions that each has to offer to a client-centered approach. The unique-
ness of the various perspectives notwithstanding, common principles include:
• A “whole-person perspective” on strengths and needs
• A sensitivity to diversity and related equity issues
81 Screening and Assessment for People with Substance Use Disorders 1263
DIVERSITY LENS
Developmental Perspective
Transitional Older
Child Adolescent Adult
Youth Adult
Screening
Stage 1
(case finding)
Stage 2
(case definition)
Assessment
Stage of Client Engagement
Stage 1
(Placement
Matching)
Stage 2
(Treatment
Planning)
Treatment &
Support
Stage 1
(within-treatment
monitoring)
Outcome
Monitoring
Stage 2
(post-treatment
monitoring)
Fig. 81.1 Conceptual framework for screening and assessment in context of collaborative care
(Adapted from Rush and Castel (2011))
required in order to offer the best service available at that point in time and to
maintain client engagement. Parikh (2008), for example, discusses the types of
evidence-based services and supports for mental health problems that can be
provided within addiction services following positive results on mental health
screening tools. Flynn and Brown (2008) note that, in the case of people with
co-occurring disorders, provision of mental health services will often reduce
81 Screening and Assessment for People with Substance Use Disorders 1265
screening questions. For example, for young people being seen on an outreach basis
in their school or street environment, it would not be appropriate to begin asking
screening questions about sensitive topics such as high-risk sexual behavior, trauma
experiences, or illegal behavior before a trusting relationship has been initiated.
This will also be the case in many other settings and populations. Interpretation and
action in response to screening results also need to be developmentally informed.
More attention has been paid to this issue with respect to children, adolescents, and
adults, but insufficient attention has been paid to further articulating the role of
developmental stages in service transitions for transitional-aged youth and older
adults. These developmental stages have been incorporated into the framework to
ensure specific consideration is given to individuals in these life stages so that their
unique issues and concerns are not overlooked.
to primary care and other health-care settings (e.g., Allen et al. 1995; McPherson
and Hersch 2000). Other reviews are more oriented to the area of co-occurring
disorders and address the potential applicability of tools for settings such as mental
health, addiction services, and criminal justice (Center for Substance Abuse Treat-
ment 2005; Health Canada 2001; Sacks 2008; Savage 2006; Centre for Addiction
and Mental Health 2006). Some reviews do not distinguish the settings for appli-
cation but rather focus on the characteristics of the tools (e.g., Dawe et al. 2002;
Tucker et al. 2004). Still others focus on children and youth as opposed to adult
populations (Pediatrics 2010; Centre for Addiction and Mental Health 2009;
Rush et al. 2009). While there is no shortage of synthesized information about the
various options for screening and assessment, it may still be a challenge to sift
through the available information as each review often has a particular focus
(setting, population, mental health broadly, or addiction specifically).
81.2.3.4 Screening
In the context of addictions, and the broader field mental health, screening is
a relatively brief process designed to identify individuals who are at risk of having
particular problems or diagnosable disorders that warrant immediate attention,
intervention, or more comprehensive review. Identifying the need for further
assessment is the primary purpose of screening.
A staged approach to screening involves the sequential use of tools for risk
assessment/case finding (Stage 1) and case definition (Stage 2). An important
objective of this staged approach is to reserve the tools that require more staff
time, resources, and training for those individuals who score above the cutoff on the
briefer, more economical tools. The organizational context will dictate whether
screening will start at Stage 1 or 2, as further described below.
questionnaires (e.g., people with psychosis: Ley et al. 2007). As noted, the AUDIT
(Babor et al. 2001) is a Stage 1 tool focused on the level of risk of alcohol consump-
tion. Others are focused on consequences, including substance use/abuse or depen-
dence (e.g., CAGE, Ewing 1984; Dhalla and Kopec 2007; BASIC, Bischof et al. 2007;
TWEAK, Russell 1994; and CRAFFT, Knight et al. 1999).
The screening for mental health problems/disorders is also highly relevant for
the assessment and treatment of people with identified substance use concerns.
With respect to screening for mental health challenges, there is an important
distinction between disorder-based tools and those based on a dimensional
approach, such as measuring mental distress. Others that are longer such as the
Beck Depression Inventory (Beck 1961), the Beck Anxiety Inventory (Beck
et al. 1988), or screeners for PTSD (SPAN: Meltzer-Brody et al. 1999) and trauma
(Klein et al. 2002) are best considered follow-up Stage 2 tools because of their
length and diagnostic specificity. Disorder-based tools that are extremely short,
such as those using 1–3 items for identifying depressive and/or anxiety
disorder (e.g., the ADD: Means-Christensen et al. 2006), are considered Stage 1
screeners. However, Stage 1 mental health screeners also include brief dimensional
measures such as the K6/K10 (Kessler et al. 2002), the five-item mental health
component of the SF-36 (Ware and Sherbourne 1992; Berwick et al. 1991);
the Psychological Screening Inventory (PSI: Lanyon 2006); and either the Brief
Symptom Inventory or the BSRS (Derogatis and Mclisaratos 1983; Lee et al. 2006),
both being shorter versions of the Symptom-Checklist 90-R (Derogatis 1983;
Benjamin et al. 2006). For children and adolescents, the Strengths and Difficulties
Questionnaire serves as a useful Stage 1 mental health screener (Goodman and
Goodman 2009).
A small number of Stage 1 screening tools focus on both mental health and
addictions, and these are highly valued because of their broader coverage and,
therefore, their applicability in multiple settings involved in a collaborative care
arrangement. The GAIN-SS (Dennis et al. 2006) is one such tool rapidly growing in
popularity across North America and now available in multiple languages.
Biological tests for alcohol and drug use may also be helpful and have the
advantage of ease of application in medical settings and their utility as
a supplement to self-reported information. Limitations include cost, lack of
specificity and, in some instances, sensitivity to recent substance use. Biological
testing includes alcohol breathalyzer testing, measures of tissue damage from
chronic substance use such as reflected in the liver enzyme gamma-glutamyl
transferase (GGT) or red blood cell mean corpuscular volume (MCV), and hair,
saliva, and urine analysis (see Tucker et al. 2004; Greenfield and Hennessey 2008
for brief reviews).
Time and resources permitting, brief screening across other selected domains
is also recommended. Screening for other health problems such as traumatic
brain injury, cognitive impairment, fetal alcohol spectrum disorder (FASD),
HIV/AIDS, and tobacco use is also of critical importance to treatment and
support planning and may be called for in some health-care settings using
additional, brief screeners.
81 Screening and Assessment for People with Substance Use Disorders 1269
81.2.4 Assessment
The ASAM model specifies the dimensions across which a clinician must
explore strengths and needs in order to make the appropriate placement match
(Gastfriend and Mee-Lee 2003). These dimensions include:
• Acute intoxication and/or withdrawal potential
• Biomedical conditions and complications
• Emotional, behavioral, or cognitive conditions and complications
• Readiness to change
• Relapse, continued use of continued problem potential
• Recovery environment
It is highly recommended that these areas be examined with a semi-structured or
a structured interview approach facilitated by validated instruments that support the
initial placement/referral.
Assessment tools and processes for Stage 1 assessment include the GAIN-Q3
Standard MI or the GAIN-I-Lite – these tools being part of the GAIN “family” of
substance abuse screening and assessment tools (www.chestnut.org). As with the
GAIN-SS, these brief assessment tools are appropriate for use with individuals from
age 10 and up. Another instrument for Stage 1 assessment is the Recovery Attitude
and Treatment Evaluation (RAATE: Gastfriend et al. 1995; Mee-Lee 1988;
Najavits et al. 1997).
These stages of the staged framework will only be briefly summarized as they are
somewhat out of the scope of the present focus on screening and assessment.
Outcome monitoring is, however, critically tied to these earlier stages because of
the need to establish baseline status early in the treatment process and to
inform and engage the client in the eventual follow-up processes, for example,
obtaining locator information. Importantly, a connection is now made between
within-treatment outcome monitoring and posttreatment outcome monitoring
with recovery checkups. Importantly, both within-treatment monitoring and
posttreatment outcome monitoring consider the contact for client and program
evaluation purposes, an extension of the treatment and support process itself.
This is conceptually quite different than a traditional “research” follow-up and much
81 Screening and Assessment for People with Substance Use Disorders 1273
more likely to engage administrative and clinical staff, as well as clients them-
selves, in the outcome monitoring process.
The usual approach to answering this question about the effectiveness of screening
is to assess whether the screening tool(s) and related process are successful in
identifying people with mental health and/addiction problems that would not have
been identified through routine care. Although this has rarely been put to the test in
1274 B. Rush
a systematic way (see Gilbody et al. 2007 for a synthesis of the research in the area
of depression), the well-documented level of undetected problems combined with
the high predictive value of many validated screening tools points to the importance
of systematic screening to improve case detection.
There are, however, two additional aspects to the effectiveness question.
The first is to ask whether the screening tools and processes, and subsequent review
of the results, contribute to the management of the index problem. In other words,
does it lead to meaningful action on the part of clinicians that would otherwise not
have occurred? Secondly, one must ask if, at the end of the day, the screening and
subsequent action have improved the index problem or related challenges.
The systematic review on screening for depression by Gilbody et al. (2007)
suggests that screening can contribute to better care management and health outcomes
if there is some selectivity in providing feedback to only moderate-to-high-risk
cases, rather than all people who may score positive according to test guidelines.
This highlights the fact that screening alone may make little difference without
a detailed response plan and follow-up intervention. In the addiction area, there is
ample evidence that screening for different levels of risk for alcohol and drug use,
accompanied by brief intervention or referral to treatment, is effective in engaging
people in both these response options and subsequent outcomes (Babor et al. 2007;
Madras et al. 2009; Kaner et al. 2009). More research is needed, however, to tease out
the most effective ingredients of the overall SBIRT protocol. More work is also
needed on addressing the challenges implementing SBIRT protocols in health care
and other settings (Johnson et al. 2010; Williams et al. 2011).
The context in which screening takes place must be carefully considered in both
implementation and evaluation of screening and assessment tools and processes.
As already mentioned, the role and purpose of screening should be well understood
and articulated in the context of the mandate and objectives of the service provider.
Organizational policy must also support the implementation of screening and
related protocols. Required staff competencies and program design should fit within
clear service delivery protocols addressing where, when, and how screening will be
administered and how the information gathered will be used. Personnel who are
administering the tools must be trained to introduce, administer, score, discuss, and
take appropriate action based on the screening results. All of this needs to be clearly
conveyed to individuals engaging with the service so that they understand how
screening can be helpful and provides fruitful ground for evaluative inquiry.
As noted above, implementing formal screening tools and processes is a logical
fit in the specialized substance abuse treatment sector. In these settings, clients have
already been identified as needing further screening, assessment, or treatment, and
consideration needs to be given to screening for co-occurring concerns beyond the
initial presenting problem, such as mental health. In other settings where routine
screening and assessment of various health concerns is already taking place
(i.e., primary care), the rationale for extending screening to identify addiction
problems is also clear. Screening in settings such as schools, employment counsel-
ing, and justice settings is important to consider given the evidence that rates of
addiction and mental health problems are high and often not identified. While these
81 Screening and Assessment for People with Substance Use Disorders 1275
settings provide important opportunities for early identification and early interven-
tion, there are a number of potential risks that must be considered, including stigma
resulting from identification and labeling, social exclusion, limitation of opportu-
nities, and false-positives consuming scarce treatment resources. Risks associated
with identification may be greater for specific individuals, for example, severe
sanctions may be imposed on those identified as being involved in substance
using activities by some schools, employment programs, shelter and housing pro-
viders, residential services in the mental health sector, long-term care facilities,
families, and specific ethno-cultural groups and communities.
Models of collaboration within which screening and assessment are core activities
provide the field with rich evaluation opportunities, including outcome and process
evaluation and an opportunity to monitor trends and performance. Outcomes can be
examined at the individual (i.e., client and service provider), organizational, and
community level. For example, at the organizational level, outcome indicators could
include changes in staff attitudes, skills, and behavioral engagement in screening and
assessment practices and change in referral practices as well as client perceptions of
care; at the community level, indicators could include increased numbers of new
clients referred to treatment and reduced number of emergency visits. It is also of
interest to evaluate the extent to which the development of collaborative models of
screening and assessment contribute to collaborative processes across agencies/
service providers – for example, increased partnership and building of partnership
capital to engage in other joint planning and service delivery. Using a consistent
screening tool across a collaborative group of service providers provides an oppor-
tunity for decision-makers, funders, and researchers to look at presenting needs
across settings and monitor trends over time within the collaborative as well as in
comparison to the general population (Henderson and Chaim 2013).
81.3 Conclusion
There is a very strong rationale for a more proactive concerted effort to screen for
mental health problems and at-risk consumption of alcohol and other drugs and
related addictions problems given the evidence concerning the level of under-
detection in routine practice and the performance of a host of screening tools and
processes. Screening in multiple sectors, along with follow-up assessment and
intervention, is one strategy to broaden the base for attending to addiction-related
concerns and increasing the scope and reach of treatment and support beyond the
traditional sector of specialized addiction services. There are many reasons to
engage in more proactive screening, and both individual and collaborating partners
need to be clear about how the information will be used, including making
improvements at the system level. When used for clinical decision-making, best
practice calls for a staged approach to maximize efficiency of the overall screening
and assessment process. The specific tools and processes must be tailored to the
setting and target population for which they are being implemented. For example,
some tools will work best for screening in primary care and other generic health and
1276 B. Rush
social service settings, and others are more appropriate for screening in specialized
mental health and addiction settings. That said, whether working in generic settings
such as primary care or specialized settings, a collaborative approach, drawing
upon multidisciplinary, multi-provider, and multi-sectoral expertise, is needed
across the stages of screening and assessment, along with a collaborative response
protocol for level-of-care placement/referral for treatment and support.
The evidence is quite strong with respect to the ability of screening tools and
processes to identify individuals needing brief intervention or other treatment and
support. This evidence underlies the best practice guidelines that call for targeted
screening in generic settings such as primary care and universal screening for all
clients engaged with specialized mental health and addiction services. However, the
effectiveness literature tells us that screening is only one part of the process of
engagement and the results are more equivocal in terms of the impact of the
screening per se on subsequent case management and health outcomes, the litera-
ture on SBIRT in the addiction field being an important exception. Collectively, the
literature that cuts across the mental health and addictions area reminds us that
screening alone is unlikely to translate into improved outcomes without a concerted
response. Collaborative care processes are likely to contribute to this response, and
more research is needed to find the active ingredients of collaborative screening,
assessment, and treatment and support processes. Much more research is also
needed on the facilitators and barriers to implementing universal or targeted
screening and assessment tools and processes at both the level of the individual
service provider and within collaborative, shared care arrangements.
References
Achenbach TM (1991) Manual for the child behavior checklist/4–18 and 1991 profile. Department
of Psychology, University of Vermont, Burlington
Alexander MJ, Haugland G, Lin SP, Bertollo DN, McCorry FA (2008) Mental health screening in
addiction, corrections and social services settings: validating the MMS. Int J Ment Heal Addict
6:105–109
Allen JP, Maisto SA, Conners GJ (1995) Self-report screening tests for alcohol problems in
primary care. Arch Intern Med 155:1726–1730
Andrew G, Cuijpers P, Craske MG, McEvoy P, Titov N (2010) Computer therapy for the anxiety
and depressive disorders is effective, acceptable and practical health care: a meta-analysis.
PLoS ONE 5(10). doi: 10.1371/journal.pone.0013196
Babor TF, Higgins-Biddle JC, Saunders JB, Monteiro MG (2001) AUDIT the alcohol use
disorders identification test: guidelines for use in primary care, 2nd edn. World Health
Organization, Geneva
Babor TF, McRee BG, Kassebaum PA, Grimaldi PL, Ahmed K, Bray J (2007) Screening, Brief
Intervention, and Referral to Treatment (SBIRT). Subst Abus 28(3):7–30
Babor TF, Stenius K, Romelsjo A (2008) Alcohol and drug treatment systems in public health
perspective: mediators and moderators of population effects. Int J Methods Psychiatr Res
17(S1):S50–S59
Barnaby B, Drummond C, McDloud A, Burns T, Omu NO (2003) Substance misuse in psychiatric
inpatients: comparison of a screening questionnaire survey with case notes. Br Med J
327:783–784
81 Screening and Assessment for People with Substance Use Disorders 1277
Beck AT (1961) Beck depression inventory. Center for Cognitive Therapy, Philadelphia
Beck AT, Epstein N, Brown G, Steer RA (1988) An inventory for measuring clinical anxiety:
psychometric properties. J Consult Clin Psychol 56:893–897
Benjamin AB, Mossman D, Graves NS, Sanders RD (2006) Tests of a symptom checklist to screen
for comorbid psychiatric disorders in alcoholism. Compr Psychiatry 47:227–233
Berwick DM, Murphy JM, Goldman PA et al (1991) Performance of a five-item mental health
screening test. Med Care 29:169–176
Bischof G, Reinhardt S, Grothues J, Meyer C, John U, Rumpf HJ (2007) Development and
evaluation of a screening instrument for alcohol-use disorders and at-risk drinking: the brief
alcohol screening instrument for medical care (BASIC). J Stud Alcohol Drugs 68(4):607
Bufka LF, Crawford JI, Levitt JT (2002) Brief screening assessments for managed care and
primary care. Handbook of assessment and treatment planning for psychological disorders.
Guilford Press, New York, pp 38–63
Carroll KM (1995) Methodological issues and problems in the assessment of substance use.
Psychol Assess 7:349–358
Center for Substance Abuse Treatment (2005) Substance abuse treatment for persons with
co-occurring disorders, vol 42, Treatment Improvement Protocol (TIP) series. Substance
Abuse Mental Health Services Administration, Rockville
Centre for Addiction and Mental Health (2006) Navigating screening options for concurrent
disorders. Centre for Addiction and Mental Health, Toronto, http://knowledgex.camh.net/
amhspecialists/Screening_Assessment/screening/navigating_screeningcd/Documents/navigating_
screening_options_CD.pdf
Centre for Addiction and Mental Health (2009) Screening for concurrent substance use
and mental health problems in youth. Centre for Addiction and Mental Health, Toronto, http://
knowledgex.camh.net/amhspecialists/Screening_assessment/screening/screen_CD_youth/
Documents/youth_screening_tools.pdf
Chalk M, Dilonardo J, Gelber Rinaldo S (2011) Purchasing integrated services for substance use
conditions in health care settings: an issue brief on lessons learned and challenges ahead.
Forum on Integration. A Collaborative for States, pp 1–36
Cunningham JA, Van Mierlo T (2009) Methodological issues in the evaluation of internet-based
interventions for problem drinking. Drug Alcohol Rev 28:12–17
Danseco, Marques (2002) Development and validation of a POSIT-Short form: screening for
problem behaviors among adolescents at risk for substance use. J Child Adolesc Subst Abus
11(3):17–36
Dawe S, Loxton NJ, Hides L, Kavanagh DJ, Mattick RP (2002) Review of diagnostic screening
instruments for alcohol and other drug use and other psychiatric disorders, 2nd edn. School of
Applied Psychology, Griffith University. Department of Psychiatry, University of Queensland:
National Drug and Alcohol Research Centre
Dennis M, Scott CK, Funk R (2003) An experimental evaluation of Recovery Management
Checkups (RMC) for people with chronic substance use disorders. Eval Program Plan
26:339–352
Dennis ML, Chan YF, Funk RR (2006) Development and validation of the GAIN Short Screener
(GSS) for internalizing, externalizing and substance use disorders and crime/violence problems
among adolescents and adults. Am J Addict 15:80–91
Derogatis LR (1983) SCL-90-R administration, scoring, and procedures manual II. Clinical
Psychometric Research, Towson
Derogatis LR, Melisaratos N (1983) The brief symptom inventory: An introductory report.
Psychol Med 13:595–605
Dhalla S, Kopec JA (2007) The CAGE questionnaire for alcohol misuse: a review of reliability and
validity studies. Clin Invest Med 30(1):33–41
Donovan DM (1999) Assessment strategies and measures in addictive behaviors. In: McCrady BS,
Epstein EE (eds) Addictions: a comprehensive guidebook. Oxford University Press,
New York, pp 187–215
1278 B. Rush
Drake RE, Mercer-McFadden C, McHugo GJ, Mueser KT, Rosenberg SD, Clark RE, Brunette MF
(eds) (1998) Readings in dual diagnosis. International Association of Psychosocial Rehabili-
tation Services, Columbia
Druss BG, Mauer BJ (2010) Health care reform and care at the behavioral health-primary care
interface. Psychiatr Serv 61(11):1087–1092
Ewing JA (1984) Detecting alcoholism: the CAGE questionnaire. J Am Med Assoc
252:1905–1907
First MB, Tasman A (2006) Clinical guide to the diagnosis and treatment of mental disorders.
Wiley, West Sussex
First MB, Spitzer RL, Gibbon M, Williams JBW (1996) Structured clinical interview for DSM-IV
axis I disorders-patient edition, SCID-I/P, version 2.0. Biometrics Research Department,
New York State Psychiatric Institute, New York
Fjeldsoe BS, Marshall AL, Miller YD (2009) Behavior change interventions delivered by mobile
telephone short-message service. Am J Preventative Med 36(2):165–173
Flynn PM, Brown BS (2008) Co-occurring disorders in substance abuse treatment: issues and
prospects. J Subst Abus Treat 34:36–47
Foy R, Hempel S, Rubenstein L, Suttorp M, Seelig M, Shanman R, Shekelle P (2010) Meta-
analysis: effect of interactive communication between collaborating primary care physicians
and specialists. Ann Intern Med 152(4):247–258
Gastfriend DR (2003) Addiction treatment matching: research foundations of the American
Society of Addiction Medicine (ASAM) criteria. Haworth Medical Press, Binghamton
Gastfriend DR, Mee-Lee K (2003) The ASAM patient placement criteria: context, concepts and
continuing development. J Addict Dis 22(Suppl 1):1–8
Gastfriend DR, Filstead WJ, Reif S, Najavits LM, Parrella DP (1995) Validity of
assessing treatment readiness in patients with substance use disorders. Am J Addict
4(3):254–260
Gastfriend DR, Lu S, Sharon E (2000) Placement matching: challenges and technical progress.
Subst Use Misuse 35(12–14):2191–2213
Gilbody S, Whitty P, Grimshaw J, Thomas R (2003) Educational and organizational interventions
to improve the management of depression in primary care. JAMA 289(23):3145–3151
Gilbody S, House AO, Sheldon TA (2007) Screening and case finding instruments for depression
(review). The Cochrane Collaboration. John Wiley & Sons Ltd
Goodman A, Goodman R (2009) Strengths and difficulties questionnaire as a dimensional measure
of mental health. J Acad Child Adolesc Psychiatry 48(4):400–403
Greenfield SF, Hennessy G (2008) Assessment of the patient (Chap. 5). In: Galanter M, Kleber HD
(eds) The textbook of substance abuse treatment. American Psychiatric Publishing Inc,
Arlington, pp 55–78
Hasin DS, Trautman KD, Miele GM, Samet S, Smith M, Endicott J (1996) Psychiatric Research
Interview for Substance and Mental Disorders (PRISM): reliability for substance abusers. Am
J Psychiatr 153(9):1195–1201
Health Canada, Rush B (2001) Best practice for concurrent mental health and substance use
disorders. Health Canada, Ottawa, Cat. No. H39-599/2001-2E/ISBN: 0-662-31388-7
Henderson J, Chaim G (2013) National youth screening project report. Centre for Addiction and
Mental Health, Toronto
Hilton T (2011) The promise of PROMIS for addictions. Drug Alcohol Depend 119:229–234
Institute of Medicine (1990) Broadening the base of treatment for alcohol problems. National
Academy Press, Washington, DC
Ivbijaro G (ed) (2012) Companion to primary care mental health. World Health Organization, Geneva
Johnson M, Jackson R, Guillaume L, Meier P, Goyder E (2010) Barriers and facilitators to
implementing screening and brief intervention for alcohol misuse: a systematic review of
qualitative evidence. J Publ Health 33(3):412–421
Jordan C, Franklin C (2011) Clinical assessment for social workers: quantitative and qualitative
methods, 3rd edn. Lyceum Books, Chicago
81 Screening and Assessment for People with Substance Use Disorders 1279
Kaner EF, Dickinson HO, Beyer FR, Campbell F, Schlesinger C, Heather N, Saunders JB,
Burnand B, Pienaar ED (2009) The Cochrane Library, Volume 4, The Cochrane Collaboration.
Published by John Wiley & Sons, Ltd.
Kessler RC, Nelson CB, McGonagle KA et al (1996) The epidemiology of co-occurring addictive
and mental disorders: implications for prevention and service utilization. Am
J Orthopsychiatry 66:17–31
Kessler RC, Andrews G, Colpe LJ, Hiripi E, Mroczek DK, Normand S-LT, Walters EE,
Zaslavsky A (2002) Short screening scales to monitor population prevalences and trends in
non-specific psychological distress. Psychol Med 32(6):959–976
Klein S, Alexander DA, Hutchinson JD, Simpson JA, Simpson JM, Bell JS (2002) The Aberdeen
trauma screening index: and instrument to predict post-accident psychopathology. Psychol
Med 32:863–871
Knight JR, Shrier LA, Bravender TD, Farrell M, Vander Bilt J, Shaffer HJ (1999) A new brief
screen for adolescent substance abuse. Arch Pediatr Adolesc Med 153:591–596
Kohn R, Saxena S, Levav I, Sacareno B (2004) The treatment gap in mental health care. Bull
World Health Organ 82(11):858–866
Kranzler HR, Kadden RM, Babor TF, Rounsaville BJ (1994) Longitudinal, expert, all data
procedure for psychiatric diagnosis in patients with psychoactive substance use disorders.
J Nerv Ment Disord 182:277–283
Lambert MJ, Burlingame GM, Umphress V, Hansen NB, Vermeersch DA, Clouse GC,
Yanchar SC (1996) The reliability and validity of the outcome questionnaire. Clin Psychol
Psychother 3(4):249–258
Lanyon RI (2006) Mental health screening: utility of the psychological screening inventory.
Psychol Serv 3(3):170–180
Lee M, Liao SC, Lee YJ, Wu CH, Tseug MC, Gau SF, Rau CI (2006) Development and
verification of validity and reliability of a short screening instrument to identify psychiatric
morbidity. J Formos Med Assoc 102(10):687–694
Ley A, Jeffery D, Shaw S, Weaver T (2007) Development of a brief screen for substance misuse
amongst people with severe mental health problems living in the community. J Ment Health
16(5):679–690
Lucas CP, Zhang H, Fisher PW, Shaffer D, Regier DA, Narrow WE et al (2001) The DISC
Predictive Scales (DPS): efficiently screening for diagnoses. J Am Acad Child Adolesc
Psychiatry 40:443–449
Lucenko BA, Mancuso D, Felver BEM, Yakup S, Huber A (2010) Co-occurring mental illness
among clients in chemical dependency treatment. Washington State Department of Social and
Health Services Research and Data Analysis Division, Olympia. http://publications.rda.dshs.
wa.gov/1409/. Retrieved 30 June10
Madras BK, Compton WM, Avula D, Stegbauer T, Stein JB, Clark HW (2009) Screening,
brief interventions, referral to treatment (SBIRT) for illicit drug and alcohol use at
multiple healthcare sites: comparison at intake and 6 months later. Drug Alcohol Depend
99(1):280–295
Magruder KM, Sonne SC, Brady KT, Quello RHM (2005) Screening for co-occurring mental
disorders in drug treatment populations. J Drug Issues 35:593–605
McGovern M, Matzkin AL, Giard J (2007) Assessing the dual diagnosis capability of addiction
treatment services: the Dual Diagnosis Capability in Addiction Treatment (DDCAT) index.
J Dual Diagn 3(2):111–123
McLellan T, Kushner H, Metzger D, Peters R, Smith J, Grissom C, Petinati H, Argeriou M (1992)
The fifth edition of the addiction severity index. J Subst Abus Treat 9:199–213
McLellan T, Lewis DC, O’Brien CP (2000) Drug dependence, a chronic medical illness:
evaluation implications for treatment, insurance, and outcomes. J Am Med Assoc
284(13):1689–1695
McPherson TL, Hersch RK (2000) Brief substance use screening instruments for primary care
settings: a review. J Subst Abus Treat 18(2):193–202
1280 B. Rush
Means-Christensen AJ, Sherbourne CD, Roy-Byrne PP, Craske MG, Stein MB (2006) Using five
questions to screen for five common mental disorders in primary care: diagnostic accuracy of
the anxiety and depression detector. Gen Hosp Psychiatry 28(2):108–118
Mee-Lee D (1988) An instrument for treatment progress and matching: the Recovery Attitude and
Treatment Evaluator (RAATE). J Subst Abus Treat 5(3):183–186
Mee-Lee D, Gastfriend DR (2008) Patient placement criteria. Chapter 5, In: Galanter M, Kleber
HD (eds) The textbook of substance abuse treatment. Arlington: American Psychiatric
Publishing Inc. pp 79–91
Meltzer-Brody S, Churchill E, Davidson JRT (1999) Derivation of the SPAN, brief diagnostic
screening test for post-traumatic stress disorder. Psychiatry Res 88:63–70
Miller P (2006) Alcohol and drug abuse. In: Hersen M (ed) Clinician’s handbook of adult
behavioral assessment. Elsevier, New York
Mitchell AJ, Meader N, Bird V, Rizzo M (2012) Clinical recognition and recording of alcohol
disorders by clinicians in primary and secondary care: meta-analysis. Br J Psychiatry
201:93–100
Najavits LM, Gastfriend DR, Nakayama EY, Barber JP, Blaine J, Frank A, Muenz LR, Thase M
(1997) A measure of readiness for substance abuse treatment. Am J Addict 6(1):74–82
National Treatment Agency (2002) Models of care for treatment of adult drug misusers. Author,
London
Parikh S (2008) Screening and treating mental disorders in addiction treatment settings: a stepped
care model. Int J Ment Heal Addict 6:137–140
Pediatrics (2010) Supplemental appendix S12: mental health screening and assessment tools for
primary care. Pediatrics 125:S173–S192. http://pediatrics.aappublications.org/content/125/
Supplement_3/S173.full.pdf%20html. Retrieved on 10 May 2013
Ramchand R, Marshall GN, Schell TL, Jaycox LH, Hambarsoomians K, Shetty V, Hinika GS,
Cryer HG, Meade P, Belzberg H (2009) Alcohol abuse and illegal drug use among Los Angeles
County trauma patients: prevalence and evaluation of single item screener. J Trauma
66(5):1461–1467
Rush BR, Castel S (2011) Screening for mental and substance use disorders. In: Cooper D (ed) Care
in mental health-substance use (Book 5, chapter 8), Mental health-substance use book series.
Radcliffe Publishing Ltd, Oxford, pp 89–105
Rush BR, Nadeau L (2011) On the integration of mental health and substance use services
and systems. In: Cooper D (ed) Responding in mental health-substance use (Book 3,
chapter 13), Mental health-substance use book series. Radcliffe Publishing Ltd, Oxford,
pp 148–175
Rush BR, Castel S, Somers J et al (2009) Systematic review and research synthesis of
screening tools for mental and substance use disorders appropriate for children and adoles-
cents: Technical report. Unpublished manuscript. Centre for Addiction and Mental Health,
Toronto
Rush BR, Castel S, Brands B, Toneatto T, Veldhuizen S (2013) Validation and comparison of
diagnostic accuracy of four screening tools for mental disorders in people with substance use
disorders. J Subst Abus Treat 44(4):375–383
Russell M (1994) New assessment tools for risk drinking during pregnancy: T-ACE, TEAK, and
others. Alcohol Health Res World 18:55–61
Sacks S (2008) Brief overview of screening and assessment for co-occurring disorders. Int J Ment
Heal Addict 6:7–19
Sareen J, Jagdeo A, Cox BJ, Clara I, ten Have M, Belik SL, de Graaf R, Stein MB (2007) Perceived
barriers to mental health service utilization in the United States, Ontario and the Netherlands.
Psychiatr Serv 58(3):357–364
Savage C (2006) Screening for alcohol use in women of childbearing age. J Addict Nurs 17:67–69
Scott CK (2004) A replicable model for achieving over 90 % follow-up rates in longitudinal
studies of substance abusers. Drug Alcohol Depend 74:21–36
81 Screening and Assessment for People with Substance Use Disorders 1281
Scott CK, Dennis ML (2009) Results from two randomized clinical trials evaluating the impact of
quarterly recovery management checkups with adult chronic substance users. Addiction
104:959–971
Shapiro S, Skinner EA, Kessler LG, Von Korff M, German PS, Tischler GL, Leaf PJ, Benham L,
Cottler L, Regier DA (1984) Utilization of health and mental health services: three epidemi-
ologic catchment area sites. Arch Gen Psychiatry 41(10):971–978
Smith PC, Schmidt SM, Allensworth-Davies D, Saitz R (2010) A single-question screening test for
drug use in primary care. Arch Intern Med 170(13):1155–1160
Sullivan JT, Skykora K, Schneiderman J (1989) Assessment of alcohol withdrawal: the revised
Clinical Institute Withdrawal Assessment for alcohol scale (CIWA-Ar). Br J Addict
84:1353–1357
Tucker JA, Vuchinich RE, Murphy JG (2004) Substance use disorders. In: Antony MA,
Barlow DH (eds) Handbook of assessment and treatment planning for psychological disorders.
Guilford press, New York
Urbanoski K, Rush BR, Wild TC, Bassani D, Castel C (2007) The use of mental health care
services by Canadians with co-occurring substance dependence and mental illness. Psychiatr
Serv 58(7):962–969
Urbanoski KA, Cairney J, Bassani D, Rush B (2008) Perceived unmet need for mental health
care among Canadians with co-occurring addiction and mental illness. Psychiatr Serv
59(3):283–289
Ware JE, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36).
I. Conceptual framework and item selection. Med Care 30(6):473–483
Weaver T, Madden P, Charles V, Stimson G, Renton A, Tyrer P, Barnes T, Bench C, Middleton H,
Wright N, Paterson S, Shanahan W, Seivewright N, Ford C (2003) Co-morbidity of substance
misuse and mental illness collaborative (COSMIC) study: findings and service development
implications of a multi-centre prevalence study in NHS drug, alcohol and adult community
psychiatric services. Br J Psychiatry 183:304–313
Williams EC, Johnson ML, Lapham GT, Caldeiro RM, Chew L, Fletcher GS et al (2011)
Strategies to implement alcohol screening and brief intervention in primary care settings:
a structured literature review. Psychol Addict Behav 25(2):206–214
Zimmerman M, Mattia JI (1999) Psychiatric diagnosis in clinical practice: is comorbidity being
missed? Compr Psychiatry 40:182–191
Zimmerman M, Mattia JI (2001) A self-report to help make psychiatric diagnosis. The psychiatric
diagnostic screening questionnaire. Arch Gen Psychiatry 58:787–794
Stepped Care Models in Addiction
Treatment 82
Ambros Uchtenhagen
Contents
82.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1284
82.1.1 A Concept for Patient Placement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1284
82.1.2 Models of Stepped Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1284
82.1.3 The Main Elements of Stepped Care Models:
A Comparative Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1286
82.1.4 Evaluation Results and Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1286
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1289
Abstract
Stepped care models aim at matching treatment intensity to defined patient
characteristics in a systematic way, thereby avoiding misplacements and making
best use of available treatment resources at the same time. In principle, treatment
planning for new patients starts with the least intensive care, progressing to more
intensive regimes for nonresponders. Such models have been introduced in
psychiatry and in other medical fields.
Models of stepwise patient placement in addiction treatment are known from
Northern America (Sobell model, model of the American Society of Addiction
Medicine, ASAM) for adults and adolescents and special models for dual-
diagnosis patients. Another model comes from Europe (the Dutch model for
triage and evaluation in addiction treatment MATE; special model for judicial
patients). The various elements and procedures of the ASAM and MATE models
are described and compared.
An overview on evaluation studies and reviews is presented, concerning
feasibility, validity, reliability, effectiveness, and cost-effectiveness of stepped
A. Uchtenhagen
Research Foundation for Public Health and Addiction, Zurich University, Zurich, Switzerland
e-mail: [email protected]
care models. Outcomes are partly positive, but limitations are mentioned and
more research is asked for.
82.1 Introduction
requires a decision about patient progress and depends on the type of disorder and
the effectiveness of available treatments. The decisions may be made on the basis of
guidelines, but should not disregard the risk of inappropriate stepping up and of
missed stepping up and should include considerations about costs of treatments at
different levels.
Stepped care models use three essential elements: patient indicators used for
determining the appropriate level of care, treatment typology in regard to intensity
of care, assessment, and referral procedures. The following figures summarize the
relevant information on these elements in the ASAM and MATE models
(Tables 82.1 and 82.2; Figs. 82.1 and 82.2).
A systematic review was made on the efficacy of stepped care models involving
different levels of psychosocial treatment for alcohol use disorders and nicotine
dependence, with or without medication (Jaehne et al. 2012). Little evidence was
found to suggest that stepping up nonresponders to more intensive therapy
improved outcomes. In one study, the application of a stepped care approach
was found to reduce treatment costs compared with usual care. There was some
evidence that the greater differentiation between the intensity of the interventions
offered at each step, the better the outcome. Further research is needed to
evaluate the efficacy of stepped care approaches to providing psychosocial
treatment.
Table 82.1 Patient characteristics used for determining appropriate level of care
ASAM assessment dimensions MATE patient indicators
Acute intoxication and/or withdrawal potential Addiction severity
Biomedical conditions and complications Psychiatric impairment
Emotional, behavioural, cognitive conditions/complications Social stability
Readiness to change Treatment history 0–1
Relapse/continued use, continued problem potential Treatment history 2
Recovery environment Treatment history 3–5
Treatment history >5
Source for ASAM: Mee-Lee and Shulman (2009), Table 27.1. Source for MATE: Schippers and
Broekman (2007)
82 Stepped Care Models in Addiction Treatment 1287
If imminent risk in relapse, continued use, recovery environment: placement in level III
If dose and intensity of services require less than 9 hours/week: placement in level I
Repeat assessment of multidimensional severity and level of function to determine need for
continued stay in present level of care, or to transfer or discharge to a less or more intensive
level of care
Fig. 82.1 Assessment and referral procedures in ASAM PPC-2r (Source: Mee-Lee and
Gastfriend 2008, Fig. 6-1)
No
Treatment history : good or
Yes Yes Outpatient
[2] moderate
No
Treatment history : Daycare /
Yes low Yes
[3-5] Residential
Care
Treatment history :
Yes (in- and
[> 5] outpatient)
Fig. 82.2 MATE guidance for matching and referral (Source: Merkx et al. 2007, Fig. 2)
interventions” to patients and therapists. The review concludes that more research is
needed in terms of rigorous evaluations of the underlying assumptions.
A summary of research on the ASAM patient placement criteria is presented in
the Textbook of Substance Abuse Treatment. The authors conclude as follows:
“More than a decade of research of the ASAM PPC supports the predictive validity
and the cost-effectiveness of the use of PPC. Based on this research, a variety of
computer assisted assessment and placement tools are in development” (Mee-Lee
and Gastfriend 2008, p. 88). Another overview is presented in the Principles of
Addiction Medicine. Nine evaluation studies were performed involving 3,641
subjects; controlled studies found that “treatment based on the ASAM PPC are
associated with less morbidity, better client functioning, and more efficient service
utilization than mismatched treatment” (Mee-Lee and Shulman 2009, p. 398).
Feasibility and field testing of the MATE in a treatment seeking population was
performed in two large treatment settings. Construct validation with related instru-
ments and evaluation of the dimensional structure of modules were performed.
Among the results are a satisfactory inter-rater reliability and concurrent validity,
indicating the usefulness of the instrument for allocating patients to substance abuse
treatment, even in a heterogeneous population (Schippers et al. 2010). However,
there were some problems with clinicians not complying with the guidelines,
resulting in mismatched patients usually allocated to outpatient treatment instead
of early interventions (Merkx et al. 2007).
A comparison of minimal interventions with a stepped care model for patients
with alcohol use disorders in the UK evidenced greater cost savings, greater
motivation for change, and greater reduction of alcohol consumption for stepped
care 6 months after randomization (Drummond et al. 2009).
82 Stepped Care Models in Addiction Treatment 1289
References
Bower P, Gilbody S (2005) Stepped care in psychological therapies: access, effectiveness and
efficiency. Narrative literature review. Br J Psychiatry 186:11–17
Breslin F, Sobell M, Sobell L (1999) Problem drinkers: evaluation of stepped care approach.
J Subst Abuse 10:217–232
Buchholz A, Rist F, K€ ufner H, Kraus L (2009) Die deutsche Version des Measurements in the
Addictions for Triage and Evaluation (MATE): Reliabilität, Validität und Anwendbarkeit.
Sucht 55:219–242
Drummond C, Coulton S, Darrenn J, Godfrey C, Parrott S, Baxter J, Ford D, Lervy B, Rollnick S,
Russell J, Peters T (2009) Effectiveness and cost-effectiveness for a stepped care intervention
for alcohol use disorders in primary care: a pilot study. Br J Psychiatry 195:448–456
Fishman MJ (ed) (2010) The ASAM patient placement criteria. Supplement on pharmacotherapies
for alcohol use disorders (1st ed). Lippincott, Williams and Wilkins, Philadelphia
Haaga DAF (2000) Introduction to the special section on stepped care models in psychotherapy.
J Consult Clin Psychol 68:547–548
Jaehne A, Loessl B, Frick K, Berner M, Hukse G, Balmford J (2012) The efficacy of stepped care
models involving psychosocial treatments in alcohol use disorders and nicotine dependence:
a systematic review of the literature. Curr Drug Abuse Rev 5:41–51
Kranzler HR, McKay JR (2012) Personalized treatment of alcohol dependence. Cum Psychiatry
Rep 14:486–493. doi: 10.1007/s11920-012-0296-5
Mee-Lee D (ed) (2001) ASAM patient placement criteria for the treatment of substance
use disorders, 2nd edn. Revised. American Society of Addiction Medicine. www.asam/org/
publications.patient-placement-criteria/ppc-2r
Mee-Lee D (2006) Development and implementation of patient placement criteria. New develop-
ments in addiction treatment. Academic highlights. J Clin Psychiatry 67(11):1805–1807
Mee-Lee D, Gastfriend DR (2008) Patient placement criteria. In: Galanter M, Kleber HD (eds)
Textbook of substance abuse treatment, 4th edn. The American Psychiatric Publishing,
Arlington, VA, pp 79–91
Mee-Lee D, Shulman GD (2009) The ASAM placement criteria and matching patients to treat-
ment. In: Ries RK, Fiellin DA, Miller SC, Saitz R (eds) Principles of addiction medicine,
4th edn. Kluwer/Lippincott, Williams & Wilkins, Philadelphia
Merkx MJM, Schippers GM, Koeter MJ, Vujik PJ, Oudejans S, De Vries CCQ, Van den Brink W
(2007) Allocation of substance use disorder patients to appropriate levels of care: feasibility of
matching guidelines in routine practice in Dutch treatment centres. Addiction 102:466–474
Richards DA, Power P, Pagel C, Weaver A, Utley M, Cape J, Pilling S, Lovell K et al (2012)
Delivering stepped care: an analysis of implementation in routine practice. Implement Sci 7:3
Schippers GM, Broekman TG (2007) MATE, measurements in the addictions for Triage and
evaluation. Final report. www.mateinfo.en/pubs/31000068.pdf. Accessed 22 Jan 2013
Schippers GM, Broekman TG, Buchholz A, Koeter MWJ, Van den Brink W (2010) Measurements
in the Addictions for Triage and Evaluation (MATE): an instrument based on the World Health
Organisation family of international classifications. Addiction 105:862–871
Sobell MB, Sobell LC (2000) Stepped care as a heuristic approach to the treatment of alcohol
problems. J Consult Clin Psychol 68:573–579
Harm Reduction Interventions
83
Dagmar Hedrich and Richard Hartnoll
Contents
83.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1292
83.2 Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1293
83.2.1 Opioid Substitution Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1293
83.2.2 Needle and Syringe Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1295
83.2.3 Supervised Drug Consumption Facilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1299
83.2.4 Overdose Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1300
83.2.5 Outreach, Peer Education, and Health Promotion . . . . . . . . . . . . . . . . . . . . . . . . . . . 1301
83.2.6 Testing, Vaccination, and Treatment of Infectious Diseases . . . . . . . . . . . . . . . . 1303
83.2.7 Interventions for Stimulant Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1304
83.2.8 Drug-Related Sexual Risk Reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1307
83.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1308
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1308
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1313
Abstract
The goal of harm reduction is to reduce both the individual and societal harms of
drug use through knowledge-based interventions that change risk behaviors and
risk settings. ▶ Chapter 84, “Harm Reduction Policies, Settings, and Chal-
lenges” in this textbook gives an overview of harm reduction as a public health
policy. This chapter describes the main harm reduction interventions
implemented in many countries around the world, synthesizes evidence on
their effectiveness and risks, and summarizes key lessons learned. The focus is
on illegal drugs, especially opioids and central nervous system stimulants. The
interventions covered are opioid substitution treatment; needle and syringe pro-
grams; supervised drug consumption facilities; drug overdose prevention; out-
reach, peer education, and health promotion; testing, vaccination, and treatment
83.1 Introduction
The goal of harm reduction is to reduce individual and societal harms of drug use
through knowledge-based interventions that change risk behaviors and risk settings.
▶ Chapter 84, “Harm Reduction Policies, Settings, and Challenges” in this text-
book gives an overview of harm reduction as a public health policy. This chapter
describes the major harm reduction interventions, synthesizes evidence on their
effectiveness, and summarizes key lessons learned. The interventions covered are:
• Opioid substitution treatment
• Needle and syringe programs
• Supervised drug consumption facilities
• Overdose prevention interventions
• Outreach, peer education, and health promotion
• Testing, vaccination, and treatment of infectious diseases
• Interventions for stimulant use
• Drug-related sexual risk reduction
This overview draws on a wide range of sources from research and practice.
Scientific reviews of experimental studies are valuable for assessing outcomes of
single, well-defined interventions. However, they are insufficient regarding
multidimensional interventions as implemented in diverse, real-life settings. Exper-
imental designs are not always appropriate, feasible, or ethical and are limited to
single types of intervention, thus excluding multiple interventions. Often, it is
necessary to draw on a wider body of descriptive studies to obtain a fuller picture.
Furthermore, it is essential to understand not only outcomes but also how interven-
tions work (process) and how settings influence outcomes. Clinical, sociological,
qualitative, modelling, and ecological studies can provide important evidence not
only on the impact of interventions and policies but also on “what works and under
what conditions.”
The focus is on illegal drugs, especially opioids and central nervous system
stimulants. Harm reduction approaches have been applied to other drugs including
83 Harm Reduction Interventions 1293
alcohol, cannabis, and tobacco and to other user groups such as young recreational
drug users (Ritter and Cameron 2006; Rhodes and Hedrich 2010).
83.2 Interventions
Other chapters in this textbook deal with opioid substitution treatment (OST) as
a treatment for heroin dependence. Here, the emphasis is on the role of OST in
reducing individual and social harms associated with illicit opioid use. Methadone
is the main drug employed, though buprenorphine has become more common since
the end of the 1990s. In some European countries, heroin-assisted treatment is
provided to long-term refractory heroin-dependent individuals who have not
responded well on methadone programs (Strang et al. 2012). OST is usually
provided in combination with psychosocial treatment, counselling, and other health
and social services.
Within a harm reduction paradigm, OST consists of the (usually long-term)
prescription of opioid agonists to prevent withdrawal symptoms and craving, thus
enabling users to lead more stable lives and to reduce illicit heroin use, risk
behavior, and criminal activity. Apart from reduced illicit heroin use, which has
been demonstrated in numerous studies (see ▶ Chap. 28 “Opioid Addiction: Short-
and Long-Acting Opioids” in this textbook), specific harm reduction outcomes that
are sought include reductions in prevalence and frequency of drug injecting and
sharing of drug using paraphernalia, incidence and prevalence of infectious diseases
(especially HIV and hepatitis C), rates of drug-related mortality (especially over-
doses), and rates of drug-related crime. Reductions in high-risk sexual behaviors, as
well as improvements in health status, quality of life, and social functioning, are
also objectives, though these are not specific to OST.
often high. While some reviews report little impact of OST as a single intervention
(Wright and Tompkins 2006), other recent studies, including a meta-analysis of
UK-based studies and cohort studies of hepatitis C incidence among OST clients,
suggest a positive impact of OST on preventing HCV infections (Turner et al. 2011;
Kimber et al. 2010; ECDC and EMCDDA 2011). There is stronger evidence that
OST combined with NSP for clients who continue drug injecting can be highly
effective in reducing hepatitis C incidence, if coverage of both interventions is high
(van den Berg et al. 2007; Des Jarlais et al. 2010; Turner et al. 2011).
There is strong, review-level evidence that OST reduces substantially the risk of
overdose mortality, as long as doses are sufficient and continuity of treatment is
maintained (Amato et al. 2005; Caplehorn et al. 1996; Kimber et al. 2010).
A systematic review and meta-analysis of mortality among regular or dependent
users of heroin from 58 prospective cohort studies, mostly of OST, found that
treatment is clearly protective against mortality (Degenhardt et al. 2011).
There is clear, consistent evidence from many studies that criminal activity,
arrest, and incarceration rates decline markedly after patients enter OST and that
this effect is stronger the longer they remain in treatment (NIDA 2006). This is
particularly true of drug-related criminal activity such as drug-dealing and acquis-
itive crime. Where sufficient coverage of opioid using populations is achieved,
decreases in drug-related crime at individual level are reflected in reduced levels of
crime at community level.
A recent systematic review of 21 studies conducted in prison settings concluded
that the benefits of OST provided in prison are similar to those obtained in
community settings (Hedrich et al. 2012). OST was significantly associated with
reduced heroin use, injecting, and syringe sharing in prison if doses were adequate.
Prerelease OST was significantly associated with increased treatment entry and
retention after release if arrangements existed to continue treatment. For other
outcomes, associations with prerelease OST were weaker. While some post-release
reductions in heroin use were observed, evidence regarding crime and
re-incarceration was equivocal. Due to lack of studies, there was insufficient
evidence concerning HIV/HCV incidence, either in prison or post-release. There
was limited evidence that prerelease OST reduces post-release mortality. Disrup-
tion of OST continuity, especially due to brief periods of imprisonment, was
associated with very significant increases in HCV incidence (Dolan et al. 2005).
There is also evidence that OST facilitates improved adherence to HIV treatment
(Palepu et al. 2006) and modest reductions in high-risk sexual behaviors (Gowing
et al. 2004; CDC 2012a).
83.2.1.2 Conclusion
Benefits of OST that have been clearly established include reduced illicit heroin
use, injecting and risk behaviors, reduced HIV incidence, overdose mortality, and
criminal activity. Reductions in HCV incidence, though reported in some studies,
are less well established.
In prison settings, OST presents an opportunity to recruit problem opioid users
into treatment, to reduce illicit opioid use and risk behaviors in prison, and
83 Harm Reduction Interventions 1295
Needle and syringe programs (NSPs) are specialized services that distribute sterile
injecting equipment to people who inject drugs. They are usually located close to
areas where drug injecting is more prevalent. They are almost always part of
a wider network of local services. Their primary objective is to facilitate more
hygienic injecting practices and to reduce sharing or reuse of needles, syringes, and
other injecting paraphernalia in order to prevent injection-related complications,
especially transmission of HIV and HCV. In addition, NSPs serve as important
contact points for drug users who have little contact with treatment or other health
services. Thus a supplementary objective is to deliver health promotion information
and to facilitate access to health care, including OST or other treatment. They
routinely distribute condoms and offer advice on safer sex. Some offer
non-injecting equipment. NSPs may be equipped to provide testing for infectious
1296 D. Hedrich and R. Hartnoll
diseases and STDs, as well as vaccination for hepatitis B and basic health care.
Dedicated NSPs are usually fixed-site, though may also have mobile units or
outreach teams. In some countries, NSPs are implemented through national net-
works of pharmacies. In other settings pharmacy-based programs and vending
machines supplement specialized NSPs. In some countries, NSPs have been
established in prisons.
83.2.2.2 Conclusion
Benefits of NSPs, when implemented appropriately, include important reductions in
injecting risk behaviors and HIV transmission. They also play a valuable role in
health promotion, sexual risk reduction, and facilitation of access to health care
including treatment. In combination with other harm reduction interventions, they
can make a significant contribution to reducing not only HIV but also HCV
transmission. There is no evidence that the establishment of NSPs encourages
non-injectors to start injecting, or that the frequency of injection increases among
those who attend them (Tilson et al. 2006). There were no reports of adverse events
involving syringes in the studies of prison-based NSPs.
Many important lessons have been learned over the past three decades. It is
essential to aim for full coverage of clients’ injecting needs. Restrictions on the
number of needles and syringes distributed, or insistence on returning used equip-
ment, can be counterproductive, especially for high-frequency injectors such as
cocaine users, since this can facilitate reuse and sharing. The underlying principle
should be at least 100 % coverage of each injection (“one shot, one syringe”) and
distribution according to need rather than one-for-one exchange. It is also important
to achieve wide coverage of local populations of drug injectors. Many NSPs allow
secondary distribution, where clients distribute clean needles and syringes to their
partners or peers. Mobile units and outreach are valuable to further extend
coverage.
Injecting equipment should be appropriate for the local context and take account
of factors such as type and preparation of drugs that are commonly injected.
Injectors often have preferences for certain types or sizes of equipment. Apart
from needles and syringes, it is necessary to provide other injecting-related para-
phernalia, including alcohol swabs, sterile water, filters, mixing vessels (e.g.,
spoons or “cookers”), and acidifiers (e.g., ascorbic acid or citric acid powders) to
assist dissolving the substance to be injected (ECDC and EMCDDA 2011).
Health promotion should cover information on viral infections, how they are
transmitted and how they can be avoided, practical advice on hygiene and safer
injecting, as well as information on STDs and on ways of reducing sexual risks.
It should include provision of condoms, information on health and social services,
and, when appropriate, referral to drug treatment. While staff can encourage clients
to consider entering treatment, or to change to safer routes of administration, this
should not be linked to pressure such as implied withdrawal of services. Since NSPs
come in contact with out-of-treatment drug injectors, it is valuable if they have the
capability to carry out on-site counselling, testing, and monitoring of HIV, viral
hepatitis, STDs, and TB, as well as vaccination for hepatitis B. Some NSPs also
provide basic health care (e.g., wound dressing) or overdose prevention education,
including naloxone.
It is important to distinguish receptive and distributive sharing. While receptive
sharing (borrowing) should be strongly avoided, even if the lender is known to be
seronegative, it is even more important that distributive sharing (lending) by
persons who are seropositive is prevented. There is evidence that drug users reduce
their distributive sharing (and also sexual risk behaviors) if they know that they are
1298 D. Hedrich and R. Hartnoll
83.2.3.2 Conclusion
Benefits of DCRs include improvements in safe, hygienic drug use, especially
among regular clients; increased access to health and social services; and reduced
public drug use and associated nuisance. The availability of safer injecting facilities
does not increase drug use or frequency of injecting, it facilitates rather than delays
treatment entry, and does not result in higher rates of local drug-related crime.
1300 D. Hedrich and R. Hartnoll
DCRs have mostly been established in specific urban settings with problems of
public drug use or where there are subpopulations of drug users with limited
possibilities of hygienic injection (e.g., homeless, living in insecure accommoda-
tion or shelters). In some cases, DCRs are also utilized for various reasons by more
socially stable clients, for example, because they live with non-using partners or
families. As with NSPs, consultation with local key actors is essential to minimize
community resistance or counterproductive police responses.
Although rising overdose deaths often serve as a catalyst for concern over drug use,
efforts to develop specific interventions to reduce overdoses have emerged more
slowly than responses to other drug-related problems like dependence, crime, or
HIV/AIDS. As noted above, OST significantly reduces overdose mortality, and
DCRs may make a contribution at the local level. A promising approach to reducing
opioid overdose deaths is offered by community-based overdose prevention pro-
grams that include peer naloxone distribution (CDC 2012b).
Naloxone (Narcan ®) is an opioid antagonist used in medical emergencies to
reverse respiratory depression caused by opioid overdose. It has no effect on
non-opioid drug overdoses and has a high safety margin. It is available in an
injectable form and, in the USA and some other countries, as an intranasal spray.
The aim of naloxone distribution programs is to increase the availability of
effective medication in places where overdoses are more likely to occur. The
rationale is that overdose is common among opioid users. In some studies, over
a third have experienced an (nonfatal) overdose and two-thirds have witnessed one
(Lagu et al. 2006). Many people who die from opioid overdose fail to receive proper
medical attention because their peers and other witnesses (often other drug users)
do not recognize the seriousness of the situation and delay or do not call emergency
services for fear of police involvement (Pollini et al. 2006).
Peer naloxone distribution programs work by training drug users and other likely
first responders (peers, families) as well as frontline services such as health-care
providers, staff in homeless shelters, and in some cases police officers on how to
recognize and respond to an overdose, including the administration of naloxone,
until emergency medical help is obtained. In the USA, the first program began
distributing naloxone in 1996. The number of programs has subsequently risen to at
least 50 in 15 states (CDC 2012b). Programs are also reported in other countries
including the UK and Australia (Strang et al. 2008; Kerr et al. 2009).
numerous deaths from opioid overdoses (CDC 2012b). There have been questions of
whether nasal administration is as effective, but several studies have found that it
can be used safely and effectively outside of hospital settings (Kerr et al. 2009;
Doe-Simkins et al. 2009), including on a take home basis (CDC 2012b). A recent
study suggests that naloxone distribution is cost-effective (Coffin and Sullivan 2013).
83.2.4.2 Conclusion
Potential benefits include substantial reductions in opioid overdose deaths, if
sufficient coverage of risk populations can be achieved. It is recommended by
CDC in the USA and by the Global Fund to Fight AIDS, TB and Malaria as
a component of a comprehensive package of services for drug users.
In most jurisdictions, naloxone is a prescription only medicine and its use is
restricted to medical personnel or to patients to whom it is prescribed. It is thus
necessary to change regulations to enable administration by laypeople, as has occurred,
for example, in several US states (CDC 2012b). The risks are low as it is a safe drug and
there is no evidence that it may encourage risky drug taking. Administration via nasal
spray offers advantages for nonmedical responders. Further information is available in
a manual developed by the Harm Reduction Coalition (2012).
Even if naloxone distribution is not feasible, increasing risk awareness and
response skills among professionals in contact with drug users, and disseminating
information to users, their peers, and families, constitutes an important part of
a comprehensive program to reduce overdose mortality. Prison release or treatment
discharge counselling on overdose risk should be a key component. Crisis interven-
tion and counselling at hospital emergency rooms following admission for overdose
have been tried in some countries. New online tools can be used for awareness raising
and risk assessment. Precautions over prescribing opioids (especially together with
CNS sedatives) are also important, since in the USA a significant proportion of drug
overdose deaths are associated with prescription opioids and sedatives (CDC 2013).
Outreach projects may operate from a stand-alone base but are often attached to
community health and social services such as NSPs, street-level low-threshold
services, treatment centers, etc. Target groups include homeless, migrant or minor-
ity group users with limited access to services, street users, sex workers, chaotic
stimulant and multiple drug users, or more private, closed groups.
Many variants of outreach have been described (Rhodes and Hartnoll 1991,
1996; NIDA 2000; Needle et al. 2005). Some are based on professional youth or
community health workers, others originated from ethnographic research involving
indigenous leaders to target at risk networks and individuals, others have focused on
promoting peer-driven outreach, and others have developed out of advocacy or self-
help organizations. Some concentrate on the individual level (information and
awareness raising, referral or support for change), while others give greater empha-
sis to a network approach involving peer education and modification of peer norms
or empowerment of vulnerable groups.
83.2.5.2 Conclusion
Outreach is a flexible and effective component of local harm reduction strategies.
It is essential that outreach workers can establish rapport with target populations
and gain acceptance as trusted and knowledgeable sources of information and
advice. It is vital to ensure confidentiality and to communicate messages clearly.
Outreach workers need adequate training, support, and protection, especially in
peer-driven interventions. This is helped by clear guidelines covering objectives,
83 Harm Reduction Interventions 1303
There is a substantial literature on harms that can arise from heavy use of cocaine or
amphetamine-type stimulants (Grund et al. 2010). However, many harm reduction
interventions are based on models developed in response to opioid use. Less
information is available on interventions that specifically target harms of
stimulant use.
Apart from dependence, harms associated with chronic stimulant use include
a variety of cardiovascular, pulmonary, or neurological damages; mental health
problems such as acute psychotic episodes; chaotic behavior, including higher rates
of needle sharing associated with intensive, high-frequency injection; increased risk
of HIV and STDs linked to high-risk sexual activity (Colfax and Shoptaw 2005);
and increased risk of HIV and HCV associated with cocaine smoking, both through
sharing paraphernalia and through sexual contact. In high cocaine prevalence areas,
significant numbers of acute cocaine episodes are seen by medical emergency
services, and cocaine (injected or smoked) is reported in a majority of overdose
deaths, often in combination with opioids (CDC 2012a).
The likelihood of harm varies according to context. For example, crack cocaine
use is most likely to be found among highly marginalized groups and is associated
with elevated levels of risk of transmission of HIV, especially for women who trade
sex for money or drugs (Booth et al. 2000). Crack is sometimes injected as well as
smoked, adding a further risk dimension (Rhodes et al. 2006). Transmission of
83 Harm Reduction Interventions 1305
HCV may also occur through sharing of crack pipes via oral sores and cracked lips
(Fischer et al. 2008). Methamphetamine use, especially by men who have sex with
men (MSM), is associated with high levels of sexual risk behavior (Shoptaw and
Reback 2006; CDC 2012a). High levels of cocaine use may also be found among
more socially integrated users who sniff rather than inject or smoke the drug. While
health risks associated with this route of administration are lower, they still remain,
especially through higher sexual risk behavior and possibly through sharing straws.
The social networks and economic resources of more socially integrated cocaine
users may enable them to resolve problems without contacting services (Decorte
2000). For the most part, problem stimulant use seen at public services is associated
with lower socioeconomic status and a range of social and legal problems, in
addition to a variety of psychiatric comorbidities (Grund et al. 2010).
Harm reduction interventions available for stimulant users include psychosocial
treatment, NSPs, outreach and peer-driven programs, sexual risk reduction educa-
tion, information campaigns including web-based dissemination, crack kits, asser-
tive community treatment, environments to reduce anxiety and increase control
over use, as well as approaches based on alternative medicine. ART preexposure
prophylaxis may also be relevant for high-risk sexual behavior.
Most DCRs were initially established for heroin injectors and often did not admit
cocaine injectors or smokers. Increasingly, these facilities adapt to client needs and
have set up separate rooms for smokers of cocaine or heroin. This has proved to be
feasible, attracting important subgroups such as crack-using sex workers, and
appears to provide benefits similar to those that obtain for heroin users (Hedrich
2004; Grund et al. 2010).
It has been suggested that traditional harm reduction services fail to reach
problem stimulant users due to opiate-centered services and social barriers to
young or female users (Grund et al. 2010). Greater emphasis needs to be placed
on outreach and peer education approaches (see above), especially for younger
users. For example, a peer-run, all night street NSP in Vancouver was able to
deliver harm reduction services to the city’s most vulnerable cocaine injectors
(Wood et al. 2003). An unpublished PhD thesis by Henskens on a randomized
controlled trial of Assertive Community Treatment for marginalized crack users in
Rotterdam indicated good program compliance and improvements in physical and
mental health (Grund et al. 2010).
In response to the risks associated with smoking crack, some programs in the
USA, Brazil, Canada, and France have developed “crack kits”. These include
a Pyrex tube, plastic tips, filters, lip balm, sterile compresses, chewing gum for
salivation, and condoms. Initial results suggest that sharing of crack pipes
decreased dramatically, while crack users reduced injecting and more often smoked
cocaine (Leonard et al. 2008). However, crack kits are controversial and rarely
funded.
Regarding crack, there is some evidence that the severity of mental health harms
associated with cocaine is related more to the intensity and context of use than to the
specific form of cocaine used (Haasen et al. 2005). Harm reduction measures aimed
at safer, more controlled, less intensive use of cocaine together with steps to
stabilize the social situation may help to decrease mental health problems.
Other approaches include acupuncture as an adjunct to treatment to reduce
craving, though a systematic review of controlled trials found no evidence of
effectiveness (Gates et al. 2006), or providing accessible and flexible walk-in
calming environments to reduce agitation and anxiety levels (Grund et al. 2010).
Advice, counselling, and treatment services for socially integrated users may be
more attractive if separated from services for opioid users and drug injectors and if
they operate at appropriate hours, for example, evenings. Interventions for less
intensive users include information dissemination on managing mental health risks
or on stimulant use via flyers or websites, personal messaging via mobile phones, or
“pill-testing” in nightlife settings.
83.2.7.2 Conclusion
Patterns of stimulant use and risks can vary greatly from one setting to another. For
example, in some former Soviet Union republics, home production of stimulants is
associated with specific and highly risky patterns of drug consumption (Grund
et al. 2010), and in the UK, groin injection of crack cocaine raises special
83 Harm Reduction Interventions 1307
challenges (Rhodes et al. 2006). In some settings, women are particularly at risk.
This means that interventions need to be thoughtfully planned to take account of
local circumstances and vulnerable groups. This should include critical reflection
on whether any unintended negative effects might arise. While there is much room
for innovative development of harm reduction responses, it should be stressed that
all interventions for stimulant users need to give high priority to sexual as well as
drug-related risks.
83.3 Conclusion
References
Amato L, Davoli M, Perucci CA, Ferri M, Faggiano F, Mattick RP (2005) An overview of
systematic reviews of the effectiveness of opiate maintenance therapies: available evidence
to inform clinical practice and research. J Subst Abus Treat 28:321–329
Booth RE, Kwiatkowski CF, Chitwood DD (2000) Sex related HIV risk behaviors: differential
risks among injection drug users, crack smokers, and injection drug users who smoke crack.
Drug Alcohol Depend 58:219–226
Caplehorn JR, Dalton MS, Haldar F, Petrenas AM, Nisbet JG (1996) Methadone maintenance and
addicts’ risk of fatal heroin overdose. Subst Use Misuse 31:177–196
Castells X, Casas M, Pérez-Mañá C, Roncero C, Vidal X, Capellà D (2010) Efficacy of
psychostimulant drugs for cocaine dependence. Cochrane Database Syst Rev (Online)
CD007380
Centers for Disease Control and Prevention (CDC) (2010) The role of STD detection and
treatment in HIV prevention – CDC fact sheet. CDC, Atlanta. http://www.cdc.gov/std/hiv/
STDFact-STD-HIV.htm. Accessed 3 Mar 2013
Centers for Disease Control and Prevention (CDC) (2012a) Integrated prevention services for HIV
infection, viral hepatitis, sexually transmitted diseases, and tuberculosis for persons who use
drugs illicitly: summary guidance from CDC and the U.S. Department of Health and Human
Services. MMWR 61(RR05):1–43. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6105a1.
htm. Accessed 5 Mar 2013
Centers for Disease Control and Prevention (CDC) (2012b) Community-based opioid overdose
prevention programs providing naloxone – United States, 2010. MMWR 61:101–105. http://
www.cdc.gov/mmwr/preview/mmwrhtml/mm6106a1.htm. Accessed 13 Mar 2013
Centers for Disease Control and Prevention (CDC) (2012c) HIV infection and HIV-associated
behaviors among injecting drug users – 20 cities, United States, 2009. MMWR 61(08):
133–138. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6108a1.htm?s_cid¼mm6108a1_w.
Accessed 14 Mar 2013
Centers for Disease Control and Prevention (CDC) (2013) Opioids drive continued increase
in drug overdose deaths. http://www.cdc.gov/media/releases/2013/p0220_drug_overdose_
deaths.html. Accessed 14 Mar 2013
Coffin PO, Sullivan SD (2013) Cost-effectiveness of distributing naloxone to heroin users for lay
overdose reversal. Ann Intern Med 158:1–9
Colfax G, Shoptaw S (2005) The methamphetamine epidemic: implications for HIV prevention
and treatment. Curr HIV/AIDS Rep 2:194–199
Decorte T (2000) The taming of cocaine use in European and American cities. VUB University
Press, Brussels
83 Harm Reduction Interventions 1309
reduction: evidence, impacts and challenges. Publications Office of the European Union,
Luxembourg, pp 191–232
Haasen C, Prinzleve M, Gossop M, Fischer G, Casas M (2005) Relationship between cocaine use
and mental health problems in a sample of European cocaine powder or crack users. World
Psychiatry: Off J World Psychiatr Assoc (WPA) 4:173–176
Hagan H, McGough JP, Thiede H, Hopkins S, Duchin J, Alexander ER (2000) Reduced injection
frequency and increased entry and retention in drug treatment associated with needle-exchange
participation in Seattle drug injectors. J Subst Abus Treat 19:247–252
Harm Reduction Coalition (2012) Overdose prevention and naloxone manual. http://
harmreduction.org/wp-content/uploads/2012/11/od-manual-final-links.pdf. Accessed 20 Mar
2013
Hedrich D (2004) European report on drug consumption rooms. EMCDDA, Lisbon. http://www.
emcdda.europa.eu/html.cfm/index54125EN.html. Accessed 21 Mar 2013
Hedrich D, Kerr T, Dubois-Arber F (2010) Drug consumption facilities in Europe and beyond. In:
Rhodes T, Hedrich D (eds) Harm reduction: evidence, impacts and challenges. Publications
Office of the European Union, Luxembourg, pp 305–331
Hedrich D, Alves P, Farrell M, Stöver H, Møller L, Mayet S (2012) The effectiveness of opioid
maintenance treatment in prison settings: a systematic review. Addiction (Abingdon, England)
107:501–517
Islam MM, Conigrave KM (2007) Assessing the role of syringe dispensing machines and mobile
van outlets in reaching hard-to-reach and high-risk groups of injecting drug users (IDUs):
a review. Harm Reduction J 4:14
Jones L, Pickering L, Sumnall H, McVeigh J, Bellis MA (2008) A review of the effectiveness and
cost-effectiveness of needle and syringe programmes for injecting drug users. Res Rep. http://
www.nice.org.uk/nicemedia/live/12130/43372/43372.pdf. Accessed 20 Mar 2013
Kerr D, Kelly A-M, Dietze P, Jolley D, Barger B (2009) Randomized controlled trial comparing
the effectiveness and safety of intranasal and intramuscular naloxone for the treatment of
suspected heroin overdose. Addiction (Abingdon, England) 104:2067–2074
Kimber J, Palmateer N, Hutchinson S, Hickman M, Goldberg D, Rhodes T (2010) Harm reduction
among injecting drug users – evidence of effectiveness. In: Rhodes T, Hedrich D (eds) Harm
reduction: evidence, impacts and challenges. Publications Office of the European Union,
Luxembourg, pp 115–164
Knapp WP, Soares BGO, Farrel M, Lima MS (2007) Psychosocial interventions for cocaine and
psychostimulant amphetamines related disorders. Cochrane Database Syst Rev (Online)
CD003023
Lagu T, Anderson BJ, Stein M (2006) Overdoses among friends: drug users are willing to
administer naloxone to others. J Subst Abus Treat 30:129–133
Latkin CA, Forman V, Knowlton A, Sherman S (2003) Norms, social networks, and HIV-related
risk behaviors among urban disadvantaged drug users. Soc Sci Med 56:465–476
Leonard L, DeRubeis E, Pelude L, Medd E, Birkett N, Seto J (2008) “I inject less as I have easier
access to pipes”: injecting, and sharing of crack-smoking materials, decline as safer crack-
smoking resources are distributed. Int J Drug Policy 19:255–264
MacArthur GJ, Minozzi S, Martin N, Vickerman P, Deren S, Bruneau J, Degenhardt L,
Hickman M (2012) Opiate substitution treatment and HIV transmission in people who inject
drugs: systematic review and meta-analysis. BMJ (Clin Res Ed) 345:e5945
Marshall BDL, Milloy M-J, Wood E, Montaner JSG, Kerr T (2011) Reduction in overdose
mortality after the opening of North America’s first medically supervised safer injecting
facility: a retrospective population-based study. Lancet 377:1429–1437
Mattick RP, Kimber J, Breen C, Davoli M (2008) Buprenorphine maintenance versus placebo
or methadone maintenance for opioid dependence. Cochrane Database Syst Rev (Online)
CD002207
Maxwell S, Bigg D, Stanczykiewicz K, Carlberg-Racich S (2006) Prescribing naloxone to actively
injecting heroin users: a program to reduce heroin overdose deaths. J Addict Dis 25:89–96
83 Harm Reduction Interventions 1311
Meader N, Li R, Des Jarlais DC, Pilling S (2010) Psychosocial interventions for reducing injection
and sexual risk behaviour for preventing HIV in drug users. Cochrane Database Syst Rev
(Online) CD007192
Meader N, Semaan S, Halton M, Bhatti H, Chan M, Llewellyn A, Des Jarlais DC (2013) An
international systematic review and meta-analysis of multisession psychosocial interventions
compared with educational or minimal interventions on the HIV sex risk behaviors of people
who use drugs. AIDS Behav. doi:10.1007/s10461-012-0403-y
Needle RH, Coyle SL, Normand J, Lambert E, Cesari H (1998) HIV prevention with drug-using
populations – current status and future prospects: introduction and overview. Pub Health Rep
(Washington, DC: 1974) 113(Suppl):4–18
Needle RH, Burrows D, Friedman SR et al (2005) Effectiveness of community-based outreach in
preventing HIV/AIDS among injecting drug users. Int J Drug Policy 16:45–57
NIDA (2000) An overview of the NIDA community-based outreach model. A manual to reduce
the risk of HIV and other blood-borne infections in drug users. NIH Publication. http://
archives.drugabuse.gov/CBOM/. Accessed 19 Mar 2013
NIDA (2006) Methadone research web guide. Part B: 20 questions and answers regarding
methadone maintenance treatment research. Question 4. Online document. National Institute
on Drug Abuse. http://international.drugabuse.gov/educational-opportunities/certificate-
programs/methadone-research-web-guide/part-b/question-4-does-m. Accessed 7 Mar 2013
Palepu A, Tyndall MW, Joy R, Kerr T, Wood E, Press N, Hogg RS, Montaner JSG (2006)
Antiretroviral adherence and HIV treatment outcomes among HIV/HCV co-infected
injection drug users: the role of methadone maintenance therapy. Drug Alcohol Depend
84:188–194
Palmateer N, Kimber J, Hickman M, Hutchinson S, Rhodes T, Goldberg D (2010) Evidence for the
effectiveness of sterile injecting equipment provision in preventing hepatitis C and human
immunodeficiency virus transmission among injecting drug users: a review of reviews. Addic-
tion (Abingdon, England) 105:844
Pizzey R, Hunt N (2008) Distributing foil from needle and syringe programmes (NSPs) to promote
transitions from heroin injecting to chasing: an evaluation. Harm Reduction J 5:24
Pollini RA, McCall L, Mehta SH, Celentano DD, Vlahov D, Strathdee S (2006) Response to
overdose among injection drug users. Am J Prev Med 31:261–264
Rhodes T, Hartnoll RL (1991) Reaching the hard to reach: models of HIV outreach health
education. In: Aggleton P, Hart G, Davies P (eds) AIDS: responses, interventions and care.
The Falmer Press, London, pp 233–248
Rhodes T, Hartnoll R (eds) (1996) AIDS, drugs and prevention: perspectives on individual and
community action. Routledge, London/New York
Rhodes R, Hedrich D (eds) (2010) Harm reduction: evidence, impacts and challenges, EMCDDA
scientific monograph series no. 10. Publications Office of the European Union, Luxembourg.
http://www.emcdda.europa.eu/publications/monographs/harm-reduction. Accessed 17 Mar 2013
Rhodes T, Stoneman A, Hope V, Hunt N, Martin A, Judd A (2006) Groin injecting in the context
of crack cocaine and homelessness: from “risk boundary” to “acceptable risk”? Int J Drug
Policy 17:164–170
Ritter A, Cameron J (2006) A review of the efficacy and effectiveness of harm reduction strategies
for alcohol, tobacco and illicit drugs. Drug Alcohol Rev 25:611–624
Rush CR, Stoops WW (2012) Agonist replacement therapy for cocaine dependence: a translational
review. Future Med Chem 4:245–265
Semaan S, Des Jarlais DC, Sogolow E, Johnson WD, Hedges LV, Ramirez G, Flores SA,
Norman L, Sweat MD, Needle R (2002) A meta-analysis of the effect of HIV prevention
interventions on the sex behaviors of drug users in the United States. J Acquir Immune Defic
Syndr 30(Suppl 1):S73–S93
Semaan S, Neumann MS, Hutchins K, D’Anna LH, Kamb ML (2010) Brief counseling for
reducing sexual risk and bacterial STIs among drug users – results from project RESPECT. Drug
Alcohol Depend 106:7–15
1312 D. Hedrich and R. Hartnoll
Shoptaw S, Reback CJ (2006) Associations between methamphetamine use and HIV among men
who have sex with men: a model for guiding public policy. J Urban Health Bull N Y Acad Med
83:1151–1157
Small W, Kain S, Laliberte N, Schechter MT, O’Shaughnessy MV, Spittal PM (2005) Incarcera-
tion, addiction and harm reduction: inmates experience injecting drugs in prison. Subst Use
Misuse 40:831–843
Sorensen JL, Copeland AL (2000) Drug abuse treatment as an HIV prevention strategy: a review.
Drug Alcohol Depend 59:17–31
Stimson G, Des Jarlais DC, Ball A (1998) Drug injecting and HIV infection: global dimensions
and local changes. University College of London Press, London
Stöver H, Nelles J (2003) Ten years of experience with needle and syringe exchange programmes
in European prisons. Int J Drug Policy 14:437–444
Strang J, Manning V, Mayet S, Best D, Titherington E, Santana L, Offor E, Semmler C (2008)
Overdose training and take-home naloxone for opiate users: prospective cohort study of impact
on knowledge and attitudes and subsequent management of overdoses. Addiction (Abingdon,
England) 103:1648–1657
Strang J, Groshkova T, Metrebian N (2012) New heroin-assisted treatment: recent evidence and
current practices of supervised injectable heroin treatment in Europe and beyond, EMCDDA
insights series no. 11. Publications Office of the European Union, Luxembourg
The National Centre for HIV Epidemiology and Clinical Research (2009) Return on investment in
needle and syringe programs in Australia: report. http://www.health.gov.au/internet/main/
publishing.nsf/content/needle-return-1-sum. Accessed 7 Mar 2013
Tilson H, Aramrattana A, Bozzette S, Falco M, Hammett TM, Kozlov AP, Lai S, Mahal A,
Schottenfeld RS, Solomon S, Celentano DD (2006) Preventing HIV infection among injecting
drug users in high risk countries: an assessment of the evidence. Committee on the prevention
of HIV infection among injecting drug users in high-risk countries, Institute of Medicine, The
National Academies Press, Washington, DC. http://www.nap.edu/catalog.php?
record_id¼11731#toc. Accessed 17 Mar 2013
Turner KME, Hutchinson S, Vickerman P et al (2011) The impact of needle and syringe provision
and opiate substitution therapy on the incidence of hepatitis C virus in injecting drug users:
pooling of UK evidence. Addiction (Abingdon, England) 106:1978–1988
van den Berg C, Smit C, Van Brussel G, Coutinho R, Prins M (2007) Full participation in harm
reduction programmes is associated with decreased risk for human immunodeficiency virus
and hepatitis C virus: evidence from the Amsterdam Cohort Studies among drug users.
Addiction (Abingdon, England) 102:1454–1462
Walley AY, Xuan Z, Hackman HH, Quinn E, Doe-Simkins M, Sorensen-Alawad A, Ruiz S,
Ozonoff A (2013) Opioid overdose rates and implementation of overdose education and nasal
naloxone distribution in Massachusetts: interrupted time series analysis. BMJ 346:f174–f174
WHO (2004a) Effectiveness of sterile needle and syringe programming in reducing HIV/AIDS
among IDUs, Evidence for action technical paper and policy brief. WHO, Geneva. http://www.
who.int/hiv/pub/idu/e4a-needle/en/index.html. Accessed 5 Mar 2013
WHO (2004b) Effectiveness of community-based outreach in preventing HIV/AIDS among
injecting drug users, Evidence for action paper. WHO, Geneva. http://www.who.int/hiv/pub/
idu/idu/en/. Accessed 3 Mar 2013
WHO (2009) Guidelines for the psychosocially assisted pharmacological treatment of
opioid dependence. WHO, Geneva. http://www.who.int/substance_abuse/publications/
9789241547543/en/index.html. Accessed 3 Mar 2013
WHO (2010) Antiretroviral drugs for treating pregnant women and preventing HIV infection in
infants: recommendations for a public health approach – 2010 version. WHO, Geneva. http://
www.who.int/hiv/pub/mtct/antiretroviral2010/en/index.html. Accessed 3 Mar 2013
WHO (2012) Guidance on prevention of viral hepatitis B and C among people who inject drugs.
WHO, Geneva. http://www.who.int/hiv/pub/guidelines/hepatitis/en/index.html. Accessed
3 Mar 2013
83 Harm Reduction Interventions 1313
Further Reading
Centers for Disease Control and Prevention (CDC) (2012) Integrated prevention services for HIV
infection, viral hepatitis, sexually transmitted diseases, and tuberculosis for persons who use
drugs illicitly: summary guidance from CDC and the U.S. Department of Health and Human
Services. MMWR 61(RR05):1–43. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6105a1.
htm. Accessed 5 Mar 2013
ECDC, EMCDDA (2011) Prevention and control of infectious diseases among people who inject
drugs, ECDC and EMCDDA joint guidance. European Centre for Disease Prevention and
Control, Stockholm
Rhodes R, Hedrich D (eds) (2010) Harm reduction: evidence, impacts and challenges, EMCDDA
scientific monograph series no. 10. Publications Office of the European Union, Luxembourg.
http://www.emcdda.europa.eu/publications/monographs/harm-reduction. Accessed 17 Mar 2013
Tilson H, Aramrattana A, Bozzette S, Falco M, Hammett TM, Kozlov AP, Lai S, Mahal A,
Schottenfeld R, Solomon RS, Celentano DD (2006) Preventing HIV infection among injecting
drug users in high risk countries: an assessment of the evidence. Committee on the prevention
of HIV infection among injecting drug users in high-risk countries, Institute of Medicine, The
National Academies Press, Washington, DC. http://www.nap.edu/catalog.php?
record_id¼11731#toc Accessed 17 Mar 2013
Harm Reduction Policies, Settings and
Challenges 84
Richard Hartnoll and Dagmar Hedrich
Contents
84.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1316
84.2 Policies, Settings, and Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1316
84.2.1 What Is Harm Reduction? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1316
84.2.2 History and Current Status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1317
84.2.3 Drug-Related Harms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1318
84.2.4 Risk Behaviors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1320
84.2.5 Risk Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1321
84.2.6 Harm Reduction as a Combination Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . 1322
84.2.7 Implementing an Integrated Approach at Local Level . . . . . . . . . . . . . . . . . . . . . 1323
84.2.8 Needs Assessment in Local Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1323
84.2.9 Enabling Environments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1324
84.2.10 Epidemiological Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1325
84.2.11 Prison Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1326
84.2.12 Law Enforcement Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1327
84.2.13 Overcoming Barriers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1328
84.2.14 Promoting Health and Equality of Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1329
84.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1329
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1330
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1335
Abstract
Harm reduction has become an increasingly important dimension of drug policy
over the past three decades. This chapter describes what harm reduction is and
how harm reduction policies take account both of individual risk behaviors and
of risky settings in order to promote improvements in individual and public
health and societal well-being. Another chapter in this textbook, ▶ Chap. 83,
“Harm Reduction Interventions”, gives an overview of specific interventions.
This chapter covers the following: what harm reduction is, its history and current
status from an international perspective, drug-related harms, risk behaviors, risk
settings, harm reduction as a combination intervention, implementing an inte-
grated approach at local level, needs assessment in local settings, enabling
environments, epidemiological settings, prison settings, law enforcement
settings, overcoming barriers, and promoting health and equality of care.
It concludes that harm reduction policies and interventions have been success-
fully implemented in many countries around the world; that over the past two
decades, political and professional opinions have increasingly promoted a
“comprehensive approach” that includes harm reduction as a central pillar; and
that while heroin use and related problems, as well as HIV among drug injectors,
are now largely under control in countries that have implemented comprehen-
sive harm reduction policies, challenges remain in those and other countries,
including hepatitis C, problems related to stimulant drug use, and continuing
sexual transmission of infectious diseases related to drug use. Apart from client-
oriented skills, practitioners need an understanding of the community and public
health settings within which drug use and drug-related harms arise.
84.1 Introduction
typically work through a hierarchy of goals in which the most pressing needs are
addressed first (IHRA 2010).
Drug-related harm refers both to individual consequences such as dependence,
overdoses, or infectious diseases contracted through sharing paraphernalia and to
social, economic, and public health harms to the community (public nuisance, crime,
health-care costs, high HIV prevalence). The underlying public health paradigm
is broader than client-centered treatment and involves balancing individual and
societal needs.
A harm reduction policy entails a “combination intervention approach” involv-
ing a coordinated response from a variety of agencies and services, including
treatment, prevention, public health, law enforcement, community groups, and
local authorities (Rhodes and Hedrich 2010; ECDC and EMCDDA 2011; WHO
et al. 2013). This approach goes beyond interventions for individuals by stressing
enabling environments to enhance protective factors, reduce harms, and promote
public health.
Harm reduction incorporates an important ethical dimension concerning human
rights, equality of access to health and social services, respect of the right to privacy
and confidentiality, and efforts to counteract social exclusion and stigma (IHRA
2010; J€urgens et al. 2010).
It also acknowledges that important unintended negative consequences can arise
from reactions to drug use (European Commission 2009; UNODC 2009). These
include structural factors such as the wider policy and legislative framework as well
as risk environments that increase social exclusion of already marginalized sections
of the community, foster reluctance to seek help for fear of arrest, or exacerbate the
HIV epidemic among drug users (Rhodes 2009; Wood et al. 2009; Degenhardt
et al. 2010).
Early examples of harm reduction include the so-called British System of opiate
maintenance for patients who, while capable of “leading a useful and fairly normal
life” on a stable dose of the drug of addiction, were unable to do so when the regular
allowance was withdrawn. In the early 1970s, various ad hoc harm reduction
responses evolved at grass roots level in some western European cities (street
agencies, outreach, user-driven organizations, and information dissemination).
Methadone maintenance, which had originated in the USA, was introduced in
a handful of European countries.
Harm reduction as a policy started to gain wider acceptance in Europe with the
emergence and rapid spread of HIV/AIDS among drug injectors in the mid-1980s.
For example in Britain, the spread of HIV was seen as “a greater danger to
individual and public health than drug misuse” (ACMD 1988). The WHO also
endorsed the underlying principles of harm reduction (WHO 1986). From 1985,
opioid substitution treatment (OST) expanded to more mostly western European
countries, and needle and syringe programs (NSPs) were progressively introduced.
1318 R. Hartnoll and D. Hedrich
Over the 1990s both OST and NSPs extended, albeit unevenly, to most countries
including central and eastern Europe (Hedrich et al. 2008).
Beyond Europe, harm reduction approaches emerged in countries such as
Australia and Canada (Pates and Riley 2012). Harm reduction interventions also
developed in the 1980s in some US cities such as San Francisco (Watters
et al. 1994), Chicago (Wiebel 1996), and New York (Des Jarlais et al. 1988) though
opposition from federal government and influential lobbies meant that they were
not described as such.
Harm reduction is now a major pillar of drug policy in all EU member states
(Hedrich et al. 2008) and globally is supported by at least 97 countries (Stoicescu
2012). It is firmly established as a mainstream systemic response promoted in
official declarations by the WHO, United Nations, and European Union as a key
element of a comprehensive approach (Council of the European Union 2003;
WHO et al. 2013).
Within these overall developments, the range of interventions and scale of
implementation vary considerably between and within countries (Mathers
et al. 2010; Stoicescu 2012). For example, in Europe OST covers over 50 % of
opioid-dependent users across most of the continent, though in a few countries
coverage is under 20 %. Syringe distribution by NSPs ranges from under 50 per user
per year to over 300 (EMCDDA 2012a).
Harm reduction developed mainly in response to public health consequences of
heroin use and drug injecting. In many parts of the world, serious problems arise
from heavy stimulant use, especially cocaine and methamphetamine. In Europe, the
USA, and other countries, an ageing population of chronic users poses new chal-
lenges (EMCDDA 2010; ▶ Chap. 128 “Older People and Substance Misuse”).
Strong religious, ideological, and political resistance remains in some countries
and within some institutions. Sometimes interventions are implemented but not
called “harm reduction.” In other cases, evidence-based harm reduction interven-
tions have been blocked, with serious consequences. In Russia, for example,
methadone was declared illegal, despite urgings to the contrary (UNAIDS 2005).
From 1995, injection-related cases of HIV in Russia rose rapidly and since
2002 account for over 80 % of all cases of HIV (Goliusov et al. 2008). Conversely,
the role of user groups and advocacy organizations has been changing from
opposition to mainstream policies towards recognized and constructive participa-
tion in developing evidence-based interventions to reduce drug-related harm
(Stoicescu 2012).
Risk of death is several times higher among injectors than non-injectors. Specific
contexts associated with dramatic increases in overdose mortality are the weeks
immediately following release from prison, discharge from inpatient detoxification,
and dropout from OST (Davoli et al. 2007; Merrall et al. 2010). In the USA, drug
overdose deaths more than doubled from 16,849 in 1999 to 38,329 in 2010 (Jones
et al. 2013). Prescription opioids in particular, as well as cocaine and heroin, were
a major component of this (CDC 2013). Among older, chronic users, comorbidities,
including alcohol and liver and cardiovascular diseases, become more important
(EMCDDA 2010).
Serious health risks (infections, overdoses) are associated with drug injecting. HIV
and especially HCV are efficiently transmitted via the sharing of injecting equip-
ment. Risks arise not only through sharing syringes and needles but also through
other materials used to prepare drugs for injection, for example, water, spoons, drug
solutions, or filters (ECDC and EMCDDA 2011). Measures sufficient to prevent
HIV transmission may not be enough to prevent HCV transmission. Risks also
accompany non-injecting use, including bridging between injecting and
non-injecting drug use populations, transmission through sharing non-injecting
materials (pipes, straws), or sexual transmission (Strathdee and Stockman 2010;
CDC 2012a).
Drug use, whether by injection or not, is strongly correlated with unsafe sexual
practices, including unprotected sex, multiple partners, and, in some cases, selling
sex for money or drugs (CDC 2012a, b). The sale of sex for money or drugs is most
clearly associated with severe dependence on heroin or crack cocaine. Use of
84 Harm Reduction Policies, Settings and Challenges 1321
Individual risk behaviors occur within a wider social context. A variety of environ-
mental factors give rise to structural and situational settings that influence differen-
tially not only harms associated with drug use but also access to health and social care
(Poundstone et al. 2004; CDC 2012a). The diversity of settings implies a diversity of
risks and responses (Hartnoll et al. 2010). Social exclusion and stigma are potent
factors linked to a mix of poverty, unemployment, lack of health care, low life
expectations, and discrimination. Racial and ethnic disparities persist regarding
drug-related harms and utilization of health care and treatment (CDC 2012a).
Criminalization and law enforcement policies often disproportionally target margin-
alized groups and communities. These structural factors can lead to environments
that encourage high rates of risk behaviors and infection among drug users
(Rhodes et al. 2005; Rhodes 2009; Strathdee et al. 2010). For example, a policy of
arresting drug users with syringes can create situations in which there is a high risk
of hasty injecting in unhygienic conditions with shared syringes (Werb et al. 2008).
Fear of arrest or of children being taken into care can act as powerful deterrents
to contacting treatment or social services among communities who already lack
equal access to services. Legislation restricting syringe provision or availability
of specific treatments can increase risk behaviors, morbidity, and mortality (Wood
et al. 2009).
Given the high rates of arrest and incarceration found among heavy drug users,
prison and other institutional settings constitute important risk environments.
Although the frequency of drug use and injecting usually diminishes during impris-
onment, when it does occur it is often under more risky circumstances than in
the community, due to a shortage of syringes, need for secrecy, and the higher
prevalence of infectious diseases in prison populations (Darke et al. 1998). Other
high-risk situations include interruptions to treatment due to short periods of
1322 R. Hartnoll and D. Hedrich
imprisonment (Dolan et al. 2005) and release from prison or discharge from drug-
free treatment (see 63.2.3.1 above).
Women who use drugs are often at higher risk than men due to various factors
related to gender, power relations, and sexual risk. Female injecting drug users are
doubly at risk for HIV infection via unprotected sex and unsafe injections and have
needs that are often not adequately addressed in HIV-prevention strategies
(El-Bassel et al. 2010). In some studies, unsafe sex is a more significant risk factor
for women than drug use (Strathdee et al. 2001). Women who inject drugs are more
likely to require assistance injecting and to engage in sex trading and unsafe sex.
They are also more likely than men to have a regular partner who injects or is HIV
positive. Intimate partner violence is much more common for female drug users
than non-drug users. Women who have experienced such violence are less able to
negotiate safe sex, less likely to use condoms, and more likely to share needles, to
have more sexual partners, and to trade sex for money or drugs, including unpro-
tected sex with dealers (Shannon et al. 2008; Folch et al. 2013). Higher levels of
psychiatric comorbidity contribute to heightened HIV risk (Gilchrist et al. 2011).
Other contextual risk factors include the prevalence of infectious diseases in
local drug-using populations (see later), historical or cultural patterns of drug use
including routes of administration and risk behaviors pertaining in given commu-
nities (Des Jarlais et al. 1988; Grund et al. 1996), and local drug market conditions
regarding what products are available, in what form and with what variability in
content (de la Fuente 1996; Topp et al. 2003).
While comprehensive national drug policies exist in most countries, it is at local level
that the interface between drug use, policies, and responses takes place. Responding
to a diversity of issues, from public concentrations of heroin and cocaine use and drug
markets in specific urban areas to less visible patterns of problematic drug use
distributed across different groups in different sections of the population, is
a complex task. Coordination of local policies and interventions is essential due to
the range of agencies involved, including health, social services, education, housing,
police and criminal justice system, politicians, as well as civil society including
nongovernmental organizations, community groups, and user organizations.
Optimizing the benefits obtained from combined interventions implies
implementing at local level a coherent package of harm reduction approaches to
problem drug use. This poses many challenges. It involves achieving understanding
and cooperation between different sectors and organizations operating at different
levels and with different agendas. Broader issues of health system organization are
beyond the scope of this chapter. The remainder of this chapter focuses on practical
questions concerning implementation of multiple harm reduction interventions in
different settings.
There can be large differences between settings in terms of drug use patterns, risk
behaviors, HIV or HCV prevalence, health and social consequences, community
characteristics, and public and professional perceptions. How does one decide what
interventions are needed in a given setting?
Assessment of the local situation and identification of needs, followed by
monitoring and evaluation, is essential for providing effective responses. Assess-
ment should cover the following areas:
• Epidemiological situation and trends (problem drug use prevalence, user
profiles, patterns of drug use, routes of administration, mortality and morbidity
including HIV/HCV prevalence and incidence, risk groups and behaviors, other
health and social problems, drug-related crime)
• Response situation (existence of enabling policy environment including coordi-
nation strategies and support for harm reduction, services available including
criminal justice settings, service policies and practices, geographical coverage,
referral pathways, service uptake and utilization, client profiles, services
provided)
• Needs assessment (coverage of target populations, gaps in responses, unmet
needs, contextual risk factors, barriers to services, professional and community
perceptions, drug users’ perceptions, engagement of stake holders)
• Recommendations (priorities for action, policy environment development, coor-
dination needs and mechanisms, service development and delivery targets,
outcome targets, key indicators for monitoring)
1324 R. Hartnoll and D. Hedrich
and community harms. However, it was also important that national policy subse-
quently changed to include harm reduction as a major pillar of drug policy,
including OST, NSPs, DCRs, and increased discretion for public prosecutors over
possession of small amounts of drugs for personal use.
More recently, the importance of nurturing enabling environments has been
stressed in studies of HIV among people who inject drugs in high-risk environments
(Rhodes 2009; Degenhardt et al. 2010; Jolley et al. 2012).
Scaling up coverage of OST and NSPs to contain the spread of HIV and HCV is
recommended in research reports (Tilson et al. 2006; Mehta et al. 2011; Grebely
and Dore 2011), drug strategies (e.g., EU drug strategies since 2004), and public
health policy guidelines (ECDC and EMCDDA 2011; WHO et al. 2013). What this
implies in practice is situation dependent. Some studies have used modelling
techniques to project the impact of different levels of coverage in different
scenarios (Vickerman et al. 2007, 2012). While this approach has limitations and
important margins of uncertainty surround projections, they do support several
general conclusions.
The impact of different levels of coverage on incidence and prevalence of HIV
and HCV is affected by baseline seroprevalence levels in risk populations as well as
by individual and collective patterns of injecting risk behavior (Vickerman and
Hickman 2010). Scaling up can have an important impact on containing or reducing
HIV incidence and prevalence. However, since HCV transmission probability is
much higher than that for HIV, higher levels of coverage and larger changes in risk
behavior are needed to make an impact on HCV than HIV. Significant reductions in
HIV transmission can be achieved by targeting high-risk drug injectors, while
targeting low-risk users brings relatively little additional benefit in terms of HIV
prevalence. For HCV, however, failure to cover lower-risk users considerably
reduces the potential impact of interventions, so all drug injectors should be
covered. In Britain, modelling studies suggest that early scaling up of OST and
NSP helped to contain the prevalence of hepatitis C among people who inject drugs
to 40 % instead of a projected 65 % that would have occurred without high coverage
(Vickerman et al. 2012). In situations where HCV prevalence is already high, long-
term reductions in the prevalence of chronic hepatitis C are likely to be modest
and require long-term sustained coverage. To achieve large reductions in HCV
incidence, it is necessary to target all injecting drug users, to reduce sharing to very
low levels, and to reach them within 12 months or so of starting to inject
(Vickerman et al. 2007).
In situations with low OST and NSP coverage, which globally is under 20 % in
most countries (Mathers et al. 2010), it makes sense to prioritize scaling up of OST
and NSPs. This also means relaxing restrictions on syringe distribution and
implementing measures to increase recruitment and retention in OST. In situations
where high levels of coverage of drug injecting populations have already been
1326 R. Hartnoll and D. Hedrich
Substantial numbers of problem drug users come into contact with the police.
Conversely, drug-related issues can take up a significant proportion of police time
and resources. Although law enforcement and health policies are not often closely
related, drug use is a field where there is considerable overlap and where both
sectors can benefit from partnerships that foster mutual understanding and cooper-
ation regarding reducing harms. Examples include support by police for OST
(usually because of crime reduction) and agreements over community policing
with regard to syringe distribution programs, the role of DCRs in reducing public
nuisance, or the status of participants in peer-based outreach. In addition to these
agreements, harm reduction interventions in law enforcement settings can include
drug overdose prevention, referral schemes, health interventions in police stations,
and diversion into treatment (Monaghan and Bewley-Taylor 2013).
Regarding overdoses, fear of police attendance can deter those present from
calling emergency services (Pollini et al. 2006). In Vancouver, police procedures
were changed so that they no longer responded routinely to overdose ambulance
calls, but only attended if requested by ambulance personnel (Thomas 2005). Some
US states have passed “good Samaritan laws” that provide immunity from drug
possession charges for overdose victims and witnesses who call emergency services
in good faith to save a life. A few have implemented programs to train police
officers to administer Naloxone (Monaghan and Bewley-Taylor 2013). In Britain,
some police authorities have issued directives that police personnel treat drug
swallowing following arrest as a medical emergency that requires immediate
hospitalization (Monaghan and Bewley-Taylor 2013). Warnings of contaminated
drugs detected in the local drug scene may also be valuable if the information is
disseminated through acceptable peer-recognized channels.
Drug referral schemes involve specialized workers based in police stations to
assess, counsel, and refer drug users to treatment. Data from a national monitoring
program in Britain showed that half of those who voluntarily asked for assistance at
arrest had never been in treatment (Sondhi et al. 2002), though uptake and retention
1328 R. Hartnoll and D. Hedrich
opening hours of contact points and services in consultation with users. Above all,
implement user-oriented policies that explicitly enshrine confidentiality and users’
rights to care, and strive to create a sympathetic and supportive service.
It is essential that practitioners understand the reasons for barriers to help seeking
and the primacy of confidentiality and trust. Quality of services is as important as
quantity. Commitment to equality of care and basic human rights does matter
(J€
urgens et al. 2010).
To summarize, the principles underlying a harm reduction approach (ECDC and
EMCDDA 2011) are:
• Pragmatic approach to health promotion
• Public health objectives
• Clients’ rights perspective
• Based on scientific evidence and expert experience
The principles of service provision are:
• Ensure confidentiality
• Promote service accessibility
• Create a user-friendly atmosphere
• Engage in dialogue with users and promote peer involvement
• Adopt a practical approach to the provision of services
• Refrain from ideological and moral judgment
• Maintain a realistic hierarchy of goals
• Promote an enabling environment as well as caring services for clients
84.3 Conclusion
References
Advisory Council on the Misuse of Drugs (ACMD) (1988) AIDS and drug misuse. HMSO,
London
Centers for Disease Control and Prevention (CDC) (2010) The role of STD detection and
treatment in HIV prevention – CDC fact sheet. CDC, Atlanta. http://www.cdc.gov/std/hiv/
STDFact-STD-HIV.htm. Accessed 3 Mar 2013
Centers for Disease Control and Prevention (CDC) (2012a) Integrated prevention services for HIV
infection, viral hepatitis, sexually transmitted diseases, and tuberculosis for persons who use
drugs illicitly: Summary guidance from CDC and the U.S. Department of Health and Human
Services. MMWR 61(RR05):1–43. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6105a1.
htm. Accessed 5 Mar 2013
Centers for Disease Control and Prevention (CDC) (2012b) HIV infection and HIV-associated
behaviors among injecting drug users – 20 cities, United States, 2009. MMWR
61(08):133–138. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6108a1.htm?s_cid ¼ mm
6108a1_w. Accessed 14 Mar 2013
Centers for Disease Control and Prevention (CDC) (2013) Opioids drive continued increase
in drug overdose deaths. http://www.cdc.gov/media/releases/2013/p0220_drug_overdose_
deaths.html
Colfax G, Shoptaw S (2005) The methamphetamine epidemic: implications for HIV prevention
and treatment. Current HIV/AIDS Reports 2:194–199
Council of the European Union (2003) Council Recommendation of 18 June 2003 on the prevention
and reduction of health-related harm associated with drug dependence (2003/488/EC).
84 Harm Reduction Policies, Settings and Challenges 1331
Goliusov AT, Dementyeva A, Ladnaya NN, Briko NI, Tumanova MS, Korzhaeva NA,
Semenchenko MV, Nietzsche-Bell A, Kobzeva VB (2008) Country progress report of the
Russian Federation on the Implementation of the Declaration of Commitment on HIV/AIDS.
Reporting period: January 2006–December 2007. Federal Service for Surveillance of Consumer
Rights Protection and Human Well-Being of the Russian Federation, Moscow. http://data.unaids.
org/pub/Report/2008/russia_2008_country_progress_report_en.pdf. Accessed 15 Mar 2013
Gossop M, Griffiths P, Powis B, Strang J (1993a) Severity of heroin dependence and HIV risk.
II. Sharing injecting equipment. AIDS Care 5:159–168
Gossop M, Griffiths P, Powis B, Strang J (1993b) Severity of heroin dependence and HIV risk.
I. Sexual behaviour. AIDS Care 5:149–157
Grebely J, Dore GJ (2011) Prevention of hepatitis C virus in injecting drug users: a narrow window
of opportunity. J Infect Dis 203:571–574
Grund JP, Friedman SR, Stern LS, Jose B, Neaigus A, Curtis R, Des Jarlais DC (1996) Syringe-
mediated drug sharing among injecting drug users: patterns, social context and implications for
transmission of blood-borne pathogens. Soc Sci Med 42:691–703
Hagan H, Pouget ER, Des Jarlais DC, Lelutiu-Weinberger C (2008) Meta-regression of hepatitis
C virus infection in relation to time since onset of illicit drug injection: the influence of time
and place. Am J Epidemiol 168:1099–1109
Hagan H, Pouget ER, Des Jarlais DC (2011) A systematic review and meta-analysis of
interventions to prevent hepatitis C virus infection in people who inject drugs. J Infect Dis
204:74–83
Hartnoll R, Hedrich D (1996) AIDS prevention and drug policy: dilemmas in the local environ-
ment. In: Rhodes T, Hartnoll R (eds) AIDS, drugs and prevention: perspectives on individual
and community action. Routledge, London, pp 42–65
Hartnoll R, Gyarmathy A, Zabransky T (2010) Variations in problem drug use patterns and their
implications for harm reduction (Chapter 15). In: Rhodes T, Hedrich D (eds) Harm Reduction:
evidence, impacts and challenges, EMCDDA. Publications Office of the European Union,
Luxembourg, pp 405–432
Hedrich D, Pirona A, Wiessing L (2008) From margin to mainstream: the evolution of harm
reduction responses to problem drug use in Europe. Drugs Educ Prev Policy 15:503–517
Hedrich D, Alves P, Farrell M, Stöver H, Møller L, Mayet S (2012) The effectiveness of opioid
maintenance treatment in prison settings: a systematic review. Addiction 107:501–517
IHRA (2010) What is harm reduction? A position statement from the International Harm
Reduction Association. IHRA, London. http://www.ihra.net/files/2010/08/10/Briefing_What_
is_HR_English.pdf. Acessed 20 Mar 2013
Jolley E, Rhodes T, Platt L, Hope V, Latypov A, Donoghoe M, Wilson D (2012) HIV among
people who inject drugs in Central and Eastern Europe and Central Asia: a systematic review
with implications for policy. BMJ Open. doi:10.1136/bmjopen-2012-001465. Accessed
16 Mar 2013
Jones CM, Mack KA, Paulozzi LJ (2013) Pharmaceutical overdose deaths, United States, 2010.
JAMA 309:657–659
J€
urgens R, Csete J, Amon JJ, Baral S, Beyrer C (2010) People who use drugs, HIV, and human
rights. Lancet 376:475–485
Kidorf M, King VL, Peirce J, Pierce J, Kolodner K, Brooner RK (2011) Benefits of concurrent
syringe exchange and substance abuse treatment participation. J Subst Abus Treat 40:265–271
MacDonald M, Atherton S, Berto D, Bukauskas A, Graebsch C, Parasanau E, Popov I, Qaramah A,
Stöver H, Sarosi P, Valdaru K (2008) Service provision for detainees with problematic drug
and alcohol use in police detention: a comparative study of selected countries in the European
Union. Paper no. 27, European Institute for Crime Prevention and Control, affiliated with the
United Nations (HEUNI), Helsinki. http://www.heuni.fi/Etusivu/Publications/HEUNIpapers/
1205254665145
Maher L, Li J, Jalaludin B, Chant KG, Kaldor JM (2007) High hepatitis C incidence in new
injecting drug users: a policy failure? Aust N Z J Public Health 31:30–35
84 Harm Reduction Policies, Settings and Challenges 1333
Martin NK, Vickerman P, Foster GR, Hutchinson SJ, Goldberg DJ, Hickman M (2011) Can
antiviral therapy for hepatitis C reduce the prevalence of HCV among injecting drug user
populations? A modeling analysis of its prevention utility. J Hepatol 54:1137–1144
Mathers BM, Degenhardt L, Ali H, Wiessing L, Hickman M, Mattick RP, Myers B, Ambekar A,
Strathdee SA (2010) HIV prevention, treatment, and care services for people who inject drugs:
a systematic review of global, regional, and national coverage. Lancet 375:1014–1028
Mehta SH, Astemborski J, Kirk GD, Strathdee SA, Nelson KE, Vlahov D, Thomas DL
(2011) Changes in blood-borne infection risk among injection drug users. J Infect Dis
203:587–594
Merrall ELC, Kariminia A, Binswanger IA, Hobbs MS, Farrell M, Marsden J, Hutchinson SJ, Bird
SM (2010) Meta-analysis of drug-related deaths soon after release from prison. Addiction
105:1545–1554
Mitchell O, Wilson DB, Eggers A, MacKenzie DL (2012) Assessing the effectiveness of drug
courts on recidivism: a meta-analytic review of traditional and non-traditional drug courts.
J Crim Justice 40:60–71
Molitor F, Truax SR, Ruiz JD, Sun RK (1998) Association of methamphetamine use during sex
with risky sexual behaviors and HIV infection among non-injection drug users. West J Med
168:93–97
Molitor F, Ruiz JD, Flynn N, Mikanda JN, Sun RK, Anderson R (1999) Methamphetamine use and
sexual and injection risk behaviors among out-of-treatment injection drug users. Am J Drug
Alcohol Abuse 25:475–493
Monaghan G and Bewley-Taylor D (2013) Police support for harm reduction policies and
practices towards people who inject drugs. International Drug Policy Consortium, London.
http://idpc.net/publications/2013/02/police-support-for-harm-reduction-policies-and-practices-
towards-people-who-inject-drugs. Accessed 15 Mar 2013
Obradovic I (2012) Réduction des risques en milieu pénitentiaire: revue des expériences
étrangères. Note n 2012-04 à l’attention de la MILDT, OFTD, Saint Denis. http://bdoc.ofdt.
fr/pmb/opac_css/index.php?lvl¼notice_display&id¼71435. Accessed 12 Mar 2013
Pates R, Riley D (2012) Harm reduction in substance use and high-risk behaviour: international
policy and practice. Wiley-Blackwell, Oxford
Pollini RA, McCall L, Mehta SH, Celentano DD, Vlahov D, Strathdee S (2006) Response to
overdose among injection drug users. Am J Prev Med 31:261–264
Poundstone KE, Strathdee SA, Celentano DD (2004) The social epidemiology of human immu-
nodeficiency virus/acquired immunodeficiency syndrome. Epidemiol Rev 26:22–35
Rhodes T (2009) Risk environments and drug harms: a social science for harm reduction approach.
Int J Drug Policy 20:193–201
Rhodes R, Hedrich D (eds) (2010) Harm reduction: evidence, impacts and challenges. EMCDDA
Scientific Monograph Series No. 10. Publications Office of the European Union, Luxembourg.
http://www.emcdda.europa.eu/publications/monographs/harm-reduction. Accessed 17 Mar 2013
Rhodes T, Singer M, Bourgois P, Friedman SR, Strathdee SA (2005) The social structural
production of HIV risk among injecting drug users. Soc Sci Med (1982) 61:1026–1044
Scheinmann R, Hagan H, Lelutiu-Weinberger C, Stern R, Des Jarlais DC, Flom PL, Strauss
S (2007) Non-injection drug use and hepatitis C virus: a systematic review. Drug Alcohol
Depend 89:1–12
Shannon K, Kerr T, Allinott S, Chettiar J, Shoveller J, Tyndall MW (2008) Social and structural
violence and power relations in mitigating HIV risk of drug-using women in survival sex work.
Soc Sci Med (1982) 66:911–921
Small W, Kain S, Laliberte N, Schechter MT, O’Shaughnessy MV, Spittal PM (2005) Incarcera-
tion, addiction and harm reduction: inmates experience injecting drugs in prison. Subst Use
Misuse 40:831–843
Sondhi A, O’Shea J, Williams T (2002) Arrest Referral: Emerging findings from the national
monitoring and evaluation programme – DPAS Briefing Paper 18. Home Office Drug Preven-
tion Advisory Service, London
1334 R. Hartnoll and D. Hedrich
Stein MD, Solomon DA, Herman DS, Anderson BJ, Miller I (2003) Depression severity and drug
injection HIV risk behaviors. Am J Psychiatry 160:1659–1662
Stoicescu C (ed) (2012) The global state of harm reduction 2012: towards an integrated response.
Harm Reduction International Association, London. http://www.ihra.net/files/2012/07/24/
GlobalState2012_Web.pdf. Accessed 16 Mar 2013
Stöver H, Nelles J (2003) Ten years of experience with needle and syringe exchange programmes
in European prisons. Int J Drug Policy 14:437–444
Strathdee SA, Stockman JK (2010) Epidemiology of HIV among injecting and non-injecting drug
users: current trends and implications for interventions. Curr HIV/AIDS Rep 7:99–106
Strathdee SA, Galai N, Safaiean M, Celentano DD, Vlahov D, Johnson L, Nelson KE (2001) Sex
differences in risk factors for hiv seroconversion among injection drug users: a 10-year
perspective. Arch Intern Med 161:1281–1288
Strathdee SA, Hallett TB, Bobrova N, Rhodes T, Booth R, Abdool R, Hankins CA (2010) HIV and
risk environment for injecting drug users: the past, present, and future. Lancet 376:268–284
Thomas G (2005) Harm reduction policies and programs for persons involved in the criminal
justice system. Canadian Centre on Substance Abuse, Ottawa. http://www.ccsa.ca/2005%
20CCSA%20Documents/ccsa-003900-2005.pdf. Accessed 15 Mar 2013
Tilson H, Aramrattana A, Bozzette S, Falco M, Hammett TM, Kozlov A, Lai S, Mahal A,
Schottenfeld RS, Solomon S, Celentano DD (2006) Preventing HIV infection among injecting
drug users in high risk countries: An assessment of the evidence. Committee on the prevention
of HIV infection among injecting drug users in high-risk countries, Institute of Medicine.
The National Academies Press, Washington, DC. http://www.nap.edu/catalog.php?record_id
¼11731#toc Accessed 17 Mar 2013
Topp L, Day C, Degenhardt L (2003) Changes in patterns of drug injection concurrent with
a sustained reduction in the availability of heroin in Australia. Drug Alcohol Depend
70:275–286
Turner KME, Hutchinson S, Vickerman P et al (2011) The impact of needle and syringe provision
and opiate substitution therapy on the incidence of hepatitis C virus in injecting drug users:
pooling of UK evidence. Addiction 106:1978–1988
UNAIDS (2005) HIV/AIDS prevention, treatment and care among injecting drug users and in
prison. Ministerial meeting on urgent response to the HIV/AIDS epidemics in the Common-
wealth of Independent States. Joint United Nations Program on HIV/AIDS, Moscow, March
31 to April 1. http://www.unodc.org/pdf/event_2005-03-31_prisons.pdf. Accessed 5 Mar 2013
UNODC (United Nations Office on Drugs and Crime) (2009) A century of international drug
control. UNODC, Vienna. http://www.unodc.org/documents/data-and-analysis/Studies/100_
Years_of_Drug_Control.pdf. Accessed 17 Mar 2013
US Department of Justice (2012) Drug courts. National Criminal Justice Reference Services.
https://www.ncjrs.gov/spotlight/drug_courts/summary.html. Accessed 15 Mar 2013
van den Berg C, Smit C, Van Brussel G, Coutinho R, Prins M (2007) Full participation in harm
reduction programmes is associated with decreased risk for human immunodeficiency virus
and hepatitis C virus: evidence from the Amsterdam Cohort Studies among drug users.
Addiction 102:1454–1462
Vickerman P, Hickman M (2010) The effect of epidemiological setting on the impact of harm
reduction targeting injecting drug users. In: Rhodes T, Hedrich D (eds) Harm reduction:
evidence, impacts and challenges. Publications Office of the European Union, Luxembourg,
pp 165–188
Vickerman P, Hickman M, Judd A (2007) Modelling the impact on hepatitis C transmission of
reducing syringe sharing: London case study. Int J Epidemiol 36:396–405
Vickerman P, Martin N, Turner K, Hickman M (2012) Can needle and syringe programmes and
opiate substitution therapy achieve substantial reductions in hepatitis C virus prevalence?
Model projections for different epidemic settings. Addiction 107:1984–1995
Watters JK, Estilo MJ, Clark GL, Lorvick J (1994) Syringe and needle exchange as HIV/AIDS
prevention for injection drug users. JAMA 271:115–120
84 Harm Reduction Policies, Settings and Challenges 1335
Further Reading
Pates R, Riley D (2012) Harm reduction in substance use and high-risk behaviour: international
policy and practice. Wiley-Blackwell, Oxford
Rhodes R, Hedrich D (eds) (2010) Harm reduction: evidence, impacts and challenges. EMCDDA
Scientific Monograph Series No. 10. Publications Office of the European Union, Luxembourg.
http://www.emcdda.europa.eu/publications/monographs/harm-reduction. Accessed 17 Mar
2013
WHO, UNAIDS, UNODC (2013) Technical guide for countries to set targets for universal access
to HIV prevention, treatment and care for injecting drug users, 2012 revision. World Health
Organization, Geneva. http://www.who.int/hiv/pub/idu/targets_universal_access/en/index.
html. Accessed 3 Mar 2013
Good Practice and Quality Standards
85
Marica Ferri and Paul Griffiths
Contents
85.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1338
85.2 From Knowledge to Implementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1339
85.2.1 Knowledge Translation into Practice: From Evidence to Change . . . . . . . . . . 1339
85.2.2 Quality of Interventions: The Main Tools and Their Life Cycle . . . . . . . . . . . 1341
85.2.3 Participation: A Key for Successful Implementation . . . . . . . . . . . . . . . . . . . . . . . . 1351
85.2.4 Examples of Frameworks for Quality Standards . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1353
85.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1356
Glossary of Terms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1356
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1357
Abstract
The present chapter is aimed at enabling the readers to master the methods to
ascertain whether an evidence-based recommendation is appropriate for real-world
patients in specific contexts. Nowadays it is crucial to develop an individual
capacity for critical assessment and to know where to search for updated and
reliable sources of evidence. The methods, the processes, and the practical mean-
ing of the most popular tools for the promotion of quality are presented with links
to current projects and free of cost resources for professionals. The ultimate goal of
the evidence-based medicine is to provide the patients with the best possible
interventions. To reach this goal, knowledge has to be translated into practice.
Guidelines and standards are popular instruments to disseminate and implement
evidence-based recommendations. Nevertheless to implement them into specific
contexts, some decisions are needed. The chapter includes a description of the
main approaches used to adapt or adopt guidelines and standards.
85.1 Introduction
The promotion of quality and the exchange of good practice are recognized as an
important strategy both to improve the effectiveness of drug-related interventions and
to ensure the efficient use of limited resources. Guidelines and standards in particular
are among the most frequently used tools for the promotion of quality through the
translation of knowledge into the daily practice of treatment of drug addiction. But it
is not always needed to publish new guidelines and standards; often the existing good
quality guiding documents can be adapted to suit a specific national or local context.
New disciplines have emerged focusing on methods for successful knowledge trans-
fer to action, such as implementation science, translational science, and knowledge
mobilization. A common recommendation is that the only way to a successful
implementation is the promotion of participation among all the stakeholders, starting
with the medical doctors and the health professionals and including the decisions
makers, the patients and their families, and the public in general.
It is therefore important that the professionals in the treatment of drug addiction
are familiar with the terminology and the methods of the quality promotion as these
are increasingly part of their daily activity.
The contents of the evidence base change rapidly as soon as new studies are
conducted and contribute with new results. This is why it is important to master the
methods to ascertain whether a recommendation is appropriate for real-world patients
in specific contexts. It becomes crucial to develop an individual capacity for critical
assessment and to know where to search for updated and reliable sources of evidence.
To this purpose the present contribution was conceived. The evolution from evidence
base to implementation is described giving some details about the terminology and
references for further reading. The methods, the processes, and the practical meaning
of the most popular tools for the promotion of quality are also presented with links to
current projects and free of cost resources for professionals. In particular it is explained
how time and resources can be saved by adapting or adopting already published
evidence-based guidelines to specific needs and contexts. The current initiatives for the
development of quality standards in drug addiction treatment at international and at
national level are described and compared, and for each of them, the links for free
downloading of documents are included. To complement the information on implemen-
tation, we included a description and references to some recent initiatives in the medical
field in which the participation of drug addiction treatment professionals is crucial but
still not sufficient. In fact all those initiatives are studying strategies to effectively
communicate with decision makers and patients. In a conclusive part, two examples of
use of standards are compared more in depth, in one case as part of an accreditation
system and in another as a support for implementation and measuring of quality criteria.
85 Good Practice and Quality Standards 1339
The overall aim of good practice sharing and standards development is the achieve-
ment of improvement in the quality of treatment. Clearly quality is not an abstract
concept but rather an umbrella definition for series of measurable achievements in
the health and well-being of the treated patients.
“Primum non nocere” – first of all do not harm – the phrase attributed to the
Hippocratic Oath, reminds that the first aim of a health intervention is to avoid harm.
And it is exactly with this intention that the pioneers of the evidence-based
medicine called the attention on the discrepancies between research results and
medical practice, which would have cost human lives (Cochrane 1999). According
to their claims the timely application to practice of the results from clinical research
would have saved many lives and reduced subsequent costs to the society (Egger
and Smith 1997). For example, randomized controlled trials proving the effective-
ness of systemic glucocorticosteroids administered to pregnant women at risk of
preterm delivery to reduce respiratory distress syndrome in newborn babies were
available already in the 1970s, but it took almost 20 years before this intervention
became a common practice (Roberts and Dalziel 2006).
The possible effect of the delay in the adoption of this practice was that
a significant number of premature babies probably suffered and possibly died and
needed more expensive treatment than was necessary (Rennick 2006).
The movement for the systematic collection of scientific results for dissemination
outside the restricted circles of researchers and academics became known worldwide
at the beginning of the 1990s (Sackett et al. 1996) and was boosted by the foundation
of the Cochrane Collaboration, an international organization aimed at helping
“healthcare providers, policy-makers, patients, their advocates and carers, make
well-informed decisions about health care, by preparing, updating, and promoting
the accessibility of Cochrane Reviews” (Chalmers and Glasziou 2004).
In 1998 an editorial group specifically devoted to drugs and alcohol was founded
with its base in Rome (Davoli and Ferri 2000), and since then around 70 reviews on
the various interventions (including prevention) for drug and alcohol problems
were published and updated.
The availability of good quality research on effectiveness of treatment for drug
problems has dramatically increased over the last years, even though important gaps
still remain to be bridged with evidence (Turner and McLellan 2009). The availability
of studies and of systematic reviews nurtured the production of clinical guidelines as
a major tool for the dissemination and application of evidence in practice.
For example, a recent survey for the identification of treatment guidelines in
Europe identified more than 140 sets of guidelines for the treatment of drug
addiction (EMCDDA 2011). Nevertheless the practical effects of such a massive
effort to produce clinical guidelines were not clear. When measured, the impact on
quality of treatment seemed not impressive. Some surveys performed in the medical
1340 M. Ferri and P. Griffiths
field, not specifically in the drug addiction one, showed that clinical guidelines are
applied to practice in only 50–70 % of day-to-day decisions, and the main reason
given for not applying them is that they are of limited relevance to patients and
healthcare staff (Parchman et al. 2011). Moreover, in a recent debate promoted by
the British Medical Journal about the effectiveness of guidelines (Grol and
Wensing 2004), it was pointed out that to ensure clinical guidelines have an impact
on actual care and practice, activities beyond the mere production and dissemina-
tion should be instigated (Ferri and Bo 2012).
This type of considerations along with the need to reduce cost and improve
quality and outcomes must be at the base of the evolution towards the knowledge
translation into practice approach (Brownson et al. 2012). In fact, moving from the
concept of evidence to that of knowledge expands an idea already present in the
definition of evidence-based medicine. The practice of evidence-based medicine
integrates clinical expertise with the best available evidence from systematic
research, explained David Sackett (1996). “Without clinical expertise, practice
risks becoming tyrannised by evidence, for even excellent external evidence may
be inapplicable to or inappropriate for an individual patient” reinforced then.
Probably “knowledge” is a better term to put together evidence with expertise.
Knowledge translation has been defined as a “dynamic and iterative process that
includes the synthesis, dissemination, exchange and ethically sound application of
knowledge to improve health, provide more effective health services and products,
and strengthen the health care system” (Canadian Institutes of Health Research
2012). Knowledge translation is not the only term that has been used to name this
tendency towards practical use of knowledge to improve practice. According to
Straus and colleagues (2009), more than 90 terms were identified in the literature.
According to them, in Europe, preferences are for “implementation science” or
“research utilization,” whereas the terms “dissemination and diffusion,” “research
use,” and “knowledge transfer and uptake” are more frequently preferred in the
United States. The Canadian “knowledge translation” has been adapted by others,
including the United States National Center for Dissemination of Disability
Research and the World Health Organization (WHO).
The lowest common denominator among the above described different terms is
a move beyond dissemination of knowledge into actual use of it to transform
practice. “Knowledge creation (i.e., primary research), knowledge distillation
(i.e., the creation of systematic reviews and guidelines) and knowledge dissemina-
tion (i.e., appearances in journals and presentations) are not enough on their own to
ensure the use of knowledge in decision-making” (Straus et al. 2009).
A definition of the “best-practice” concept was recently developed by a group of
European experts convened by the EMCDDA. In brief, best practice is the best
application of the available evidence to current activities in the drugs field.
A number of factors were identified as contributing to making an intervention
qualify as “best practice.” In summary, a best-practice intervention is based on
the most robust scientific evidence available regarding what is known to be
effective in producing successful outcomes, and it is tailored to the needs of those
it addresses. Methods used will be transparent, reliable, and transferable and can be
85 Good Practice and Quality Standards 1341
85.2.2 Quality of Interventions: The Main Tools and Their Life Cycle
Several are nowadays the international inventories of guidelines from all over
the world which can be consulted freely to find relevant documents. Among those,
the more important are the inventory maintained by the Guidelines International
Network (http://www.g-i-n.net/library) containing over 6,000 sets of guidelines
for evidence-based healthcare (in multiple languages) and the National Guide-
lines Clearinghouse (http://www.guideline.gov/), an initiative of the Agency for
Healthcare Research and Quality (AHRQ) in the United States, which publishes
guidelines from any countries provided they are in English. The website of the
National Guidelines Clearinghouse offers an automated function to compare
different guidelines upon their main characteristics and to obtain synthesis of
guidelines. The main aim of the inventories of guidelines is to avoid duplication
of efforts making good quality guidelines available for adoption or adaptation in
different contexts.
Table 85.1 Recently published quality standards in the treatment of drug addiction
Supporting
Title and year of publication organization Target groups Structure of the standards Web address
European Minimum Quality European Professionals performing Structural standards of services www.isgf.ch
Standards (EQUS) 2012 commission interventions, service directors Process standards at the
and managers responsible for service level
the functioning of their Process standards of
institutions and staff, and interventions
health authorities, planners,
Outcome standards at the
and policy makers who are
system level
mainly concerned with the
drug demand reduction
activities at the system and
network level
Proposed continental African Union Unspecified 14 principles of effective drug http://www.au.int/en/
minimum quality standards dependence treatment
for treatment of drug 15 standards for treatment of
dependence 2012 drug dependence and
3 standards for evaluation and
assessment
Principles of drug UNODC WHO Unspecified 9 principles: http://www.who.int/substance_abuse/
dependence treatment 2008 Description and justification publications/
Components principles_drug_dependence_treatment.
pdf
Actions to promote each
principle
M. Ferri and P. Griffiths
85
National standards
Service delivery for people New Zealand This guidance document is General principles http://www.health.govt.nz/publication/
with coexisting mental health Ministry of aimed at all those who have an Tips for mental health and service-delivery-people-co-existing-
and addiction 2010 Health interest and responsibility for addiction planners and funders mental-health-and-addiction-problems-
planning, funding and Tips for mental health and integrated-solutions-2010
providing mental health and addiction service managers
addiction services including and clinical leaders
District Health Boards, Non-
Suggested actions for local
governmental organisations
planning
and the Ministry of Health.
The content will be of interest
to staff working in services,
consumers and service users,
carers and others who have
Good Practice and Quality Standards
The outcome standards proposed at the system level included the goals of
health and social stabilization of patients and the reduction of illegal or
non-prescribed psychotropic substances. Monitoring included the level of
utilization (each service should provide information on the number of slots or
bed utilized) and the ratio of discharges occurred as planned or for different
reasons.
Internal and external evaluation of services was also proposed as a standard.
Beyond the list of proposed standards, the project-added value lies on the
process adopted to consult the stakeholders and to identify several levels of
standards. Namely, the stakeholders were interviewed by rounds of Internet-based
consultations about the level of implementation status and acceptability of the
proposed standards in their respective countries. Through this strategy it was
possible to identify a long list of standards and grade them by priority of imple-
mentation. In fact, the EQUS study also included a review, involving experts from
24 European countries, of existing quality standards already implemented at
the national level. With regard to drug treatment processes, the standards
most frequently reported as already implemented were in the areas of client data
confidentiality and assessment of clients’ drug use history, whereas the standards
concerned with routine cooperation with other services, and those focusing on
continuous staff training, were less often implemented. In the area of treatment
outcomes, the two types of standard most frequently reported as implemented were
those with goals linked to health improvement and reduced substance use. Among
the standards less likely to be applied were those focusing on external evaluation
and monitoring client discharge; problems related to the implementation of these
standards were reported.
This approach may allow the participating countries to set their own goals
and to pace the achievement of them on the basis of their own capacity and
priority. This process would also be greatly facilitated by the existence of the
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA),
a decentralized agency whose aim is to provide sound and comparable information
on drugs in Europe. Thanks to its impartiality and comprehensiveness of informa-
tion, EMCDDA can support the countries volunteering for the adoption of the
quality standards in setting their goals and measuring their successes.
The European standards have not been formally adopted yet, but the EQUS
study represents the beginning of an ongoing process to reach consensus over
a minimum set of quality standards in drug demand reduction.
Another initiative at supranational level was undertaken by the African Union
which has recently proposed a list of Continental Minimum Standards for treatment
of drug dependence as a guide to member states (African Union 2012). In the
introduction of these standards, there is a synthesis of the current situation of drug
consumption in Africa stating that “the levels of drug consumption continue to
grow in Africa while there is a tendency toward stabilisation in North America and
Europe”; therefore, “an in-depth revision of current drug policies has become
necessary (in Africa) in view of the increasing human and social costs and threats
to democratic institutions.”
1350 M. Ferri and P. Griffiths
The text supports that “provisions should be made towards treatment of drug
users which was instrumental in stabilising drug consumption in the West,” while
“The criminalisation and marginalisation of drug users has increased drug-related
health problems and contravened universal fundamental human rights.” In sum-
mary those standards are presented as an application of the lessons learned in
a different context to change a particular situation. This intention captures the
exact spirit of sharing of good practice. A general description of recent initiatives
of standards for the treatment of drug addiction is reported in Table 85.2, and some
of them will be deeply explored.
In general terms it can be observed that the existing standards (at their different
level of implementation) seem to be triggered by several reasons: the harmonization
of the existing services, the translation in practice of the evidence-based guidelines,
the consistency between policy decisions and service provision, and the need to
measure the results of interventions. These reasons are diversely reflected in the
mentioned initiatives mainly in relation with the level where the standards are
proposed. The life cycle of quality standards depends on the supporting evidence,
but not completely. In fact when it comes to human rights or general safety
measures, the relevant principles are imperishable.
Clinical pathways are structured, multidisciplinary plans of care designed to
support the implementation of clinical guidelines and protocols. In a recent past it
was considered that this definition was variedly interpreted by different stake-
holders until a recent systematic review (Kinsman et al. 2010) clarified the concept.
The clinical pathways are essential to the translation of evidence-based guidelines
at service level. They are in fact meant to “detail essential steps in care of patients
with a specific clinical problem” and sequence “the actions of a multidisciplinary
team” (De Bleser et al. 2006). In clarifying which actions should be undertaken to
practice evidence-based recommendations, clinical pathways “facilitate translation of
national guidelines into local protocols” (Campbell et al. 1998) and allow continuous
improvement by monitoring and evaluating variances.
85 Good Practice and Quality Standards 1351
Clinical pathways are commonly adopted in the United States where in 2003 it
was reported that almost 80 % of the hospitals used this tool (Kinsman et al. 2010).
Evidence supports the adoption of clinical pathways at hospital level for the reduction
of in-hospital complications (such as infections, bleeding, and pneumonia), improved
documentation, and possibly a reduction in the length of stay (Rotter et al. 2010). An
experience of integrated clinical pathways in mental health has been reported in
Scotland where the National Health Service (NHS) Scotland is taking a national
approach to improving the quality and safety of mental health services. The program
started with the publication of national standards by NHS Quality Improvement
Scotland (NHS QIS), setting out the framework for development at local level.
The emphasis of development and implementation of the ICPs lies with local
NHS boards to ensure they are developed with local ownership and to meet the
needs of the local population. However, to ensure accreditation by NHS QIS, the
local ICPs must incorporate the national standards and evidence improvement to
the quality of care provided (El-Ghorr 2010). In Belgium there is the European
Association for the development of clinical pathways (http://www.e-p-a.org/about-
epa/index.html. Among the objectives of this organization, there is the setup of an
international network for pooling know-how on clinical pathways and the promo-
tion and fostering of international cooperation between healthcare researchers,
managers, and healthcare providers from European countries and the wider inter-
national community. The association has a journal which publishes research results
on the development of clinical pathways.
There are two main elements underlying all the instruments for quality improve-
ment mentioned in the previous paragraphs (evidence-based clinical guidelines,
quality standards, and clinical pathways). These two elements are the evidence base
and the stakeholders consensus. The last three decades have been devoted to
define and share a valid methodology for the identification assessment and synthesis
of the available evidence. This activity successfully brought to a general under-
standing about the terminology and the sources of correct information. Nowadays
the role of evidence to base decisions is widely recognized, and the access to good
quality sources of evidence is increasingly available.
The new challenge seems to lie on the promotion of an authentic participatory
implementation of evidence-based interventions.
The same pioneers of the evidence-based medicine are now exploring strategies
to communicating and involving two crucial stakeholders: the decisions makers and
the patients (this latter category includes also family members, civil society orga-
nizations, community representatives (Deber et al. 2005)). Projects like SUPPORT
financed by the European Commission’s 6th Framework Programme (Lavis 2009)
and the most recent DECIDE (Treweek et al. 2013) co-funded by the European
Commission under the Seventh Framework Programme are both aimed at
supporting decision makers in the use of evidence.
1352 M. Ferri and P. Griffiths
be in fact found on long-term observational studies, and in some cases they require
qualitative analysis which is more difficult to be systematically retrieved with
the typical search strategies adopted in systematic reviews and even more difficult
to be assessed for quality and included in meta-analysis (Gough 2012). Neverthe-
less there are some added values in the drug addiction field which compensate for
those extra efforts. The impact of interventions on public health and security makes
drug addiction an important point on every political agenda and need to be based on
the best available evidence.
Several evidence-based guidelines are currently available for the treatment of drug
addiction, in particular for the combined pharmacological and psychological
approaches for opioid dependence, and these guidelines are issued at international
and national level. Differently, the publication of quality standards for drug addic-
tion treatment is less common, as the majority of the existing standards in drug
addiction refer to prevention (UNODC 2013; EMCDDA 2012). Following we will
describe two examples of standards for drug addiction treatment at national level, in
European countries, namely, in the Czech Republic and in the United Kingdom.
In Czech Republic the implementation of quality standards for treatment of drug
addiction dates back to 1995 for initiative of the Interdepartmental National Drug
Commission (now Government Council for Drug Policy Coordination). Called
minimal standards, these were adopted by the Association of Non-Governmental
Organizations (ANO) for Addiction Prevention and Treatment for evaluating the
quality of member organizations and newly established facilities. After further
elaboration occurred in the subsequent 4 years, those standards became the basis
for a certification process, which recognizes that a specific service provider is in line
with predefined quality standards. Since 2004 the adherence to quality standards is
assessed by specifically trained external evaluators. The current process for the
certification of treatment providers was kicked off in 2005, and it included
a transition period to allow the treatment provider services to start the certification
process. After that period, certification became a prerequisite for applying for state
grant programs. The overall aim of the certification process was the improvement of
the quality of the network of services including a cost-effective administration of
public funds. The certification process brought to the integration of the drug
addiction services into the medical and social national system.
The underlying principles are as follows: voluntariness, certification is not required
to provide drug services but only to apply for public funds; transparency, the evalu-
ation process is carried out according to published criteria; and objectivity, the actual
evaluation of quality is performed by an independent agency who appoints trained
evaluators and the facility providers can point out any possible conflict of interest.
The standards are at the base of certification and accreditation process. The core
activity of the certification process includes that a group of trained assessors visits
the service providers to collect relevant information. Active participants in this
1354 M. Ferri and P. Griffiths
process are the facilities requesting the certificate of quality (those wishing to apply
for public funds); the Certification Agency (an independent institution that arranges
on-site examinations, communication between the parties of the certification pro-
cess, and training of certificators); the certification team carrying out on-site
examinations (composed by at least three trained certificators); the Certification
Board of the Government Council for Drug Policy Coordination (deciding about
certification request results and validity of certification ranging from 1 to 4 years);
and the Executive Board of the Government Council for Drug Policy
Coordination – to which the facilities can address their complaints about, for
example, the composition of the certification team. In fact, before the certification
can start, the agency and the requesting facility have to agree on the date and the
composition of the team of assessors. Subsequently a number of previously iden-
tified employees and clients are interviewed with semi-structured questionnaires.
The on-site examination in general lasts one day at the end of which the team of
assessors drafts a report with a proposal for certification or suggestions for improve-
ment. The report is shared with the interested facility which is given the opportunity
to comment in writing.
The report is therefore completed and forwarded by the Certification Agency
to the Certification Board of the Government Council for Drug Policy for the final
decision.
Overall the process takes around 2 months, and the facilities requesting certifi-
cation have 15 days to contest the results.
In the United Kingdom the National Institute for Clinical Excellence (NICE)
publishes evidence-based clinical guidelines for many different medical disciplines
including drug addiction. Sets of quality standards are derived from the best
available evidence such as NICE guidance and other evidence sources accredited.
They are developed in collaboration with NHS and social care professionals, their
partners, and service users. The standards consider issues like evidence of effec-
tiveness and cost-effectiveness, people’s experience, safety, equality, and cost
impact. The quality standards are considered central to supporting the govern-
ment’s vision for an NHS and social care system focused on delivering the best
possible outcomes for people who use services (Health and Social Care Act 2012).
This act clarifies that the Secretary of State “must have regard to the quality
standards prepared by NICE.” The care system should consider those standards in
planning and delivering services to secure continuous improvement in quality.
NICE quality standards do not provide service specifications but rather define
priority areas for quality improvement. Nevertheless those standards are the basis
to ensure that the providers of health and adult social care in England meet the
standards of quality and safety required to by the Care Quality Commission.
The standards developed by NICE are typically composed of a general statement
complemented by a measure. These quality measures are drafted only after the
quality statement wording has been agreed and addresses the structure of care or
services, process of care or service provision, and, if appropriate, outcome of care
or service provision. The majority of measures refer to process and are expressed as
a numerator and denominator to define a proportion in which the numerator is
85 Good Practice and Quality Standards 1355
a subset of the denominator population. For example, for the standard “People who
inject drugs have access to needle and syringe programmes in accordance with
NICE guidance,” there is a measure at the structure level, which is “Evidence of
local arrangements to ensure people who inject drugs have access to needle and
syringe programmes in accordance with NICE guidance,” complemented by
a measure of outcome: (a) proportion of people who inject drugs who access needle
and syringe programs, wherein the numerator is the number of people who access
needle and syringe programs and the denominator is the estimated prevalence of
injecting drug users, and (b) incidence of blood-borne viruses among people who
inject drugs.
To clarify the implications of the standard, a breakdown of meanings of the
standard for each stakeholder is included: service providers ensure systems are in
place for people who inject drugs to have access to needle and syringe programs in
accordance with NICE guidance; needle and syringe program staff ensure people
who inject drugs have access to needle and syringe programs in accordance with
NICE guidance; commissioners ensure they commission services for people who
inject drugs to have access to needle and syringe programs in accordance with NICE
guidance; and people who inject drugs have access to needle and syringe programs
that are nearby, have suitable opening hours, and provide injecting equipment and
advice on reducing the risk of harm. The standards include also that the sources of
data should be considered in the measurement. Furthermore, at NICE there is an
implementation team to support key audiences and organizations to maximize the
uptake of guidance and quality standards. The team assesses the aids and barriers to
implementation and provides practical support tools for commissioning, service
improvement and audit, education, and learning. The team prepares reports on the
uptake of guidance that are used to inform the development of the quality standard.
The implementation team collaborates with national bodies and local organizations,
through local implementation consultants, to support the use of quality standards and
to facilitate shared learning. Overall the process to produce standards at the National
Institute for Clinical Excellence lasts indicatively for 42 weeks.
These two examples suggest the possibility of different approaches to the use of
quality standards. In the Czech experience in fact, the development of the standards
represents an initial effort, whereas the actual focus seems to lie on the certification
and accreditation process including several levels of training and a “learning by
experience” process. Furthermore, the entire experience initiated around 20 years ago
has been conceived and developed specifically in the treatment of drug addiction.
On the other hand the National Institute for Clinical Evidence has created along
with the Department of Health and other key partners a core library of topics for
quality standard development in health-related topics, among which alcohol depen-
dence and drug use were included. In this case the focus seems to be on the
development itself of the standards which translate the evidence-based guidelines
into general statements and measures of outcomes at the system level including the
indication of the sources of data to be used for the assessment of the implementa-
tion. Furthermore, NICE offers the support of an implementation team to enhance
local adoption initiatives.
1356 M. Ferri and P. Griffiths
85.3 Conclusion
Glossary of Terms
References
AGREE Collaboration (2003) Development and validation of an international appraisal instru-
ment for assessing the quality of clinical practice guidelines: the AGREE project. Qual Saf
Health Care 12:18–23
African Union (2012) Proposed continental minimum quality standards for treatment of
drug dependence. http://www.au.int/ar/sites/default/files/02%20Concept%20Note.pdf
Brownson RC, Colditz GA, Proctor EK (2012) Dissemination and implementation research in
health. Oxford University Press, New York
Brunsson N, Jacobsson B (eds) (2000) A world of standards. Oxford University Press, New York
Burgers J, Grol RICH, Klazinga NS, Mãkelã MARJ, Zaat JOOS, For the AGREE Collaboration
(2003) Towards evidence-based clinical practice: an international survey of 18 clinical guide-
line programs. Int J Qual Health Care 15(1):31–45, http://intqhc.oxfordjournals.org/content/
15/1/31.abstract
Campbell H, Hotchkiss R, Bradshaw N, Porteous M (1998) Integrated care pathways. BMJ
316(7125):133–137, PM: 9462322
Canadian Institutes of Health Research (2012) About knowledge translation
Chalmers I, Glasziou P (2004) Avoidable waste in the production and reporting of
research evidence. Lancet 374(9683):86–89, http://www.sciencedirect.com/science/article/
pii/S0140673609603299
Cochrane AL (1999) Effectiveness and efficiency: random reflections on health services. Royal
Society of Medicine Press, London
Connis RT, Nickinovich DG, Caplan RA, Arens JF (2000) The development of evidence-based
clinical practice guidelines. Integrating medical science and practice. Int J Technol Assess
Health Care 16(4):1003–1012, PM:11155824
Davoli M, Ferri M (2000) The Cochrane Review Group on drugs and alcohol. Addiction
95(10):1473–1474, PM:11070523
De Bleser L, Depreitere R, De WK, Vanhaecht K, Vlayen J, Sermeus W (2006) Defining
pathways. J Nurs Manag 14(7):553–563, PM:17004966
Deber RB, Kraetschmer N, Urowitz S, Sharpe N (2005) Patient, consumer, client, or customer:
what do people want to be called? Health Expect 8(4):345–351, PM:16266422
Egger M, Smith GD (1997) Meta-analysis. Potentials and promise. Br Med
J 315(7119):1371–1374, PM:9432250
El-Ghorr A et al (2010) Scotland’s national approach to improving mental health services:
integrated care pathways as tools for redesign and continuous quality improvement. Int J
Care Pathways 14.2:57–64
EMCDDA (2011) Guidelines for the treatment of drug dependence: a European perspective.
Publications Office of the European Union, Luxembourg
EMCDDA (2012) European drug prevention quality standards. A manual for prevention
professionals. Lisbon
1358 M. Ferri and P. Griffiths
Ferri M, Bo A (2012) Drug demand reduction: global evidence for local action, Drugs in
focus briefings from the European Monitoring Centre for Drugs and Drug Addiction 1, Publi-
cations Office of the European Union # European Monitoring Centre for Drugs and Drug
Addiction
Gough B, Madill A (2012) Subjectivity in psychological science: from problem to prospect.
Psychol Methods 17(3):374–384
Grol R, Wensing M (2004) What drives change? Barriers to and incentives for achieving evidence-
based practice. Med J Aust 180.6(Suppl):S57–S60
Groot P, Hommersom A, Lucas P (2008) Adaptation of clinical practice guidelines. Stud Health
Technol Inf 139:121–139, PM:18806324
Guidelines International Network (2012) Annual report 2012. Ref Type: Online Source
Guyatt GH et al (2011) GRADE guidelines: 4. Rating the quality of evidence-study limitations
(risk of bias). J Clin Epidemiol 64.4:407–415
Harrison MB, Legare F, Graham ID, Fervers B (2010) Adapting clinical practice guidelines to
local context and assessing barriers to their use. CMAJ 182(2):E78–E84, PM:19969563
Institute of Medicine (2011) Clinical practice guidelines we can trust. The National Academies
Press, Washington, DC
ISO (2004) ISO/TMB policy and principles statement global relevance of ISO technical work and
publications. http://www.iso.org/iso/global_relevance.pdf
ISO (2013) Structure and governance. International Standards Organization, Geneva. Ref Type:
Online Source
Khunti K, Lakhani M (1998) Barriers to the implementation of guidelines in general practice.
Asthma Gen Pract 6(1):7–8
Kinsman L, Rotter T, James E, Snow P, Willis J (2010) What is a clinical pathway? Development
of a definition to inform the debate. BMC Med 8:31, PM:20507550
Lavis JN et al (2009) SUPPORT tools for evidence-informed health policymaking (STP). Health
Res Policy Syst 7(Suppl 1):I1
Liberati A (2011) Need to realign patient-oriented and commercial and academic research. Lancet
378(9805):1777–1778, http://linkinghub.elsevier.com/retrieve/pii/S0140673611617728
NICE (2012) Health and social care directorate quality standards process guide. National Institute
for Health and Clinical Excellence, Manchester
Oxman AD, Lewin S, Lavis JN, Fretheim A (2009) SUPPORT Tools for evidence-informed
health policy making (STP) 15: engaging the public in evidence-informed policymaking.
Health Res Policy Syst 7(Suppl 1):S15, PM:20018105
Parchman ML, Scoglio CM, Schumm P (2011) Understanding the implementation of evidence-
based care: a structural network approach. Implement Sci 6:14
Parliament of the United Kingdom, Health and Social Care Act (2012). Ref Type: Online Source
Petit-Zeman S, FAU - Cowan K, Cowan K Patients/carers and clinicians can set joint priorities for
research in cleft lip and palate. (1872–8464 (Electronic))
Rennick GJ (2006) Use of systemic glucocorticosteroids in pregnancy: be alert but not alarmed.
Australas J Dermatol 47(1):34–36, PM:16405480
Roberts D, Dalziel S (2006) Antenatal corticosteroids for accelerating fetal lung maturation for
women at risk of preterm birth. Cochrane Database Syst Rev (3): CD004454. Available at:
PM:16856047
Rotter T, Kinsman L, James E, Machotta A, Gothe H, Willis J, Snow P, Kugler J (2010)
Clinical pathways: effects on professional practice, patient outcomes, length of stay and
hospital costs. Cochrane Database Syst Rev 17(3):CD006632. doi:10.1002/14651858.
CD006632.pub2. Review
Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS (1996) Evidence based
medicine: what it is and what it isn’t. BMJ 312(7023):71–72, PM:8555924
Schardt C, Adams MB, Owens T, Keitz S, Fontelo P (2007) Utilization of the PICO framework to
improve searching PubMed for clinical questions. BMC Med Inform Decis Mak 7:16,
PM:17573961
85 Good Practice and Quality Standards 1359
Schaub MP, Uchtenhagen A, EQUS Expert Group (2013) Building a European consensus on
minimum quality standards for drug treatment, rehabilitation and harm reduction. Eur Addict
Res 19(6):314–24. doi:10.1159/000350740. Epub 2013 Jun 14
SIGN (2011) SIGN 50: a guideline developer’s handbook. Scottish Intercollegiate Guidelines
Network
Straus SE, Tetroe J, Graham I (2009) Defining knowledge translation. Can Med Assoc
J 181(3–4):165–168, http://www.cmaj.ca/content/181/3-4/165.short
Treweek S, Oxman AD, Alderson P, Bossuyt PM, Brandt L, Brozek J et al (2013) Developing and
evaluating communication strategies to support informed decisions and practice based on
evidence (DECIDE): protocol and preliminary results. Implement Sci 8:6
Turner BJ, McLellan AT (2009) Methodological challenges and limitations of research on alcohol
consumption and effect on common clinical conditions: evidence from six systematic reviews.
J Gen Intern Med 24(10):1156–1160, PM:19672662
Uchtenhagen A, Schaub M (2011) Minimum quality standards in drug demand reduction EQUS
UNODC (2013) International standards on drug use prevention. Ref Type: Online Source
WHO (2009) Guidelines for the psychosocially assisted pharmacological treatment of opioid
dependence. World Health Organisation, Geneva
WHO (2013) International Clinical Trials Registry Platform (ICTRP). http://www.who.int/ictrp/en/
Ethical and Legal Aspects of Interventions
in Addiction Treatment 86
Ambros Uchtenhagen
Contents
86.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1362
86.2 International Frameworks and National Diversities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1362
86.2.1 Legal Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1362
86.2.2 Ethical Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1365
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1373
Abstract
The UN conventions present the international legal framework; they urge mem-
ber states to provide treatment and rehabilitation but prohibit consumption and
possession of scheduled drugs. This creates problems for providing treatment
and harm reduction programs to patients who are not or not yet ready to stop
illicit drug use. Other international documents, notably from the World Health
Organization and the United Nations Office on Drugs and Crime, are strongly in
favor of agonist substitution treatment and harm reduction measures. Within this
framework, national legislation has much room for diverse preferences; the
International Narcotic Control Board regularly comments the national practices,
as well as the European Monitoring Centre for Drugs and Drug Addiction for the
EU member states. An international trend gradually prefers therapeutic mea-
sures over criminal sanctions for drug users.
The international ethical framework is set by the universal declaration and
European convention on human rights, striking a balance between individual
rights and societal interests. Less ambiguous guidance comes from medical
ethics claiming the full range of patient’s rights for addicted persons.
Note: Some of the material is based on earlier work of the author about ethical aspects of treatment
and care in addiction (Uchtenhagen & Guggenb€ uhl 2000; Uchtenhagen et al. 2005; Uchtenhagen
2010a, b).
A. Uchtenhagen
Research Foundation for Public Health and Addiction, Zurich University, Zurich, Switzerland
e-mail: [email protected]
The respective conduct codes for medical professions are regional or national
and include procedures how to deal with ethical conflicts. Conflicting situations
frequently occur, e.g., around the principles of autonomy or of confidentiality.
An essential ethical element of treatment is its effectiveness and avoidance of
harm, asking for scientific evaluation of therapeutic approaches, services, and
systems. The ethical acceptability of agonist substitution treatment and of harm
reduction measures is based on rigorous evidence of their effectiveness. Other
aspects concern the limits of social acceptability of addictive behavior and the
limits of what can be attained for an individual patient by therapeutic interven-
tions; avoidance of harm often is the more immediate objective than full
recovery. In a public health perspective, effects at population level rather than
at individual level are a priority, aiming at good coverage of treatment needs by
good accessibility and affordability of services.
86.1 Introduction
Addiction treatment is historically and until present guided by the basic under-
standing of addictive behavior. Interventions are shaped accordingly to prevailing
paradigms explaining substance use and substance dependence. Legislation is
a preferred instrument to limit consumption and addictive behavior, through pre-
ventive interventions as well as sanctions. The development of liberal societies
caring for individual freedom and responsibility, less interference with lifestyles
and personal choices, and the need for ethical standards in human behavior came to
the forefront and resulted in various rules guiding interventions and therapist’s
conduct. This process in the area of addiction treatment has been taken at hand, but
with persisting differences in orientation and a need for conflict management.
Implicitly, this includes criminalization of use (no use without preparatory acts).
The International Narcotic Control Board (INCB) was set up in 1968, with the
main task to control and facilitate the implementation of the Single Convention at
national level. The following conventions have revised and restated the functions of
the Board.
In summary, the UN conventions urge the treatment and rehabilitation of drug
abusers but prohibit the consumption of narcotics and psychotropic substances
(including tranquilizers and sedatives), which creates problems for patients in treat-
ment (continued use is often a reason to exclude patients from treatment) and even
more problems for harm reduction approaches designed to diminish the medical risks
of substance use (for persons in addiction treatment and outside of treatment).
Agonist maintenance treatment is viewed critically by INCB as a potential source
of diversion of narcotics to the illegal market (INCB 2011). However, the conven-
tions allow diversion to treatment as an alternative to punishment.
The World Health Organization (WHO) and the United Nations Office on
Crime and Drugs (UNODC) published Principles of Drug Dependence Treatment
in 2008. This discussion paper is in strong support of agonist maintenance treatment
for opioid dependence: “Opioid agonist pharmacotherapy is one of the most
effective treatment options for opioid dependence when methadone or
buprenorphine are administered at an individualized dosage for a period of several
months to years.” The discussion paper also urges to implement legal frameworks
which guarantee protection from potential sanctions for those seeking treatment
(WHO/UNODC 2008).
The UNODC, WHO, and UNAIDS “Technical Guide for countries to set targets
for universal access to HIV prevention, treatment and care for injecting drug users,”
published in 2009, has a range of preventive measures (e.g., needle and syringe
exchange programs) among its recommendations, thereby complementing the
treatment recommendations (UNODC/WHO/UNAIDS 2009).
In Europe, the EU Action Plan 2005–2008 (EU 2005) foresaw harm reduction
measures as a specific action for the implementation of Objective 14 (prevention of
health risks related to drug use) and Objective 15 (availability and access to harm
reduction services). The implementation process and the available evidence on
outcomes is presented in a monograph (Rhodes and Hedrich 2010).
86.2.1.4 Sanctions
Use and possession of illegal drugs for personal use are prohibited in a range of
countries. For Europe, an analysis of national practices is presented (EMCDDA
2009). Only rarely, prison sentences are handed out in case of infraction. In other
regions, imprisonment and compulsory treatment are more common, e.g., in labor
camps (WHO 2009).
In some countries, drug possession is an offence which may entail imprisonment
or even capital punishment. A systematic overview is not available. In Islamic law,
use of any drugs including alcohol is prohibited and sanctioned, but it also provides
care of those suffering from medical conditions.
Agonist maintenance therapy is prohibited in Russia (MHR 1995), while a
growing number of countries supports and expands this approach, replacing crim-
inal sanctions.
avoid such negative consequences. Among the appropriate measures are all treat-
ments which help to bring a majority of addicts into treatment, without disregarding
their autonomy, and to optimize accessibility of treatment services. In the case of
hazardous and harmful use, treatment by early and short interventions (e.g., moti-
vational interviewing) can have positive effects.
As in other medical fields, therapeutic interventions are justifiable if efficient and
effective. This principle is part of what is named “consequential ethics,” in contrast
to dogmatic ethics which call for complying with a given norm whatever the
consequences may be.
Substance use is a factor in many social and cultural events, as a facilitator of
social contact and a source of emotional well-being but also of destructive or
aggressive behavior. The acceptable limits of intoxication and behavior, of sub-
stances used and of opportunities for consumption, are cultural specific and are to
be respected when dealing with substance dependence (Edwards and Arif 1980).
For instance, a major difference between western and Asian cultures is the place of
the individual within the family system; while the individual’s interests and auton-
omy are a core concept of most western psychotherapies, the integrity and the
interests of the family are the higher value in many Asian societies.
In a paternalistic attitude, substance-dependent persons must be protected
against wasting their personal resources and potential achievements. However,
such an attitude collides with the present position that interference is only justified
on the basis of negative consequences of a person’s behavior for others. Also, many
people have lived or live a productive life in spite of their substance dependence,
and to interfere with their lifestyle would cause more ethical concerns than to
respect their autonomy.
Developing one’s own resources and shaping one’s own life is to be facilitated
by education and by societal organization, but it is ultimately in the responsibility of
the person itself. Conditional are the freedom of choice – and the freedom of the
will. Is addiction leaving any room for choices, is it a negation of free will and
therefore the basis for involuntary intervention? This has been debated extensively.
At present and on the basis of research evidence, we have a more differentiated
view. The decision of many to change their lifestyle and go to treatment (Ekendahl
2007; Bergmark 2008) or to stop the dependence without professional support (the
so-called self-healers) (Klingemann and Sobell 2007) demonstrates the ability of
many addicts to make a choice and stick to it.
This notion is reinforced by observations of regaining consumption control by
former addicts (Kaya et al. 2004) and that not the substance alone but also the
personality and the social environment had a role in the development of dependence
and that many users keep their consumption under control or regain control under
more favorable conditions (Zinberg 1984; Robins 1993).
A basic ambivalence – substance dependence as a medical condition or a moral
weakness – is reflected in the opposition of medical and moral treatment. Moral
treatment is understood to be educational and admonishing. The medical approach
is to help the addict in getting motivated for change by appropriate empathy and
information, while confrontation and reproaches risk to reinforce the resistance
1368 A. Uchtenhagen
against any change. It is important to give the patient the feeling that he is taking the
decisions and doing the necessary steps forward himself. Special methods have
been developed for enhancing the motivation for change, and they have become an
important element in today’s treatment of alcohol and other drug problems (Moyer
et al. 2002; Gossop 2006).
In summary, treatment of substance dependence is expected to help the individ-
ual to make his own choices and to regain self-responsibility, rather than to make
the decisions for him.
dose per day can block the heroin craving effectively). The model included
ancillary care for medical and social conditions of enrolled patients.
Apart from opiate replacement, only nicotine replacement has been introduced
into present medical practice, while former alcohol maintenance for alcoholics is
discontinued.
Results: Methadone maintenance is one of the most frequently and best
researched therapeutic approaches. Extensive reviews of the pharmacological
aspects, of service delivery, and of therapeutic outcomes have been published
(Arif and Westermeyer 1990; Ward et al. 1998; Uchtenhagen 2003; Farrell
et al. 2004; Health Canada 2008). In addition to methadone, buprenorphine and
retarded morphine have been introduced and researched as replacement medicines
in the treatment of opioid dependence, with similar outcomes. The positive findings
in terms of health and social improvements, including a massive reduction of
delinquency, were complemented by the fact that agonist maintenance treatment
has the greatest potential to bring heroin-dependent persons into contact with
therapy and care. It therefore became one of the most welcome instruments for
limiting the spread of blood-borne diseases – HIV/Aids and hepatitis – among drug
injectors. The reduction of risky injecting behavior and of seroconversion rates in
methadone patients became evidenced for community-based programs (Metzger
et al. 1993) and for prison-based programs (Stallwitz and Stoever 2007). Economic
evaluation documented the cost-effectiveness of methadone and buprenorphine
maintenance treatment (Connock et al. 2007).
Based on the evidence, methadone and buprenorphine have been scheduled by
the World Health Organization as essential medicines (WHO 2004a, b). Also,
international evidence-based scientific guidelines for agonist maintenance treat-
ments have been published (WHO 2008).
Concerns: A major concern was a weakening of the motivation to change and
therefore a prolongation of addictive behavior through agonist maintenance treat-
ment. There is no evidence for this claim. A multisite major cohort study showed
a relapse rate of methadone maintenance patients to daily opiate use of only 27 % at
12 year follow-up (Marsh et al. 1990). The DATOS study from USA and the
NTORS study of the UK, both multisite prospective cohort studies, found compa-
rable outcomes at 5 year follow-up in patients who were enrolled in residential
drug-free and in methadone maintenance treatment (Hubbard et al. 2003; Gossop
et al. 2003).
In summary, the ethical justification of agonist maintenance treatment in the
modern form was to provide otherwise treatment-resistant heroin addicts with an
effective approach to improve their health and social situation without asking for
total abstinence from narcotic substances.
principle is permitted. In other situations, there is no such solution. The way out is
indicated by the ethical code of AMA: to engage in an effort to change laws which
prove to be incompatible with responsible care for the addicts (AMA 2001).
There is not much to be added. The statement applies fully as the main recom-
mendation for all treatments of substance dependence. It is a perpetual agenda for
future generations.
References
AMA (2001) Principles of medical ethics. In: Code of medical ethics. American Medical Asso-
ciation, Chicago
APA (2000) Diagnostic and statistical manual of mental disorders DSM IV TR. American
Psychiatric Association, Arlington
Arif A, Westermeyer J (1990) Methadone maintenance in the management of opioid dependence:
an international review. Praeger, New York
Arosemena G (2013) Conflicts of rights in international human rights: a meta-rule analysis. Glob
Const 2:6–36
Bergmark A (2008) Specific and contextual treatment mechanisms. Nordic Stud Alcohol Drugs
25:277–285
Connock M, Juarez-Garcia A, Jowett S, Frew E, Liu Z, Taylor RJ, Fry-Smith A, Day E,
Lintzeris N, Roberts T, Burls A, Taylor RS (2007) Methadone and buprenorphine for the
management of opioid dependence: a systematic review and economic evaluation. Health
Technol Assess 11:1–171
Council of Europe (1950) Convention for the protection of human rights and dignity of the human
being with regard to the application of biology and medicine: convention on human rights and
biomedicine. Council of Europe, Rome
Department of Health (2002) Models of care for substance misuse treatment. Promoting
quality, efficiency and effectiveness in drug misuse treatment services. Department of Health,
London
Dole VP, Nyswander ME (1965) A medical treatment for diacetyl-morphine (heroin) addiction.
JAMA 193:646–650
Edlin BR, Keal KH, Lorwock J, Kral AH, Ciccarone DH, Moore LD, Lo B (2001) Is it justifiable to
withhold treatment for hepatitis C from illicit drug users? New Engl J Med 345:211–215
1374 A. Uchtenhagen
Edwards G, Arif A (1980) Dug problems in a socio-cultural context. A basis for policy and
programme planning. Public health papers no. 73. World Health Organisation, Geneva
Ekendahl M (2007) Will and skill – an exploratory study of substance abuser’s attitudes towards
life-style changes. Eur Addict Res 13:148–155
Elliot HM (1920) Memoirs of Jahangir. Islamic Book Service, Lahore
Emcdda (2009) Special issue 2009. Drug offences; sentencing and other outcomes. European
Monitoring Centre on Drugs and Drug Addiction, Lisbon. www.emcdda.europa.eu/publications/
selected-issues/sentencing-statistics. Accessed 14 Feb 2013
EMCDDA (2012) www.emcdda.europa.eu/publications/country-overviews
EU (2005) EU drug action plan. Brussels, Amtsblatt der Europäischen Union 2005/C168/01
Farrell M, Ward J, Mattick R, Hall W, Stimson GV, des Jarlais D, Gossop M, Strang J (2004)
Methadone maintenance treatment in opiate dependence: a review. Brit Med J 309:997–1001
Fireman M, Rabkin JM (2001) Outcome of liver transplantation in patients with alcohol and other.
Chemical dependence. Psychosomatics 42:172–173
€
Freud S (1884). Uber Coca. Centralblatt f€
ur die gesamte Therapie 2:289–314
General Medical Council (2006) Good medical practice. Regulating doctors. Ensuring good
medical practice. General Medical Council, London
Gerdner A (1998) Patient and programme factors with impact on outcome in Swedish compulsory
care of addicts: a systematic review. Lund University, Sweden
Gerstein DR, Datta AR, Ingels JS, Johnson RA, Rasinski KA, Schildhaus S, Talley K (1997)
NTIES. The National Treatment Improvement Evaluation Study. Final report. National Opin-
ion Research Center, Chicago
Gossop M (2006) Treating drug misuse problems: evidence of effectiveness. National Treatment
Agency for Substance Misuse, London
Gossop M, Marsden J, Stewart D, Kidd T (2003) The National Treatment Outcome Research
Study (NTORS): 4–5 year follow-up results. Addiction 98:291–303
Health Canada (2008) Literature review – methadone maintenance treatment. Public Works and
Government Services Canada, Ottawa
Hubbard RL, Craddock SG, Anderson J (2003) Overview of 5-year follow-up outcomes in the
drug abuse treatment outcome studies (DATOS). J Subst Abuse Treat 25:126–134
INCB (2011) Report of the International Narcotic Control Board for 2011. http://www.incb.org/
incb/en/publications/annual-reports/annual-report-2011.html
Kaya CY, Tugai Y, Filar JA, Agrawal MR, Ali RL, Gowing LR, Cooke R (2004) Heroin users in
Australia: population trends. Drug Alcohol Rev 23:107–116
Klingemann H, Sobell LC (2007) Promoting self-change from addictive behaviors. Practical
implications for policy, prevention and treatment. Springer, New York
Kramer JC (1977) Heroin in the treatment of morphine addiction. J Psychedelic Drugs
197:193–197
Leshner A (1997) Addiction is a brain disease, and it matters. Science 278:45–47
Marsh KL, Joe GW, Simpson DD, Lehmann WEK (1990) Treatment history. In: Simpson DD,
Sells SB (eds) Opioid addiction and treatment: a 12-year follow-up. Krieger, Malabar,
pp 137–156
McLellan AT, Grissom GR, Zanis D, Randall M, Brill P, O’Brien CP (1997) Problem-service
‘matching’ in addiction treatment. A prospective study in 4 programs. Arch Gen Psychiat
54:730–735
Metzger DS, Woody GE, McLellan AT (1993) Human Immunodeficiency Virus seroconversion
among intravenous drug users in- and out-of-treatment: an 18-month prospective follow-up.
J Acquir Immune Defic Syndr 6:1049–1056
MHR (1995) Order from the Ministry of Health of Russia dated 14 August 1995 #239, titled About
additional measures on control of narcotic drugs, dangerous substances and poisons
Miller N, Flaherty JA (2000) Effectiveness of coerced addiction treatment (alternative conse-
quences) a review of the clinical research. J Subst Abuse Treat 18:9–16
86 Ethical and Legal Aspects of Interventions in Addiction Treatment 1375
Moyer A, Finney JW, Swearingen CE, Vergun P (2002) Brief interventions for alcohol problems:
a meta-analytic review of controlled investigations into treatment-seeking and non-treatment-
seeking populations. Addiction 97:279–292
NIDA (2012) Principles of drug addiction treatment. A research-based guide. National Institute of
Drug Abuse, Bethesda
Rhodes T, Hedrich D (eds) (2010) Harm reduction: evidence, impact and challenges. EMCDDA
Monograph. European Monitoring Centre for Drugs and Drug Addiction, Lisbon
Robins LN (1993) Vietnam veterans rapid recovery from heroin addiction – a fluke or normal
expectation. Addiction 88:1041–1054
Rust A (2000) Ethische Aspekte. In: Uchtenhagen A, Zieglgänsberger W (eds) Suchtmedizin.
Konzepte, Strategien und therapeutisches Management. Urban & Fischer, M€ unchen,
pp 573–584
Schumacher JE, Milby JB, Wallace D, Meehan DC, Kertesz S, Vuchinich R, Dunning J, Usdan S
(2007) Meta-analysis of day treatment and contingency-management dismantling research:
Birmingham homeless cocaine studies (1990–2006). J Consult Clin Psychol 75:823–828
Stallwitz A, Stoever H (2007) The impact of substitution treatment in prisons – a literature review.
Int J Drug Policy 18:464–474
Stevens A, Hallam C, Trace M (2006) Treatment for dependent drug use. A guide for
policymakers. Beckley Foundation, London
Tännsjö T (1999) Coercive care. The ethics of choice in health and medicine. Routledge, London
Uchtenhagen A (2003). Substitution management in opioid dependence. J Neurol Transmission,
suppl 66: Fleischhacker WW, Brooks DJ (eds) Addictions, mechanisms, phenomenology and
treatment, p 33–60
Uchtenhagen A (2010a) Treatment of substance dependence: ethical aspects. In: Helmchen H,
Sartorius N (eds) Ethics in psychiatry – European contributions. Springer, Amsterdam,
pp 381–400
Uchtenhagen A (2010b) Ethical perspectives in caring for people living with addictions: the
European experience. Int Rev Psychiatry 22:274–280
Uchtenhagen A, Guggenb€ uhl L (2000) Adequacy in Drug Abuse Treatment and Care in Europe
(ADAT). Commissioned by World Health Organisation, Regional Office for Europe. Research
Institute for Public Health and Addiction, Zurich
Uchtenhagen A, Ladjevic T, Rehm J (2005) Guidelines for psychosocially assisted pharmacolog-
ical treatment of persons dependent on opioids. Working paper for World Health Organisation.
Research Institute for Public Health and Addiction, Zurich
UN (1948) Universal declaration of human rights. United Nations, New York
UN (1961) Single convention on narcotic drugs. United Nations, New York
UN (1971) Convention on psychotropic substances. United Nations, New York
UN (1988) United Nations convention against illicit traffic in narcotic drugs and psychotropic
substances. United Nations, New York
UNODC/WHO/UNAIDS (2009) Technical guide for countries to set targets for universal access to
HIV prevention, treatment and care for injecting drug users. United Nations Office on Drugs
and Crime, Vienna
Ward J, Mattick R, Hall W (1998) Methadone maintenance treatment and other opioid replace-
ment therapies. Harwood, Amsterdam
Weisner C (1990) Coercion in alcohol treatment. In: Institute of Medicine (ed) Broadening the
base for the treatment of alcohol problems. The National Academic Press, Washington, DC,
pp 579–610
Westermeyer J (1982) Poppies, pipes and people: opium and its use in Laos. University of
California Press, Berkeley
Westermeyer J (2006) The switch from opium to heroin smoking. Addiction 92:686–687
WHO (2004a) Proposal for the inclusion of Methadone in the WHO model list of essential
medicines. World Health Organisation, Geneva
1376 A. Uchtenhagen
WHO (2004b) Proposal for the inclusion of buprenorphine in the WHO model list of essential
medicines. World Health Organisation, Geneva
WHO (2008) Guidelines for psychosocially assisted pharmacological treatments of opioid depen-
dence. World Health Organisation, Geneva
WHO (2009) Assessment of compulsory treatment of people who use drugs in Cambodia, China,
Malaysia and Viet Nam: an application of selected human rights principles. World Health
Organisation, Manila
WHO (2010) International classification of diseases (10th ed) Version for 2010. World Health
Organisation, WHO/UNODC (2008). Principles of drug dependence treatment. A discussion
paper. World Health Organisation, Geneva
Wild DC, Cunningham JA, Ryan RM (2006) Social pressure, coercion, and client engagement at
treatment entry: a self-determination theory perspective. Addict Behav 31:1858–1872
Zinberg NE (1984) Drug, set and setting. Yale University Press, New Haven
The UN Drug Conventions: Evidence on
Effects and Impact 87
Robin Room
Contents
87.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1378
87.2 Intended Functions of the Treaties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1379
87.2.1 A Penal Regime to Enforce Drug Prohibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1379
87.2.2 A Trading and Marketing Control Regime . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1380
87.2.3 A Central Planning Scheme to Supply Medical Needs . . . . . . . . . . . . . . . . . . . . . . 1380
87.3 Institutional Arrangements for Implementation of the Treaties . . . . . . . . . . . . . . . . . . . . . . 1380
87.4 What Can Be Said About the Effects and Impact of the System? . . . . . . . . . . . . . . . . . . . . 1382
87.5 Signs and Directions of Change . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1383
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1384
Abstract
The three international drug treaties cover many psychoactive substances
(“drugs”), although not tobacco (now under a separate treaty) or alcohol. They
include a penal regime to enforce the limitation of use to medical or scientific
purposes, a trade regime concerning drugs for medical use, and a planning
scheme to ensure adequate supplies of medical opiates. The system, initiated
in 1912, had shifted its main focus by the 1988 treaty to combating the illicit
markets which accompany a prohibitory system. The place of the drug treaties in
the United Nations system and the bodies which compose the system are briefly
characterized. Nearly every country has signed each treaty, though often with
R. Room
Centre for Alcohol Policy Research, Turning Point, Fitzroy, VIC, Australia
Melbourne School of Population and Global Health, University of Melbourne, Carlton,
VIC, Australia
Centre for Social Research on Alcohol and Drugs, Stockholm University, Stockholm, Sweden
e-mail: [email protected]
87.1 Introduction
The United Nations drug control system is organized around three international
treaties: the Single Convention on Narcotic Drugs of 1961, as amended by
a protocol of 1972; the Convention on Psychotropic Substances of 1971; and the
UN Convention Against Trafficking in Narcotic Drugs and Psychotropic
Substances of 1988. Their texts and the official commentaries on them are
conveniently available online: https://www.unodc.org/unodc/treaties/index.html.
The treaties, of course, do not cover the whole range of psychoactive substances.
There is a separate treaty on tobacco, the Framework Convention on Tobacco
Control of 2003, negotiated under the auspices of the World Health Organization,
and an International Convention Against Doping in Sport (many of the substances
covered by it are psychoactive), adopted in 2005 under the auspices of
UNESCO. Notably absent from the list of substances under international control
is alcohol, although it was actually the subject of the first international drug treaty,
controlling “trade spirits” in colonial Africa, negotiated in 1889 but now in abey-
ance (Bruun et al. 1975). The 2012 WHO Expert Committee on Drug Dependence
briefly discussed whether alcohol would qualify for listing under the UN drug
conventions and referred this for consideration at a future Expert Committee
meeting (WHO 2012, p. 16).
From the perspective of the inherent harmfulness of different psychoactive
substances (e.g., Nutt et al. 2010), what is included and what is excluded in
the three “drug treaties” are not easily defensible except as reflecting the
vagaries of history. But despite the ongoing convergence in scientific thinking
about psychoactive substances (Courtwright 2005), it is still true that discus-
sions of international drug control which take account of the whole range of
drugs and their regulation are rare (for an exception, see Braithwaite and
Drahos 2000).
In this chapter, however, attention remains focused on the three UN drug
treaties. We consider the intended functions of the treaties, the institutional arrange-
ments for their implementation, and what evidence is available on effects and
impact of the system. As this is written at a moment when change in the system
seems increasingly possible, a brief discussion of potential future developments is
also included.
87 The UN Drug Conventions: Evidence on Effects and Impact 1379
The treaties have three main functions: as a penal regime to enforce limitation of
use of scheduled substances to medical or scientific purposes, as a specialized trade
treaty controlling international trade in psychoactive substances for medical use,
and as a central planning scheme to ensure adequate supplies particularly of opiates
for medical use.
The Single Convention, as its name conveys, replaced an array of treaties and
protocols which had accumulated since the first opium treaty, the Hague Convention
of 1912. But the Single Convention went well beyond what was in the previous
treaties, signaling a change in the system’s orientation (Carstairs 2005). Whereas the
prime concern of the previous treaties had been with regulating international trade in
plant-derived drugs (opiates, cocaine, and cannabis), the 1961 Convention introduced
requirements that possession and delivery, along with a wide variety of market-
related actions concerning the drugs covered, be criminalized under a country’s
domestic laws (Bewley-Taylor and Jelsma 2012). What had been a system concerned
primarily with controlling international movement of drugs became a system com-
mitted to enforcing prohibitions on nonmedical use of the drugs, with each country’s
criminal laws as means of enforcement. The international prohibition system as it
now exists can thus be said to have begun with the 1961 treaty.
The 1971 treaty greatly expanded the scope of the system by including a wide
range of synthetic substances, many of them with pharmaceutical uses. The market
controls in the 1971 treaty are weaker than those in the 1961 treaty, reflecting the
powerful influence of the pharmaceutical industry on the treaty negotiations
(McAllister 1991). The requirement concerning criminalization under domestic
law is more simply stated than in the 1961 treaty, requiring penalization of “any
action contrary to a law or regulation adopted in pursuance of its obligations under
this Convention.” But since the convention requires a medical prescription to
authorize use of a covered drug, any possession or use without a prescription should
be criminalized.
The 1988 treaty, as its name reveals, represented a further shift in the system’s
focus, with more attention focused on combating the illicit markets which had
emerged as a by-product of the prohibition system, including for the first time
controls on precursor chemicals used in the preparation of controlled drugs. But in
an effort to eliminate any remaining ambiguity, it also included a further provision
on criminalization at the level of the individual drug user: that a signatory country
should “establish as a criminal offence under its domestic law, when committed
intentionally, the possession, purchase or cultivation of narcotic drugs or psycho-
tropic substances for personal consumption.”
The system of treaties inaugurated by the 1961 Convention, then, has as a main
goal the elimination or at least suppression of any nonmedical use of drugs, aiming
1380 R. Room
The treaties also set up a trading and marketing regime, a special kind of trade treaty
which aims more to structure and direct international trade, rather than the more
usual main aim of trade treaties – to facilitate trade. Requiring that an import permit
be issued by the receiving country before drugs can be shipped to it means that
a country can control and indeed cut off the legal supply of a drug to its residents.
Although the drug treaty system was established before the formation of the
current system of international trade treaties, it has served an informal function of
protecting the substances under its jurisdiction from any trade disputes seeking to
open up markets for controlled drugs. This contrasts with the situation for alcohol
and tobacco (O’Brien 2013; Baumberg and Anderson 2008; Shaffer et al. 2005).
Particularly through the 1961 treaty and its predecessors, and particularly for opiates,
the international system is intended to ensure that supplies of opium-derived drugs
for medical use are available globally. Each signatory country is supposed to send to
the International Narcotics Control Board (INCB) annual data on medical use of
opioids and estimates of requirements for the next year. There is a system of permits
for countries to grow opium to meet the demand from the medicinal market
(around 2010, nearly half the legal supply was grown in Tasmania). Particularly
with respect to opium, the aim is a globally controlled system of cultivation,
manufacture, and supply which will ensure that medical needs everywhere for opioid
medications are met.
In the United Nations system, the drug treaties come under the jurisdiction of the
UN’s Economic and Social Council (ECOSOC), which serves as the final deciding
body for issues such as the scheduling of drugs under the treaties and determines
87 The UN Drug Conventions: Evidence on Effects and Impact 1381
and strategy, and as the global public health agency, WHO was necessarily
committed to its promotion. However, prior to 2009 the USA had insisted that the
concept and term “harm reduction” not be used in the work of the international
treaty agencies. After 2009, relationships between UNODC and WHO have been
revitalized, including joint work on treatment guidelines (Room and Reuter 2012).
87.4 What Can Be Said About the Effects and Impact of the
System?
One measure of the success of the system is its near universality, in terms of formal
adherence to the treaties. Each year’s INCB report notes with some pride the tally of
countries which are signed up to each treaty. The desire for universality triumphed
in the case of Bolivia’s recent denunciation and reaccession to the 1961 treaty,
despite disapproval by the INCB and other guardians of the system. Bolivia took
this route to add a reservation to the treaty which would then allow Bolivians to
chew coca leaves without contravening Bolivia’s treaty commitments. Thwarted in
an attempt to make this change by international consensus, Bolivia denounced
(announced its withdrawal from) the treaty, proposing to reaccede with
a reservation concerning coca chewing if the reservation was accepted (Room
2012a). If one-third of countries acceding to the treaty had objected, Bolivia’s
reaccession would not have gone into effect. It is a mark of the system’s commit-
ment to universality that there were only a few objections, despite considerable
displeasure expressed by the INCB and others about Bolivia’s reservation.
A second measure is in terms of its success in ensuring access to pain medica-
tion. For developed countries, this is not generally a problem. But the WHO has
estimated that 80 % of the world’s population lacks adequate access to effective
pain medication (WHO 2007). Part of the problem, of course, is a lack of resources
to procure or supply the medication. But another part is the indirect result of the
treaty system. In consequence of the system’s emphasis on law enforcement,
decisions on importation of controlled drugs are often in the hands of police, who
may choose to restrict or stop imports in order to impede diversion of the medicine
to illicit markets. Reflecting concern about this, the most recent WHO Expert
Committee decided that ketamine, a cheap and relatively safe anesthetic widely
used in poor countries, should not be brought under the treaties. “Concerns were
raised that if ketamine were placed under international control, this would
adversely impact its availability and accessibility. This in turn would limit access
to essential and emergency surgery, which would constitute a public-health crisis
in countries where no affordable alternative anaesthetic is available. On this basis,
the Expert Committee decided that bringing ketamine under international control is
not appropriate” (WHO 2012, p. 9). Reflecting a greater priority still being placed
on prohibition of nonmedical use than on the availability of needed medications,
many national delegations and three regional groupings expressed concerns or
regret about the WHO decision at the May 2013 meeting of the CND (IDPC
2013, p. 11).
87 The UN Drug Conventions: Evidence on Effects and Impact 1383
The failure of the international drug prohibition system in terms of its most public
goal, of eliminating or minimizing illicit markets, has been apparent for some
decades. At national and subnational levels, there have been initiatives and exper-
iments since the 1960s in moving in other directions, although these initiatives have
been greatly hampered by the perceived necessity of operating within the
constraints of the international system. Thus, even the Dutch “coffee shop” system
for quasi-legal retail sale of cannabis, the most far-reaching attempt to move from
an illicit to a regulated market, was handicapped by the “back door” problem – that
cannabis which was sold under license at the front door had come in the back door
illegally, since no way could be found to reconcile a legal wholesale supply with
national obligations under the treaty (Korf 2008).
But there are signs of change in the early 2010s, particularly in the Americas.
A diverse array of Latin American countries have shown a growing impatience with
the status quo and have been willing to push against the long-standing “Washington
consensus” for the status quo on drug policies. First several retired Latin American
presidents, and then some sitting presidents, have expressed the need for new
directions. The motivations have been diverse. In Mexico and Central America,
the primary issue has been the carnage in their populations from a “war on drugs”
aimed at cutting off the supply to the insatiable demand from northern neighbors.
1384 R. Room
Acknowledgment Dave Bewley-Taylor and Ambros Uchtenhagen are thanked for their sugges-
tions and prompts, but are not of course responsible for the results.
References
Babor T, Caulkins J, Edwards G, Fischer B, Foxcroft D, Humphreys K, Obot I, Rehm J, Reuter P,
Room R, Rossow I, Strang J (2010) Drug policy and the public good. Oxford University Press,
Oxford
Baumberg B, Anderson P (2008) Trade and health: how World Trade Organization (WTO) law
affects alcohol and public health. Addiction 103:1952–1958
Bewley-Taylor D, Jelsma M (2012) Regime change: re-visiting the 1961 single convention on
narcotic drugs. Int J Drug Policy 23:72–81
Bewley-Taylor D, Trace M (2006) The INCB: watchdog or guardian of the UN drug control
conventions? Beckley Foundation, Oxford, UK. http://www.beckleyfoundation.org/pdf/
Report_07.pdf
Braithwaite J, Drahos P (2000) Drugs. In: Global business regulation. Cambridge University Press,
Cambridge, UK, pp 360–398
Bruun K, Pan L, Rexed I (1975) The gentlemen’s club: international control of drugs and alcohol.
University of Chicago Press, Chicago/London
87 The UN Drug Conventions: Evidence on Effects and Impact 1385
Carstairs C (2005) The stages of the international drug control system. Drug Alcohol Rev
24:57–65
Courtwright DT (2005) Mr. ATOD’s wild ride: what do alcohol, tobacco, and other drugs have in
common? Soc Hist Alcohol Drugs 20:105–124
IDPC (2013) The 2013 commission on narcotic drugs: report of proceedings. International Drug
Policy Consortium, London. http://idpc.net/publications/2013/05/idpc-report-of-proceedings-
the-2013-commission-on-narcotic-drugs
Jelsma M (2011) The development of international drug control: lessons learned and strategic
challenges for the future. Working paper prepared for the first meeting of the global commis-
sion on drug policies, Geneva, 24–25 Jan 2011. http://www.canadianharmreduction.com/sites/
default/files/Dvlpt%20of%20Intnl%20Drug%20Control%20-%20Lessons%20%26%20Challenges
%20-%202011_0.pdf
Korf D (2008) An open front door: the coffee shop phenomenon in the Netherlands. In: Rødner
Sznitman S, Olsson B, Room R (eds) A Cannabis reader: global issues and local
experiences – perspectives on Cannabis controversies, treatment and regulation in Europe,
vol 8, EMCCDA monograph. Office for Official Publications of the European Communities,
Luxembourg, pp 140–154. http://www.emcdda.europa.eu/attachements.cfm/att_53355_EN_
emcdda-cannabis-mon-full-2vols-web.pdf
McAllister WB (1991) Conflict of interest in the international drug control system. J Policy Hist
3:143–166
Nutt DJ, King LA, Phillips LD (2010) Drug harms in the UK: a multicriteria decision analysis.
Lancet 376:1558–1565
O’Brien P (2013) Australia’s double standard on Thailand’s alcohol warning labels. Drug Alcohol
Rev 32:5–10
OAS (2013) The drug problem in the Americas. Organization of American States, Washington,
DC. http://www.oas.org/en/media_center/press_release.asp?sCodigo¼E-194/13
Reuter P, Trautmann F, Pacula R, Kilmer B, Gageldonk A, van der Gouwe D (2009) Assessing
changes in global drug problems 1998–2007: main report. http://www.rand.org/pubs/
technical_reports/2009/RAND_TR704.pdf
Room R (2012a) Reform by subtraction: the path of denunciation of international drug treaties and
reaccession with reservations. Int J Drug Policy 23:401–406
Room R (ed) (2012b) Roadmaps to reforming the UN drug conventions. Beckley Foundation, Oxford,
UK. http://www.beckleyfoundation.org/wp-content/uploads/2012/12/Roadmaps_to_Reform.pdf
Room R, Reuter P (2012) How well do international drug conventions protect public health?
Lancet 379:84–91
Room R, Fischer B, Hall W, Lenton S, Reuter P (2010) Cannabis policy: moving beyond
stalemate. Oxford University Press, Oxford
Room R (2014a) Cannabis legalization and public health: legal niceties, commercialization and
countercultures. Addiction 109:358–359
Room R (2014b) Legalising a market for cannabis for pleasure: Colorado, Washington, Uruguay
and beyond. Addiction 109:345–351
Shaffer ER, Brenner JE, Houston TP (2005) International trade agreements: a threat to tobacco
control policy. Tobacco Control 14(Suppl II):ii19–ii25. http://www.ncbi.nlm.nih.gov/pmc/
articles/PMC1766197/pdf/v014p0ii19.pdf
Walsh J (2013) Q&A: Legal Marijuana in Colorado and Washington. Brookings Institution,
Washington, DC. http://www.brookings.edu/research/papers/2013/05/21-legal-marijuana-
colorado-washington
WHO (2007) “Access to controlled medications programme”. Briefing note. World Health
Organization, Geneva. http://www.who.int/medicines/areas/quality_safety/ACMP_BrNote-
Genrl_EN_Feb09.pdf
WHO (2012) WHO expert committee on drug dependence: thirty-fifth report. World Health
Organization, Geneva. http://apps.who.int/iris/bitstream/10665/77747/1/WHO_trs_973_eng.pdf
Monitoring and Evaluation of Addiction
Treatment 88
Ambros Uchtenhagen
Contents
88.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1388
88.2 Main Aspects of Monitoring and Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1388
88.2.1 Definitions and Rationale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1388
88.2.2 Preparing for Monitoring and Evaluation (M & E) . . . . . . . . . . . . . . . . . . . . . . . . . . 1389
88.2.3 Implementation of M & E . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1397
88.2.4 Treatment Outcomes: Selected Evidence-Based Guidelines
and Systematic Reviews . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1401
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1402
Abstract
Monitoring and evaluation (M & E) are research activities dedicated to document
and analyze the processes and outcomes of addiction treatment. Before starting
M & E, some conceptual issues apply, such as considering the objectives of a given
treatment or treatment system, the outcome indicators to be used, the characteristics
of the target population, and the basic understanding of the nature of addiction.
A range of different goals can be envisaged in M & E projects, from
measuring treatment implementation and the use of the available resources
to measuring efficacy and effectiveness. The overall goal in general is the
improvement of services and treatment systems. The main steps in developing
M & E projects are determining the research questions, the appropriate type and
design of evaluation, and the resources and partners needed. Also, it is helpful to
identify expected problems and obstacles.
Lists of evidence-based guidelines and instruments for evaluation are
attached, as well as lists of high-quality publications reviewing the outcomes
of evaluation studies.
A. Uchtenhagen
Research Foundation for Public Health and Addiction, Zurich University, Zurich, Switzerland
e-mail: [email protected]
88.1 Introduction
Monitoring and evaluation (M & E) are essential instruments for an optimal drug
demand reduction through treatment and prevention. They serve the commitment to
effective interventions, which are based on scientific evidence. Only a good knowl-
edge on the effects of interventions can provide the evidence base for an adequate
substance abuse policy.
The main objective of M & E is to assess the available intervention system at
country, regional, or local level, to determine its adequacy for covering the
treatment needs in the respective population, and to measure its intermediate,
short-term, and long-term outcomes. This is instrumental for a targeted
improvement of available intervention systems, as well as for an adaptation to
new challenges from changes in substance using populations and the health and
social consequences of use. Monitoring trends in substance using populations
out of treatment is helpful in order to observe such changes, e.g., the arrival of
new drugs.
M & E also cover structural and procedural properties of services and systems, as
major instrumental elements for outcomes.
M & E can also serve other purposes, such as providing arguments for legiti-
mizing the treatment or prevention approach against repressive approaches.
88.2.1.5 Meta-evaluation
The growing number of evaluation studies and their unequal quality invited an
effort to review evaluation studies, on the basis of rigorous methodological analy-
sis, resulting in reliable information about “what works” and “what works for
whom.”
A detailed M & E project is the key to the feasibility of data collection, to the
validity of data, and to the usefulness of results. The following issues and steps
must be considered before starting a project. It is recommendable to set up an
M & E project in collaboration with an expert.
Outcome Criteria
If not specific treatment objectives are in place, any M & E project has to determine
which type of outcomes are to be measured. This may be those mentioned above,
but also others such as the quality of life of patients/clients or the reduction of
negative consequences of addiction at population level in terms of substance-
related crime and nuisance or blood-borne infectious disease. The following is
a catalogue of the most frequently used outcome indicators (adapted from
EMCDDA 2007, Table 2) (Table 88.1):
The choice of outcome criteria should meet the interests of all stakeholders
including the mandating and/or funding bodies for the project.
Understanding Addiction
Also, the kind of data to be collected for M & E depends on how addictive behavior
is interpreted. Various paradigms apply here: the use of psychotropic substances
can be understood as self-medication for symptom relief (Khantzian 1997), as
a special variation of self-manipulation, tailoring use to a desired state of mind,
or as instrumental for self-enhancement, optimizing function and output (Harris
2007). Or else, substance use is understood as a lifestyle phenomenon, in the sense
of “consumerism” or of an expression of subcultural identity. On the other side,
88 Monitoring and Evaluation of Addiction Treatment 1391
Legitimation of Treatment
A frequent purpose of evaluation projects is demonstrating the value of a given
intervention or service, in terms of desired outcomes, patient/client satisfaction, and
positive economic balance of input and outcome. This can be done through a single-
service follow-up study or a nonrandomized comparative study. The main issues
why it is important to assure the legitimacy must be considered in the research
questions and the study design.
Structure Evaluation
Evaluation of the appropriateness of infrastructure and other structural elements to
facilitate the desired outcomes of treatment. This includes location, safety provisions,
financial resources, staff composition and qualification, governance, and organization.
Process Evaluation
Process evaluation documents and analyzes how treatment is delivered. Assessment
procedures, indication criteria, treatment planning, programming, qualification and
attitudes of staff, continued training of staff, house rules, sanctions, etc. are some of
the elements to be considered (WHO workbook 4, extensive list of available
instruments for process evaluation on the EMCDDA instrument bank EIB).
Outcome Evaluation
The focus is on the consequences of treatment for patients/clients, their families,
and the community. It provides information on which treatment modality has which
consequences for which target groups and under which conditions. It may consider
the impact on other treatment approaches. It may become relevant for treatment
motivation in the target population.
Outcome is measured against predefined behavior norms (normative evalua-
tion), baseline pretreatment status (evaluation of change during treatment), or
predefined treatment goals (goal attainment evaluation). Outcome evaluation
mainly uses quantitative methods (by RCTs or cohort studies), eventually
a combination of quantitative and qualitative methods (WHO workbook 7, instru-
ments on EIB of EMCDDA).
Economic Evaluations
Various designs are used to describe and analyze economic factors in addiction
treatment. Cost analysis measures the cost factors and overall costs of treatment
(e.g., per patient day, per treatment episode, per treatment modality, etc.).
Cost-benefit evaluation determines the relation between costs and financial benefits
(e.g., in terms of reduced health and social costs in a defined posttreatment period as
compared to pretreatment values). Cost-effectiveness evaluation measures costs in
relation to a specific unit of outcome (e.g., significant health improvement
or significant reduction in addictive behavior). Cost-utility evaluation measures
the utility of treatment for patients/clients, e.g., in terms of disability adjusted life-
years DALYs (Anand and Hanson 1997) or as quality adjusted life-years QALYs
(Nord 1992, Whitehead and Ali 2010). For cost evaluations see also WHO
workbook 5, for economic evaluations WHO workbook 8, and for instruments
EIB of EMCDDA.
1394 A. Uchtenhagen
Formal Evaluation
This is an assessment of service compliance with professional, ethical, and legal
standards.
Meta-evaluation
Meta-evaluation is made on the basis of recognized procedures to combine quan-
titative results from several studies about the same or similar interventions, in order
to establish composite outcome scores. This allows assessing the effectiveness of
a given intervention with greater confidence than on the basis of a single study.
88.2.2.7 Resources
Estimations must be made on the amount of funds and type of manpower in order to
conduct the planned M & E project, and the availability of these resources must be
checked in advance, in order to avoid delays or restrictions during implementation.
Also, the infrastructure for data storage and analysis must be made available.
In view of the difference in available resources between high-income and
low-/middle-income countries, priority-oriented monitoring and evaluation
research as well as transnational collaboration is recommendable.
Financial Resources
If an M & E study is mandated by an external agency (governmental or
nongovernmental), the budget available for the study must be identified, in order
to design the study accordingly. Or else, the research group planning the study has
to present a budget proposal and apply to a funding agency (Research council,
Foundation, Health Authority, etc.).
If there are doubts about the feasibility of the study (e.g., access to services and
patients/clients), a stepwise procedure may be preferred. In this case, a separate
budget for the feasibility study is needed, and the results will determine the budget
of the ensuing evaluation study.
Human Resources
Which staff is needed for carrying out a planned project? Various functions must be
considered: expert support for setting up the research questions and protocol, for
determining the appropriate methods and instruments, for training of interviewers,
etc. Staff responsible for data collection, interviewers, staff for data control and
entering into a master file, statistician for data analysis, etc. are needed. It is helpful
to identify staff in advance, in order to avoid delays in implementation and in order
to establish a realistic budget.
Infrastructure
Access to the necessary equipment for staff and for safe storage of data is to be
ensured, as well as the disposition of the appropriate software for data handling and
analysis.
88.2.2.8 Partners
Most M & E project are a collaborative effort between various partners, especially
in case of external evaluation of services and networks. Clear agreements on
functions, responsibilities, temporal availability, and costs are recommended, even-
tually with written contracts.
Funding Partners
Agreements on the overall budget, bookkeeping, financial controls, timing of
payments, and financial reports help to prevent misunderstandings and litigations.
Such agreements should be made to protect the interests of all parties.
1396 A. Uchtenhagen
Therapeutic Partners
All projects on external evaluation are based on collaboration between researchers
and treatment providers. Agreements are needed on the access to patient/client data
and service data, access to patients/clients for external interviewers, responsible
person in a given service for organizing and facilitating the research process,
ownership of data, and arrangements for publishing the study results. Procedures
in case of upcoming problems during project implementation should also be agreed
upon in advance.
A special situation is created in case of a systematic evaluation at the system
level involving all or selected treatment providers.
Research Partners
In case multiple researchers or research groups are involved, a clear working
arrangement should identify the functions, tasks, and responsibilities of the indi-
vidual persons. If a service provider hires a researcher or research group for an
internal or external evaluation or monitoring system, there is also a need to identify
the various functions, tasks, and responsibilities.
External Interference
It may happen that family members of patients/client or other third parties raise
opposition against an M & E project, on the basis of ethical concerns. It is advisable
to have an explicit permission from an ethical committee, if not already prescribed
by law.
88 Monitoring and Evaluation of Addiction Treatment 1397
EMCDDA Guidelines for the Evaluation of Treatment in the Field of Problem Drug
Use. A Manual for Researchers and Professionals (EMCDDA 2007)
This publication provides basic information on the options, elements, and pro-
cedures of drug-related treatment evaluation. It also contains an overview of
European and international evaluation and research networks.
Cross-Sectional Studies
One-time studies to compare treatment services, treatment populations, and treat-
ment outcomes at a given moment in time (e.g., intermediate outcomes during
treatment or after terminating treatment). Cross-sectional studies cannot describe
processes of change over time.
Cohort Studies
Cohort studies describe the course and outcomes of treatment populations which
receive their treatment as usual in practice, not allocated by randomization
(observational or “naturalistic” studies). Cohort studies use retrospective or
prospective data.
least two measurement points in time; its usefulness however depends on the
availability and quality of anamnestic data.
Double-Blind Randomized
If assignment to the experimental or the control group is not revealed to patients and
therapists, their preferences are better (although not completely) ruled out and the study
gets more reliable results about comparative treatment efficacy. This design is mainly
used for a comparison of medications; psychosocial interventions cannot be “blinded.”
Quasi-experimental Designs
Instead of comparing two or more modalities, the effects of an experimental
modality can be compared to the course while waiting to be accepted for that
modality. In this case, the control group receives treatment as usual or no treatment
while waiting.
In the Zelen design, informed consent is only asked after randomization and only
from patients assigned to the experimental group, while those who are randomized to
treatment as usual need not to consent to participation in the study (Torgerson and
Roland 1998). This design makes it easier for patients to participate, because they do
not have to consent to be randomized. Of course, blinding is not possible in this design.
Another design uses different sequences of treatment modalities, e.g., A-B-A
compared with B-A-B or B-B-A.
depending on the type of study design (see also GRADE working group 2004).
The following is an adapted version (Table 88.3).
Qualitative Methods
Qualitative methods are mainly used for process evaluation. When indicating
problem areas in the provision of treatments, they can also be useful for improve-
ments and for generating new research questions. They provide information for the
construction of questionnaires in process and outcome evaluation, and they can be
used for the interpretation of quantitative findings (Neale et al. 2005).
88 Monitoring and Evaluation of Addiction Treatment 1401
References
AGREE II (2009) Appraisal of guidelines for research and evaluation II. The AGREE Next Steps
Consortium. www.agreetrust.org
Anand S, Hanson K (1997) Disability adjusted life years: a critical review. J Health Econ
16:658–702
Campbell collaboration www.campbellcollaboration.org, Campbell library www.campbellcolla-
boration.org/library
Cochrane collaboration www.cochrane.org, Cochrane library www.thecochranelibrary.com
88 Monitoring and Evaluation of Addiction Treatment 1403
EIB: Evaluation Instrument Bank of the European Monitoring Centre for Drugs and Drug
Addiction, Lisbon. www.emcdda.europa.eu/eib
EMCDDA (2007) Guidelines for the evaluation of treatment in the field of problem drug use.
A manual for researchers and professionals. European Monitoring Centre for Drugs and Drug
Addiction, Lisbon
Glaser BG, Straus AI (1967) The discovery of grounded theory: strategies for qualitative research.
Aldine Publishing Company, Chicago
Gossop M, Marsden J, Stewart D, Kidd T (2003) The National Treatment Outcome Research
Study (NTORS): 4–5 year follow-up results. Addiction 98:291–303
GRADE working group (2004) Grading quality of evidence and strength of recommendations.
BMJ 328:1490
Graham ID, Harrison MB (2005) Evaluation and adaptation of clinical practice guidelines. Evid
Based Nurs 8:68–72
Gupta SK (2011) Intention-to-treat concept: a review. Perspect Clin Res 2:109–112
Harris J (2007) Enhancing evolution. The ethical case for making better people. Princeton
University Press, Oxford
Khantzian EJ (1997) The self-medication hypothesis of substance use disorders: a reconsideration
and recent applications. Harv Rev Psychiatry 4:231–244
Lawrinson P, Ali R, Uchtenhagen A et al (2008) Key findings from WHO collaborative study on
substitution therapy of opioid dependence and HIV/AIDS. Addiction 103:1484–1492
Leshner I (1997) Addiction is a brain disease, and it matters. Science 278:45–47
Malivert M, Fatséas M, Denis C et al (2012) Effectiveness of therapeutic communities:
a systematic review. Eur Addict Res 18:1–11
McLellan AT, Lewis DC, O’Brien CP, Kleber HD (2000) Drug dependence, a chronic medical
illness. Implications for treatment, insurance and outcomes evaluation. JAMA 284:1689–1696
Neale J, Allen D, Coombes L (2005) Qualitative research methods within the addictions. Addic-
tion 100:1584–1584
NIDA (2012) Principles of drug addiction treatment. A research-based guide, 3rd edn. National
Institute of Drug Abuse, Bethesda
Nord E (1992) Methods for quality adjustment of life years. Soc Sci Med 34:559–569
Rush B, Krywonis M (1996) Evaluation and continuous quality improvement of substance abuse
services and systems. Addiction Research Foundation, Toronto
Simpson DD (ed) (2003) Special section: 5-year follow-up treatment outcome studies from
DATOS. J Subst Abuse Treat 25:123–186
Torgerson DJ, Roland M (1998) What is Zelen’s design? BMJ 316:606
UNODC (2002) Contemporary drug abuse treatment. A review of the evidence base. United
Nations, New York
UNODC (2008) International network of drug dependence, treatment and rehabilitation resource
centers. Good practice documents. www.unodc.org/treatment/
Volkow ND, Fowler JS, Wang G-J (2004) The addicted human brain viewed in the light of
imaging studies: brain circuits and treatment strategies. Neuropharmacology 47:3–13
Whitehead SJ, Ali S (2010) Health outcomes in economic evaluation; the QALY and utilities. Br
Med Bull 96:5–21
WHO (2009) Guidelines for the psychosocially assisted pharmacological treatment of opioid
dependence. World Health Organisation, Geneva
WHO/UNODC/EMCDDA (2000) Evaluation of psychoactive substance use disorder treatment,
workbook series. World Health Organisation, Geneva
Section VII
Behavioural Addictions and
Management Applications
N. el-Guebaly (*)
Division of Addiction, Department of Psychiatry, University of Calgary, Alberta Gambling
Research Institute, Calgary, AB, Canada
e-mail: [email protected]
H. Tavares
Department of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil
e-mail: [email protected]
Contents
90.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1412
90.2 Behavioral Addictions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1415
90.2.1 Pathological Gambling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1415
90.2.2 Internet Addiction Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1421
90.2.3 Problematic Video-Game Playing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1424
90.2.4 Hypersexual Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1426
90.2.5 Food Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1427
90.2.6 Compulsive Shopping Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1431
90.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1432
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1433
Abstract
Neurobiological and clinical data indicate that maladaptive engagement in certain
behaviors warrants consideration as “behavioral” or non-substance addictions.
The present chapter reviews existing neurobiological and genetic/family history
evidence for behavioral addictions involving gambling, Internet use, video-game
Y.H.C. Yau
Department of Psychiatry, Yale University, New Haven, CT, USA
Yale Child Study Center, Yale University, New Haven, CT, USA
e-mail: [email protected]
R.F. Leeman
Department of Psychiatry, Yale University, New Haven, CT, USA
e-mail: [email protected]
M.N. Potenza (*)
Department of Psychiatry, Yale University, New Haven, CT, USA
Department of Neurobiology, Yale University, New Haven, CT, USA
Yale Child Study Center, Yale University, New Haven, CT, USA
e-mail: [email protected]
90.1 Introduction
While the term addiction has traditionally been associated with excessive alcohol and
drug use (Maddux and Desmond 2000), the Latin word (addicere) from which it is
derived was not linked to substance use. Addiction professionals and the public are
recognizing that certain behaviors bear resemblance to alcohol and drug dependence,
and data have been forwarded that these behaviors warrant consideration as
non-substance or “behavioral” addictions (Frascella et al. 2010; Karim and Chaudhri
2012; Potenza 2006). Excessive engagement in behaviors such as gambling, Internet
use, video-game play, sex, eating, and shopping may represent addictions (Holden
2010), with a minority of individuals displaying such habitual or compulsive engage-
ment (Brewer and Potenza 2008; Chambers et al. 2007). Some of these behaviors
were considered as “Impulse Control Disorders Not Elsewhere Classified” in the
DSM-IV-TR, a separate category from substance use disorders (SUDs) (American
Psychiatric Association 2000). Shaffer et al. (2004) proposed that addiction should be
considered as a syndrome with multiple opportunistic expressions (e.g., substance
abuse, pathological gambling, and food addictions). Aided by data from neurobio-
logical studies, this view has gained momentum in the past decade and has led to the
consideration of categorizing substance and non-substance-related addictions under
one diagnostic category, “Substance Use and Addictive Disorders,” in the recently
published DSM-5 (American Psychiatric Association 2013). Establishing nomencla-
ture and criteria for behavioral addictions may enhance our capacity to recognize and
define their presence.
Biochemical, functional neuroimaging, genetic, and pharmacological research in
substance addiction has implicated several neurobiological processes. Multiple neuro-
transmitters (e.g., serotonergic, dopaminergic, noradrenergic, and opioidergic) are
thought to play a role in the pathophysiology of substance addictions (Koob and
Volkow 2010; Potenza 2008). For example, dysregulated dopamine systems, which
are involved with learning, motivation, and salience of stimuli and rewards, and
serotonin (5-HT) systems, implicated in behavioral control, may significantly contrib-
ute to addictive disorders (Fineberg et al. 2009; Potenza 2008). Prolonged engagement
90 Biological Underpinning of Behavioural Addictions and Management Implications 1413
Table 90.1 Overview of neural system results for selected behavioral addictions, with a focus on
fronto-striatal findings
Behavioral Similarities and differences with key
addiction Key results results in substance use disorders
Pathological Frontal areas Between-group differences observed
gambling Cognitive tasks: most findings in SUD and control comparison
suggest reduced activity in multiple subjects with many tasks indicating
frontal regions in PG, but also some reduced frontal activity, but precise
suggesting increased activity and nature of differences warrants
negative findings additional study
Cue-induction studies: suggest
differences in activity, but the precise
nature of differences warrants
additional study
Striatal areas
Cognitive tasks: reduced ventral Many findings suggest reduced
activity to reward anticipation ventral striatal activity in individuals
Cue-induction studies: mixed with with SUDs compared to controls
some studies showing reduced striatal
activity in PG compared to controls
Others: ventral striatal activity
inversely correlated with impulsivity
measures and problem-gambling
severity
White and gray matter: poorer white Poorer white matter integrity and
matter integrity in multiple regions; decreased gray matter volumes in
no volumetric differences in gray or SUDs
white matter between PG and
controls
Internet addiction Frontal areas
disorder Cognitive tasks: EEG studies indicate Underactive feedback valence in
diminished efficiency of response individuals with SUDs
inhibition
Resting state: differences in regional Preliminary studies suggest reduced
homogeneity in multiple frontal regional homogeneity in SUDs
regions, but the precise nature of
differences warrants additional study
White and gray matter: lower gray Poorer white matter integrity and
matter density in multiple regions decreased gray matter volumes in
including dlPFC, ACC, and insula; SUDS
differences in white matter integrity
between IAD and controls, but the
precise relationship is unclear
Problematic Frontal areas Underactive feedback valence in
video-game Cognitive tasks: EEG studies indicate individuals with SUDs
playing diminished efficiency of response
inhibition
(continued)
90 Biological Underpinning of Behavioural Addictions and Management Implications 1415
In the last decade, pathological gambling (PG) has developed a strong research base
in the wake of worldwide legalized gambling and concerns over gambling’s
possible health and social impacts. Similar to substance addictions, PG can include
preoccupations with gambling, gambling with greater amounts of money to receive
the same level of desired experience (tolerance), repeated unsuccessful efforts to
control or stop gambling, restlessness/irritability when trying to stop gambling
1416 Y.H.C. Yau et al.
Table 90.3 Overview of selected genetic results for selected behavioral addictions
Similarities and differences with
Behavioral key results in substance use
addiction Key results disorders (SUDs)
Pathological Family history: PG highly heritable; twin SUDs highly heritable; twin
gambling studies indicate genetic factors may share studies indicate genetic and
similar magnitudes with or contribute more environmental factors share similar
than environmental factors to overall risk magnitudes of influence on overall
for developing PG risk for developing a drug use
disorder
Molecular genetics: preliminary findings Associations with polymorphisms
suggest genetic polymorphisms related to related to dopamine and serotonin
dopamine (DRD2) and serotonin transmission; genome-wide
transmission (5HTTLPR, MAO-A); recent associations indicate some different
genome-wide association study did not contributions to individual SUDs
identify different contributions to
individuals with PG
Internet Molecular genetics: preliminary findings Associations with serotonin
addiction suggest overexpression of SS-5HTTLPR in transporter gene polymorphisms
disorder males with IAD
Problematic Molecular genetics: preliminary findings Links between SUDs and Taq1A
video-game suggest presence of Taq1A polymorphism polymorphisms, but not universally
playing of DRD2 receptor gene and low activity replicated; the low activity COMT
COMT alleles more likely in males with variant linked to various SUD (e.g.,
online PVG nicotine, methamphetamine, and
alcohol)
Hypersexual Family history: more likely to have parent Individuals with SUDs more
disorder with hypersexual disorder; more likely to likely to have first-degree relative
have first-degree relative with SUDs with various SUDs and
psychopathology
Food Family history: obesity tenfold more likely Individuals with SUDs more
addiction in people with an obese first-degree relative likely to have first-degree relative
with various SUDs and
psychopathology
Molecular: obese individuals with BED, Associations with polymorphisms
compared to non-BED, had lower related to dopamine and serotonin
frequencies of the Taq1A1 polymorphism transmission; OPRM1
of DRD2 receptor gene and higher polymorphisms may mediate
frequencies of the G118 polymorphism of reward effects of drugs of abuse
the mu-opioid receptor gene (OPRM1); (e.g., opiates, alcohol, and heroin);
overexpression of SS-5HTTLPR in however, result in clinical
overweight adolescent populations have been mixed
Compulsive Family history: relationship to parental Individuals with SUDs more likely
shopping history of CSD and first-degree relative with to have first-degree relative with
disorder SUDs various SUDs and psychopathology
Molecular: negative findings for 5HTTLPR Associations with serotonin
polymorphisms transporter gene polymorphisms
PG pathological gambling, SUDs substance use disorders, IAD Internet addiction disorder, PVG
problematic video-game playing, CSD compulsive shopping disorder, DRD2 dopamine receptor
D2, 5HTTLPR serotonin transporter-linked polymorphic region, MAO-A monoamine oxidase A,
COMT catechol-O-methyltransferase, OPRM1 opioid receptor, mu 1
90 Biological Underpinning of Behavioural Addictions and Management Implications 1419
90.2.1.2 Neurochemistry
Dopaminergic findings in PG present a complicated picture. Using positron emis-
sion tomography (PET) with the tracer [11C]raclopride, a recent study reported that
not only did PG perform worse on the IGT than controls, among PG, dopamine
release in the ventral striatum was positively associated with excitement levels
(Linnet et al. 2011). Increased dopamine levels may serve a “double deficit”
function by reinforcing PG behavior through increasing excitement levels while
simultaneously reducing inhibition of risky decisions. D2/D3 receptor availability
has also been shown to negatively correlate with mood-related impulsivity
(“urgency”) within the striatum (Clark et al. 2012) and positively correlate with
problem-gambling severity within the dorsal striatum (Boileau et al. 2013) among
PG. However, unlike findings in substance addiction literature (Volkow
et al. 2001), no significant difference in D2/D3 receptor availability at resting
state was observed between PG and control subjects (Boileau et al. 2013; Clark
et al. 2012; Linnet et al. 2011). However, a between-group difference in ventral
striatum dopamine D2-like receptor availability and dopamine release has been
reported in individuals with Parkinson’s disease (Steeves et al. 2009). While there
were no differences in the magnitude of dopamine release between PG and controls
during a slot machine gambling task, among PG, dopamine release correlated
positively with problem-gambling severity (Joutsa et al. 2012). Dopamine agonists
have been associated with impulse control disorders in Parkinson’s disease
(Leeman et al. 2012). Further, oral administration of a D2-like receptor antagonist,
haloperidol, increased gambling motivations among PG subjects, while no such
effect was observed among controls (Zack and Poulos 2007), although individual
differences appear to be important (Tremblay et al. 2011). Individual differences
may explain with the lack of efficacy of D2-like antagonist drugs (e.g., olanzapine)
in the treatment of PG (Fong et al. 2008; Grant and Potenza 2004; McElroy
et al. 2008). Taken together, these data suggest a role for dopamine in PG, but
one that may include within-group individual differences.
Pharmacological studies also implicate serotonin in PG. Selective serotonin recep-
tor inhibitors (SSRIs) have had mixed results for PG and substance addictions
(Potenza et al. 2009). For example, some randomized control trials have found
fluvoxamine and paroxetine to be superior to placebo in treatment of PG (Hollander
et al. 2000; Kim et al. 2002), while others have reported negative findings (Blanco
et al. 2002; Grant et al. 2003). Heterogeneity in treatment response may result from
individual differences, with some data suggesting that individuals with co-occurring
anxiety disorders may respond well to SSRIs (Bullock and Potenza 2012).
90 Biological Underpinning of Behavioural Addictions and Management Implications 1421
90.2.1.4 Conclusion
PG has been the most frequently studied behavioral addiction and is the most likely
to be reclassified from an Impulse Control Disorder (ICD) to the proposed DSM-5
category, “Addiction and Related Disorders” (American Psychiatric Association
2012). Although the neurobiology of PG is incompletely understood, recent
neuroimaging, neurocognitive, neurochemical, and genetic work indicate similar-
ities with SUDs (Leeman and Potenza 2012).
The Internet is integrated firmly into modern society and has radically changed the
way we conduct our daily lives. Its popularity, particularly among youth, has raised
1422 Y.H.C. Yau et al.
concern over its potential harms. While moderate Internet use may enhance one’s
quality of life by widening social circles and enhancing psychological well-being
(Chen et al. 2002; Willoughby 2008), diminished control over Internet use may
impact negatively on daily function, family relationships, physical and mental
health, and may lead to incarceration and legal troubles (Anderson 2000;
Ko et al. 2012; Sanders et al. 2000; Willoughby 2008). While no formal diagnostic
criteria for “Internet addiction disorder” (IAD) or problematic Internet use currently
exist in the DSM, the condition may involve excessive or poorly controlled urges
and a maladaptive obsession with the Internet (Ko et al. 2012). Definitions of IAD
are often based on DSM-IV-TR criteria for pathological gambling (Dowling and
Quirk 2009; Ko et al. 2009b; Young 1999) with some, such as Young’s Internet
Addiction Scale, having demonstrated sufficient reliability (Bernardi and Pallanti
2009; Widyanto and McMurran 2004). In terms of comorbidity, IAD may
frequently co-occur with not only SUDs (Bai et al. 2001; Lam et al. 2009;
Yen et al. 2009) but also various psychiatric conditions including impulse control,
mood, and personality disorders (Bernardi and Pallanti 2009; Dowling and Brown
2010; Dowling and Quirk 2009; Mazhari 2012).
Evidence also indicates potential structural differences. Using MRI, lower gray
matter density in regions tied to emotion regulation including the ACC, posterior
cingulate cortex, insula, and lingual gyrus has been found (Zhou et al. 2011).
Moreover, gray matter volumes of the right dorsolateral prefrontal cortex
(dlPFC), left ACC, the right supplementary motor area, and white matter
FA measures in the posterior limb of the internal capsule have been negatively
correlated with the duration of IAD (Yuan et al. 2011).
In the same study, Yuan et al. (2011) also reported increased FA within the
region of the left internal capsule accompanied by decreased FA within the right
parahippocampal gyrus among IAD adolescents. This finding appears to contrast
with results from Lin et al. (2012) who reported widespread reduction of FA in
major white matter pathways and abnormal white matter structure in IAD adoles-
cents. Taken together, these data suggest involvement of white matter microstruc-
tures in the pathophysiology of IAD, although the precise relationship warrants
further research.
90.2.2.2 Neurochemistry
Several small studies have explored dopaminergic functioning in IAD. A recent
study using single-photon emission computed tomography (SPECT) scans reported
decreased striatal dopamine transporter expression among male IAD subjects
compared to age-matched controls (Hou et al. 2012). In addition, the authors
reported significantly decreased volume of the bilateral corpus striatum among
IAD subjects. Another study using [11C]raclopride (PET) scanning reported that
adult males with IAD (versus male controls) had reduced dopamine D2-like
receptor availability in subdivisions of the striatum including the bilateral dorsal
caudate and left dorsal putamen compared to controls; moreover, receptor avail-
ability was negatively correlated with IAD severity (Kim et al. 2011). Interestingly,
dopamine receptor availability in the ventral striatum did not differ between the
control and IAD groups (Kim et al. 2011), contrasting results from SUDs (Dalley
et al. 2007; Heinz et al. 2004). Further studies are needed regarding the role of
dopamine in IAD.
90.2.2.4 Conclusion
IAD is a behavioral addiction that may be increasingly prevalent concurrent
with increased Internet availability, accessibility, and popularity. Although the
neurobiology of IAD remains under-researched, recent years have shown prom-
ising progress. It is important to note that most studies have targeted adolescent
males and have been performed in Asia; therefore, results may not be generaliz-
able to other populations. IAD was proposed for inclusion in Sect. III, a part of the
DSM-5 in which conditions that require further research are located. ‘Internet
Gaming Disorder’ has been included in Sect. III and has been flagged as a possible
candidate for future inclusions in the addictions category. However, criteria for
this condition are currently limited to Internet gaming and does not include
Internet use for other purposes including for online gambling, or social media.
time on the Cambridge Gambling Task (CGT). Striatal differences have also been
noted in cue-induction studies. Post-cue changes indicative of increased activity
have been found in the right NAc and right caudate nucleus among male adults
playing >30 h/week on the “World of Warcraft” game compared to “non-heavy”
gamers playing <2 h/week (Ko et al. 2009a).
In addition to striatal findings, Ko et al. (2009) also reported greater activation in
the right OFC, bilateral ACC, medial frontal cortex, and right dlPFC in heavy (versus
non-heavy) players following cue presentation. Activation of these areas was posi-
tively correlated with self-reported gaming urge and recall of gaming experience
provoked by “World of Warcraft” pictures (Ko et al. 2009a). Similar findings have
been reported in subsequent studies examining individuals with current PVG (Han
et al. 2010b; Sun et al. 2012) and those in remission from online PVG
(Ko et al. 2011). Healthy male adults who played a novel video game for 60 min
per day for 10 days showed stronger activation of the left inferior frontal gyrus, left
parahippocampal gyrus, bilateral parietal lobes, thalamus, and right cerebellum in
response to video-game stimuli compared to neutral-control stimuli (Han et al. 2011).
Activation of the right medial frontal lobe and right parahippocampal gyrus also
positively correlated with gaming urge (Han et al. 2011).
90.2.3.2 Neurochemistry
In an early neurobiological study of video-game playing using [11C]raclopride
(PET) scanning, increased release of dopamine to D2-like receptors in the ventral
striatum was observed following 50 min of video-game playing in healthy adult
males (Koepp et al. 1998). A more recent study using SPECT similarly suggested
increased dopamine release in the caudate during a motorbike racing computer
game, compared to baseline measures among healthy adult males (Weinstein 2010).
While video-game playing may be capable of inducing dopamine release that is
comparable to the effects of psychoactive substances (Farde et al. 1992; Volkow
et al. 1994), the role of dopamine dysfunction in PVG is unclear, and to date, no
study has directly investigated a relationship.
Following a 6-week trial of bupropion (a drug with influences on dopaminergic
and other neurotransmitter systems), individuals with online PVG (>30 h StarCraft/
week) demonstrated decreased craving for video-game play, reduced total game
play time, and less cue-induced brain activity in the dlPFC compared to
pretreatment (Han et al. 2010a).
90.2.3.4 Conclusion
Despite public attention, PVG remains understudied, and findings are often difficult
to compare between studies given the use of different measures across studies.
1426 Y.H.C. Yau et al.
90.2.4.2 Neurochemistry
Our current understanding of the neurochemistry of hypersexual disorder is pre-
dominantly derived from pharmacological studies. In a double-blind, placebo
control study of hypersexual disorder in homosexual and bisexual men, the selec-
tive serotonin reuptake inhibitor (SSRI) citalopram was found to reduce sexual
desire without lessening sexual satisfaction (Wainberg et al. 2006). Another SSRI,
fluoxetine, was found effective in reducing symptoms in men with either paraphilia
or paraphilia-related disorders (Kafka and Hennen 2000). In addition, better results
were obtained when methylphenidate was used in conjunction with fluoxetine,
suggesting an additive effect and implicating possible involvement of dopamine
and norepinephrine (Kafka and Hennen 2000).
90 Biological Underpinning of Behavioural Addictions and Management Implications 1427
90.2.4.4 Conclusion
Hypersexual disorder is a serious clinical condition that can have detrimental
effects on daily life. Neurobiological research in hypersexual disorder, particularly
with respect to neuroanatomical and neurocircuitry data, is currently very limited.
Food addiction has been discussed in the popular media and has received some
research attention. Addictive processes have been suggested to underlie obesity
(Volkow and O’Brien 2007). Emerging neurobiological research suggests both
substance use and eating behaviors engage similar neurocircuitry and has conse-
quently led to the conceptualization of “foods as drugs” (Davis and Carter 2009).
However, the concept of food addiction remains debated with some investigators
arguing that existing research has yielded conflicting results (Ziauddeen
et al. 2012a, b) and others arguing that this construct may be particularly relevant
to certain subgroups of obese individuals, such as those with binge eating disorder
(BED) (Avena et al. 2012; Gearhardt et al. 2011a). Although not labeled as such,
several core features of BED share similarities with those for substance dependence
including strong food cravings and diminished control over eating (Gearhardt
et al. 2011a). Over a quarter of clinicians report often or always using addiction-
based therapies for BED (von Ranson and Robinson 2006), further suggesting
clinical and phenomenological similarities. It is important to note that for some
individuals, overeating is a relatively passive event that takes the form of liberal
snacking, eating large portions, and physical inactivity (Avena et al. 2011; Marcus
and Wildes 2009), and the extent to which these behaviors constitute an addiction
may be debated. Individuals with food addiction may be more impulsive, display
1428 Y.H.C. Yau et al.
greater emotional reactivity and food cravings than obese individuals without food
addiction (Davis et al. 2011), and thus have clinically relevant features associated
with food addiction.
individuals (Balodis et al. 2013). Taken together, these results suggest that neural
differences exist between obesity subgroups.
To our knowledge, only one neuroimaging study has directly assessed food
addiction. Gearhardt et al. (2011b) found that activation in the ACC, medial
orbitofrontal cortex, and amygdala in response to anticipated receipt of food was
positively correlated with food addiction scores among lean and obese young
females. Furthermore, females with high food addiction scores, compared to
those with low scores, showed decreased activation in the OFC during food intake.
No significant correlation was observed between food addiction score and BMI,
suggesting that food addiction and related neural functioning may occur among
individuals with a range of body weights.
90.2.5.2 Neurochemistry
Dopamine release has been related to food and food cues (Di Chiara and Imperato
1988). Administration of dopamine antagonists can abolish the responding for food
in rats (Wise and Rompre 1989). Development of addiction-like reward deficits and
onset of compulsive-like food seeking was accelerated by lentivirus-mediated
knockdown of striatal D2-like receptor in rats with extended access to palatable,
high-fat food (Johnson and Kenny 2010). Studies using [11C]raclopride (PET)
scanning have demonstrated that D2-like receptor availability is reduced in obese
individuals (Wang et al. 2009) and mice (Geiger et al. 2008; Huang et al. 2006).
Moreover, among obese individuals, D2-like receptor availability correlated
negatively with body mass index (BMI) scores (Wang et al. 2001).
Data from animal models suggest ingestion of foods of different palatability, and
energy density produces different effects in the dopaminergic system. Rats classi-
fied as prone to binge eating consumed significantly more highly palatable and
energy-dense (high fat, high sugar) food and tolerated higher levels of foot-shock
for such foods than binge eating-resistant rats (Oswald et al. 2011). Regular
consumption of energy-dense food may have lasting consequences on the brain.
Using a diet-induced model of obesity, rats fed a high-sugar diet compared to those
on an unrestricted diet showed decreased dopamine release in the NAc following
36 h of food deprivation (Avena et al. 2008). Similarly, Alsiö et al. (2010) found
that rats fed a high-fat (versus unrestricted) diet showed decreased expression of D1
and D2 receptors in the VTA, NAc, and PFC following an 18-day withdrawal.
Furthermore, obesity-prone rats showed increased craving and anxiety compared to
obesity-resistant rats during the second withdrawal week following discontinuation
of the energy-dense diet (Pickering et al. 2009). Future studies are needed to
examine whether these dietary findings extend to human subjects.
The serotonin and norepinephrine reuptake inhibitors sibutramine and SSRI
fluoxetine have shown some efficacy in treating eating disorders and are approved
by the Food and Drug Administration for treatment of obesity and bulimia nervosa,
respectively, although the former has been recalled in the United States for cardio-
vascular safety concerns (McElroy et al. 2012). SSRIs in general have been shown
to be effective in targeting binge eating, psychiatric, and weight symptoms (Reas
and Grilo 2008), although the effectiveness and duration of these medications
1430 Y.H.C. Yau et al.
remain under debate. Open-label studies report initial SSRI (citalopram and fluox-
etine) administration reduced binge eating and weight loss in BED patients; at a
6-month follow-up, these beneficial effects were maintained with continuation of
SSRI treatment (Leombruni et al. 2006, 2008). In a randomized, double-blind,
12-week study of escitalopram for the treatment of individuals with co-occurring
BED and obesity, individuals receiving high-dose escitalopram treatment had
significantly greater reductions in weight, BMI, frequency of binge episodes, and
global severity of illness scores than those receiving placebo treatment
(Guerdjikova et al. 2008). Fluoxetine treatment for BED significantly increased
the odds of binge abstinence immediately posttreatment; however, these effects
may not be long-lasting as no significant improvement in BED symptoms was
observed during the 29-month follow-up despite improvements in depressive
symptoms (Devlin et al. 2007).
Opioids are implicated in eating behavior (Kelley et al. 2002), although the
precise nature of their influences are unclear. High doses of the opiate antagonist,
naloxone, increased sugar consumption and opiate-like withdrawal symptoms
including elevated plus-maze anxiety, teeth chattering, and head shakes in sugar-
binging rats following a period of abstinence (Avena et al. 2008, 2009; Colantuoni
et al. 2002). These findings may, however, be unique to sugar binging. A recent
study by Bocarsly et al. (2011) reported that rats on high-fat diets did not show signs
of opiate-like withdrawal when exposed to naloxone. Taken together, these findings
suggest that the brain opioid system may be differently affected by the overeating of
different nutrients.
90.2.5.4 Conclusion
Unlike some behavioral addictions, eating behaviors have been tested extensively
using animal models, and a considerable amount of neurobiological research has
been generated. Data suggest that animal results may be transferable to human
90 Biological Underpinning of Behavioural Addictions and Management Implications 1431
90.2.6.2 Neurochemistry
Beneficial results of citalopram, an SSRI, have been reported in a small 12-week
open-label trial, and in a 6-month follow-up, CSD patients continuing citalopram
were less likely to relapse than those who discontinued the medication (Koran
et al. 2002). A subsequent study found those assigned placebo were more likely to
relapse compared to those randomized to continue taking citalopram in a 9-week
double-blind, placebo-controlled administration following a 7-week open-label
trial (Koran et al. 2003). Further research is needed to understand the effects of
citalopram discontinuation.
Findings from other SSRIs have been negative. Another study by Koran
et al. (2007) found no difference between escitalopram and placebo conditions.
Double-blind comparisons of fluvoxamine and placebo similarly found no differ-
ence in compulsive shopping symptom reduction (Black et al. 2000; Ninan
et al. 2000). As such, further research is needed prior to the clinical utilization of
SSRIs for compulsive shopping.
90.2.6.4 Conclusion
Our current knowledge of the neurobiology and genetics of CSD is limited, but
preliminary research suggested altered neurofunctional responses to shopping
stimuli. Further research is needed to determine the role of various neurotrans-
mitters, the efficacy of different medications, and the underlying biology of the
disorder.
90.3 Conclusion
References
Alsiö J, Olszewski PK, Norbäck AH, Gunnarsson ZEA, Levine AS, Pickering C, Schiöth HB
(2010) Dopamine D1 receptor gene expression decreases in the nucleus accumbens upon long-
term exposure to palatable food and differs depending on diet-induced obesity phenotype in
rats. Neuroscience 171(3):779–787
American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders.
(4th ed., text rev.) Washington, DC: American Psychiatric Press, Inc.
American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders,
Fifth Edition (DSM-5). Washington, DC: American Psychiatric Press, Inc.
Anderson KJ (2000) Internet use among college students: an exploratory study. J Am Coll Health
50(1):21–26
Avena NM, Bocarsly ME, Rada P, Kim A, Hoebel BG (2008) After daily bingeing on a sucrose
solution, food deprivation induces anxiety and accumbens dopamine/acetylcholine imbalance.
Physiol Behav 94(3):309–315
Avena NM, Rada P, Hoebel BG (2009) Sugar and fat bingeing have notable differences in
addictive-like behavior. J Nutr 139(3):623–628
Avena NM, Bocarsly ME, Hoebel BG, Gold MS (2011) Overlaps in the nosology of substance
abuse and overeating: the translational implications of “food addiction”. Curr Drug Abuse Rev
4(3):133–139
Avena NM, Gearhardt AN, Gold MS, Wang G-J, Potenza MN (2012) Tossing the baby out with
the bathwater after a brief rinse? The potential downside of dismissing food addiction based on
limited data. Nat Rev Neurosci 13(7):514–514
Bai YM, Lin CC, Chen JY (2001) Internet addiction disorder among clients of a virtual
clinic. Psychiatr Serv 52(10):1397
Balodis IM, Kober H, Worhunsky PD, Stevens MC, Pearlson GD, Potenza MN (2012a)
Diminished frontostriatal activity during processing of monetary rewards and losses in
pathological gambling. Biol Psychiatry 71:749–757
Balodis IM, Lacadie CM, Potenza MN (2012b) A preliminary study of the neural correlates of the
intensities of self-reported gambling urges and emotions in men with pathological gambling.
J Gambl Stud 28(3):493–513
Balodis IM, Molina ND, Kober H, Worhunsky PD, White MA, Sinha R, Potenza MN (2013)
Divergent neural substrates of inhibitory control in binge eating disorder relative to other
manifestations of obesity. Obesity 21(2):367–377
Balodis IM, Kober H, Worhunsky PD, White MA, Stevens MC, Pearlson GD et al (2013)
Monetary reward processing in obese individuals with and without binge eating disorder.
Biol Psychiatry 73:877–886
Beck AT, Schlagenhauf F, Wustenberg T, Hein J, Kienast T, Kahnt T, Wrase J (2009) Ventral
striatal activation during reward anticipation correlates with impulsivity in alcoholics. Biol
Psychiatry 66(8):734–742
Bernardi S, Pallanti S (2009) Internet addiction: a descriptive clinical study focusing on
comorbidities and dissociative symptoms. Compr Psychiatry 50(6):510–516
Black DW (2007) A review of compulsive buying disorder. World Psychiatry 6(1):14–18
Black DW, Gabel J, Hansen J, Schlosser S (2000) A double-blind comparison of fluvoxamine
versus placebo in the treatment of compulsive buying disorder. Ann Clin Psychiatry
12(4):205–211
Blanco C, Petkova E, Ibanez A, Saiz-Ruiz J (2002) A pilot placebo-controlled study of
fluvoxamine for pathological gambling. Ann Clin Psychiatry 14(1):9–15
Blanco C, Myers J, Kendler KS (2012) Gambling, disordered gambling and their association with
major depression and substance use: a web-based cohort and twin-sibling study. Psychol Med
42(3):497–508
Block JJ (2008) Issues for DSM-V: internet addiction. Am J Psychiatry 165(3):306–307
1434 Y.H.C. Yau et al.
Bocarsly ME, Berner LA, Hoebel BG, Avena NM (2011) Rats that binge eat fat-rich food do not
show somatic signs or anxiety associated with opiate-like withdrawal: implications for
nutrient-specific food addiction behaviors. Physiol Behav 104(5):865–872
Boileau I, Payer D, Chugani B, Lobo D, Behzadi A, Rusjan P, Zack M (2013) The D2/3 dopamine
receptor in pathological gambling: a positron emission tomography study with
[11C]-(+)-propyl-hexahydro-naphtho-oxazin and [11C]raclopride. Addiction (Early Online).
doi:10.1111/add.12066
Brewer JA, Potenza MN (2008) The neurobiology and genetics of impulse control disorders:
relationships to drug addictions. Biochem Pharmacol 75(1):63–75
Bullock SA, Potenza MN (2012) Pathological gambling: neuropsychopharmacology and
treatment. Curr Psychopharmacol 1(1):67–85
Carnes PJ (1998) The obsessive shadow: profiles in sexual addiction. Prof Couns 13(1):15–17,
40–41
Chambers RA, Bickel WK, Potenza MN (2007) A scale-free systems theory of motivation and
addiction. Neurosci Biobehav Rev 31(7):1017–1045
Chen WJ, Boase J, Wellman B (2002) The global villagers: comparing internet users and uses
around the world. In: Wellman B, Haythornthwaite C (eds) The internet in everyday life.
Blackwell, Oxford, pp 74–113
Choi J-S, Shin Y-C, Jung WH, Jang JH, Kang D-H, Choi C-H, Kwon JS (2012) Altered
brain activity during reward anticipation in pathological gambling and obsessive-compulsive
disorder. PLoS ONE 7(9):e45938
Clark L, Stokes PR, Wu K, Michalczuk R, Benecke A, Watson BJ, Lingford-Hughes AR
(2012) Striatal dopamine D2/D3 receptor binding in pathological gambling is correlated with
mood-related impulsivity. Neuroimage 63(1):40–46
Colantuoni C, Rada P, McCarthy J, Patten C, Avena NM, Chadeayne A, Hoebel BG (2002)
Evidence that intermittent, excessive sugar intake causes endogenous opioid dependence.
Obes Res 10(6):478–488
Comings DE, Rosenthal RJ, Lesieur HR, Rugle LJ, Muhleman D, Chiu C, Gade R (1996) A study
of the dopamine D2 receptor gene in pathological gambling. Pharmacogenetics 6(3):223–234
Comings DE, Gade-Andavolu R, Gonzalez N, Wu S, Muhleman D, Chen C, Rosenthal RJ
(2001) The additive effect of neurotransmitter genes in pathological gambling. Clin Genet
60(2):107–116
Crockford DN, Goodyear B, Edwards J, Quickfall J, el-Guebaly N (2005) Cue-induced brain
activity in pathological gamblers. Biol Psychiatry 58(10):787–795
Dalley JW, Fryer TD, Brichard L, Robinson ESJ, Theobald DEH, Laane K, Robbins TW
(2007) Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement.
Science 315(5816):1267–1270
Dannon PN, Lowengrub K, Musin E, Gonopolsky Y, Kotler M (2007) 12-month follow-up study
of drug treatment in pathological gamblers: a primary outcome study. J Clin Psychopharmacol
27(6):620–624
Davis C, Carter JC (2009) Compulsive overeating as an addiction disorder. A review of theory and
evidence. Appetite 53(1):1–8
Davis CA, Levitan RD, Reid C, Carter JC, Kaplan AS, Patte KA, Kennedy JL (2009) Dopamine
for “Wanting” and opioids for “Liking”: a comparison of obese adults with and without binge
eating. Obesity 17(6):1220–1225
Davis JF, Loos M, Di Sebastiano AR, Brown JL, Lehman MN, Coolen LM (2010) Lesions of the
medial prefrontal cortex cause maladaptive sexual behavior in male rats. Biol Psychiatry
67(12):1199–1204
Davis C, Curtis C, Levitan RD, Carter JC, Kaplan AS, Kennedy JL (2011) Evidence that ‘food
addiction’ is a valid phenotype of obesity. Appetite 57(3):711–717
de Castro IP, Ibánez A, Saiz-Ruiz J, Fernández-Piqueras J (1999) Genetic contribution to patho-
logical gambling: possible association between a functional DNA polymorphism at the sero-
tonin transporter gene (5-HTT) and affected men. Pharmacogenet Genomics 9(3):397–400
90 Biological Underpinning of Behavioural Addictions and Management Implications 1435
Gold SN, Heffner CL (1998) Sexual addictive disorders include non-substance-related conditions?
Clin Psychol Rev 18:367–381
Goldstein RZ, Volkow ND (2002) Drug addiction and its underlying neurobiological basis:
neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry
159(10):1642
Goldstein RZ, Volkow ND (2011) Dysfunction of the prefrontal cortex in addiction: neuroimaging
findings and clinical implications. Nat Rev Neurosci 12(11):652–669
Goudriaan AE, De Ruiter MB, Van Den Brink W, Oosterlaan J, Veltman DJ (2010) Brain
activation patterns associated with cue reactivity and craving in abstinent problem gamblers,
heavy smokers and healthy controls: an fMRI study. Addict Biol 15(4):491–503
Grant J, Kim SW (2001) A case of kleptomania and compulsive sexual behavior treated with
naltrexone. Ann Clin Psychiatry 13(4):229–231
Grant JE, Potenza MN (2004) Impulse control disorders: clinical characteristics and pharmaco-
logical management. Ann Clin Psychiatry 16(1):27–34
Grant JE, Potenza MN (2012) The Oxford handbook of impulse control disorders. Oxford
University Press, Oxford
Grant JE, Kim SW, Potenza MN, Blanco C, Ibanez A, Stevens L, Zaninelli R (2003) Paroxetine
treatment of pathological gambling: a multi-centre randomized controlled trial. Int Clin
Psychopharmacol 18(4):243–249
Grant JE, Correia S, Brennan-Krohn T (2006) White matter integrity in kleptomania: a pilot study.
Psychiatry Res 147(2–3):233–237
Grant JE, Chamberlain SR, Odlaug BL, Potenza MN, Kim SW (2010a) Memantine shows promise
in reducing gambling severity and cognitive inflexibility in pathological gambling: a pilot
study. Psychopharmacology (Berl) 212(4):603–612
Grant JE, Odlaug BL, Potenza MN, Hollander E, Kim SW (2010b) Nalmefene in the treatment of
pathological gambling: multicentre, double-blind, placebo-controlled study. Br J Psychiatry
197(4):330–331
Grant JE, Potenza MN, Weinstein A, Gorelick DA (2010c) Introduction to behavioral addictions.
Am J Drug Alcohol Abuse 36(5):233–241
Griffiths MD (2002) The educational benefits of videogames. Educ Health 20:47–51
Guerdjikova AI, McElroy SL, Kotwal R, Welge JA, Nelson E, Lake K, Hudson JI (2008)
High-dose escitalopram in the treatment of binge-eating disorder with obesity: a placebo-
controlled monotherapy trial. Hum Psychopharmacol: Clin Exp 23(1):1–11
Han DH, Lee YS, Yang KC, Kim EY, Lyoo IK, Renshaw PF (2007) Dopamine genes and reward
dependence in adolescents with excessive internet video game play. J Addict Med 1(3):133–138
Han DH, Hwang JW, Renshaw PF (2010a) Bupropion sustained release treatment decreases
craving for video games and cue-induced brain activity in patients with internet video game
addiction. Exp Clin Psychopharmacol 18(4):297–304
Han DH, Kim YS, Lee YS, Min KJ, Renshaw PF (2010b) Changes in cue-induced, prefrontal
cortex activity with video-game play. Cyberpsychol Behav Soc Netw 13(6):655–661
Han DH, Bolo N, Daniels MA, Arenella L, Lyoo IK, Renshaw PF (2011) Brain activity and desire
for internet video game play. Compr Psychiatry 51:88–95
Heinz A, Siessmeier T, Wrase J, Hermann D, Klein S, Gr€ usser-Sinopoli SM, Gr€ under G (2004)
Correlation between dopamine D2 receptors in the ventral striatum and central processing of
alcohol cues and craving. Am J Psychiatry 161(10):1783–1789
Holden C (2010) Behavioral addictions debut in proposed DSM-V. Science 327(5968):935
Hollander E, DeCaria CM, Finkell JN, Begaz T, Wong CM, Cartwright C (2000) A randomized
double-blind fluvoxamine/placebo crossover trial in pathologic gambling. Biol Psychiatry
47(9):813–817
Hommer DW, Bjork JM, Gilman JM (2011) Imaging brain response to reward in addictive
disorders. Ann N Y Acad Sci 1216(1):50–61
Hou H, Jia S, Hu S, Fan R, Sun W, Sun T, Zhang H (2012) Reduced striatal dopamine transporters
in people with internet addiction disorder. J BioMed Biotechnol. Article ID 854524
90 Biological Underpinning of Behavioural Addictions and Management Implications 1437
Huang XF, Zavitsanou K, Huang X, Yu Y, Wang H, Chen F et al (2006) Dopamine transporter and
D2 receptor binding densities in mice prone or resistant to chronic high fat diet-induced
obesity. Behav Brain Res 175(2):415–419
Hyman SE, Malenka RC, Nestler EJ (2006) Neural mechanisms of addiction: the role of
reward-related learning and memory. Annu Rev Neurosci 29:565–598
Ibanez A, Perez de Castro I, Fernandez-Piqueras J, Blanco C, Saiz-Ruiz J (2000) Pathological
gambling and DNA polymorphic markers at MAO-A and MAO-B genes. Mol Psychiatry
5(1):105–109
Jastreboff AM, Sinha R, Lacadie C, Small DM, Sherwin RS, Potenza MN (2013) Neural correlates
of stress- and food- cue-induced food craving in obesity: association with insulin levels.
Diabetes Care 36:394–402
Johnson PM, Kenny PJ (2010) Dopamine D2 receptors in addiction-like reward dysfunction and
compulsive eating in obese rats. Nat Neurosci 13(5):635–641
Joutsa J, Saunavaara J, Parkkola R, Niemelä S, Kaasinen V (2011) Extensive abnormality of brain
white matter integrity in pathological gambling. Psychiatry Res: Neuroimaging 194(3):340–346
Joutsa J, Johansson J, Niemelä S, Ollikainen A, Hirvonen MM, Piepponen P, Kaasinen V (2012)
Mesolimbic dopamine release is linked to symptom severity in pathological gambling.
Neuroimage 60(4):1992–1999
Kafka MP, Hennen J (2000) Psychostimulant augmentation during treatment with selective
serotonin reuptake inhibitors in men with paraphilias and paraphilia-related disorders: a case
series. J Clin Psychiatry 61(9):664–670
Kafta MP (2010) Hypersexual disorder: a proposed diagnosis for DSM-V. Arch Sex Behav
39:377–400
Karim R, Chaudhri P (2012) Behavioral addictions: an overview. J Psychoactive Drugs 44(1):5–17
Kelley AE, Bakshi VP, Haber SN, Steininger TL, Will MJ, Zhang M (2002) Opioid modulation of
taste hedonics within the ventral striatum. Physiol Behav 76(3):365–377
Kendler KS, Chen XN, Dick D, Maes H, Gillespie N, Neale MC, Riley B (2012) Recent advances
in the genetic epidemiology and molecular genetics of substance use disorders. Nat Neurosci
15(2):181–189
Kim SW, Grant JE, Adson DE, Shin YC (2001) Double-blind naltrexone and placebo comparison
study in the treatment of pathological gambling. Biol Psychiatry 49(11):914–921
Kim SW, Grant JE, Adson DE, Shin YC, Zaninelli R (2002) A double-blind placebo-controlled
study of the efficacy and safety of paroxetine in the treatment of pathological gambling. J Clin
Psychiatry 63(6):501–507
Kim SH, Baik S-H, Park CS, Kim SJ, Choi SW, Kim SE (2011) Reduced striatal dopamine D2
receptors in people with internet addiction. NeuroReport 22(8):407–411
Ko C-H, Liu G-C, Hsiao S, Yen J-Y, Yang M-J, Lin W-C, Chen C-S (2009a) Brain activities
associated with gaming urge of online gaming addiction. J Psychiatr Res 43(7):739–747
Ko CH, Yen JY, Chen SH, Yang MJ, Lin HC, Yen CF (2009b) Proposed diagnostic criteria and the
screening and diagnostic tool of internet addiction in college students. Compr Psychiatry
50:378–384
Ko CH, Liu GC, Yen JY, Chen CY, Yen CF, Chen CS (2011) Brain correlates of craving for online
gaming under cue exposure in subjects with Internet gaming addiction and in remitted subjects.
Addict Biol 18(3):559–569
Ko CH, Yen JY, Yen CF, Chen CS, Chen CC (2012) The association between internet addiction
and psychiatric disorder: a review of the literature. Eur Psychiatry 27:1–8
Koepp MJ, Gunn RN, Lawrence AD, Cunningham VJ, Dagher A, Jones T, Grasby PM (1998)
Evidence for striatal dopamine release during a video game. Nature 393(6682):266–268
Koob GF, Volkow ND (2010) Neurocircuitry of addiction. Neuropsychopharmacology 35(1):217–238
Kor A, Fogel Y, Reid C, Potenza MN (2013) Should hypersexual disorder be classified as an
addiction?. Sex Addict Compulsivity (Early Online). doi:10.1080/10720162.2013.768132
Koran LM, Bullock KD, Hartston HJ, Elliott MA, D’Andrea V (2002) Citalopram treatment of
compulsive shopping: an open-label study. J Clin Psychiatry 63(8):704–708
1438 Y.H.C. Yau et al.
Koran LM, Chuong HW, Bullock KD, Smith SC (2003) Citalopram for compulsive shopping
disorder: an open-label study followed by double-blind discontinuation. J Clin Psychiatry
64(7):793–798
Koran LM, Aboujaoude EN, Solvason B, Gamel NN, Smith EH (2007) Escitalopram for
compulsive buying disorder: a double-blind discontinuation study. J Clin Psychopharmacol
27(2):225–227
Kraepelin E (1915) Psychiatrie, 8th edn. Barth, Leipzig
Kreek MJ, Nielsen DA, Butelman ER, LaForge KS (2005) Genetic influences on impulsivity, risk
taking, stress responsivity and vulnerability to drug abuse and addiction. Nat Neurosci
8(11):1450–1457
K€uhn S, Romanowski A, Schilling C, Lorenz R, Morsen C, Seiferth N, Gallinat J (2011) The
neural basis of video gaming. Transl Psychiatry 1:e53
Lam LT, Peng ZW, Mai JC, Jing J (2009) Factors associated with Internet addiction among
adolescents. CyberPsychology Behav 12(5):551–555
Lee YS, Han D, Yang KC, Daniels MA, Na C, Kee BS, Renshaw PF (2008) Depression like
characteristics of 5HTTLPR polymorphism and temperament in excessive internet users.
J Affect Disord 1–2:165–169
Leeman RF, Potenza MN (2012) Similarities and differences between pathological gambling and
substance use disorders: a focus on impulsivity and compulsivity. Psychopharmacology (Berl)
219(2):469–490
Leeman RF, Potenza MN (2013) A targeted review of the neurobiology and genetics of behavioral
addictions: an emerging area of research. Can J Psychiatry 58(5):260–273
Leeman RF, Billingsley BE, Potenza MN (2012) Impulse control disorders in Parkinson’s disease:
background and update on prevention and management. Neurodegener Dis Manag 2(4):389–400
Leombruni P, Piero A, Brustolin A, Mondelli V, Levi M, Campisi S, Fassino S (2006) A 12 to
24 weeks pilot study of sertraline treatment in obese women binge eaters. Hum
Psychopharmacol 21(3):181–188
Leombruni P, Piero A, Lavagnino L, Brustolin A, Campisi S, Fassino S (2008) A randomized,
double-blind trial comparing sertraline and fluoxetine 6-month treatment in obese patients with
binge eating disorder. Prog Neuropsychopharmacol Biol Psychiatry 32(6):1599–1605
Lin F, Zhou Y, Du Y, Qin L, Zhao Z, Xu J, Lei H (2012) Abnormal white matter integrity in
adolescents with internet addiction disorder: a tract-based spatial statistics study. PLoS ONE
7(1):e30253
Lind PA, Zhu G, Montgomery GW, Madden PA, Heath AC, Martin NG, Slutske WS (2012)
Genome-wide association study of a quantitative disordered gambling trait. Addict Biol
18(3):511–522
Linnet J, Møller A, Peterson E, Gjedde A, Doudet D (2011) Dopamine release in ventral striatum
during Iowa gambling task performance is associated with increased excitement levels in
pathological gambling. Addiction 106(2):383–390
Littel M, van den Berg I, Luijten M, van Rooij AJ, Keemink L, Franken IHA (2012) Error
processing and response inhibition in excessive computer game players: an event-related
potential study. Addict Biol 17(5):934–947
Liu J, Gao XP, Osunde I, Li X, Zhou SK, Zheng HR, Li LJ (2010) Increased regional homogeneity
in internet addiction disorder: a resting state functional magnetic resonance imaging study.
Chin Med J (Engl) 123(14):1904–1908
Lobo DS, Kennedy JL (2009) Genetic aspects of pathological gambling: a complex disorder with
shared genetic vulnerabilities. Addiction 104(9):1454–1465
Lobo DSS, Souza RP, Tong RP, Casey DM, Hodgins DC, Smith GJ, Kennedy JL (2010)
Association of functional variants in the dopamine D2-like receptors with risk for gambling
behaviour in healthy Caucasian subjects. Biol Psychol 85(1):33–37
Lorains FK, Cowlishaw S, Thomas SA (2011) Prevalence of comorbid disorders in problem and
pathological gambling: systematic review and meta-analysis of population surveys. Addiction
106(3):490–498
90 Biological Underpinning of Behavioural Addictions and Management Implications 1439
Raymond NC, Grant JE, Kim SW, Coleman E (2002) Treatment of compulsive sexual behaviour
with naltrexone and serotonin reuptake inhibitors: two case studies. Int Clin Psychopharmacol
17(4):201–205
Reas DL, Grilo CM (2008) Review and meta-analysis of pharmacotherapy for binge-eating
disorder. Obesity (Silver Spring) 16(9):2024–2038
Redish AD, Jensen S, Johnson A (2008) A unified framework for addiction: vulnerabilities in the
decision process. Behav Brain Sci 31(4):415–437
Reuter J, Raedler T, Rose M, Hand I, Glascher J, Buchel C (2005) Pathological gambling is linked to
reduced activation of the mesolimbic reward system. Nat Neurosci 8(1097–6256 (Print)):147–148
Rolls ET (2004) The functions of the orbitofrontal cortex. Brain Cogn 55(1):11–29
Rothemund Y, Preuschhof C, Bohner G, Bauknecht HC, Klingebiel R, Flor H, Klapp BF
(2007) Differential activation of the dorsal striatum by high-calorie visual food stimuli in
obese individuals. Neuroimage 37(2):410–421
Sanders CE, Field TM, Diego M, Kaplan M (2000) The relationship of Internet use to depression
and social isolation among adolescents. Adolescence 35:237–242
Schneider JP, Schneider BH (1996) Couple recovery from sexual addiction: research findings of
a survey of 88 marriages. Sex Addict Compulsivity 3:111–126
Sealy JR (1995) Psychopharmacologic intervention in addictive sexual behavior. Sex Addict
Compulsivity 2(4):257–276
Segal NL, Allison DB (2002) Twins and virtual twins: bases of relative body weight revisited. Int
J Obes Relat Metab Disord 26(4):437–441
Shaffer HJ, LaPlante DA, LaBrie R, Kidman RC, Donato AN, Stanton MV (2004) Toward
a syndrome model of addiction: multiple expressions, common etiology. Harv Rev Psychiatry
12:367–374
Shah KR, Eisen SA, Xian H, Potenza MN (2005) Genetic studies of pathological gambling:
a review of methodology and analyses of data from the Vietnam Era twin registry. J Gambl
Stud 21(2):179–203
Sim T, Gentile DA, Bricolo F, Serpelloni G, Gulamoydeen F (2012) A conceptual review of research
of pathological use of computers, video games, and the internet. Int J Ment Health Addict
10(5):748–769
Slutske WS, Zhu G, Meier MH, Martin NG (2010) Genetic and environmental influences on
disordered gambling in men and women. Arch Gen Psychiatry 67(6):624–630
Sokhadze E, Stewart C, Hollifield M, Tasman A (2008) Event-related potential study of executive
dysfunctions in a speeded reaction task in cocaine addiction. J Neurother 12(4):185–204
Sookoian S, Gemma C, Garcı́a SI, Gianotti TF, Dieuzeide G, Roussos A, Pirola CJ (2007) Short
Allele of serotonin transporter gene promoter is a risk factor for obesity in adolescents. Obesity
15(2):271–276
Steeves TDL, Miyasaki J, Zurowski M, Lang AE, Pellecchia G, Van Eimeren T (2009) Increased
striatal dopamine release in Parkinsonian patients with pathological gambling: a [lsqb]11C
[rsqb] raclopride PET study. Brain 132:1376–1385
Stice E, Spoor S, Bohon C, Veldhuizen MG, Small DM (2008) Relation of reward from food
intake and anticipated food intake to obesity: a functional magnetic resonance imaging study.
J Abnorm Psychol 117(4):924–935
Stice E, Spoor S, Ng J, Zald DH (2009) Relation of obesity to consummatory and anticipatory food
reward. Physiol Behav 97(5):551–560
Stoeckel LE, Weller RE, Cook EW 3rd, Twieg DB, Knowlton RC, Cox JE (2008) Widespread
reward-system activation in obese women in response to pictures of high-calorie foods.
Neuroimage 41(2):636–647
Sun Y, Ying H, Seetohul RM, Xuemei W, Ya Z, Qian L, Ye S (2012) Brain fMRI study of crave
induced by cue pictures in online game addicts (male adolescents). Behav Brain Res
233:563–576
Sussman S, Lisha N, Griffiths M (2011) Prevalence of the addictions: a problem of the majority or
the minority? Eval Health Prof 34(1):3–56
90 Biological Underpinning of Behavioural Addictions and Management Implications 1441
Yau YHC, Crowley MJ, Mayes LC, Potenza MN (2012) Are internet use and video-game-playing
addictive behaviors? Biological, clinical and public health implications for youths and adults.
Minerva Psichiatr 53:153–170
Yen J-Y, Ko C-H, Yen C-F, Chen C-S, Chen C-C (2009) The association between harmful alcohol
use and internet addiction among college students: comparison of personality. Psychiatry Clin
Neurosci 63(2):218–224
Yip SW, Lacadie CM, Xu J, Worhunsky PD, Fulbright RK, Constable RT, Potenza MN (2013)
Reduced genual corpus callosal white matter integrity in pathological gambling and its
relationship to alcohol abuse or dependence. World J Biol Psychiatry 14(2):129–138
Young KS (1999) Internet addiction: symptoms, evaluation and treatment. In: VandeCreek L,
Jackson T (eds) Innovations in clinical practice: a source book, vol 17. Professional Resource
Press, Sarasota, pp 19–31
Yuan K, Qin W, Wang G, Zeng F, Zhao L, Yang X, Tian J (2011) Microstructure abnormalities in
adolescents with internet addiction disorder. PLoS One 6(6):e20708
Zack M, Poulos CX (2007) A D2 antagonist enhances the rewarding and priming effects of
a gambling episode in pathological gamblers. Neuropsychopharmacology 32(8):1678–1686
Zhou Y, Lin FC, Du YS, Qin LG, Zhao ZM, Xu KR, Lei H (2011) Gray matter abnormalities in
Internet addiction: a voxel-based morphometry study. Eur J Radiol 79:92–95
Ziauddeen H, Farooqi IS, Fletcher PC (2012a) Food addiction: is there a baby in the bathwater?
Nat Rev Neurosci 13(7):514–514
Ziauddeen H, Farooqi IS, Fletcher PC (2012b) Obesity and the brain: how convincing is the
addiction model? Nat Rev Neurosci 13(4):279–286
The Psychological Underpinnings of
Addictive Behaviours 91
Tanya E. Mudry, Jonathan N. Stea, and David C. Hodgins
Contents
91.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1444
91.2 A Syndrome Model of Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1444
91.2.1 Impairment of Control and Craving . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1445
91.2.2 Expectancies and Motives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1454
91.2.3 Personality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1459
91.2.4 Summary and Integration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1464
91.2.5 Implications for Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1465
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1467
Abstract
Conceptualizing, diagnosing, and treating behavioral or process addictions
(addictions to nondrug activities, such as gambling, sex, Internet use and gam-
ing, eating, shopping, work, and exercise) have proven to be conceptually
complex. As a means of addressing this complexity, we adopt a syndrome
model of addiction, which views the disorder of addiction as a syndrome with
multiple opportunistic expressions and multiple, interacting biological, psycho-
logical, and experiential elements. In this chapter we refine our focus to how
the psychological factors of impairment of control, craving, motives and
T.E. Mudry
Educational Studies in Psychology, University of Calgary, Calgary, AB, Canada
e-mail: [email protected]
J.N. Stea
Clinical Psychology, University of Calgary, Calgary, AB, Canada
e-mail: [email protected]
D.C. Hodgins (*)
Clinical Psychology, University of Calgary, Calgary, AB, Canada
Department of Psychology, University of Calgary, Calgary, AB, Canada
e-mail: [email protected]
91.1 Introduction
the most common conceptual error committed by clinicians, researchers, and public
policymakers is to think that addiction resides as a latent property of an object (i.e., a drug
or game of chance) . . . When a particular pattern of behaviour can reliably and robustly
change emotional experience in a desirable way, the potential for addiction emerges.
The relationship of the addicted person with the object of that person’s excessive
behaviour – not just the attributes of the object – is what defines addiction. (p. xxxii)
According to the DSM-IV, the essential feature of impulse control disorders such as
pathological gambling is the failure to resist an impulse, drive, or temptation to
perform an act that is harmful to an individual (American Psychiatric Association
2000). This description contains features that are similar to the central attributes of
our common conceptions of addiction – some degree of impairment of control over
1446 T.E. Mudry et al.
(Charlton and Danforth 2007; Griffiths 2000; Meerkerk et al. 2010; Wood and
Griffiths 2007). A qualitative study of online gamers in treatment found that
participants described losing control as an important marker of the development
of their problem (Beranuy et al. 2013). A number of studies have identified
correlates of impaired control over gaming, including impulsivity (Meerkerk
et al. 2010) and low self-esteem (Armstrong et al. 2000). Impaired control defined
as “refusal self-efficacy” (i.e., lack of confidence in one’s ability to refuse involve-
ment) was linked to impulsivity, lower academic performance, insecure attachment,
and male gender in Taiwanese college students (Lin et al. 2011). No gaming or
Internet-specific impairment of control assessment tool has been described,
although a number of Internet and gaming “addiction” scales include individual
loss of control items (e.g., Yen et al. 2009; Young 1998).
Although the impairment of control construct is not used in the compulsive
shopping and buying literature, concepts such as “failure of self-control”
(Baumeister 2002), “low levels of effortful control” (Claes et al. 2010), and “failure
of self-regulation” (Peters and Bodkin 2007) appear to capture a similar phenom-
enon. Similarly, the term “dietary restraint” is frequently used in the eating disorder
literature and low restraint suggests lack of control. Impaired control in eating has
been described as a natural adaptation to food deprivation and low weight.
The difference of this concept from drugs and alcohol is that the desire to eat is
biologically adaptive and successful recovery requires a reduction of dietary
restraint (Wardle 2011).
91.2.1.2 Craving
The craving construct has also been utilized in conjunction with a number of
behavioral addictions. In the area of gambling, a recent review of research on
assessment of craving uncovered a number of studies that illustrate the impor-
tance of craving as an element of gambling disorders (Ashrafioun and Rosenberg
2012), in particular its predictive validity of relapse and recovery after treatment
(Cantinotti et al. 2007; Hodgins and el-Guebaly 2004; Ladouceur et al. 2007;
Smith et al. 2010) and persistence after gambling losses (Young and Wohl 2009).
A number of imaging studies have used gambling cues to assess the neurocir-
cuitries associated with cravings in gambling disorders (e.g., Crockford
et al. 2005; Goudriaan et al. 2010; van Holst et al. 2010), and results generally
show commonalities with substance abuse addictions (Mudry et al. 2011). Two
studies directly compared self-reports of craving from alcoholics and pathological
gamblers and found that the intensity of craving was greater for gambling
(de Castro et al. 2007; Tavares et al. 2005). Craving has been shown to be
associated with psychosocial stress (Elman et al. 2010) and gambling advertising
(Binde 2009), but, unexpectedly, not with attentional bias to gambling cues
(Brevers et al. 2011). Craving severity has also been shown to decrease with
use of naltrexone in treatment efficacy studies (e.g., Kim et al. 2001; Walther
et al. 2012).
In their review, Ashrafioun and Rosenberg (2012) identified a number of well-
validated self-report scales of craving in gambling, as well as indirect measures
1454 T.E. Mudry et al.
such as physiological reactivity that had been used in substance abuse craving
research. Beyond the gambling area, specific measures of craving have not been
developed for other behavioral addictions, although some research exists.
The literature on craving in Internet and video gaming is smaller than gambling
but seems to be developing along similar lines. A qualitative study of online gaming
addicts receiving treatment found that craving is an indicator of problem develop-
ment (Beranuy et al. 2013). A recent study of 160 gamers involved in massive
multiplayer online role-playing games concluded that gaming shows the same
emotional pattern as gambling-related craving. Craving correlated with both posi-
tive and negative affect when individuals were engaged in the activity but only
negative affect when prevented from playing (Stoeber et al. 2011). From
a neurobiological perspective, imaging studies have suggested that the
neurocircuitry associated with gaming craving is similar to gambling and substance
abuse (Han et al. 2010b; Ko et al. 2009, 2011). An open-label trial has demonstrated
a decrease in craving associated with administration of bupropion, an antidepres-
sant used for smoking and other addictions (Han et al. 2010a).
The concept of craving has been infrequently investigated in the area of sexual
behavior although sexual urges are considered part of the phenomenology of
compulsive sexual behavior (e.g., Coleman 1992; Goodman 2001). Fong (2006)
reviewed a small literature of treatment of sexual addictions, including an open-
label trial of naltrexone that reduced cravings (Ryback 2004). In the eating litera-
ture, the effect of food cues has been investigated in a number of behavioral and
imaging studies. For example, it has been shown that craving is elicited by exposure
to food cues, and degree of reactivity is predictive of binge eating in women,
although perhaps not men (Sobik et al. 2005). Similarly, in imaging studies in
other behavioral addictions, the neurocircuitry involved seems similar to substance
abuse craving (Pelchat et al. 2004). However, whether craving for food is qualita-
tively similar to craving in other addictions is controversial, as is the conceptual-
ization of compulsive overeating as an addiction more broadly (Davis and Carter
2009; Liu et al. 2010; Wardle 2011; Wilson 1991, 2010).
Expectancies and motives are two closely linked, albeit distinct social-cognitive
constructs. They were first heavily researched in the alcohol literature as determi-
nants of alcohol use and problematic drinking and have since been applied to other
substances and addictive behaviors. Whereas expectancies refer to an individual’s
belief regarding the effects or outcome of a particular substance or addictive
behavior, motives refer to an individual’s reasons for using a particular substance
or engaging in a particular addictive behavior (Cooper 1994; Goldman et al. 2006).
Cox and Klinger (1988) first articulated the relationship between expectancies
and motives in their motivation model for alcohol use. According to their model,
drinking behavior is embedded in historical (e.g., genetic disposition), personality
(e.g., extraversion, sensation seeking), sociocultural (e.g., drinking styles),
91 The Psychological Underpinnings of Addictive Behaviours 1455
91.2.2.1 Expectancies
There is a rich literature providing empirical evidence for the explanatory role of
alcohol expectancies in the variation of drinking patterns, whereby among both
adolescents and adults, alcohol expectancies have been found to have moderate to
strong associations with drinking (Goldman et al. 2006). Typically, positive expec-
tancies (e.g., beliefs that positive feelings will be enhanced and negative feelings
will be reduced) have been found to be related to initiation and early consumption
of alcohol use, whereas negative expectancies (e.g., beliefs that negative conse-
quences will occur) have been found to be related to reduction and cessation of
alcohol use (Jones et al. 2001).
While research into the etiology and maintenance of behavioral addictions is
relatively new compared to substance-related addictions, the concept of expectancy
has been applied to gambling (e.g., Gillespie et al. 2007; Shead et al. 2008; Walters
and Contri 1998; Wickwire et al. 2010), sexual behavior (e.g., Gilbert et al. 1986;
Katz et al. 2000; Lavery et al. 1993), Internet and gaming addiction (e.g., Lin
et al. 2008; Yen et al. 2011), and eating disorders (e.g., Annus et al. 2008; Hohlstein
et al. 1998; Smith et al. 2007). To our knowledge, not a single study has investi-
gated expectancies in the context of shopping, exercise, or work, which clearly
points to the need for future research in these areas.
In the area of gambling, Gillespie and colleagues (2007) have developed
a Gambling Expectancy Questionnaire (GEQ) that taps five distinct outcome
expectancy constructs: three related to positive expectancies (enjoyment/arousal,
self-enhancement, and money) and two related to negative expectancies
(over-involvement and emotional impact). Using the GEQ, the authors found that
probable pathological gamblers were more likely to endorse both positive and
negative expectancies relative to non-gamblers, social gamblers, and at-risk gam-
blers. Similar findings have been reported demonstrating that positive and negative
expectancies with respect to gambling outcomes – especially affective types of
expectancies – are associated with gambling frequency and gambling-related prob-
lems (e.g., Shead et al. 2008; Walters and Contri 1998; Wickwire et al. 2010).
The small expectancy literature in the area of sexual behavior has been equiv-
ocal. Whereas one study demonstrated strong associations between expectancies
and sexual practices (Gilbert et al. 1986), other studies have found weak or no
associations (Katz et al. 2000; Lavery et al. 1993). Katz and colleagues speculate
1456 T.E. Mudry et al.
that one reason for the weak or no associations observed might be due to the notion
that the potential costs and benefits of sexual behavior vary considerably depending
on particular individuals and circumstances (e.g., the potential consequences asso-
ciated with having unprotected sex with a monogamous partner differ from those
associated with having unprotected sex with a stranger).
Two studies based in Taiwan have examined the expectancy construct with
respect to Internet and gaming addiction. In the first study, both positive and
negative Internet use expectancies were significantly and positively correlated
with an Internet addiction measure among college students (Lin et al. 2008).
In the second study, young adults with Internet gaming addiction reacted faster in
an implicit association task to congruent pairing of Internet gaming screenshots and
liked words compared to control participants, thereby suggesting that the Internet
gaming addiction group held greater levels of implicit positive expectancies for
Internet gaming (termed by the authors as positive motivational implicit responses)
(Yen et al. 2011).
Compared to other behavioral addictions, relatively more rigorous research with
respect to expectancies has been applied to eating disorders. For example, positive
expectancies for eating have been found to differentiate bulimia nervosa patients
from anorexia nervosa patients, normal controls, and psychiatric controls
(Hohlstein et al. 1998). Longitudinally, thinness/restricting and eating expectancies
have been found to predict the subsequent onset of binge eating and purging
behavior among adolescent girls (Smith et al. 2007). Moreover, compared to
a psychoeducational intervention, a thinness expectancy manipulation intervention
has been found to produce greater declines in thinness expectancies, body dissat-
isfaction, and overall eating-disordered attitudes, thereby providing further support
for the role of expectancies in the etiology of eating-disordered behaviors (Annus
et al. 2008).
91.2.2.2 Motives
Motives have been described as more proximal and diagnostic than expectancies
(Cooper 1994). Following Cox and Klinger’s (1988) motivational model, Cooper
(1994) first proposed a framework of motives, whereby motives are characterized
by valence (positive vs. negative) and source (internally generated vs. externally
generated). The result of this framework produced a four-factor model of drinking
motives: drinking to obtain social rewards (social motives), drinking to enhance
positive affect (enhancement motives), drinking to cope with negative affect
(coping motives), and drinking to avoid social rejection (conformity motives).
Originally, Cooper and colleagues demonstrated differential associations between
drinking motives and alcohol use behavior; for example, social and enhancement
motives were found to be related to heavy drinking and to drinking in situations
where heavy drinking is tolerated (such as at parties), whereas coping motives were
found to be related to drinking in isolation (such as at bars) (Cooper 1994; Cooper
et al. 1995). As with expectancies, a wealth of empirical research has since
demonstrated that drinking motives are associated with and can predict alcohol
use behavior, whereby in general, social motives appear to be associated with
91 The Psychological Underpinnings of Addictive Behaviours 1457
moderate alcohol use, enhancement motives with heavy drinking, and coping
motives with alcohol-related problems (Kuntsche et al. 2005; Schelleman-
Offermans et al. 2011).
With respect to behavioral addictions, motives have been investigated in the
context of gambling (e.g., Lee et al. 2007; Stewart and Zack 2008; Stewart
et al. 2008), sexual behavior (e.g., Cooper et al. 1998, 2011), Internet and gaming
addiction (e.g., Junghyun et al. 2009; Ko et al. 2005; Sun et al. 2008), eating
disorders (e.g., Jackson et al. 2003; Luce et al. 2007), shopping (e.g., Arnold and
Reynolds 2003; Farrag et al. 2010; Kellet and Bolton 2009), exercise (e.g.,
Bratland-Sanda et al. 2010; Cash et al. 1994; Keele 2009; Mond and Calogero
2009), and work (e.g., Van den Broeck et al. 2011).
Derived from Cooper’s (1994) alcohol motives model, at least two gambling
motives questionnaires have been developed: one is a five-factor model
(socialization, amusement, avoidance, excitement, and monetary motives) (Lee
et al. 2007) and the other is a three-factor model (enhancement, coping, and social
motives) (Stewart and Zack 2008). Both questionnaires have been used to demon-
strate associations between gambling motives and gambling frequency and sever-
ity. Moreover, Stewart and colleagues (2008) used their gambling motives
questionnaire to demonstrate that relative to social and enhancement gamblers,
coping gamblers scored higher on a variety of different gambling activities and
gambling problems and even scored higher on drinking frequency, drinking prob-
lems, and drinking coping motives, thereby supporting an empirical approach to
subtyping gamblers based on motives and suggesting consistency of motives across
addictive behaviors.
Shortly after Cooper (1994) developed her alcohol motives model, the frame-
work was applied to the area of sexual behavior in the form of a four-factor model:
having sex to enhance physical or emotional pleasure (enhancement motives),
having sex to cope with threats to self-esteem or to minimize negative emotions
(coping motives), having sex to bond with a socially significant other (intimacy
motives), and having sex to avoid disapproval by a socially significant other (peer/
partner approval motives) (Cooper et al. 1998). This model has been used to
demonstrate that both intimacy and enhancement motives were strongly associated
with positive feelings about sex, more frequent intercourse, and higher levels of
satisfaction. Coping and peer/partner approval motives were associated with neg-
ative responses to sex, low levels of sexual satisfaction, and decreased frequency of
sex and are thought to lead to riskier and more maladaptive sexual behavior
(Cooper et al. 2011).
Although not explicitly derived from Cooper’s (1994) alcohol motives model,
the concept of motives has been investigated in the area of Internet and gaming
addiction. For example, one study found that among Taiwanese adolescents, males
were more likely than females to score higher on a measure of online gaming
addiction and were more likely to endorse playing online games for reasons to
pursue feelings of achievement and make social contacts (Ko et al. 2005). Another
study reported that among American adults, the motives of substitution (a ritualized
orientation to fill time, relax, and escape), information seeking, and social
1458 T.E. Mudry et al.
interaction were related to a measure of Internet use dependency (Sun et al. 2008).
Consistent with the construct of coping motives, yet another study reported that
among American undergraduate students, motives related to being lonely and using
the Internet to relieve psychosocial problems were associated with measures of
compulsive Internet use and negative outcomes (Junghyun et al. 2009).
Cooper’s (1994) alcohol motives model has been specifically applied to eating
disorders, whereby a four-factor model yielding the following motives has been
developed and validated: coping, social, compliance, and pleasure motives
(Jackson et al. 2003). Each motive was found to be associated with a unique pattern
of eating behavior, such that coping and compliance motives were positively
associated with restrictive eating, bingeing, and purging; pleasure motives were
positively associated with binge eating, were negatively associated with restrictive
eating, and were unrelated to purging; and social motives were negatively associ-
ated with restrictive eating and purging but were positively associated with binge-
ing. As in the gambling motives literature, the relationship between eating disorders
and drinking motives has also been investigated, whereby eating-disordered groups
have been found to endorse drinking coping motives (Luce et al. 2007), suggesting
consilience of motives across addictive disorders.
While Cooper’s (1994) alcohol motives model has not yet been explicitly applied
to the area of shopping, motives for shopping have been investigated in a rather
piecemeal fashion in two related but distinct literatures: clinical research that exam-
ines shopping addiction versus consumer marketing research. For example, one
consumer marketing study using an Egyptian sample identified seven main shopping
motives (three functional motives, safety, bargain hunting, and convenience; and four
hedonic motives, entertainment, freedom, appreciation of modernity, and self-
identity) (Farrag et al. 2010), whereas another consumer marketing study identified
six hedonic shopping motives (adventure, gratification, role, value, social, idea)
(Arnold and Reynolds 2003). While these two studies did not attempt to link motives
with shopping-related problems or addiction, it is noteworthy that the gratification
motive in Arnold and Reynolds’ (2003) study resembles the construct of coping
motives, as it describes shopping for reasons of stress relief and to alleviate negative
mood. Indeed, Kellet and Bolton (2009) have posited a cognitive-behavioral model of
compulsive buying, whereby they allude to more clinically based research suggesting
that the primary motivation for compulsive buying is mood alteration.
As with the shopping motives literature, a perusal of the exercise motives
literature also reveals a schism between two literatures: one that examines exercise
motives in the context of eating-disordered individuals and one that examines
exercise motives among nonclinical samples. For example, Keele (2009) developed
an exercise motivation questionnaire with Mexican American adults in the general
population and discovered five factors (telic/planning, telic/serious, paratelic, mas-
tery, sympathy), all of which were more highly endorsed among regular exercisers
versus non-regular exercisers. In contrast, several studies have investigated exces-
sive exercise motives among eating-disordered populations and have employed
a modified Reasons for Exercise Inventory (Cash et al. 1994) with four factors that
are reminiscent of Cooper’s (1994) model: weight/appearance, fitness/health, mood
91 The Psychological Underpinnings of Addictive Behaviours 1459
regulation, and socializing. For example, Mond and Calogero (2009) found that
eating-disordered patients were more likely to endorse excessively exercising for
body weight and shape reasons as compared to healthy women; and Bratland-Sanda
et al. (2010) found that among adult female excessive exercisers receiving inpatient
treatment for eating disorders, reduced eating disorder psychopathology was cor-
related with a reduction in perceived importance of exercise to regulate negative
affect, but not with importance of exercise for weight/appearance (these associa-
tions were not found in non-excessive exercisers).
Finally, to our knowledge, only one research group has investigated motives in the
context of excessive or compulsive work (see Van den Broeck et al. 2011). This line
of research has applied self-determination theory (Deci and Ryan 2000) to derive two
primary motives: controlled motivation (working for external and internal rewards
and avoiding punishments) versus autonomous motivation (working for personal
importance of an activity and interest). In one of their studies, the researchers
found that autonomous motivation was positively associated with excessive work,
whereas controlled motivation was positively associated with compulsive work
(Van den Broeck et al. 2011).
91.2.3 Personality
Just as Internet and online gaming have similarities and differences to gambling,
so too does compulsive shopping or buying. Impulsivity (Black et al. 2012;
Lejoyeux et al. 1997) and novelty seeking (Black et al. 2012) may be important
in compulsive buying similar to other behaviors, as well as narcissism and materi-
alism (Rose 2007). In a large Spanish study examining “buying addiction,”
Rodriguez-Villarino and colleagues (2006) found evidence for a connection
between addictive buying and symptoms of emotional distress (anxiety, depression,
and obsessive-compulsiveness), the presence of specific personal qualities
(low conscientiousness, low self-esteem, external locus of control, and sensation
seeking), and the tendency to escape from or avoid stress produced in daily life.
The tendency to use shopping as a means to escape stress or negative feelings
may be a component of compulsive buying or a characteristic of a particular type of
compulsive buying. In a small clinical sample in Germany, researchers found two
distinct personality clusters (Mueller et al. 2010). The first cluster showed average
scores on all the Big Five personality traits, whereas the participants in cluster II
scored significantly higher on neuroticism and lower on the other four personality
traits (negative scores on extraversion, openness, agreeableness, and conscientious-
ness). Subjects in cluster II showed higher severity of compulsive buying and
a lower degree of control over compulsive buying symptoms and were more
anxious, interpersonally sensitive, and impulsive.
Claes and Mueller (2011) found evidence to distinguish between impulsive and
compulsive buying, based on personality traits of a nonclinical student sample.
They argued that impulsive buying is related to extraversion (positive affectivity,
sensation seeking), whereas compulsive buying is related to neuroticism (emotional
instability, negative affect), with both impulsive buying and compulsive buying
related to lack of conscientiousness (lack of self-regulation or effortful control).
Excessive engagement in work or “workaholism” is usually composed of three
factors (work involvement, work drive, and work enjoyment) (Spence and Robbins
1992). Associations have been found between components of workaholism and
narcissism (Andreassen et al. 2012; Clark et al. 2010), conscientiousness
(Andreassen et al. 2010; Aziz and Tronzo 2011), extraversion (Andreassen
et al. 2010; Burke et al. 2006), openness to experience (Andreassen et al. 2010;
Aziz and Tronzo 2011; Burke et al. 2006), agreeableness (Andreassen et al. 2010;
Aziz and Tronzo 2011), and neuroticism (Andreassen et al. 2010; Burke et al. 2006).
Different personality dimensions seem to be related to different aspects of the work
construct. For example, conscientiousness (Aziz and Tronzo 2011), agreeableness
(Aziz and Tronzo 2011; Andreassen et al. 2010), extraversion (Andreassen
et al. 2010; Burke et al. 2006), and openness to experience (Andreassen et al. 2010)
have been found to be positively associated with work involvement. Work enjoyment
has been positively associated with agreeableness (Aziz and Tronzo 2011), consci-
entiousness (Aziz and Tronzo 2011), extraversion (Andreassen et al. 2010; Burke
et al. 2006), and openness to experience (Andreassen et al. 2010; Aziz and Tronzo
2011) and negatively associated with neuroticism (Andreassen et al. 2010; Aziz and
Tronzo 2011). While conscientiousness (Andreassen et al. 2010; Burke et al. 2006;
91 The Psychological Underpinnings of Addictive Behaviours 1463
Aziz and Tronzo 2011) and neuroticism (Andreassen et al. 2010; Burke et al. 2006)
were positively related to work drive, agreeableness was negatively associated with
work drive (Andreassen et al. 2010), and openness to experience had contradictory
associations with work drive (Burke et al. 2006; Aziz and Tronzo 2011).
The somewhat contradictory personality characteristics associated with the
different facets of work addiction lend support to the notion subtypes of “worka-
holics.” In this model, “enthusiastic workaholics” are highly involved with work,
driven by internal pressure to work, and find great pleasure in doing so. Whereas
“non-enthusiastic workaholics” are also highly involved in work-related activities
and driven to work but seem not to derive enjoyment from doing so (Alvarez-Moya
et al. 2007).
In the small domain of excessive exercise, researchers have found higher levels
of harm avoidance and persistence and lower self-directness and less mature
character among those who exercise excessively (Grandi et al. 2011). Among
American university students, Hausenblas and Giacobbi (2004) found extraversion,
neuroticism, and low agreeableness to predict exercise dependence symptoms.
They reasoned that individuals with high neuroticism could be using exercise as
a coping strategy for their stress or using exercise to address excessive worry or
concern over their appearance/health. They also suggest that upbeat, energetic
(extraverted) individuals may be drawn to exercise, and individuals who are low
in agreeableness tend to be egocentric, skeptical of others’ intentions, and compet-
itive, with excessive exercising satisfying a competitive nature.
Few researchers have examined personality traits common to or differentiating
between multiple addictive behaviors. In a Spanish study, researchers compared
binge-eating disorders and pathological gambling with controls (Claes et al. 2012).
They found that both eating-disordered individuals and pathological gamblers
showed significantly higher scores on harm avoidance and lower self-directedness
compared with control subjects. In addition, compared to control subjects, gamblers
were characterized more by novelty seeking and persistence. Also in Spain,
Alvarez-Moya and colleagues (2007) examined the personality risk factors in
bulimia nervosa and pathological gambling and found high novelty seeking to be
specifically associated with a diagnosis of problem gambling and low self-
directedness to be associated with both bulimia nervosa and gambling. In addition,
women with both bulimia nervosa and pathological gambling displayed higher
harm avoidance and cooperativeness than control women, whereas men with
problem gambling reported higher reward dependence and persistence than control
men, highlighting potential differences between sexes.
Two studies examined compulsive buying and eating disorders. Davenport
et al. (2012) found reward sensitivity and cognitive anxiety to be positively related
to excessive eating and compulsive buying. Impulsivity was positively related to
compulsive buying, whereas somatic anxiety and social desirability were nega-
tively related. Claes and colleagues (2011) found compulsive buying among
Belgian and German individuals to be positively related to BAS reactivity
(fun seeking, reward responsiveness, impulsivity) and low effortful control,
1464 T.E. Mudry et al.
whereas eating disorder symptoms were found to be related to high BIS reactivity
(especially drive for thinness) and low effortful control. They concluded that
compulsive buying is more impulsivity driven, whereas eating disorder symptoms
(especially drive for thinness) are more anxiety related.
Finally, Walther et al. (2012) conducted a large German study examining
personality factors related to substance use, gambling, and computer gaming.
High impulsivity was the only personality characteristic associated with all addic-
tive behaviors. Depression and extraversion were specific to substance users.
Four personality characteristics were specifically associated with problematic
computer gaming: irritability/aggression, social anxiety, attention deficit hyperac-
tivity disorder (ADHD), and low self-esteem. Problematic computer gamers and
gamblers did not match in any personality characteristics apart from high
impulsivity. The authors argued that problematic gamblers seem to be more similar
to substance users than problematic computer gamers.
Personality traits often interact with other psychological factors and situational vari-
ables to produce emotional and cognitive states, which then result in certain types of
1466 T.E. Mudry et al.
References
Agrawal A, Dick DM, Bucholz KK, Madden PAF, Cooper ML, Sher KJ, Heath AC (2008) Drink-
ing expectancies and motives: a genetic study of young adult women. Addiction 103:194–204
Alvarez-Moya EM, Jimenez-Murcia S, Granero R, Vallejo J, Krug I, Bulik CM, Fernandez-
Aranda F (2007) Comparison of personality risk factors in bulimia nervosa and pathological
gambling. Compr Psychiatry 48:452–457
Alvarez-Moya EM, Jimenez-Murcia S, Aymami MN, Gomez-Pena M, Granero R, Santamaria J,
Menchon JM, Fernandez-Aranda F (2010) Subtyping study of a pathological gamblers sample.
Can J Psychiatry 55:498–506
American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders
text revision. American Psychiatric Association, Washington, DC
Andreassen CS, Ursin H, Eriksen HR (2007) The relationship between strong motivation to work,
“workaholism”, and health. Psychol Health 22:615–629
Andreassen CS, Hetland J, Pallesen S (2010) The relationship between ‘workaholism’, basic needs
satisfaction at work and personality. Eur J Pers 24:3–17
Andreassen CS, Ursin H, Eriksen HR, Pallesen S (2012) The relationship of narcissism with
workaholism, work engagement, and professional position. Soc Behav Pers 40:881–890
Annus AM, Smith GT, Masters K (2008) Manipulation of thinness and restricting expectancies:
further evidence for a causal role of thinness and restricting expectancies in the etiology of
eating disorders. Psychol Addict Behav 22:278–287
Armstrong L, Phillips JG, Saling LL (2000) Potential determinants of heavier internet usage. Int
J Hum Comput Stud 53:537–550
Arnold MJ, Reynolds KE (2003) Hedonic shopping motivations. J Retail 79:77–95
Ashrafioun L, Rosenberg H (2012) Methods of assessing craving to gamble: a narrative review.
Psychol Addict Behav 26:536–549
Aziz S, Tronzo CL (2011) Exploring the relationship between workaholism facets and personality
traits: a replication in American workers. Psychol Rec 61:269–286
Bancroft J (2008) Sexual behavior that is “out of control”: a theoretical conceptual approach.
Psychiatr Clin North Am 31:593–601
Bancroft J, Graham CA, Janssen E, Sanders SA (2009) The dual control model: current status and
future directions. J Sex Res 46:121–142
Baron E, Dickerson M (1999) Alcohol consumption and self-control of gambling behavior.
J Gambl Stud 15:3–14
Barry D, Clarke M, Petry NM (2009) Obesity and its relationship to addictions: is overeating
a form of addictive behavior? Am J Addict 18:439–451
Baumeister RF (2002) Yielding to temptation: self control failure, impulsive purchasing, and
consumer behavior. J Consum Res 28:670–676
Benjamin L, Wulfert E (2005) Dispositional correlates of addictive behaviors in college women:
binge eating and heavy drinking. Eat Behav 6:197–209
Benson LA, Norman C, Griffiths MD (2012) The role of impulsivity, sensation seeking, coping,
and year of study in student gambling: a pilot study. Int J Ment Health Addict 10:461–473
Beranuy M, Carbonell X, Griffiths MD (2013) A qualitative analysis of online gaming addicts in
treatment. Int J Ment Health Addict 11:1–13
Binde P (2009) Exploring the impact of gambling advertising: an interview study of problem
gamblers. Int J Ment Health Addict 7:541–554
1468 T.E. Mudry et al.
Black DW, Shaw M, McCormick B, Bayless JD, Allen J (2012) Neuropsychological performance,
impulsivity, adhd symptoms, and novelty seeking in compulsive buying disorder. Psychiatry
Res 200:581–587
Blaszczynski A, Nower L (2002) A pathways model of problem and pathological gambling.
Addiction 97:487–499
Boyer M, Dickerson M (2003) Attentional bias and addictive behaviour: automaticity in
a gambling specific modified stoop task. Addiction 98:61–70
Bratland-Sanda S, Sundgot-Borgen J, Ro O, Rosenvinge JH, Hoffart A, Martinsen EW
(2010) Physical activity and exercise dependence during inpatient treatment of longstanding
eating disorders: an exploratory study of excessive and non-excessive exercisers. Int J Eat
Disord 43:266–273
Brevers D, Cleeremans A, Bechara A, Laloyaux C, Kornreich C, Verbanck P, Noël X (2011) Time
course of attentional bias for gambling information in problem gambling. Psychol Addict
Behav 25:675–682
Burke RJ, Matthiesen SB, Pallesen S (2006) Personality correlates of workaholism. Pers Individ
Differ 40:1223–1233
Cantinotti M, Ladouceur R, Tavares H (2007) Impaired control: a look at the laying brick of
pathological gambling. Rev Bras Psiquiatr 29:203–204
Cantinotti M, Ladouceur R, Jacques C (2009) Lay and scientific conceptualizations of impaired
control at electronic gambling machines. Addict Res Theor 17:650–667
Carnes P (1991) Don’t Call it love: recovery from sexual addiction. Bantam, New York
Cash TF, Novy PL, Grant JR (1994) Why do women exercise? Factor analysis and furterh
validation of the Reasons for Exercise Inventory. Percept Mot Skills 78:539–44
Charlton JP, Danforth IDW (2007) Distinguishing addiction and high engagement in the context of
online game playing. Comput Human Behav 23:1531–1548
Charlton JP, Danforth IDW (2010) Validating the distinction between computer addiction and
engagement: online game playing and personality. Behav Inform Technol 29:601–613
Cherpitel CJ, Borges G, Ye Y, Bond J, Cremonte M, Moskalewicz J, Swiatkiewicz G (2010)
Performance of a craving criterion in DSM alcohol use disorders. J Stud Alcohol Drugs 71:674
Chiu J, Storm L (2010) Personality, perceived luck and gambling attitudes as predictors of
gambling involvement. J Gambl Stud 26:205–227
Claes L, Mueller A (2011) Personality and compulsive buying disorder. In: Mueller A, Mitchell JE
(eds) Compulsive buying: clinical foundations and treatment. Routledge/Taylor & Francis,
New York, pp 105–113
Claes L, Bijttebier P, Eynde FVD, Mitchell JE, Faber R, Zwaan M, Mueller A (2010) Emotional
reactivity and self-regulation in relation to compulsive buying. Pers Individ Differ 49:526–530
Claes L, Bijttebier P, Mitchell JE, de Zwaan M, Mueller A (2011) The relationship between
compulsive buying, eating disorder symptoms, and temperament in a sample of female
students. Compr Psychiatry 52:50–55
Claes L, Jimenez-Murcia S, Aguera Z, Sanchez I, Santamaria J, Granero R, Fernandez-Aranda
F (2012) Eating disorders and pathological gambling in males: can they be differentiated by
means of weight history and temperament and character traits? Eat Disord 20:395–404
Clark MA, Lelchook AM, Taylor ML (2010) Beyond the big five: how narcissism, perfectionism,
and dispositional affect relate to workaholism. Pers Individ Differ 48:786–791
Cloninger CR (1987) A systematic method for clinical description and classification of personality
variants: a proposal. Arch Gen Psychiatry 44:573–588
Cloninger CR, Przybeck TR, Svrakic DM, Wetzel RD (1994) The Temperament and Character
Inventory (TCI): a guide to its development and use. Center for Psychobiology of Personality,
St. Louis
Coleman E (1992) Is your patient suffering from compulsive sexual behavior? Psychiatr Ann
22:320–325
Cooper ML (1994) Motivations for alcohol use among adolescents: development and validation of
a four-factor model. Psychol Assess 6:117–128
91 The Psychological Underpinnings of Addictive Behaviours 1469
Cooper ML, Frone MR, Russell M, Mudar P (1995) Drinking to regulate positive and negative
emotions: a motivational model of alcohol use. J Pers Soc Psychol 69:990–1005
Cooper ML, Shapiro CM, Powers AM (1998) Motivations for sex and risky sexual behavior among
adolescents and young adults: a functional perspective. J Pers Soc Psychol 75:1528–1558
Cooper ML, Barber LL, Zhaoyang R, Talley AE (2011) Motivational pursuits in the context of
human sexual relationships. J Pers 79:1333–1368
Corless T, Dickerson M (2006) Gamblers’ self-perceptions of the determinants of impaired
control. Br J Addict 84:1527–1537
Cox WM, Klinger E (1988) A motivational model of alcohol use. J Abnorm Psychol 97:168–180
Crockford DN, Goodyear B, Edwards J, Quickfall J, el-Guebaly N (2005) Cue-induced brain
activity in pathological gamblers. Biol Psychiatry 58:787–795
Davenport K, Houston JE, Griffiths MD (2012) Excessive eating and compulsive buying
behaviours in women: an empirical pilot study examining reward sensitivity, anxiety,
impulsivity, self-esteem and social desirability. Int J Ment Health Addict 10:474–489
Davis C, Carter JC (2009) Compulsive overeating as an addiction disorder. A review of theory and
evidence. Appetite 53:1–8
de Castro V, Fong T, Rosenthal RJ, Tavares H (2007) A comparison of craving and emotional
states between pathological gamblers and alcoholics. Addict Behav 32:1555–1564
Deci EL, Ryan RM (2000) The “what” and “why” of goal pursuits: human needs and the
self-determination of behavior. Psychol Inq 11:319–338
Dickerson M (1993) Internal and external determinants of persistent gambling: problems in
generalising from one form of gambling to another. J Gambl Stud 9:225–245
Dickerson M, O’Connor J (2006) Gambling as an addictive behaviour. Impaired control, harm
minimisation, treatment and prevention. Cambridge University Press, Cambridge, UK
Eiser JR (1990) Social cognition and comparative substance use. In: Warburton DM
(ed) Addiction controversies. Harwood Academic Publishers, Chur, pp 271–282
Ellard KK, Fairholme CP, Boisseau CL, Farchione TJ, Barlow DH (2010) Unified protocol for the
transdiagnostic treatment of emotional disorders: protocol development and initial outcome
data. Cogn Behav Pract 17:88–101
Elman I, Tschibelu E, Borsook D (2010) Psychosocial stress and its relationship to gambling urges
in individuals with pathological gambling. Am J Addict 19:332–339
Farrag DA, El Sayed IM, Belk RW (2010) Mall shopping motives and activities: a multimethod
approach. J Int Consum Mark 22:95–115
Fong TW (2006) Understanding and managing compulsive sexual behaviors. Psychiatry 3:51
Forbush KT, Shaw M, Graeber MA, Hovick L, Meyer VJ, Moser DJ, Bayless J, Watson D, Black
DW (2008) Neuropsychological characteristics and personality traits in pathological gambling.
CNS Spectr 13:306–315
Garcia FD, Thibaut F (2010) Sexual addictions. Am J Drug Alcohol Abuse 36:254–260
Gilbert MA, Bauman KE, Udry R (1986) A panel study of subjective expected utility for
adolescent sexual behavior. J Appl Soc Psychol 16:745–756
Gillespie MA, Derevensky J, Gupta R (2007) The utility of outcome expectancies in the prediction
of adolescent gambling behaviour. J Gambl Issues 19:69–85
Goldberg LR (1990) An alternative “description of personality”: the big-five factor structure.
J Pers Soc Psychol 59:1216–1229
Goldman MS, Darkes J, Reich RR, Brandon KO (2006) From DNA to conscious thought: the
influence of anticipatory processes on human alcohol consumption. In: Munafo M, Albery IP
(eds) Cognition and addiction. Oxford University Press, New York, pp 149–186
Goodman A (1990) Addiction: definition and implications. Br J Addict 85:1403–1408
Goodman A (2001) What’s in a name? Terminology for designating a syndrome of driven sexual
behavior. Sex Addict Compulsivity J Treat Prev 8:191–213
Goudriaan AE, De Ruiter MB, Van den Brink W, Oosterlaan J, Veltman DJ (2010) Brain
activation patterns associated with cue reactivity and craving in abstinent problem gamblers,
heavy smokers and healthy controls: an fMRI study. Addict Biol 15:491–503
1470 T.E. Mudry et al.
Ko CH, Liu GC, Hsiao S, Yen JY, Yang MJ, Lin WC, Yen CF, Chen CS (2009)
Brain activities associated with gaming urge of online gaming addiction. J Psychiatr Res
43:739–747
Ko CH, Hsiao S, Liu GC, Yen JY, Yang MJ, Yen CF (2010) The characteristics of decision
making, potential to take risks, and personality of college students with Internet addiction.
Psychiatry Res 175:121–125
Ko CH, Liu GC, Yen JY, Chen CY, Yen CF, Chen CS (2011) Brain correlates of craving for online
gaming under cue exposure in subjects with internet gaming addiction and in remitted subjects.
Addict Biol 18:559–569
Kuntsche E, Knibbe R, Gmel G, Engels R (2005) Why do young people drink? A review of
drinking motives. Clin Psychol Rev 25:841–861
Kuntsche E, Knibbe R, Engels R, Gmel G (2007) Drinking motives as mediators of the link
between alcohol expectancies and alcohol use among adolescents. J Stud Alcohol Drugs
68:76–85
Ladouceur R, Sylvain C, Gosselin P (2007) Self-exclusion program: a longitudinal evaluation
study. J Gambl Stud 23:85–94
Lavery B, Siegel AW, Cousins JH, Rubovits DS (1993) Adolescent risk-taking: an analysis of
problem behaviors in problem children. J Exp Child Psychol 55:277–294
Lee HP, Chae PK, Lee HS, Kim YK (2007) The five-factor gambling motivation model.
Psychiatry Res 159:21–32
Lejoyeux M, Tassain V, Solomon J, Ades J (1997) Study of compulsive buying in depressed
patients. J Clin Psychiatry 58:169–173
Lin MP, Ko HC, Wu YWJ (2008) The role of positive/negative outcome expectancy and refusal
self-efficacy of internet use on internet addiction among college students in Taiwan.
Cyberpsychol Behav 11:451–457
Lin MP, Ko HC, Wu JYW (2011) Prevalence and psychosocial risk factors associated with internet
addiction in a nationally representative sample of college students in Taiwan. Cyberpsychol
Behav Soc Netw 14:741–746
Liu Y, von Deneen KM, Kobeissy FH, Gold MS (2010) Food addiction and obesity: evidence from
bench to bedside. J Psychoactive Drugs 42:133–145
Luce KH, Engler PA, Crowther JH (2007) Eating disorders and alcohol use: group differences in
consumption rates and drinking motives. Eat Behav 8:177–184
MacLaren VV, Fugelsang JA, Harrigan KA, Dixon MJ (2011) The personality of pathological
gamblers: a meta-analysis. Clin Psychol Rev 31:1057–1067
Marsh A, Smith L, Saunders B, Piek J (2002) The impaired control scale: confirmation of factor
structure and psychometric properties for social drinkers and drinkers in alcohol treatment.
Addiction 97:1339–1346
Meerkerk GJ, Van Den Eijnden R, Franken IHA, Garretsen HFL (2010) Is compulsive internet use
related to sensitivity to reward and punishment, and impulsivity? Comput Human Behav
26:729–735
Mehroof M, Griffiths MD (2010) Online gaming addiction: the role of sensation seeking,
self-control, neuroticism, aggression, state anxiety, and trait anxiety. Cyberpsychol Behav
Soc Netw 13:313–316
Mick TM, Hollander E (2006) Impulsive-compulsive sexual behavior. CNS Spectr 11:944–955
Mond JM, Calogero RM (2009) Excessive exercise in eating disorder patients and in healthy
women. Aust NZ J Psychiatry 43:227–234
Montag C, Jurkiewicz M, Reuter M (2010) Low self-directedness is a better predictor
for problematic internet use than high neuroticism. Comput Human Behav 26:1531–1535
Montag C, Flierl M, Markett S, Walter N, Jurkiewicz M, Reuter M (2011) Internet addiction and
personality in first-person-shooter video gamers. J Media Psychol 23:163–173
Mudry TE, Hodgins DC, el-Guebaly N, Wild TC, Colman I, Patten SB, Schopflocher DP
(2011) Conceptualizing excessive behaviour syndromes: a systematic review. Curr Psychiatry
Rev 7:138–151
1472 T.E. Mudry et al.
Mueller A, Claes L, Mitchell JE, Wonderlich SA, Crosby RD, de Zwaan M (2010) Personality
prototypes in individuals with compulsive buying based on the big five model. Behav Res Ther
48:930–935
Myrseth H, Pallesen S, Molde H, Johnsen BH, Lorvik IM (2009) Personality factors as predictors
of pathological gambling. Pers Individ Differ 47:933–937
Nixon G, Theriault B (2012) Nondual psychotherapy and second stage sexual addictions recovery:
transforming “master of the universe” narcissism into nondual being. Int J Ment Health Addict
10:368–385
Nordin C, Nylander PO (2007) Temperament and character in pathological gambling. J Gambl
Stud 23:113–120
O’Brien C (2011) Addiction and dependence in DSM-V. Addiction 106:866–867
O’Connor J, Dickerson M (2003) Impaired control over gambling in gaming machine and
off-course gamblers. Addiction 98:53–60
Orford J (1978) Hypersexuality: implications for a theory of dependence. Br J Addict Alcohol
Other Drugs 73:299–310
Pelchat ML, Johnson A, Chan R, Valdez J, Ragland JD (2004) Images of desire: food-craving
activation during fMRI. Neuroimage 23:1486–1493
Peters C, Bodkin CD (2007) An exploratory investigation of problematic online auction behaviors:
experiences of eBay users. J Retail Consum Serv 14:1–16
Peters CS, Malesky AJ (2008) Problematic usage among highly-engaged players of massively
multiplayer online role playing games. Cyberpsychol Behav 11:481–484
Reid RC, Carpenter BN, Spackman M, Willes DL (2008) Alexithymia, emotional instability, and
vulnerability to stress proneness in patients seeking help for hypersexual behavior. J Sex
Marital Ther 34:133–149
Reid RC, Li DS, Lopez J, Collard M, Parhami I, Karim R, Fong T (2011) Exploring facets of
personality and escapism in pathological gamblers. J Soc Work Pract Addict 11:60–74
Rodriguez-Villarino R, Gonzalez-Lorenzo M, Fernandez-Gonzalez A, Lameiras-Fernandez M,
Foltz ML (2006) Individual factors associated with buying addiction: an empirical study.
Addict Res Theor 14:511–525
Rose P (2007) Mediators of the association between narcissism compulsive buying: the roles of
materialism impulse control. Psychol Addict Behav 21:576–581
Rosenberg H (2009) Clinical laboratory assessment of the subjective experience of drug craving.
Clin Psychol Rev 29:519–534
Ryback RS (2004) Naltrexone in the treatment of adolescent sexual offenders. J Clin Psychiatry
65:982–986
Sayette MA, Shiffman S, Tiffany ST, Niaura RS, Martin CS, Schadel WG (2000) The measure-
ment of drug craving. Addiction 95:189–210
Schelleman-Offermans K, Kuntsche E, Knibbe RA (2011) Associations between drinking motives
and changes in adolescents’ alcohol consumption: a full cross-lagged panel study. Addiction
106:1270–1278
Shaffer HJ (2012) APA addiction syndrome handbook. American Psychological Association,
Washington, DC
Shaffer HJ, LaPlante DA, LaBrie RA, Kidman RC, Donato AN, Stanton MV (2004) Toward
a syndrome model of addiction: multiple expressions, common etiology. Harv Rev Psychiatry
12:367–374
Shead NW, Callan MJ, Hodgins DC (2008) Probabilistic discounting among gamblers: differences
across problem gambling severity and affect-regulation expectancies. Pers Indiv Differ
45:536–541
Shepherd L, Dickerson M (2001) Situational coping with loss and control over gambling in regular
poker machine players. Aus J Psychol 53:160–169
Slutske WS, Caspi A, Moffitt TE, Poulton R (2005) Personality and problem gambling:
a prospective study of a birth cohort of young adults. Arch Gen Psychiatry 62:769–775
91 The Psychological Underpinnings of Addictive Behaviours 1473
Smith GT, Simmons JR, Annus AM, Hill KK (2007) Thinness and eating expectancies predict
subsequent binge eating and purging behavior among adolescent girls. J Abnorm Psychol
116:188–197
Smith D, Harvey P, Battersby M, Pols R, Oakes J, Baigent M (2010) Treatment outcomes and
predictors of drop out for problem gamblers in South Australia: a cohort study. Aust N Z
J Psychiatry 44:911–920
Sobik L, Hutchison K, Craighead L (2005) Cue-elicited craving for food: a fresh approach to the
study of binge eating. Appetite 44:253–262
Spence JT, Robbins AS (1992) Workaholism: definition, measurement, and preliminary results.
J Pers Assess 58:160–178
Stewart SH, Zack M (2008) Development and psychometric evaluation of a three-dimensional
gambling motives questionnaire. Addiction 103:1110–1117
Stewart SH, Martin Z, Collins P, Klein RM, Fragopoulos F (2008) Subtyping pathological
gamblers on the basis of affective motivations for gambling: relations to gambling
problems, drinking problems, and affective motivations for drinking. Psychol Addict Behav
22:257–268
Stoeber J, Harvey M, Ward JA, Childs JH (2011) Passion, craving, and affect in online gaming:
predicting how gamers feel when playing and when prevented from playing. Pers Individ
Differ 51:991–995
Sullivan S, Cloninger CR, Przybeck TR, Klein S (2007) Personality characteristics in obesity and
relationship with successful weight loss. Int J Obes 31:669–674
Sun S, Rubin AM, Haridakis PM (2008) The role of motivation and media involvement in
explaining internet dependency. J Broadcast Electron 52:408–431
Tavares H, Gentil V (2007) Pathological gambling and obsessive-compulsive disorder: towards
a spectrum of disorders of volition. Rev Bras Psiquiatr 29:107–117
Tavares H, Zilberman ML, Hodgins DC, el-Guebaly N (2005) Comparison of craving between
pathological gamblers and alcoholics. Alcohol Clin Exp Res 29:1427–1431
Tice DM, Bratslavsky E, Baumeister RF (2001) Emotional distress regulation takes precedence
over impulse control: if you feel bad, do it! J Pers Soc Psychol 80:53–67
Tsai HF, Cheng SH, Yeh TL, Shih CC, Chen KC, Yang YC, Yang YK (2009)
The risk factors of internet addiction-a survey of university freshmen. Psychiatry Res
167:294–299
Vachon DD, Bagby RM (2009) Pathological gambling subtypes. Psychol Assess 21:608–615
Van den Broeck A, Schreurs B, De Witte H, Vansteenkiste M, Germeys F, Schaufeli W (2011)
Understanding workaholics’ motivations: a self-determination perspective. Appl Psychol-Int
Rev 60:600–621
van Holst RJ, Van den Brink W, Veltman DJ, Goudriaan AE (2010) Brain imaging studies in
pathological gambling. Curr Psychiatry Rep 12:418–425
Walters GD, Contri D (1998) Outcome expectancies for gambling: empirical modeling of
a memory network in federal prison inmates. J Gambl Stud 14:173–191
Walther B, Morgenstern M, Hanewinkel R (2012) Co-occurrence of addictive behaviours:
personality factors related to substance use, gambling and computer gaming. Eur Addict Res
18:167–174
Wardle J (2011) Compulsive eating and dietary restraint. Br J Clin Psychol 26:47–55
Wickwire EM, Whelan JP, Meyers AW (2010) Outcome expectancies and gambling behavior
among urban adolescents. Psychol Addict Behav 24:75–88
Wilson GT (1991) The addiction model of eating disorders: a critical analysis. Adv Behav Res
Ther 13:27–72
Wilson GT (2010) Eating disorders, obesity and addiction. Eur Eat Disord Rev 18:341–351
Wood RTA, Griffiths MD (2007) Online guidance, advice, and support for problem gamblers and
concerned relatives and friends: an evaluation of the Gam-Aid pilot service. Br J Guid Couns
35:373–389
1474 T.E. Mudry et al.
Yen JY, Yen CF, Chen CS, Tang TC, Ko CH (2009) The association between adult ADHD
symptoms and internet addiction among college students: the gender difference. Cyberpsychol
Behav 12:187–191
Yen JY, Yen CF, Chen CS, Tang TC, Huang TH, Ko CH (2011) Cue-induced positive motiva-
tional implicit response in young adults with internet gaming addiction. Psychiatry Res
190:282–26
Young KS (1998) Internet addiction: the emergence of a new clinical disorder. Cyberpsychol
Behav 1:237–244
Young MM, Wohl MJ (2009) The gambling craving scale: psychometric validation and behavioral
outcomes. Psychol Addict Behav 23:512–522
Zuckerman M (2012) Psychological factors and addiction: personality. In: Shaffer HJ (ed) APA
addiction syndrome handbook. American Psychological Association, Washington, DC,
pp 175–194
Clinical Management of Gambling
Disorder 92
Enrique Echeburúa
Contents
92.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1476
92.2 Main Interventions for Gambling Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1477
92.2.1 Psychological Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1477
92.2.2 Pharmacotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1483
92.2.3 Issues in Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1484
92.2.4 Internet Gambling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1486
92.3 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1487
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1488
Abstract
This chapter deals with the new developments in the treatment of disordered
gambling, as well as with the challenges for further research. Abstinence versus
moderated gambling as therapeutic goals is an issue that raises many concerns
and that needs to be addressed. Current psychological treatment for disordered
gambling involves a number of different options, including inpatient treatments,
individual and group cognitive-behavioral options, Gamblers Anonymous, and
pharmacotherapy, as well as an intervention in relapse prevention. Most of the
treatment is delivered on an outpatient basis. Cognitive-behavioral therapy and
motivational enhancement therapy may have a success rate ranging from 50 % to
80 % of treated patients in a long-term follow-up. Psychopharmacological
therapy may have incremental benefit when patients have comorbid depression
or high impulsivity. A relevant issue relates to treatment intensity and the
emergence of a plethora of so-called brief interventions. Responsible gambling
may be a therapeutic option for young gamblers or people without a severe
E. Echeburúa
Department of Clinical Psychology, University of the Basque Country UPV/EHU, Avda. de
Tolosa, 70, San Sebastián, Spain
e-mail: [email protected]
92.1 Introduction
disorders (e.g., anxiety and mood disorders) tend to have high rates of gambling
problems. However, since the occurrence of PG varies from country to country and
the measures for calculating the prevalence are not always the same, current
estimates of the prevalence of GD must be treated with a degree of caution
(Kessler et al. 2008).
Men are more likely to be gamblers than women and also more likely to develop
gambling-related problems than them. However, there is evidence that gambling
problems have increased among women in recent years. In addition, GD is associ-
ated with poorer measures of mental health in women compared to men. Women
are more likely than men to gamble in order to relieve feelings of depression and
anxiety and to escape dysphoria. Whereas men frequently begin gambling early in
life, report slow emergence of problems, and seek help well after developing
problems; women start gambling later in life, then rapidly develop dependence,
and seek help more quickly (Echeburúa et al. 2011a).
The interventions for GD that have been developed and reported in the literature are
quite similar to methods of treating other addictions and include approaches that are
psychoanalytic, behavioral, cognitive, pharmacological, addiction based and
multimodal, and self-help. Often these approaches are combined to varying degrees
in most treatment programs or counseling settings. Although gambling treatment
dates several decades, few empirically supported treatments for GD have been
developed.
Behavioral Therapies
Behavioral approach considers gambling behavior as having three components:
antecedents (financial pressure, gambling cues, positive or negative emotions, inter-
personal factors, urges to gamble), overt or covert behavior itself (money spent in
gambling, coping strategies to deal with anxiety or depression, thinking about gam-
bling or about how to attain money), and consequences, both positive (autonomic
arousal, opportunities to socialize, escape from personal problems, monetary gain)
and negative (anxiety and depression, low self-esteem, work and relationship conflict,
financial loss). Anyway gambling-based arousal is the central factor in the reinforce-
ment process. Approach to gambling in regular gamblers is triggered by a wide range
of environmental features: driving the car, leaving work, the sight of money in the
wallet, and so on. Gambling is also highly reinforcing because of the variable pattern
of reinforcement and the tension relief (Hodgins and Holub 2007).
Behavioral therapy considers pathological gambling a learned behavior and
relies on techniques such as stimulus control, systematic exposure, and skill devel-
opment (e.g., relaxation techniques and improving stress management and social
skills) to reverse the learned behavior and the association between arousal and
conditioned elicitors. Reduction in gambling is expected if patients can successfully
develop and use alternative coping responses to deal with urges to gamble. Behav-
ioral counseling, in which the gambler is given verbal reinforcement for desired
outcome behaviors, and in vivo exposure, in which the gambler is exposed to
gambling behaviors but is not allowed to gamble, are also mentioned in the
literature (Hodgins and Holub 2007).
Stimulus control involves limiting access to money, not visiting venues that
offer gambling and not spending time with people associated with heavy gambling.
As treatment advances, the control of stimuli is gradually faded, except avoiding
gambling friends and to signing up for the self-exclusion program. Recovering
gamblers are also encouraged to take themselves off mailing lists from the casino,
to meet with a financial planner, to cancel all credit cards, and to turn over control of
money to another person. Self-exclusion from gaming venues can be an adjunct to
treatment. Actually participants tend to comply with the commitment of abstinence
and have more positive outcomes when they are also involved in complementary
treatment or self-help groups (Nelson et al. 2010).
92 Clinical Management of Gambling Disorder 1479
gambled did not exceed the amount gambled in the week prior to treatment) of 69 %
and 37 %, respectively. The behavioral therapy was found to be more effective than
the group cognitive restructuring in terms of reducing gambling frequency.
Grant et al. (2009) compared a six-session CBT program, combining imaginal
cue-exposure plus the negative mood induction (focused on the negative
consequences of gambling while the urge is active) with GA. The 64 % of
participants assigned to behavioral program maintained abstinent at 1-month
follow-up as opposed to only 17 % of patients assigned to GA.
In sum, according to the meta-analysis of Pallesen et al. (2005), interventions
involving developing relaxation skills, exposure to gambling cues, and direct
behavioral action are effective in improving gambling urges, time and money
spent, and abstinence. In addition, behavioral change is related to cognitive change
after treatment.
Cognitive-Behavioral Therapies
Excessive gambling can be driven by distorted and maladaptive cognitions, such as
illusion of control, superstitious thinking, or misperception of probability. Two
major beliefs (gambling outcomes can be correctly predicted and controlled) appear
to describe the problem gamblers’ irrational cognition. Disordered gamblers
believe they have the ability to control random or chance events by relying on
superstitious behavior or methods. This illusion of control is stronger as gamblers
become more familiar with a game. Thus they can believe that a big win is
imminent and persists despite mounting losses, with an unrealistic hope that they
will recover their losses if they persevere with the gambling (the gambler’s fallacy)
(Ladouceur and Walker 1998).
Cognitive therapy aims to help patients challenge and overcome irrational
thoughts that are believed to initiate and maintain the undesirable behavior. Patients
are taught to be aware of the link among thoughts, behavior, and emotion. Many
patients do not understand the concepts of probability and randomness, believing
that they can exert some control over whether they win or lose. Treatment typically
involves teaching patients strategies to correct their erroneous thinking by
providing corrective information through education, logical discussion, or
behavioral experimentation. Thus the therapist will ask the gamblers to describe
what they are saying to themselves when gambling. If the erroneous perceptions
and understanding of randomness in the gambler can be corrected, then the
motivation to gamble should decrease dramatically. Cognitive therapy also aids
gamblers in coping with urges to gamble, managing negative emotions and training
in problem solving techniques (Ladouceur and Walker 1998).
The more recent randomized clinical trials have focused on combined cognitive
and behavioral approaches (cognitive correction, problem solving training, and
social skills training). In two different trials Ladouceur et al. (2001, 2003)
compared a 12-month follow-up individual and a 24-month follow-up group CBT
(ten weekly sessions), respectively, with a wait-list control group. In the second
trial a relapse prevention component was also included. People receiving treatment
met fewer DSM criteria for pathological gambling, and treatment gains were
92 Clinical Management of Gambling Disorder 1481
maintained over the follow-up period. However, dropout rates were high (47 % in
the first trial and 26 % in the second one).
An individual eight-session manualized form of CBT has also been compared
(either delivered by a professional counselor or completed alone by the patient in
a self-help workbook) with a group referred to GA. Although participants
in all groups reduced gambling, CBT in both conditions was better than GA in
terms of days gambled and number of gambling criteria met. In the GA group
attendance at meetings was positively associated with abstinence from gambling
(Petry et al. 2006).
In the Jiménez-Murcia et al. study (2012), exposure and response prevention do
not improve the results of a group CBT for male gamblers due to its increasing
effect on the dropout rates. However, in other studies with different results,
exposure and response prevention are used together with stimulus control in
a behavioral management program and in an individual format (e.g., Echeburúa
et al. 1996, 2000, 2011b).
In sum, both individual and group CBT appear effective for reducing gambling.
Individual CBT may be enhanced if patients receive compliance-improving inter-
ventions, such as a reinforcement of self-efficacy, reminder phone calls, assessment
feedback, and a weekly decisional balance exercise to complete. Group CBT may
be enhanced if individuals have interactive written exercises. In this way that
mapping may serve to individualize the group treatment, leading to greater effect
(Melville et al. 2004).
However, the cognitive therapy studies have not yet determined the optimal
number of sessions needed to reduce gambling symptoms and maintain improve-
ment (Grant and Odlaug 2012).
group (Diskin and Hodgins 2009; Hodgins et al. 2009), patients who received the
motivational interviewing plus workbook gambled less and spent less money than
workbook-only group.
A combined motivational interviewing and CBT program applied in group
or individual format, or even adapted to a web-based format (Carlbring and
Smit 2008), can improve GD behaviors, as well as gambling correlates. Moreover
the addition of motivational interviewing to CBT can reduce treatment attrition and
improve outcomes (Wulfert et al. 2006).
However, these motivational approaches, which are more attractive to gamblers
and may result in an increase of treatment seekers, cannot be so effective with
severe pathological gamblers or patients with comorbid pathology. More research is
needed to determine the efficacy of these programs when compared to more
established CBT.
Gamblers Anonymous
Modeled after the traditions and spiritual principles of Alcoholic Anonymous,
Gamblers Anonymous (GA) is the primary self-help group and uses an
abstinence-based treatment program. DG is conceptualized as an illness which
can be arrested but never cured, so people affected by this problem have a
permanent predisposition for losing control over their gambling.
The therapeutic rationale for GA is that the 12 steps to recovery will lead
gamblers to attain abstinence. The group format is intended to provide a sense of
common purpose and understanding, emotional and spiritual support, and hope.
Anonymity allows for members to feel safe in sharing openly with other members
(Hodgins and Holub 2007).
The efficacy of GA has not been demonstrated in controlled studies.
Relapse rates tend to be quite high. Stewart and Brown (1988) found that total
abstinence was reported by only 7.5 % of members surveyed 1 year after their first
attendance and by 7.3 % at 2 years. Attrition rate is also high. People attending GA
have better gambling outcomes than those who do not, even though they are
engaged in professional treatment concurrently (Petry et al. 2006).
The therapeutic effectiveness of Gamblers Anonymous has also been explored
with respect to participation by the gambler’s partner. There is a trend for higher
abstinence rates for gamblers whose partners are present at meetings compared with
gamblers whose partners do not attend.
There is a particular need for studies of the role of GA in recovery and treatment
outcomes. A recent study found that there were not any differences on key
gambling variables (e.g., frequency, abstinence rates, money wagered) at 12 months
between a program of CBT and 12-step therapy (Toneatto and Dragonetti 2008).
If there is a high dropout rate from Gamblers Anonymous, as the literature
suggests, then it is important to investigate its causes and strategies for reducing it.
In sum, GA may be increasing in popularity, but whether participating in
meetings makes a significant and lasting impact is still not well known.
92 Clinical Management of Gambling Disorder 1483
92.2.2 Pharmacotherapy
Only a small proportion of the individuals who are suffering from GD (about 6 %)
seek formal treatment. The satisfactions provided by their addiction, a desire to
92 Clinical Management of Gambling Disorder 1485
handle the problem by themselves, and shame have been identified as contributing
factors to resistance to treatment. Motivation becomes adequate when people
identify gambling as a destructive agent in their life. Natural recovery from problem
gambling can occur in about 35 %, but most disordered gamblers report a chronic
course, with symptom severity fluctuating over time (Grant and Odlaug 2012).
Therapists have been confronted with the problem of treatment compliance.
For pathological gamblers, compliance is an issue because they are often ambiva-
lent about giving up their gambling or altering long-standing patterns of coping, no
matter how ineffective. Some people do not seek treatment, some drop out after one
or two sessions, and some can decide to terminate treatment after a few weeks
thinking that their problem has been solved. It is a challenge to identify the
characteristics and the reasons of individuals who refuse treatment, drop out, or
simply do not show up for the first session. There are no obvious solutions to these
matters, but motivational enhancement therapy, behavior contracts, and flexible
treatment goals might improve treatment compliance.
Despite the growing trend toward harm reduction strategies and controlled behav-
ior approaches for addiction problems, most gambling treatment programs, like those
that treat substance abuse, favor abstinence. Some programs, however, particularly
those dealing with problem gamblers in their early stages, aim at reducing and
controlling rather than stopping gambling. Anyway clinical trials comparing treat-
ments with varying treatment goals are necessary (Ladouceur et al. 2009).
A relevant issue relates to treatment intensity and the emergence of a plethora of
so-called brief interventions. A distinction should be drawn between minimal
intervention or advice in a primary care setting and brief intervention within
a specialist context (one to three sessions). It is difficult to know if there are
remarkable differences between brief and extended interventions for pathological
gamblers. For instance, there are important differences between treatment-seeking
populations as distinct from those that are selected as a result of opportunistic
screenings. Anyway it is relevant to investigate the active ingredients of brief
interventions which seem to be, at least, relatively successful (Grant and Odlaug
2012).
Interventions should be tailored to the needs of the patients. Substantial progress
has been made in understanding the treatment of this disorder, but there is not yet
research basis for matching patients to treatments according to different character-
istics (e.g., subtypes of gamblers, different type of gambling, or gender of
gamblers). That is, individuals with gambling problems cannot be treated as
a homogeneous group, but refinement in matching treatment strategies with
gambler typologies must await completion of controlled treatment studies.
Advances in family therapy for treating substance abuse problems have been
adapted for gambling disorders, such as a self-help workbook of the Community
Reinforcement and Family Therapy (CRAFT) model (focused on the training of
family members to use behavioral principles to reinforce non-gambling behaviors)
(Hodgins et al. 2007) or a coping skills training program for those with
a pathological-gambling partner (Rychtarik and McGillicuddy 2006). Further
research is warranted to improve the design and targeting of these approaches.
1486 E. Echeburúa
Internet gambling can be defined as any type of wagering that takes place by using
the Internet. Common forms of online gambling are online poker, online casino,
sports betting, and online bingo; though, there are some other ways to gamble
using the Internet that hold strong potential for additional growth, e.g.,
gambling by mobile devices and gambling on the Internet games (Laplante and
Braverman 2010).
Men are more likely to gamble using the Internet than women. Emotional
states, maladaptive cognitions, and life events can serve as triggers for Internet
abuse. The pervasiveness of Internet gambling sites on the web makes it an
especially risky form of gambling. One of the most attractive features of Internet
gambling is its convenience (e.g., playing comfortably at home and at
a convenient time is reported to be the most important reason for playing online
poker). The anonymity of Internet gambling presents an opportunity for the
development of gambling-related problems. For example, because of anonymity,
people may gamble under the influence of alcohol or drugs, be underage, or even
gamble from the school or workplace. Solitary gambling, like Internet gambling,
where people can gamble at their own pace with no outsiders interrupting or any
other distractions, is also a risky factor. Computers and the Internet create
isolation and a sense of fantasy. In summary, a cursory consideration of numerous
risk areas logically suggests that the Internet might increase the speed of
the negative effects of gambling or exacerbate gambling-related problems
(Griffiths and Barnes 2008).
Minors might gain access to a credit card and gamble with other people’s
money. This raises concerns that children and adolescents’ participation basically
is unrestricted. In addition to being illegal, such an occurrence would be problematic
because early exposure to gambling is linked with the development and persistence
of gambling-related problems (Derevensky and Gupta 2007).
Appropriate treatment for online gambling addiction is still being researched.
Treatments that are effective for gambling addiction work well for online gambling
addiction. It is important to consider the individual needs when devising a treatment
plan to tackle an online gambling addiction. Every person is different and could be
addicted for different reasons.
Stimulus control involves for the Internet gambling addicts to engage in opposite
activities, use of timers to end online sessions, set time limits, prioritize tasks, and
record Internet usage to abstain from Internet abuse.
Group therapy is commonly suggested as a treatment option as well. If patients
are attending support groups such as GA, they can use that group to help cope with
their online gambling addiction.
Online gambling addiction, gambling addiction, and Internet addiction, which
are all closely related, can create problems outside of the individual. They can cause
damage to one’s finances, marriage, and even their entire family. In these cases,
financial counseling, marriage counseling, and family therapy are all beneficial
treatment options.
92 Clinical Management of Gambling Disorder 1487
References
Blaszczynski A, McConaghy N, Frankova A (1991) A comparison of relapsed and non-relapsed
abstinent pathological gamblers following behavioural treatment. Br J Addict 86:1485–1489
Carlbring P, Smit F (2008) Randomized trial of internet-delivered self-help with telephone support
for pathological gamblers. J Consult Clin Psychol 76:1090–1094
Derevensky JL, Gupta R (2007) Adolescent gambling: current knowledge, myths, assessment
strategies, and public policy implications. In: Smith G, Hodgins DC, Williams RJ (eds)
Research and measurement issues in gambling studies. Elsevier, Amsterdam, pp 437–463
Diskin KM, Hodgins DC (2009) A randomized controlled trial of a single session motivational
intervention for concerned gamblers. Behav Res Ther 47:382–388
Echeburúa E, Báez C, Fernández-Montalvo J (1996) Comparative effectiveness of three thera-
peutic modalities in the psychological treatment of pathological gambling: long-term outcome.
Behav Cogn Psychother 24:51–72
Echeburúa E, Fernández-Montalvo J, Báez C (2000) Relapse prevention in the treatment of
pathological gambling: long-term outcome. Behav Ther 31:351–364
Echeburúa E, Fernández-Montalvo J, Báez C (2001) Predictors of therapeutic failure in slot-
machine pathological gamblers following behavioural treatment. Behav Cogn Psychother
29:379–383
Echeburúa E, González-Ortega I, Corral P, Polo-López R (2011a) Clinical gender differences
among adult pathological gamblers seeking treatment. J Gambl Stud 27:215–227
Echeburúa E, Gómez M, Freixa M (2011b) Cognitive-behavioural treatment of pathological
gambling in individuals with chronic schizophrenia. A pilot study. Behav Res Ther
49:808–814
El-Guebaly N, Mudry T, Zohar J, Tavares H, Potenza MN (2012) Compulsive features in
behavioural addictions: the case of pathological gambling. Addiction 107:1726–1734
Gooding P, Tarrier N (2009) A systematic review and meta-analysis of cognitive-behavioural
interventions to reduce problem gambling: Hedgings our bets? Behav Res Ther 47:592–607
92 Clinical Management of Gambling Disorder 1489
Grant JE, Odlaug BL (2012) Psychosocial interventions for gambling disorders. Increasing the
odds (vol 7). What clinicians need to know about gambling disorders. National Center for
Responsible Gaming, Washington, DC, pp 38–51
Grant JE, Donahue CB, Odlaug BL, Kim SW, Miller MJ, Petry NM (2009) Imaginal desensitiza-
tion plus motivational interviewing for pathological gambling: randomized controlled trial.
Br J Psychiatry 195:266–267
Grant JE, Odlaug BL, Schreiber LRN (2012) Pharmacological treatments in pathological gam-
bling. Br J Clin Pharmacol. doi:10.111/j.1365-2125.2012.04457.x
Griffiths MD, Barnes A (2008) Internet gambling: an online empirical study among student
gamblers. Int J Ment Health Addict 6:194–204
Hodgins DC, Holub A (2007) Treatment of problem gambling. In: Smith G, Hodgins DC,
Williams RJ (eds) Research and measurement issues in gambling studies. Elsevier, Amster-
dam, pp 372–397
Hodgins DC, Currie SR, el-Guebaly N (2001) Motivational enhancement and self-help treatments
for problem gambling. J Consult Clin Psychol 69:50–57
Hodgins DC, Toneatto T, Makarchuk K, Skinner W, Vincent S (2007) Minimal treatment
approaches for concerned significant others of problem gamblers: a randomized controlled
trial. J Gambl Stud 23:215–230
Hodgins DC, Currie SR, Currie G, Fick GH (2009) Randomized trial of brief motivational treatments
for pathological gamblers: more is not necessary better. J Consult Clin Psychol 77:950–960
Hollander E, Sood E, Pallanti S, Baldini-Rossi N, Baker B (2005) Pharmacological treatment of
pathological gamblers. J Gambl Stud 21:101–110
Jiménez-Murcia S, Aymanı́ N, Gómez-Peña M, Santamarı́a JJ et al (2012) Does exposure and
response prevention improve the results of group CBT for male slot machine pathological
gamblers? Br J Clin Psychol 51:54–71
Kessler RC, Hwang I, LaBrie R, Petukhova M, Sampson NA, Winters KC et al (2008) DSM-IV
pathological gambling in the National Comorbidity Survey Replication. Psychol Med
38:1351–1360
Ladouceur R, Walker M (1998) Cognitive approach to understanding and treating pathological
gambling. In: Bellack AS, Hersen M (eds) Comprehensive clinical psychology, vol 6. Elsevier,
Amsterdam, pp 587–601
Ladouceur R, Sylvain C, Boutin C, Lachance S, Doucet C, Leblond J, Jacques C (2001) Cognitive
treatment of pathological gambling. J Nerv Ment Dis 189:774–780
Ladouceur R, Sylvain C, Boutin C, Lachance S, Doucet C, Leblond J (2003) Cognitive treatment
of pathological gambling. Behav Res Ther 41:587–596
Ladouceur R, Lachance S, Fournier PM (2009) Is control a viable goal in the treatment of
pathological gambling? Behav Res Ther 47:189–197
Laplante DA, Braverman J (2010) El juego en Internet: situación actual y propuestas para la
prevención y la intervención. In: Echeburúa E, Becoña E, Labrador FJ (eds) El juego
patológico. Avances en la clı́nica y en el tratamiento. Pirámide, Madrid, pp 323–358
Lorains FK, Cowlishaw S, Thomas SA (2011) Prevalence of comorbid disorders in problem and
pathological gambling: systematic review and meta-analysis of population surveys. Addiction
106:490–498
McConaghy N, Blaszczynski A, Frankova A (1991) Comparison of imaginal desensitisation with
other behavioural treatments of pathological gambling. A two-to nine-year follow-up.
Br J Psychiatry 159:390–393
Melville CL, Davis CS, Matzenbacher DL, Clayborne J (2004) Node-link-mapping-enhanced
group treatment for pathological gambling. Addict Behav 29:73–87
Nelson SE, Kleschinsky JH, LaBrie RA, Kaplan S, Shaffer HJ (2010) One decade of self
exclusion: Missouri casino self-excluders four to ten years after enrolment. J Gambl Stud
26:129–144
Oei TPS, Raylu N, Casey L (2010) The effectiveness of group versus individual CBT programs for
problem gamblers: a randomized clinical trial. Behav Cogn Psychother 2010(38):233–238
1490 E. Echeburúa
Contents
93.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1492
93.2 The Clinic Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1492
93.2.1 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1493
93.2.2 Education and Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1496
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1497
Abstract
The National Problem Gambling Clinic is the first and only National Health
Service clinic (provider of free state medical treatment) designated to the
treatment of pathological gamblers from all over the UK.
The current prevalence of problem gambling in Great Britain is 0.9 %
according to the latest British Gambling Prevalence Survey (NatCen 2010).
This showed a 50 % increase since the previous survey of 2007 reported
a prevalence of 0.6 %.
Currently therefore, there are deemed to be at least half a million patholog-
ical gamblers in the country with as many more scoring on screening for at-risk
behaviors in relation to gambling (Natcen 2010).
Our clinic was set up by Dr. Henrietta Bowden-Jones as a direct result of the
public concerns at a time when the British government was planning to allow the
construction of several more casinos and when advertising gambling products
had become legal.
H. Bowden-Jones (*)
National Problem Gambling Clinic and Division of Brain Science, Imperial, London, UK
e-mail: [email protected]
N. Smith
National Problem Gambling Clinic, London, UK
e-mail: [email protected]
The idea behind the project was to provide patients with a gold standard,
evidence-based time-limited service providing specialist treatment delivered by
psychologists and psychiatrists.
We have now had over 3,000 referrals and own the largest problem gambling
database in Europe, and the amount of information collected has allowed us to
reach in-depth understanding of the clinical subtypes presenting.
93.1 Introduction
The National Problem Gambling Clinic is the first and only National Health Service
clinic (provider of free state medical treatment) designated to the treatment of
pathological gamblers from all over the UK.
The current prevalence of problem gambling in Great Britain is 0.9 %
according to the latest British Gambling Prevalence Survey (NatCen 2010).
This showed a 50 % increase since the previous survey of 2007 reported a prev-
alence of 0.6 %.
Currently therefore, there are deemed to be at least half a million pathological
gamblers in the country with as many more scoring on screening for at-risk
behaviors in relation to gambling (Natcen 2010).
Our clinic was set up by Dr. Henrietta Bowden-Jones as a direct result of the public
concerns at a time when the British government was planning to allow the con-
struction of several more casinos and when advertising gambling products had
become legal.
The idea behind the project was to provide patients with a gold standard,
evidence-based time-limited service providing specialist treatment delivered by
psychologists and psychiatrists.
We have now had over 3,000 referrals and own the largest problem gambling
database in Europe, and the amount of information collected has allowed us to
reach in-depth understanding of the clinical subtypes presenting.
The types of gambling that patients are involved in are also recorded.
The most frequent activities are sports betting and electronic roulette machines,
called fixed odds betting terminals in the UK. Internet gambling is increasing and
about a third of our patients are now doing this regularly, sometimes to the
exclusion of land-based gambling following a migration of habit.
Personal and psychiatric histories are also collected in an attempt to link activity
and experience to outcomes; this is particularly relevant when we look at early
adverse events in childhood and their predisposing negative impact on future
illness.
Our patients tend to be male and aged between 30 and 40 years old, and most will
be in either full-time or part-time employment.
93 The National Problem Gambling Clinic 1493
Many, 84 %, have committed illegal acts to fund their gambling at some point in
their lives.
Twenty percent have lost their jobs due to gambling, and 50 % have lost
significant relationships such as their marriage due to gambling.
Many of the patients we see are depressed or anxious at the time of assessment
and about a third have lifelong comorbid presentations, at times with severe and
enduring mental illnesses such as schizophrenia.
Our approach is to treat everyone apart from the acutely psychotic patients, but
even then, we advise on the best antipsychotic and agree to delay treatment
temporarily so we do not turn people away as our strength is in understanding the
complexities of dual diagnosis presentations.
The yearly funding for the treatment of what are now over 700 referrals a year
comes in several ways, but the main bulk of the money, about £330,000, is received
from the Responsible Gambling Trust, a government charity set up to distribute
voluntary donations from the gambling industry to avoid a compulsory levy based
on earnings.
Other funds come from government working parties attended by the Director of
the clinic, court reports written by forensic psychiatrists trained at the clinic in
pathological gambling expertise, industry training days, some Employee Assistance
work, and lecturing fees. Further funds come via the successful research grant
applications that may free up the clinical time of some researchers to contribute in
clinical time for the access to problem gamblers in research projects of which there
are many.
Although cognitive behavioral therapy is deemed to be a highly effective way of
treating problem gamblers, we do offer other interventions such as a Money
Management assistance service which in the UK is funded by the banking world
to assist people with mental health issues. This service provides a session of
psychoeducation around managing finances but also individual help with setting
up repayment plans.
Another integral part of the clinic is the assistance we offer to relatives and
carers of problem gamblers. Often, it will be an elderly mother who has read about
us in the newspapers and has referred her son for treatment. At other times, spouses
of gamblers are brought into clinic once the patient begins therapy. The support we
offer to carers is also manualized and linked to psychological outcomes to deter-
mine the usefulness of the intervention, but we are more relaxed about our data
collection as we really do want to help the individuals feel more supported in their
suffering.
93.2.1 Treatment
Pathological gamblers who attend our clinic are offered a 90-min face-to-face
assessment with a clinician. This assessment covers current and previous gambling
history including first gambling experiences and emotional links to the gambling,
for example, some patients only spent time with their father in childhood when they
1494 H. Bowden-Jones and N. Smith
were gambling. This has important implications for the right treatment approach as
we do offer some more psychodynamic treatment for some patients who need
a more interpretative approach. A history of medical and psychiatric difficulties is
also taken along with any history of parental gambling problems. A brief personal
life history is also obtained. Clients also complete a comprehensive battery of
questionnaires including gambling and mental health screens. All assessments are
discussed in a weekly multidisciplinary team (MDT) meeting where decisions are
made regarding treatment packages offered.
The basic treatment offered by the clinic is an eight-session cognitive behavioral
therapy treatment developed from work conducted by Nancy Petry (2005; Petry
et al. 2006). The treatment is manualized in the sense that there are a set number of
sessions and each session topic is guided by a specific handout. Within this
protocol, therapists are expected to deliver the treatment flexibly in order to best
meet the client’s individual needs. Homework is an essential component of this
treatment, with each session topic having comprehensive handouts including home-
work tasks. Clients are informed that homework is essential to change. Topics
covered include stimulus control, rewards, coping with cravings, increasing pleas-
ant activities, trigger management, understanding lapses, coping with gambling
thoughts, and managing lapses. The treatment includes a strong psychoeducational
component where clients are socialized to an addiction model of problem gambling,
drawing on research from scanning studies to highlight commonalities with drug
and alcohol addiction. This serves to “normalize” the problem and reduce confusion
and the degree of personal guilt and judgment that clients often present with.
The service is guided by the “pathways model” of problem gambling
(Blaszczynski and Nower 2002). This seminal paper suggested that three levels
of severity of difficulties can be observed in problem gamblers. These levels relate
to different etiological factors for problem gambling and increasing levels of
associated and comorbid difficulties, with each level requiring more intensive
treatment. In the MDT, a decision is made as to whether the individual assessed
is of a “lower,” “moderate,” or “higher” severity, based on criteria derived from the
pathways model and from internal audits of client characteristics.
Patients who present at the “lower” end of the severity spectrum are offered
a brief intervention. This comprises the provision of an 85-page self-help work-
book, with four individual sessions with a therapist. The workbook contains all
handouts from the eight-session CBT treatment, with guided self-help exercises
included.
Clients assessed as being of “moderate” severity are invited to attend the eight-
session manualized treatment delivered in a group format. These sessions are of
90 min length and up to 20 individuals are invited to each group. Sessions involve
group feedback of progress and homework and delivery of session topic content and
finish with reflections on the session and homework for the coming week. Groups
are strongly encouraged by the service; gathering with other individuals has the
effect of normalizing a problem that often presents in highly isolated individuals.
Clients assessed as being of “higher” severity will receive the eight-session
group CBT program plus additional individual CBT sessions with a therapist.
93 The National Problem Gambling Clinic 1495
If individuals are happy with the treatment they received, they are invited to
attend the Aftercare Group. This is held once a month and patients who complete
treatment can attend for as long as they wish. The Aftercare Group is an open-
forum group; facilitators start by setting an agenda of topics that the attendees
wish to discuss. These topics may involve positive or negative experiences of
recovery. The conversations are then steered by the facilitators to cover the topics
in the manualized treatment. The group serves as a reminder for individuals of
techniques and strategies learned in the CBT sessions they attended. Members are
invited to support each other within this group, but preferably by suggesting
techniques from the manualized intervention.
Because the clinic is the only one, it has a significant role in British society that goes
far beyond its remit to treat problem gamblers.
Here is a list of activities we believe a National Clinic needs to attend to as well
as deliver high-quality treatment:
• Any time a newspaper article or other media program is planned, the clinic will
be asked to contribute to it in light of its expertise and perspective.
• The aim for us is to remain as politically neutral as possible while still enforcing
what we believe are fundamental societal needs to protect gamblers, such as
adequate self-exclusion policies, the protection of children and young people
from the proliferation of gambling products, the need for more stringent laws
around advertising gambling activities, and ensuring enough attention is paid to
the quality of treatment services at a national level when they fall outside the
remit of the NHS.
• Peer-reviewing journals.
• Training the next generations of psychiatrists and psychologists.
• Maintaining links both nationally and internationally in the field writing articles
on case studies and disseminating knowledge about problem gambling to pro-
fessional groups (Bowden-Jones and Clark 2011).
• Lecturing to medical students and other mental health professionals on the topic
of problem gambling.
• Teaching the general public about the issues via open lectures and invited talks.
• Facilitating the work of the neurobiological research group currently neuroim-
aging the gamblers.
All of the above need to be addressed and constantly updated if we are to
continue leading the way in the UK.
Our hope is that in the future, the State will recognize the need to fund
problem gambling treatment throughout the UK and include pathological gam-
bling in the illnesses it recognizes. The need for smaller clinics set up to be
linked up to our central “hub” is a cost-effective one that we will be working on
for years to come.
93 The National Problem Gambling Clinic 1497
References
Blaszczynski A, Nower L (2002) A pathways model of problem and pathological gambling.
Addiction 97:487–499
Bowden-Jones H, Clark L (2011) Pathological gambling: a neurobiological and clinical update. Br
J Psychiatry 199(2):87–89
Petry NM et al (2005) Pathological gambling. APA Publishers
Petry NM et al (2006) Cognitive behavioural therapy for pathological gamblers. J Consult Clin
Psychol 74(3):555–567
Wardle H et al (2011) British Gambling Prevalence Survey 2010. National Centre for Social
Research
Internet Addiction
94
Sophia Achab, Olivier Simon, Stéphanie Mu €ller, Gabriel Thorens,
Giovanni Martinotti, Daniele Zullino, and Yasser Khazaal
Contents
94.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1500
94.2 Epidemiological Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1501
94.3 Internet Addiction Screening Tools . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1502
94.4 IAD Determinants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1503
94.5 IAD and Related Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1504
94.6 What Is Addictive About the Internet? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1505
94.7 Treatment of Internet Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1507
94.7.1 Nonspecific Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1507
94.7.2 Treatment of Comorbidities and Pharmacological Approaches . . . . . . . . . . . . . 1510
94.7.3 Cognitive-Behavioral Approach for Family Members and Significant
Others . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1510
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1510
S. Achab
Division of Addictology, Department of Mental Health and Psychiatry, Geneva University
Hospital and University of Geneva, Geneva, Switzerland
EA 481 “Neurosciences Laboratory”, Franche–Comté University, Besançon, France
O. Simon • S. M€uller
Centre du jeu Excessif, Community Psychiatry Department, Lausanne University Hospital,
Lausanne, Switzerland
G. Thorens • D. Zullino • Y. Khazaal (*)
Division of Addictology, Department of Mental Health and Psychiatry, Geneva University
Hospital and University of Geneva, Geneva, Switzerland
e-mail: [email protected]; [email protected]
G. Martinotti
Department of Neuroscience and Imaging, Institute of Psychiatry “G. d’Annunzio”, University of
Chieti-Pescara, Chieti, Italy
Abstract
This paper investigates the concept of Internet addiction disorder (IAD).
The phenomenon of excessive Internet use is increasingly becoming a public health
issue. Increasing research evidence indicates common clinical, neurobiological,
and neuroimaging findings between IAD and addictive disorders. Different clinical
descriptions and research findings suggest however the existence of various types of
Internet addictions (i.e., gaming, cyberpornography, etc.). The Internet could be
then rather the facilitating vector of an addiction to a given behavior linked to
specific stimuli and operant conditioning mechanisms.
As an attempt to increase understanding and knowledge related to IAD,
a number of screening tools were studied. Various forms of excessive Internet
use or IAD seem also associated with a number of coping strategies as well as
personality characteristics and possible comorbid psychiatric disorders.
In spite of a number of clinical treatment programs dedicated to IAD, there
are still limited publications on the efficacy of such treatments. The few existing
ones mostly relate to interventions inspired by cognitive-behavioral therapy.
The determinants, the evolution of the possible IAD-related disorders, as well
as the validation of adequate treatments are yet to be clearly established.
Longitudinal studies using large and representative samples are required.
94.1 Introduction
One way to assess the stability of IAD as a disorder, and determine its prevalence, is to
screen for it in the general population and specific samples. Lack of epidemiological
studies and adult samples limits our understanding of the phenomenon. The major
obstacle that the scientific community has faced in the last decade is the lack of validated
and consensual screening tools. Prevalence rates of IAD are reported to vary from 2.7 %
(Dong et al. 2010) to 20.9 % (Kormas et al. 2011) for 10–30-year-old Internet users.
Similarly, they range from 3 % to 36.8 % (Zanetta Dauriat et al. 2011) for 10–54-year-
old online video games. Furthermore, variation between countries (Durkee et al. 2012;
Sun et al. 2012) suggests cultural factors may influence Internet use habits.
This increases the complexity of evaluating IAD.2
1
For further details, see “What Is Addictive in the Internet” section.
2
For epidemiological data from the USA, Asia, and Europe, see Moreno et al. (2011) and Durkee
et al. (2012).
1502 S. Achab et al.
The differences in IAD prevalence are due to differences in the samples studied
but also to the variety of the assessment tools used. In a 28-month period (January
2010 to April 2012), 37 articles were published and indexed in PubMed, containing
14 different screening tools (Achab et al. 2012). The most frequently used (39 %) is
the 20-item IAT (Young 1996). However, using the same tool (e.g., IAT), and
focusing on similar student samples, variation in prevalence rates was still found
(2.7–20.9 %). Gender characteristics and differences in IAD cutoff scores contrib-
ute to these disparities. Furthermore, variations on the focus of interest (i.e., general
Internet overuse, video games, Internet-based sexual addiction, etc.) also affect
prevalence figures. Finally, selection bias was found, with two thirds of the studies
involving nonrepresentative samples of students.
These findings are supported by a recent review on PIU using the Strengthening
the Reporting of Observational Studies in epidemiology (STROBE) criteria.
Particularly Moreno et al. (2011) found weak internal and external validity of
the concept when using epidemiological data from similar populations (i.e., US
adolescents and college students).
A number of IAD screening tools are available. Screening tools have been found to
strongly correlate with each other and also with self-reported Internet addiction
(Achab et al. 2011; Widyanto et al. 2011). The theoretical construct underlying the
development of IAD screening tools followed different models. (a) The addiction
model is the basis for some tools that are adapted from DSM IV substance
dependence criteria. For these tools, the word substance was substituted with
online activity or online video gaming (DSM Adapted Scale for online video
gaming (DAS) (Achab et al. 2011). (b) The impulse control disorder model is
the basis for other tools adapted from DSM pathological gambling criteria [the
Young Diagnostic Questionnaire (YDQ) and Young Internet Addiction Test (IAT)]
(Moreno et al. 2011). Other tools were inspired by the (c) cognitive and behavioral
PIU model (Davis 2001). This defines PIU as a four-dimensional entity consisting
of diminished impulse control, loneliness/depression, social comfort, and distrac-
tion (Davis’ Online Cognition Scale OCS) (Moreno et al. 2011). (d) The PIU
behavioral addiction model is the basis for the Compulsive Internet Use Scale
(CIUS) (Meerkerk et al. 2009). It also informs the Griffith Addiction Components
Criteria (i.e., salience, mood modification, tolerance, withdrawal, relapse, and harm)
(Moreno et al. 2011).3,4 Other attempts to define PIU have included the amount of
time spent online. However, this is not considered to be a necessary condition for
IAD (King et al. 2013).
3
Beard (2005) identifies the theoretical concepts underlying the IA assessment tools in his review.
4
For a detailed review of Internet addiction assessment tools, translated versions, and further
possible improvements, see King et al. (2013).
94 Internet Addiction 1503
The Internet provides a new lifestyle for the population by providing immediate and
extensive information. It also enables interaction with others and/or software through
a wide range of leisure activities. Individuals can interact in an unlimited and
“anonymous” way. However, several negative aspects balance these positive ones.
Particularly, the Internet can be overused as a maladaptive coping strategy. It may
become a “vector of social reward,” source of “displacement from offline to online
social interactions” or “compensation strategy” for life difficulties (Shen and Williams
2011). Some aspects of psychopathology are associated with problematic Internet use
such as personality traits and environment characteristics (Shen and Williams 2011).
Risk factors contributing to the development of PIU have recently been
investigated (Tsitsika et al. 2011). Data on European college students suggests
that young males who lack emotional and psychological support are more likely to
demonstrate PIU (Durkee et al. 2012). Psychoticism was also linked to excessive
Internet use in a recent study on Greek adolescents (Fisoun et al. 2012).
In addition to sociodemographic and psychological determinants, neuroimaging
studies have been conducted. These demonstrate similarities between IAD and
substance abuse disorders, suggesting there may be common neural substrates.
Cue-induced craving for online activities, for example, has shown the same func-
tional cerebral images as substance dependence (Ko et al. 2009). Similarly, reduced
dopamine levels and glucose metabolism have been found in cerebral regions
associated with impulse control and reward processing (Schoenbaum et al. 2003).
Enhanced reward sensitivity and reduced loss sensitivity have also been reported
(Dong et al. 2011a). These neural findings in IAD subjects give weight to the
addictive spectrum theory.
In comparison with controls, people with IAD show impaired executive func-
tions. This includes longer reaction times and a greater number of errors in a color-
word Stroop task (Dong et al. 2011b). Poorer cognitive control has been reported
(Dong et al. 2010). Delayed strategy learning is possibly more marked than in other
addictive behaviors (Sun et al. 2009). However, compared to drug abusers and
pathological gamblers, people with IAD demonstrate better response inhibition
(Sun et al. 2009). Decision-making in college students has been found to improve
in IAD subjects during a repetitive risky condition task (IGT).5 This is reported to
5
Iowa Gambling Task (IGT) tests the somatic marker hypothesis postulating that biasing signals,
arising from neural emotional circuitry, influence reasoning. (Bechara and Damasio 2002).
1504 S. Achab et al.
Excessive Internet use has been reported to correlate with numerous conditions
including impaired social and professional functioning, some personality traits, and
psychiatric disorders.
Family dysfunction or problems, poor academic performance, and limited
hobbies have been found to be more frequent for teenagers with IAD (Huang and
Leung 2009; Tsitsika et al. 2011). In adult samples IAD included a self-perceived
negative impact on family, partners, work, emotional state, hobbies, sleep quality,
friendships, and health (Achab et al. 2011; Bergmark et al. 2011). However, no
longitudinal data currently exists on this. Comorbid psychopathology with PIU has
received some scientific interest. Two recent reviews (Ko et al. 2012; Carli
et al. 2013) summarize the published findings, the majority of which use Asian
samples. In the cited studies, PIU was significantly associated with depression,
ADHD, anxiety, obsessive-compulsive symptoms, and hostility/aggression.
Surprisingly, PIU was not found to be correlated with social phobia (Carli
et al. 2013). The strongest link was found between PIU and depression
(Carli et al. 2013) (major depressive disorder, dysthymic disorder, and suicidal
ideation). It is possibly linked to Internet-based perceived social support, escapism,
achievement, and sense of control (Ko et al. 2012). The clinical results are
94 Internet Addiction 1505
consistent with the common biological vulnerability found within depression and IAD
(i.e., transporting serotonin polymorphism) (Wrase et al. 2006). The literature review
also highlighted more ADHD symptoms in children and adults with IAD. Furthermore,
a tendency to become addicted to the Internet was found for adolescents with ADH-
D. This could be explained by some Internet characteristics (e.g., rapid response, easier
and delayed interpersonal relationships, immediate reward, multiple stimulating tasks).
Such characteristics may serve to reduce boredom and provide stimulation and a sense
of efficiency. However, the contribution of these potential gains is yet to be established.
Methylphenidate showed possible efficacy in treating coexisting IAD and ADHD, in
favor of possible common biological substrate (Ko et al. 2012). PIU was also associated
with the presence of a hostility trait. Internet could be a means of expressing this
personality trait or escaping from resulting interpersonal difficulties in the real world
(Ko et al. 2012). An association was found between social anxiety symptoms and
PIU. This is proposed to be due to online social support and avoidance of face-to-face
interactions, provided by the Internet (Ko et al. 2012). One study (Yen et al. 2012)
showed that symptoms decreased during online social interactions in comparison with
offline interactions. This suggests that progressive exposure to social situations could
be a suitable psychotherapeutic approach. Surprisingly in a recent systematic review of
publications, no correlation has been found between PIU and social phobia, after
controlling for confounding variables6 (Carli et al. 2013). The cooccurrence of
IAD and substance use disorders has been reported in some studies involving adoles-
cents. However, the link remains unclear (problematic behavioral model, common
neurocognitive substrates) and needs further research (Ko et al. 2012).
In summary, the causality and the evolution of disorders related to IAD are yet to
be clearly established. Longitudinal studies using large and representative samples
are required.
6
For a detailed review, see Carli et al. (2013).
1506 S. Achab et al.
(hardware) are the first-order vectors (the carrier of a product). Hardware has
different characteristics which influence how or when a product can be used. This
may be constant (smartphone), difficult to access (expensive Internet café in some
countries), high-speed connection or not, etc. The software (online games, social
networks) are the second-order vector.
If we want to understand what is addictive about the Internet, we have to identify
the addictive product on the Internet. This product may be delivered in a more or
less efficient manner. Using our example of tobacco consumption, some pertinent
questions are as follows: Is it easy and cheap to find tobacco? How should it be
consumed? (in a cigarette or chewed?) But these questions are relevant only if
tobacco contains nicotine; without nicotine, no addiction process is possible.
To understand what is addictive about the Internet, specific stimuli that are
available online need to be studied. Causes of behavioral addictions are now
understood to be salient stimuli that trigger the reinforcement process (via the
mesolimbic dopaminergic system). This leads to compulsive and automatic behav-
iors (Walter et al. 2005). Rewards generated by substance abuse are triggered by the
neurobiological actions of the substance. This leads to an increase in the extracel-
lular concentration of dopamine in the nucleus accumbens (Volkow and Li 2004).
Increases in dopamine can also be achieved by nonpharmacological stimuli such as
monetary rewards (Izuma et al. 2008). Similarly, this effect can be created by
sexual stimuli, social acceptance, fairness, cooperative social interactions
(Tabibnia and Lieberman 2007), social hierarchies, or humor. Internet software
(the first-order vector) can contain varying amounts of salient stimuli. The intuitive
idea that gaming or social networking software are more addictive than work
software is true when looking at the amount of salient stimuli in these programs.
To be addictive, the presence of salient stimuli alone is not enough. The schedule
of the rewards in terms of amount and frequency is crucial to the addictiveness of
any stimuli. A parallel with gambling is useful here: The addictive properties of slot
machine (fast-paced rewards, delivered in a reinforcing manner) are greater than
those of a once-weekly lottery game, with low gain probability (Griffiths 1999).
One theory that explains the addictive properties of Internet contents is operant
conditioning (Skinner 1977). According to this theory, the likelihood of a specific
behavior is increased or decreased through positive or negative reinforcement.
Different types of operant conditioning exist, but the vast majority, found in
Internet addictive components, are variable-ratio schedules: These arise when
a behavior is reinforced after an unpredictable number of responses. Variable
reinforcement schedules create a high steady rate of responding and are efficient
for maintaining a behavior. This type of schedule is mostly seen in online role-
playing games where repeated actions by an avatar can trigger a variable reward.
An example is the repeated action of killing enemies in games. In World of
Warcraft, the most popular massive online role-playing game, most of the actions
involve defeating monsters. When a monster is defeated, the avatar gains a virtual
reward. There are similarities, here, with the reward schedule used in slot machines.
The avatar has a small chance of winning a rare item such as a powerful weapon.
Winning this weapon can be compared to winning the jackpot in a slot machine, as
94 Internet Addiction 1507
the probability of winning modest rewards (1X your bet in slot machines or a
“standard weapon”) is higher. Social network programs such as Facebook use the
same mechanism. The whole structure of Facebook promotes certain behaviors or
actions: posting comments, videos, and pictures and obtaining a reward (a number
of friends answering to this post or liking this post). The number of comments or
likes varies in terms of time and quantity. As mentioned before, the content of these
comments is salient stimuli (positive social interactions, social acceptance).
In conclusion, the distinction between vectors and products helps us to be more
accurate when defining an Internet addiction. Internet is then probably a vehicle of
possible addictive products. The identification of specific stimuli and operant
conditioning mechanisms present in the Internet product will predict their addictive
risks. It is therefore not surprising that the contents of MMORPGs (first-order
vector) are one of the most addictive products on the Internet as these contain
numerous salient stimuli. Furthermore, rewards are mainly delivered on a
variable-ratio schedule.
Today there are many specialized clinic treatment programs which exist mainly in
Asian countries. These are also found in Europe and English-speaking countries.
The programs are often developed in association with dedicated gambling addiction
programs. There are however limited publications on the efficacy of such
treatments. The few existing publications (Khazaal et al. 2012) primarily relate
to interventions inspired by cognitive-behavioral therapy (for details, see
Table 94.1). Pharmacotherapy in Internet addiction has also known few scientific
interest (Achab, Bertolini and Karila 2012).
A preliminary meta-analysis (Winkler et al. 2013) highlights the limited number
of existing controlled studies. Findings highlighted a number of limitations such as
absence of clear definition for the disorder treated and limitations of the instruments
used. Moreover, there are omissions in the description of participants and inclusion
processes. A further difficulty is linked to the wide diversity of Internet-related
disorders. The Internet may amplify another primary addiction (sexual behaviors,
purchasing, gambling). It can also be integral to the structural characteristics of
a primary addiction (MMORPG-type video games). The vast majority of studies
describe interventions for people presenting with a MMORPG addiction.
Currently, the studies that have been published are based upon current techniques
for addiction treatment. These include self-support concepts adapted from the
12 steps model, rehabilitation programs in residential setting, the motivational
approach, cognitive-behavioral techniques to identify triggers and cognitive distor-
tions, and psychoeducation for emotions (King et al. 2011, 2012). It is not often clear
1508
Table 94.1 Psychosocial treatment for Internet addiction: open-label studies and controlled trials
Publication Assessment Method Population Treatment Outcome Effect size
Bai and Chinese addiction Open-label College students Multilevel counseling Reduction of Internet IA: 1.45
Fan (2007) scale – revised study N ¼ 48 Age: m ¼ 19 model: CBT, social addiction symptoms
China 16.7 % women competence training,
self-control strategies,
communication skills
(in group)
Cao et al. YDQ/Chinese addiction Open-label 2,620 students from four CBT Reduction of emotional IA: 1.09
(2007) scale revised/screening for study N ¼ 57 middle schools of Changsha symptoms
China childhood related anxiety City were surveyed using Reduction of addiction Anxiety: 0.78
disorders YDQ symptoms
Following clinical interview,
students who met IA criteria
were recruited
Du et al. Beard’s Diagnostic Randomized School students Multilevel school-based Reduction of Internet use and Posttreatment
(2010) Questionnaire controlled Age: m ¼ 12–17 intervention involving anxiety IA: Cohen’s
China trial N ¼ 56 Met diagnostic criteria 8 sessions of group-based d ¼ 1.08
according to Beard’s CBT Improvement in time Follow-up
Diagnostic Questionnaire management (6 months) IA:
Treatment gains observed at Cohen’s
6 months follow-up d ¼ 1.35
Kim Korean Internet addiction Controlled University student Group counseling Reduction of Internet Not reported
(2008) trial N ¼ 25 addiction symptoms
Korea Volunteers from a sample of Reality therapy (5 weeks) Increase in self-esteem
32 Internet addicts who were
screened
Lanjun Internet addiction scale, Open-label College students 45.71 % Multilevel counseling Reduction of anxiety IA: 2.98
(2009) State-trait anxiety study N ¼ 70 women model: CBT + sport Reduction of addiction Anxiety: 0.43
China inventory for adults symptoms
S. Achab et al.
94
Li and Dai Chinese Internet addiction Controlled Adolescents 10.53 % women CBT (individual) Reduction of addiction IA: 1.46
(2009) scale trial N ¼ 76 symptoms
China Reduction of anxiety,
depression, and compulsions
Orzack Orzack Time Intensity Open-label Men age: m ¼ 26–59 Multilevel counseling Better quality of life Time: 0.27
et al. Scale (OTIS) study N ¼ 32 Involved in Internet-related model: CBT, readiness to
(2006) US Beck Depression Inventory problematic sexual behavior change, motivational Reduction in depressive Depression: .35
Internet Addiction
whether individual or group interventions have been used. When Internet use arises as
part of another addiction, the clinical approach focuses on that domain (see chapters
VII-3, VII-6, VII-8). There has also been an emergence of Internet-based therapeutic
programs (Su et al. 2011). These can be a suitable gateway to care for intensive
electronic media users (Zematten et al. 2010).
Two pilot studies have investigated methylphenidate and bupropion for people with
a MMORPG addiction. At posttest (6–8 weeks), a reduction in the length of gaming
sessions in addition to a reduction in cue-induced brain activity was observed (Han
et al. 2009, 2010). However, the study on methylphenidate included a population
with ADHD and also included a high dropout rate. The study on bupropion
excluded subjects with a comorbid axis I diagnosis. In practice, so far, no medica-
tion has received accreditation for the treatment of behavioral addictions. In clinical
practice, the indication of pharmacotherapy is then based on the presence of
possible comorbid disorders such as symptoms anxiety or mood disorders
(Ko et al. 2012).
To our knowledge, a single randomized study has been published for family
approach of Internet addictions (Du et al. 2010). The study focused on young
adult online players. A multimodal behavioral intervention for groups was evalu-
ated. The program emphasized communication techniques and management of
triggers, alongside parents monitoring their children’s emotions. It also included
problem-solving techniques and practical advice for parents on limiting home
Internet use. In addition, an electronic media awareness program for relevant school
professionals was implemented. When compared to the control condition, a signif-
icant reduction in Internet use was observed at posttest and maintained at 6 months
follow-up. A lasting reduction in anxiety and improved time management were also
observed.
References
Achab S, Nicolier M et al (2011) Massively multiplayer online role-playing games: comparing
characteristics of addict vs non-addict online recruited gamers in a French adult population.
BMC Psychiatry 11:144
94 Internet Addiction 1511
Izuma K, Saito DN, Sadato N (2008) Processing of social and monetary rewards in the human
striatum. Neuron 58(2):284–294
Khazaal Y, Xirossavidou C, Khan R, Edel Y, Zebouni F, Zullino D (2012) Cognitive-behavioral
treatments for “Internet Addiction”. Open Addict J M5(Suppl 1):30–35
Kim J (2008) The effect of a R/T group counseling program on the internet addiction level and
self-esteem of internet addiction university students. Int J Real Ther 27:4–12
King DL, Delfabbro PH, Griffiths MD, Gradisar M (2011) Assessing clinical trials of internet
addiction treatment: a systematic review and CONSORT evaluation. Clin Psychol Rev
31:1110–1116
King DL, Delfabbro PH, Griffiths MD, Gradisar M (2012) Cognitive behavioral approaches to
outpatient treatment of internet addiction children and adolescents. J Clin Psychol
68(11):1185–1195
King DL, Haagsma MC et al (2013) Toward a consensus definition of pathological video-gaming:
a systematic review of psychometric assessment tools. Clin Psychol Rev 33(3):331–342
Ko CH, Liu GC et al (2009) Brain activities associated with gaming urge of online gaming
addiction. J Psychiatr Res 43(7):739–747
Ko CH, Hsiao S et al (2010) The characteristics of decision making, potential to take risks, and
personality of college students with internet addiction. Psychiatry Res 175(1–2):121–125
Ko CH, Yen JY et al (2012) The association between internet addiction and psychiatric disorder:
a review of the literature. Eur Psychiatry 27(1):1–8
Koh YS (2007) Development and application of K-scale as diagnostic scale for Korean internet
addiction. International symposium on the counseling and treatment of youth internet addic-
tion. National Youth Commission, Seoul
Kormas G, Critselis E et al (2011) Risk factors and psychosocial characteristics of potential
problematic and problematic internet use among adolescents: a cross-sectional study. BMC
Public Health 11:595
Kraut R, Patterson M et al (1998) Internet paradox. A social technology that reduces social
involvement and psychological well-being? Am Psychol 53(9):1017–1031
Lanjun Z (2009) The applications of group mental therapy and sport exercise prescriptions in the
intervention of internet addiction disorder. Psychol Sci (China) 32:738–741
Le Bihan D, Mangin JF et al (2001) Diffusion tensor imaging: concepts and applications. J Magn
Reson Imaging 13(4):534–546
Li G, Dai XY (2009) Control study of cognitive-behavior therapy in adolescents with internet
addiction disorder. Chin Ment Health J 23:457–470
Meerkerk GJ, Van Den Eijnden RJ, Vermulst AA, Garretsen HF (2009) The Compulsive Internet
Use Scale (CIUS): some psychometric properties. Cyberpsychol Behav 12(1):1–6
Moreno MA, Jelenchick L et al (2011) Problematic internet use among US youth: a systematic
review. Arch Pediatr Adolesc Med 165(9):797–805
Orzack MH, Voluse AC, Wolf D, Hennen J (2006) An ongoing study of group treatment for
men involved in problematic internet-enabled sexual behavior. Cyberpsychol Behav
9:348–360
Schoenbaum G, Setlow B et al (2003) Encoding predicted outcome and acquired value in
orbitofrontal cortex during cue sampling depends upon input from basolateral amygdala.
Neuron 39(5):855–867
Shek DT, Yu L (2012) Internet addiction phenomenon in early adolescents in Hong Kong. Sci
World J 2012:104304
Shen C, Williams D (2011) Unpacking time online: connecting internet and massively multiplayer
online game use with psychosocial well-being. Commun Res 38(1):123–149
Skinner BF (1977) The experimental analysis of operant behavior. Ann N Y Acad Sci
291:374–385
Su W, Fang X, Miller JK, Wang Y (2011) Internet-based intervention for the treatment of online
addiction for college students in China: a pilot study of the health online self-helping center.
Cyberpsychol Behav Soc Netw 14(9):497–503
94 Internet Addiction 1513
Sun P, Johnson CA, Palmer P, Arpawong TE, Unger JB, Xie B, et al. (2012) Concurrent and
Predictive Relationships Between Compulsive Internet Use and Substance Use: Findings from
Vocational High School Students in China and the USA. Int J Environ Res Public Health
9(3):660–673
Sun DL, Chen ZJ et al (2009) Decision-making and prepotent response inhibition functions in
excessive internet users. CNS Spectr 14(2):75–81
Tabibnia G, Lieberman MD (2007) Fairness and cooperation are rewarding: evidence from social
cognitive neuroscience. Ann N Y Acad Sci 1118:90–101
Tonioni F, D’Alessandris L et al (2012) Internet addiction: hours spent online, behaviors and
psychological symptoms. Gen Hosp Psychiatry 34(1):80–87
Tsitsika A, Critselis E et al (2011) Determinants of internet addiction among adolescents: a case-
control study. Sci World J 11:866–874
Volkow ND, Li TK (2004) Drug addiction: the neurobiology of behavior gone awry. Nat Rev
Neurosci 5(12):963–970
Walter H, Abler B, Ciaramidaro A, Erk S (2005) Motivating forces of human actions. Neuroim-
aging reward and social interaction. Brain Res Bull 67(5):368–381
Widyanto L, McMurran M (2004) The psychometric properties of the internet addiction test.
Cyberpsychol Behav 7(4):443–450
Widyanto L, Griffiths MD et al (2011) A psychometric comparison of the internet addiction test,
the internet-related problem scale, and self-diagnosis. Cyberpsychol Behav Soc Netw
14(3):141–149
Winkler A, Dörsing B, Rief W, Shen Y, Glombiewski JA (2013) Treatment of internet addiction:
a meta-analysis. Clin Psychol Rev 33:317–329
Wrase J, Reimold M et al (2006) Serotonergic dysfunction: brain imaging and behavioral
correlates. Cogn Affect Behav Neurosci 6(1):53–61
Yellowlees PM, Marks S (2007) Problematic internet use or internet addiction? Comput Hum
Behav 23:1447–1453
Yen JY, Yen CF et al (2012) Social anxiety in online and real-life interaction and their associated
factors. Cyberpsychol Behav Soc Netw 15(1):7–12
Young KS (1996) Internet addiction: the emergence of a new clinical disorder. Cyberpsychol
Behav 1(3):237–244
Young KS (2007) Cognitive behavior therapy with internet addicts: treatment outcomes and
implications. Cyberpsychol Behav 10:671–679
Young KS, Rogers RC (1998) The relationship between depression and internet addiction.
Cyberpsychol Behav 1(1):25–28
Zanetta Dauriat F, Zermatten A et al (2011) Motivations to play specifically predict excessive
involvement in massively multiplayer online role-playing games: evidence from an online
survey. Eur Addict Res 17(4):185–189
Zematten A, Jermann F, Khazaal Y, Zullino D, Bondolfi G (2010) Traiter l’addiction aux jeux de
hasard et d’argent: un programme internet. Inf Psychiatr 86:753–757
Zhou Y, Lin FC et al (2011) Gray matter abnormalities in Internet addiction: a voxel-based
morphometry study. Eur J Radiol 79(1):92–95
Internet Gaming Addiction: The Case of
Massively Multiplayer Online Role-Playing 95
Games
Contents
95.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1516
95.2 Massively Multiplayer Online Role Playing Games (MMORPGs) . . . . . . . . . . . . . . . . . . 1517
95.2.1 Structural Characteristics of MMORPGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1517
95.2.2 Psychological Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1518
95.2.3 Neurobiological Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1520
95.2.4 Treatment of MMORPG Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1522
95.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1523
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1524
Abstract
Internet gaming disorder is one of the main types of Internet-related disorders.
Recently, and despite inconsistencies in classification and limited data regarding
the etiology of the condition, Internet gaming disorder has been included in
Sect. 3 (research appendix) of the DSM-5. The focus of the current chapter was
the dysfunctional involvement in a specific type of video game which has some
inherent characteristics reinforcing its addictive nature: Massively Multiplayer
Online Role-Playing Games (MMORPGs). MMORPGs are indeed one of the
most recent and popular types of video games played worldwide, and problematic
and uncontrolled involvement in playing MMORPGs is the most frequently
reported activity by people seeking help for an Internet-related problem. In this
chapter, we first described the specific structural characteristics of MMORPGs
95.1 Introduction
There is growing evidence to support the claims that the use of the Internet can
become dysfunctional and cause negative impact in daily living and has given birth to
the construct of “Internet addiction.” Internet addiction is generally considered as an
addictive disorder that shares most features of drug addictions (i.e., salience, craving,
tolerance, loss of control, mood modification, withdrawal, relapse). Over the last few
years, there have been a number of calls to incorporate Internet addiction as a new
diagnostic category in the next edition of the DSM. However, the DSM-5 task force
recently decided that there is not enough empirical research to warrant inclusion of
“Internet addiction” as a new psychiatric disorder in the DSM-5.
The validity of the Internet addiction construct is challenged by theoretical and
empirical concerns. Internet addiction is indeed an umbrella construct that encompasses
a variety of different dysfunctional behaviors related to the involvement in online
activities that do not necessarily coexist (e.g., video game playing, cybersex, social
networking, online gambling, etc.). Nevertheless, the empirical evidence regarding the
risk factors that are shared among cyber addictions (i.e., factors implicated in the
etiology of all cyber addictions) from those that are specific (i.e., factors implicated
in the etiology of a specific cyber addiction, e.g., online gambling) is scarce. Another
concern is raised by the elevated comorbidity rates between cyber addictions and other
psychiatric disorders, which implies that cyber addictions can be either primary or
secondary disorders (e.g., resulting from a depressive disorder) (Gentile et al. 2011).
Recently, and notwithstanding inconsistencies in classification and limited data
regarding the course and the etiology of the condition, Internet Gaming Disorder
has been included as a new clinical entity in Sect. 3 of the DSM-5 (Petry and
O’Brien 2013). The goal of this section is to foster research on the conditions
included therein. In this context, the current chapter focuses on the dysfunctional
involvement in a specific type of video game which has some inherent character-
istics reinforcing its addictive nature: Massively Multiplayer Online Role-Playing
Games (MMORPGs). Problematic and uncontrolled involvement in playing
MMORPGs is indeed the most frequently reported activity by people seeking
help for an Internet-related problem (e.g., Thorens et al. 2013).
95 Internet Gaming Addiction 1517
MMORPGs are one of the most recent and popular types of video games played
worldwide. An estimation of the total number of MMORPG players around the world
is 20 million. MMORPGs are a type of computer role-playing game in which a large
number of players interact with one another in a persistent virtual world – an
environment that exists independently of the players. Consequently, both events and
interactions between other players occur while the user is absent from the persistent
world. In MMORPGs, players assume the role of a fictional character (often in heroic-
fantasy-based worlds such as the one depicted by writer J. R. R. Tolkien in the saga
“Lord of the Rings”) and take control of many of that character’s actions. Character
creation typically involves various components such as the selection of an avatar
(i.e., a visual representation of the character in the virtual world) but also specific skills
and attributes that define the character (e.g., gender, race, profession, physical
aspects). The concept of advancement is a fundamental characteristic of playing
MMORPGs, implying that a user’s character will acquire new powers, skills, and
items (i.e., objects that can be found in the game, such as a special weapon or gold
pieces) as rewards for succeeding in certain missions or quests (e.g., defeating an
opponent or exploring a special place in the virtual world). Another important feature
of playing MMORPGs is social interaction. It is indeed possible, when playing, to
communicate easily with other players (written chat or audio). Furthermore, players
can also regroup themselves in virtual social networks named guilds, which are
persistent hierarchical organizations of characters with common objectives and back-
grounds. Each guild has its own rules and users who want to be enrolled generally
need to present their motivations and proofs that their characters meet the guild’s
requirement. These abovementioned specificities (permanent world, advancement and
reinforcement system, social interactions aspects) have been proposed as structural
characteristics reinforcing the addictive nature of this specific type of video game
(e.g., King et al. 2010). It has, for example, been shown in a longitudinal study by
Smyth (2007) that MMORPG players, in comparison to other types of video game
players (e.g., arcade, console or solo-computer players), reported significantly more
hours spent playing, worse health (e.g., more cigarettes smoked, less physical exercise,
worse sleep quality, etc.), and greater interference in real-life socializing and academic
work at a 1-month follow-up. This finding was confirmed in a recent cross-sectional
study by Kuss et al. (2012) that emphasized MMORPG players (compared to those
playing other types of video games) more often displayed signs of dysfunctional use.
In the last years, a growing number of studies have focused on problematic involve-
ment in video games and more particularly in the playing of MMORPGs (see Kuss
and Griffiths 2012a, for a review). Most of these studies, which have considered
dysfunctional use within the framework of “behavioral addictions”, tried to identify
the psychological factors and/or the neurobiological correlates involved in its
development and maintenance.
1518 J. Billieux et al.
A large body of evidence tied dysfunctional video game use (and more largely
Internet-related disorders) to poor self-control (e.g., traits of impulsivity and
sensation seeking, lack of inhibitory control, impaired decision-making, reward
drive) (see Billieux and Van der Linden 2012, for a review about Internet-related
disorders and self-regulation).1 This focus on self-control and impulsivity lies in the
fact that dysfunctional video game involvement is most of the time conceptualized
as an addictive behavior and that uncontrolled use is a key symptom of this disorder
(King et al. 2013).
Several studies have highlighted that video game addicts have higher levels of
self-reported impulsivity. In particular, a study by Gentile and colleagues (2011)
found in a 2-year longitudinal study that greater impulsivity acts as a risk factor for
the development of problematic use of video games. Impulsivity is however an
umbrella construct that encompasses a combination of multiple and separable
psychological dimensions. In the last decade, a growing number of researches
supported a model that clarifies the multidimensionality of impulsivity by
subdividing it into four dimensions, which are related but also specific (the UPPS
model of impulsivity; Whiteside and Lynam 2001). These four dimensions are
defined as follows: urgency, the tendency to act rashly when experiencing intense
emotions (both positive and negative); premeditation, the tendency to take into
account the consequences of an act before engaging in that act; perseverance, the
capacity to remain focused on a boring and/or difficult task; and sensation seeking,
the tendency to enjoy and pursue new and exciting activities. Notably, a growing
number of studies have highlighted specific links between these impulsivity facets
and various psychiatric disorders (e.g., substance abuse, problem gambling,
compulsive buying, suicide ideations and attempts, aggressive behaviors). Recent
studies showed that problematic MMORPG involvement (measured with scales
assessing addiction symptoms, such as loss of control, as well as with the related
impact on various spheres of daily life) is firstly predicted by the urgency facet of
impulsivity (when controlling for other impulsivity components), although relation-
ships with low premeditation and perseverance were also emphasized (Billieux
et al. 2011, 2014). In contrast, the sensation-seeking facet of impulsivity was
inconsistently related to problematic MMORPGs use (and more largely Internet
overuse). A potential explanation for the absence of a systematic relationship
between sensation seeking and dysfunctional MMORPGs use is that the question-
naires targeting this impulsivity component probably do not assess how people seek
stimulation and rewards through online game involvement.
Recent evidence suggests that the various facets of impulsivity are related to
specific psychological executive and motivational mechanisms involved in the
regulation of behaviors. More precisely, it has been emphasized that three of the
dimensions of impulsivity (urgency, lack of premeditation, lack of perseverance)
1
See Billieux and Van der Linden (2012) and Kuss and Griffiths (2012a) for comprehensive lists of
publications having investigated self-regulation-related constructs in Internet and video games
addictions.
1520 J. Billieux et al.
Griffiths (2012b) found that in eighteen empirical studies,2 neuroimaging has been
used in order to elucidate Internet and gaming addiction against the background of
more traditional substance-related addictions. State-of-the-art neuroimaging tech-
niques have been used in the included studies, namely, electroencephalograms
(EEG), positron emission tomography (PET), single-photon emission computed
tomography (SPECT), as well as functional and structural magnetic resonance
imaging (fMRI and sMRI). With EEG, brain activity in the cerebral cortex is
assessed. PET measures the level of positively charged electrons in the brain
which provides an indicator for metabolic neuronal activity, whereas SPECT
measures neuronal activity following the injection of radioactive tracers. With
fMRI, brain blood oxygen levels are quantified in order to demarcate regions of
activity. Finally, sMRI images brain structure, using methods such as voxel-based
morphometry (VBM) and diffusion-tensor imaging (DTI).
Using these neuroimaging techniques, the systematic literature review revealed
that Internet and gaming addiction are in no way inferior to substance-related
addictions on three levels. On a biochemical level, frequent engagement in online
and gaming activities has been shown to alter neuronal dopamine levels via
reductions in dopamine transporter availability. This may lead to molecular dys-
functions in the dopaminergic system. On the level of neural networks, brain
alterations appear as a result of excessive engagement with the Internet and online
games. The brain adapts to the perpetual reinforcing stimulation and in turn
becomes desensitized to natural reinforcers and thus needs more of the former,
putting in motion a vicious cycle. The studies show that the function and structure
of the orbitofrontal cortex gyrus changed as a consequence of excessive Internet use
and gaming. The latter becomes more salient for the users who lose control over
their behaviors. They have learned to use the Internet and games compulsively to
recreate neuronal homeostasis. Finally, studies combining neuroimaging and
behavioral techniques confirmed that people suffering from Internet and gaming
addiction develop a number of cognitive deficits, including impairments in execu-
tive and attentional controls. However, on the bright side, a number of skills are
advanced in this group. Studies indicate that the integration of perceptual informa-
tion to the brain via the nervous system is facilitated, and hand-eye coordination is
improved (Kuss and Griffiths 2012b).
In sum, state-of-the-art neuroimaging research offers compelling evidence for
the similarities between Internet and gaming addiction with substance-related
addictions. From the cited review, it appears that Internet and gaming addiction
can be classed as behavioral addiction as the former fulfills a variety of character-
istics that typify addictions. Correspondence between addictions exists on
a molecular, neurocircuitry, and behavioral basis, indicating the addiction may
best be conceptualized as a syndrome with common etiology, but different mani-
festation (Shaffer et al. 2004).
2
For a detailed listing and evaluation of included empirical studies, refer to the original systematic
review paper (Kuss and Griffiths 2012b).
1522 J. Billieux et al.
Internet addiction in general and addiction to playing MMORPGs are relatively new
clinical phenomena. Consequently, research on their treatment is limited. However,
a couple of systematic studies with the goal of evaluating treatment effectiveness have
been published (King et al. 2011; Liu et al. 2012). Each of these is briefly outlined.
King et al. (2011) made use of the gold standard of clinical trial evaluation, the
CONSORT (Consolidated Standards of Reporting Trials) statement (Schulz
et al. 2010), in order to evaluate Internet addiction treatment studies (including
MMORPG addiction). The CONSORT statement sets out a number of quality
indicators for pharmacological and non-pharmacological clinical trials, such as trans-
parence in justifying and reporting study methodology. These include stating eligibil-
ity criteria for participants, description of respective treatments, and a power analysis
for the utilized sample size (Schulz et al. 2010). Only eight studies3 met the established
criteria, including one randomized controlled trial. The included studies differed
significantly in design, definition, and assessment of Internet addiction, treatment,
follow-up assessments, randomization and blinding, sampling, and recruitment.
As regards treatment, it was particularly varied ranging from cognitive-behavioral
therapy (CBT), motivational interviewing (MI), reality training, and individually
designed therapy including psychological and or counseling elements. Overall, treat-
ment was provided by trained professionals or via especially developed computer
programs, lasting between one session and 19 months in total (King et al. 2011).
For their empirical review, Liu et al. (2012) selected Internet addiction outcome
studies based on whether they reported treatment outcomes, included young Inter-
net addiction patients aged 9–23 years, and were carried out in China, resulting in
a final sample of 24 studies.4 In order to evaluate these studies, criteria from the
CONSORT statement were adopted including objectivity, sample size, power,
outcome, randomization, active comparison, baseline, manualization, treatment
adherence rating, collateral report, objective measures, intention to treat (ITT)
analysis, and blinding. In terms of the outcome, more than half of the included
studies were considered “methodologically strong” in sequence generation and ITT
analysis, however weak with regard to the remaining criteria. With regard to
treatment approaches, exercise programs, cognitive-behavioral therapy, electroa-
cupuncture, family therapy, group-based treatment, motivational interviewing, and
psychotropic medication were used most commonly, with over 50 % of studies
using multimodal techniques. On average, the effect size was high (i.e., 1.89),
suggesting that Internet addiction therapy is efficacious; however, the quality of
the results was found to be low. The highest effect size was found for the most
prominent multimodal treatment, CBT combined with psychopharmacotherapy,
i.e., 3.93, attesting to its efficaciousness (Liu et al. 2012).
3
For a detailed description of the included studies, please refer to the original review paper by King
et al. (2011).
4
A detailed description of studies is provided in Liu et al. (2012).
95 Internet Gaming Addiction 1523
From the reported reviews of treatment studies, it appears that there is no single
standardized evidence-based Internet addiction treatment available to date.
The treatment studies published to date offer a wide range of therapy approaches,
using dissimilar diagnostic criteria and heterogeneous treatment delivery. Taken
collectively, more treatment research that fulfills high-quality standards is available
in the Chinese-speaking rather than English-speaking world, indicating that the
problem of Internet and MMORPG addiction may be more pressing in the former.
From the few studies to date, it appears that a combination of CBT with pharma-
cotherapy yields the most promising results. The first cognitive-behavioral therapy
manual for the treatment of computer game and Internet addiction has now been
published in Germany (Wölfling et al. 2013). It combines group with individual
therapy sessions on an outpatient basis. The manualization of Internet and
MMORPG addiction treatment may be taken as first step toward the adoption of
established clinical protocols, which will benefit managing risks, implementing
research findings promptly, and standardizing treatment that is more cost-effective
and efficient in the long run.
95.3 Conclusion
• The studies now being carried out are becoming better both methodologically
(e.g., development of in-game tracking techniques) and theoretically (e.g.,
development of psychological models of problematic use) although there is
still a heavy reliance on self-selected samples. Further studies should thus
focus on the recruitment of more representative samples.
• Recent studies challenged the demographic characteristics regarding individuals
involved in playing online video games. First, this activity is no longer just
a male adolescent or preadolescent activity, and online games are now also
played by adults. The mean age of MMORPG players in many recent studies is
often between 25 and 30 years old. In addition, it appears that there is an
increasing feminization of gaming with more girls and women becoming
gamers.
• The gaming studies field needs to develop better instrumentation to assess the
symptomatology and prevalence of MMORPG addiction with sufficient speci-
ficity and sensitivity. In addition to diagnostic tools (i.e., scales used to differ-
entiate problematic and non-problematic gamers), it would also be necessary to
develop instruments that allow multidimensional scoring (e.g., loss of control,
withdrawal, conflict, craving, compromised time control, hedonic aspects, mood
regulation). Indeed, available studies often provided limited comprehension of
the factors involved in the etiology of MMORPG addiction (e.g., personality
traits, motives), as they have too often been conducted without considering its
multifaceted nature. For example, a study designed to elucidate the role of self-
regulation in dysfunctional online game symptomatology would benefit from
using a scale able to measure aspects such as loss of control or pleasure seeking
(psychological mechanisms or processes) as separate from aspects such as
negative impact upon daily living (outcomes of the problematic behavior).
• Although MMORPGs appear to be more attractive video games when compared
to “stand-alone” console-type games (due to structural characteristics such as
24/7 availability mentioned above), other less researched genres of online
gaming (such as Real Time Strategy Games and First Person Shooters) may
also require similar consideration in the future.
References
Billieux J, Van der Linden M (2012) Problematic use of the internet and self-regulation: a review
of the initial studies. Open Addict J S1:24–29
Billieux J, Chanal J, Khazaal Y, Rochat L, Gay P, Zullino D, Van der Linden M (2011)
Psychological predictors of problematic involvement in massively multiplayer online role-
playing games: illustration is a sample of male cybercafé players. Psychopathology
44:165–171
Billieux J, Van der Linden M, Achab S, Khazaal Y, Paraskevopoulos L, Zullino D, Thorens
G (2013) Why do you play World of Warcraft? An in-depth exploration of self-reported
motivations to play online and in-game behaviours in the virtual world of Azeroth. Comp
Hum Behav 29:103–109
Billieux J, Thorens G, Achab S, Khazaal Y, Zullino D, Van der Linden M (2014) Pathological use
of online video games: a cluster analytic approach. Manuscript in revision
95 Internet Gaming Addiction 1525
Gentile DA, Choo H, Liau A, Sim T, Li D, Fung D, Khoo A (2011) Pathological video game use
among youths: a two-year longitudinal study. Pediatrics 127:e319–e329
King DL, Delfabbro P, Griffiths MD (2010) Video game structural characteristics: a new psycho-
logical taxonomy. Int J Ment Health Addict 8:90–106
King DL, Delfabbro PH, Griffiths MD, Gradisar M (2011) Assessing clinical trials of internet
addiction treatment: a systematic review and CONSORT evaluation. Clin Psychol Rev
31:1110–1116
King DL, Haagsma MC, Delfabbro PH, Gradisar M, Griffiths MD (2013) Toward a consensus
definition of pathological video-gaming: a systematic review of psychometric assessment
tools. Clin Psychol Rev 33:331–342
Kuss DJ, Griffiths MD (2012a) Internet gaming addiction: a systematic review of empirical
research. Int J Ment Health Addict 10:278–296
Kuss DJ, Griffiths MD (2012b) Internet and gaming addiction: a systematic literature review of
neuroimaging studies. Brain Sci 2:347–374
Kuss DJ, Louws J, Wiers RW (2012) Online gaming addiction? Motives predict addictive play
behavior in massively multiplayer online role-playing games. Cyberpsychol Behav Soc Netw
15:480–485
Littel M, Luijten M, van den Berg I, van Rooij A, Keemink L, Franken I (2012) Error-processing
and response inhibition in excessive computer game players: an ERP study. Addict Biol
17:934–947
Liu C, Liao M, Smith DC (2012) An empirical review of internet addiction outcome studies in
China. Res Soc Work Pract 22:282–291
Mittal VA, Dean D, Pelletier A (2013) Internet addiction, reality substitution, and longitudinal
changes in psychotic-like experiences in young adults. Early Interv Psychiatry 7:261–269
Pawlikowski M, Brand M (2011) Excessive internet gaming and decision making: do excessive
World of Warcraft players have problems in decision making under risky conditions? Psychiat
Res 188:428–433
Petry NM, O’Brien CP (2013) Internet gaming disorder and the DSM-5. Addiction
108:1186–1187
Schulz KF, Altman DG, Moher D (2010) CONSORT 2010 statement: updated guidelines for
reporting parallel group randomized trials. Ann Intern Med 152:1–8
Shaffer HJ, LaPlante DA, LaBrie RA, Kidman RC, Donato AN, Stanton MV (2004) Toward
a syndrome model of addiction: multiple expressions, common etiology. Harv Rev Psychiatry
12:367–374
Smyth J (2007) Beyond self-selection in video game play: an experimental examination of the
consequences of massively multiplayer online role-playing game play. Cyberpsychol Behav
10:717–721
Thorens G, Achab S, Billieux J, Khazaal Y, Khan R, Pivin E, Gupta V, Zullino D (2013)
Characteristics and treatment response of self-identified problematic Internet users in a behav-
ioral addiction outpatient clinic. J Behav Addict 3:78–81
Whiteside SP, Lynam DR (2001) The five factor model and impulsivity: using a structural model
of personality to understand impulsivity. Pers Indiv Diff 30:669–689
Wölfling K, Jo C, Bengesser I, Beutel ME, M€ uller KW (2013) Computerspiel- und Internetsucht.
Ein kognitiv-behaviorales Behandlungsmanual. Kohlhammer, Stuttgart
Yee N (2006) Motivations for play in online games. Cyberpsychol Behav 9:772–775
Compulsive Buying Disorder
96
Tatiana Zambrano Filomensky and Hermano Tavares
Contents
96.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1528
96.2 A Biopsychosocial View of Compulsive Buying . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1529
96.2.1 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1529
96.2.2 Diagnosis and Assessment Scales . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1531
96.2.3 Psychiatric Comorbidity and Relationship with Other Mental
Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1533
96.2.4 Clinical Manifestations and Subtypes of Compulsive Buyers . . . . . . . . . . . . . . 1534
96.2.5 Social-Cultural Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1535
96.2.6 Neurobiology, Genetics, and Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1536
96.2.7 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1537
96.2.8 Self-Help/Community Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1539
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1539
Abstract
The increasing availability of credit has made buying a frequent behavior in
everyone’s life. Compulsive buying disorder (CBD) is characterized by loss of
control over buying, accruing debts, and psychosocial distress. Reported by the
founding fathers of modern psychiatry, Kraepelin and Bleuler described it as
a monomania and named it oniomania. CBD may have a profound impact upon
both individuals and society; however, it remains absent from current diagnostic
classifications. There are still doubts regarding the psychopathology and nature
of CBD; some regard it as a behavioral addiction or a member of two different
groups, either the bipolar spectrum or the obsessive-compulsive spectrum of
96.1 Introduction
Since antiquity, the act of buying has been present in society. The emergence of
currency modified cultural and moral values, marking a period in which power went
from being determined by the family name to being defined by commerce, gaining
momentum with the adoption of monetary systems (Vissering 2008). The act of
buying continued to distract and enrapture people throughout the subsequent
millenniums, driving commerce and influencing governmental structure. The lack
of control over this behavior aroused the concern that we could be facing a clinical
disorder.
Compulsive buying disorder (CBD) was described at the beginning of the
twentieth century by two descriptive psychiatrists, Kraepelin (1915) and Bleuler
(1924). Both founded their descriptions on Esquirol’s (1838) concept of monoma-
nia. Kraepelin (1915), the first to elaborate the syndrome, titled it oniomania – from
the Greek onios (for sale) and mania (insanity), describing it as a pathological
impulse. He underscored the predominance of the female sex and believed that
oniomania would be a subclinical variation of kleptomania. Bleuler (1924) empha-
sized the impulsive nature of the disorder and likened it to the insanities of impulse
along with pyromania (apparently much more abundant at that period that it appears
to be today) and kleptomania (Tavares et al. 2008).
CBD did not arouse the interest of researchers in the following decades, except
among the study of consumer behavior (O’Guinn and Faber 1989; Elliott 1994) and
psychoanalysts that elaborated case reports (Krueger 1988). During the early 1990s,
three independent clinical case series studies involving 90 individuals were
published, after which CBD once again returned to be globally discussed
(Christenson et al. 1994; Schlosser et al. 1994), with reports originating
from countries such as Germany (Scherhorn et al. 1990), Brazil (Bernik
et al. 1996), Canada (Valence et al. 1988), France (Lejoyeux et al. 1997),
96 Compulsive Buying Disorder 1529
England (Elliott 1994), and the USA. This renewed interest was probably fostered
by the perception of the profound impact that CBD may have upon individuals as
well as on society. Indeed, it is estimated that in the USA compulsive consuming
generates more than US$4 billion in annual purchasing (Kacen and Lee 2002;
Tavares et al. 2008).
Despite being described by researchers and scholars for more than a century,
CBD continues to be, inexplicably, undefined and understudied. It is absent from
modern classifications in psychiatry, except possibly for the classification in the
residual category of Impulse Control Disorders Not Otherwise Specified in the
Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) (APA 2000)
or the International Classification of Diseases of the World Health Organization,
10th Edition (ICD-10) (Filomensky et al. 2012). A possible explanation for this
state of affairs is the existence of diagnostic doubts regarding the psychopatholog-
ical nature of CBD. Some researchers consider CBD to be an addictive disorder,
incorporating it into the classification of drug and alcohol abuse disorders, or
behavioral addictions, which include pathological gambling, kleptomania, Internet
addiction, and compulsive sexual behavior (Glatt and Cook 1987). Others consider
CBD to be an excessive behavior secondary to mood disorders, associated within
the frameworks of mania, hypomania, or mixed episodes in bipolar disorder
(Lejoyeux et al. 1996), or as a subsidiary symptom of hoarding, on the obsessive-
compulsive disorder spectrum (Hollander et al. 1996; Filomensky et al. 2012).
There is also a stream of researchers who criticize the attempts to classify com-
pulsive consumption as a disorder, stating that it implies medicalization of variations
within the spectrum of consuming behaviors (Lee and Mysyk 2004). Unfortunately,
this view ignores the reality that CBD is a prevalent and severe syndrome and
stigmatizes the attempts to recognize, understand, and treat the condition.
96.2.1 Epidemiology
Studies estimating the prevalence of CBD in the general and specific populations
report rates of approximately 2–8 %. In spite of the increasing scientific and layman
interest in the disorder, there is no evidence to suggest that the prevalence of CBD is
increasing. A study by Faber and O’Guinn (1992) selected 292 Americans from the
general population in Illinois to respond to the Compulsive Buying Scale (CBS)
estimated that almost 6 % of the population would be at risk for CBD. Grant
et al. (2005) evaluated 204 psychiatric inpatients and reported a prevalence rate
of CBD over the lifetime of 9 %. More recently, a study by Koran et al. (2006)
interviewed approximately 2,500 American adults through an anonymous tele-
phone questionnaire. They determined a CBD prevalence rate of about 5 %, and
a ratio of men to women of 1:1, which indicates a rather larger participation of men
than previously reported. The anonymous nature of this telephone survey may have
1530 T.Z. Filomensky and H. Tavares
helped male compulsive shoppers to be open about their difficulties. Indeed, other
reports that pointed to male-to-female ratio around 1:4–1:5 were almost all
conducted in clinical settings (Filomensky et al. 2012). Kraepelin and Bleuler had
already proposed the predominance of the female gender in CBD, suggesting that
the female compulsive buyer was in search of risk and excitement, much like the
risk-seeking behavior in pathological gambling predominantly seen among men.
For Dittmar and Drury (2000), the prevalence of the female gender in CBD appears
as a compensation strategy to combat negative emotions and low self-esteem.
They state that the gender difference is genuine and should not be attributed to the
underrepresentation of males in clinical samples, basing their conclusion in a study
conducted in the general population of the UK, in which 92 % of the respondents
classified as compulsive buyers were women. Interestingly, in 2005 Dittmar carried
out another survey about consuming behaviors in adolescents. Two-hundred and five
teenagers between the ages of 16 and 18 were selected from two schools in England.
The results indicated a CBD prevalence ratio similar to the adult survey, but without
gender imbalance, suggesting that regarding uncontrolled shopping men are likely to
catch up with women in the near future (Dittmar 2005). Nonetheless, gender differ-
ences regarding favored purchasing will likely remain, with female compulsive
shoppers targeting mainly clothes, handbags, shoes, perfumes, makeup, and jewelry,
while men prefer electronics and objects that display elevated social status such as
expensive suits, watches, electronic gadgets, and cars (Christenson et al. 1994;
McElroy et al. 1994; Black 1996, 2001).
It is believed that CBD begins toward the end of adolescence, around 18 years of
age, or at the beginning of adulthood. This is the period in which the adolescent
develops more autonomy and emancipation from the nuclear family, when they are
likely to acquire credit for the first time (Black 2001). Nevertheless, the perception
of buying behavior as a problem occurs later, around 30 years of age, and treatment
seeking between 31 and 39 years of age.
Before 18 years of age, uncontrolled buying is generally associated with a more
diffuse general pattern of behavioral disinhibition, which can include smoking,
alcohol and drug misuse, and premature sex (Roberts and Tanner 2002). Besides,
24-h shopping made possible by online credit card purchasing could be
a contributing factor to adolescent onset. Indeed, it has been reported that among
computer compulsive users, up to 19 % would fulfill the criteria for CBD (Black
2001). In view of this fact, it is likely that some compulsive shoppers will enter their
adult lives already with a substantial debt.
CBD is commonly associated with severe personal impairment, both financial
and familial (Black 2001), as well as other psychiatric disorders, including
personality disorders (Black 2007; Tavares et al. 2008). Although there are
a lack of longitudinal studies for CBD, some studies indicate that the course of
the disorder can be chronic or recurrent (Christenson et al. 1994; Schlosser
et al. 1994). However, the treatment of CBD can modify the course of the
disorder, as shown in a study in which patients who responded to treatment with
citalopram maintained states of remission during 1 year (Koran et al. 2003;
Aboujaoude et al. 2003).
96 Compulsive Buying Disorder 1531
The association of CBD with other psychiatric disorders is the rule rather than the
exception, with comorbidity most often seen with mood, anxiety, substance use,
eating, and other impulse control disorders (Christenson et al. 1994; McElroy
et al. 1994; Schlosser et al. 1994; Black et al. 1998, 2000; Ninan et al. 2000;
Black 2001; Mitchell et al. 2006; Mueller et al. 2009).
A bicentric study analyzed data from US and Germany treatment centers and
found that approximately half of the sample had at least one current psychiatric
comorbidity, mainly an anxiety disorder, and that 90 % fulfilled criteria for at least
one Axis I diagnosis during the lifetime. The main diagnoses were mood disorder
(74 %), anxiety disorder (57 %), and impulse control disorder (21 %) of which
intermittent explosive disorder was most common (Mueller et al. 2010).
It is not uncommon for CBD patients to build up collections of similar items
varying one single aspect, e.g., color, size, or design, to zealously stock and hoard
them, not allowing other people to interfere with them. For this reason,
a relationship with obsessive-compulsive disorder (OCD) has been speculated.
However, only one study has found a relevant association, reporting that seven
(35 %) out of 20 patients consecutively admitted for CBD treatment had a lifetime
diagnosis of OCD (McElroy et al. 1994). Conversely, CBD has been described as
a frequent comorbidity among OCD and eating disorder patients (Fernández-
Aranda et al. 2008, 2006), with a suggestion that in OCD such an association
represents a more impulsive subtype (approximately 10 % of the OCD
patients – Hantouche et al. 1997; du Toit et al. 2001). The hoarding behavior
seems to be the psychopathological link between the two disorders and for both
of them a marker of a compulsive trait and severity (Frosts et al. 2009). For CBD,
severity goes hand in hand with psychiatric comorbidity; thus, the presence of
hoarding behavior is associated with mood, anxiety, and eating disorders
(Kyrois et al. 2004).
On the other hand, the frequent comorbidity with depression and unrestrained
expenditure have been pointed as evidences of a link between CBD and bipolar
disorder and the former as a member of the so-called bipolar spectrum of disorders
(Akiskal et al. 2000). In trying to clarify if CBD should be regarded as a
sub-syndromal bipolar disorder, an OCD-related disorder, or a condition apart
from the spectrums of both disorders, Filomensky and colleagues (2012) investi-
gated 80 individuals undergoing outpatient treatment for either bipolar disorder,
OCD, or CBD regarding impulsivity, obsessive-compulsive traits, hoarding, and
mood spectrum of symptoms. Compared to the other two conditions, CBD patients
scored significantly higher on all impulsivity measures and especially on the
non-planning subdimension. In the hoarding spectrum, they scored higher for the
acquisition subdimension, but not for difficulty discarding or cluttering
subdimensions. Manic symptoms were distinctive of BD patients, while elevated
scores on the contamination/washing and checking dimensions differentiated
OCD patients. A discriminant model built with these variables correctly classified
1534 T.Z. Filomensky and H. Tavares
Compulsive buyers divert their attention away from these internal negative emo-
tions and onto external stimuli, which generates an increase in risky compulsive
behaviors (Faber and Vohs 2004; Baumeister 1991; Claes et al. 2010; Mueller
et al. 2011).
In the cognitive sphere, compulsive buying episodes have been associated with
means of identity building, “all or nothing” attitudes toward money, hindsight
appraisal of purchasing, and gift buying as a way to garner affection and avoid
embarrassment (Mitchell et al. 2006; Filomensky and Tavares 2009). Dittmar
and Drury (2000) propose that self-image image building is more related to
women than men.
It is common for these episodes to occur in a solitary manner, routinely or in the
form of purchasing binges. Sometimes to lessen the guilt, compulsive buyers will
also buy for their partners, family members, or friends. When buying for them-
selves, they often – though not necessarily – hide the objects in closets, drawers, or
the car trunk. Many of such purchases may never be used. There is no pattern to
stores or commercial places in which these episodes of excessive spending occur;
however, buyers do have their “favorite” shopping places, catalogues, and online
sites. A study that evaluated excessive Internet use among compulsive and
non-compulsive buyers concluded that buying through the Internet is more com-
mon among compulsive buyers. The same applies for purchases made through the
television (Mueller et al. 2011).
DeSarbo and Edwards (1996) described two subtypes of compulsive buyers: one
group in which the principal trigger of a compulsive episode was the materialism
and desire for objects with a tendency to be more impulsive and the second group in
which the compulsive episode was more motivated by internal emotions such as
low self-esteem and little control over the desire to buy. This second group
presented with a higher propensity to develop depression. Likewise, another
study pointed to two distinct groups among compulsive buyers: one in which the
motivation for the purchase was guided by positive reinforcement related to
pleasant aspects of the purchase and the other in which the purchase occurred as
a result of emotional suffering associated with financial problems, interpersonal
relationships, and emotional questions, revealing a group with significantly higher
levels of debt (Thornhill et al. 2012).
Therefore, like previously described for pathological gambling, CBD seems to
encompass a double nature, an impulsive side related to purchase cravings and lack
of planning and a compulsive side characterized by the avoidance of negative
emotions and attempts to control one’s affective state, both combined lead to loss
of control over buying. The determination of the subtype depends upon which side
prevails (Tavares and Gentil 2007).
is a worldwide phenomenon, and in the last decades there have been a shift in
advertising strategies from focusing on the qualities of the purchase to how good
purchasing makes you feel. This is especially true for countries in which the
economy is consumer based (Black 2007).
An almost universal selling strategy is to anticipate the pleasure of the acquisi-
tion through credit card shopping or other option and to delay the “pain” of
payment, to which impulsive individuals may be particularly vulnerable. Indeed,
several measures of compulsive shopping have a strong correlation with credit card
use and credit card minimum payment (Faber and O’Guinn 1992; Ridgway
et al. 2008). The credit card has become a cultural icon, going beyond a mere
form of modern “plastic cash,” something particularly noticeable in developing
economies and most appealing to vulnerable women as a promise of more auton-
omy in societies largely dominated by men (Hanley and Wilhelm 1992).
96.2.7 Treatment
96.2.7.1 Psychotherapy
Over the past 5 years, studies regarding the treatment of CBD established important
advances, as what existed were previous case reports aligned to the theoretical
orientation of the authors. Still, controlled studies evaluating treatment efficacy for
CBD, independent of therapeutic modality, remain scarce (Kellett and Bolton 2009;
Benson and Gengler 2004; Mitchell et al. 2006; Steketee and Frost 2003).
Cognitive-behavioral models remain as the most tested and studied treatment
programs. The first studies were by Lejoyeux et al. (1996) and Bernik et al. (1996),
both of which suggested that cue exposure and response prevention may be useful
in the treatment. Bernik and colleagues (1996) reported on two cases treated with
clomipramine for panic attacks, who also presented with CBD. The medication did
not improve compulsive buying behavior; however, both responded well to
3–4 weeks of buying cue exposure and response prevention, although no
posttreatment information was provided.
1538 T.Z. Filomensky and H. Tavares
One of the first to use the cognitive behavioral therapy group were Burgard and
Mitchell (2000). A pilot study carried out by Mitchell et al. (2006) involved
28 patients with CBD diagnoses for the treatment with a cognitive-behavioral
model and 11 controls on the waiting list. At the end of 12 weeks, the results showed
significant advantages of cognitive-behavioral therapy, with subjects outperforming
the waiting list controls in terms of the number of compulsive buying episodes and
time spent buying. This improvement was maintained over the following 6 months.
In 2008, Mueller et al., inspired by the Mitchell et al. (2006) study, treated 31
compulsive buyers with a 12-week cognitive-behavioral intervention and compared
them with 29 control patients on the waiting list. The treatment sessions specifically
dealt with problems related to compulsive buying, restructuring of negative thoughts
and emotions regarding buying, control over buying behavior, and problem-solving
skills. Throughout the next 6 months, the patients continued to present with improve-
ments when compared with the control group.
Imaginary desensitization was also used to treat a female compulsive buyer with
a treatment package that also included motivational interviewing, financial plan-
ning, leisure, and cognitive restructuring. The final evaluation was positive, show-
ing a reduction in compulsive episodes (Donahue et al. 2011). Another uncontrolled
study reported on a cognitive-behavioral group intervention with an emphasis on
cognitive restructuring. Specific sessions were devised to deal with the most
common cognitive distortions related to buying such as buying as a way of coping
with emotions and building an identity and “all or nothing” type of thinking.
The nine patients who participated all reported improvement of both cognitions
and behaviors related to CBD (Filomensky and Tavares 2009).
96.2.7.2 Psychopharmacology
Similar to psychotherapeutic treatments, controlled clinical trials for CBD are
scarce. Lejoyeux et al. (1995) suggest that depressive compulsive buyers have an
increased chance of improving their compulsiveness when treated with antidepres-
sants than compulsive buyers without depression. A clinical trial with ten patients
evaluated the use of fluoxetine in compulsive buyers over 9 weeks. Nine of the ten
patients showed improvement, suggesting that it is not necessary for patients to be
depressed in order to benefit from antidepressants (Black et al. 1997).
Two randomized controlled clinical trials with fluoxetine were carried out soon
after. The first treated 37 compulsive buyers over the course of 12 weeks and did not
find a difference between fluoxetine and placebo (Ninan et al. 2000). The second
studied a sample of 23 CBD inpatients without depression (Black et al. 2000).
The participants were randomly distributed to fluoxetine (n ¼ 12) or placebo (n ¼ 11).
At the end of 9 weeks and applying the Scale of Global Clinical Improvement, 50 % of
the patients in the fluoxetine group and 64 % of those in the placebo group were
classified as showing “great” or “very great” improvement. The positive response of
the placebo group points to the need to undertake more randomly controlled trials with
longer follow-up periods (Christenson et al. 1994; Black 2001).
A clinical trial with citalopram showed favorable results in the double-blind
discontinuation study carried out by Koran et al. (2003). Twenty-four patients with
96 Compulsive Buying Disorder 1539
CBD were selected, and after 6 weeks of treatment, 17 patients presented with
a significant reduction in spending and purchases and an improvement in global
functioning. Then, these patients were randomly assigned to either citalopram or
placebo maintenance for 9 more weeks. The seven patients that took citalopram did
not relapse, while five of the eight patients who took the placebo relapsed. After
1 year, 73 % of the seven patients who took medication remained in remission from
compulsive symptoms even after having interrupted medication. The authors
suggested that citalopram treatment might have modified the natural course of the
disorder. On the other hand, another study with a similar design using escitalopram
found no significant effect (Koran et al. 2007).
Grant (2003) reported on the successful treatment of three patients with naltrex-
one, and recently memantine was tested in nine CBD patients with encouraging
results (Grant et al. 2012).
References
Aboujaoude E, Gamel N, Koran LM (2003) A 1-year naturalistic following of patients with
compulsive shopping disorder. J Clin Psychiatry 64(8):946–950
Akiskal HS, Bourgeois ML, Angst J, Post R, Moller H-J, Hirschfeld R (2000) Re-evaluating the
prevalence of and diagnostic composition within the broad clinical spectrum of bipolar
disorders. J Affect Disord 59:5–30
American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders,
4rd edn, text revised. APA, Washington, DC
Baumeister RF (1991) The self against itself: escape or defeat? In: Curtis RC (ed) The rational self:
theoretical convergence in psychoanalysis and social psychology. The Guilford Press,
New York, pp 238–256
Benson AL, Gengler M (2004) Treating compulsive buying. In: Coombs RH (ed) Handbook of
addictive disorders. Wiley, Hoboken, pp 451–491
Bernik MA, Akerman D, Amaral JA, Braun RC (1996) Cue exposure in compulsive buying. J Clin
Psychiatry 57(2):90
Black DW (1996) Compulsive buying: a review. J Clin Psychiatry 57(Suppl 8):50–55
1540 T.Z. Filomensky and H. Tavares
Black DW (2001) Compulsive buying disorder: definition, assessment, epidemiology and clinical
management. CNS Drugs 15(1):17–27
Black DW (2007) A review of compulsive buying disorder. World Psychiatry 6:14–18
Black DW, Monahan P, Gabel J (1997) Fluvoxamine in the treatment of compulsive buying. J Clin
Psychiatry 58(4):159–163
Black DW, Repertinger S, Gaffney GR, Gabel J (1998) Family history and psychiatric
comorbidity in persons with compulsive buying: preliminary findings. Am J Psychiatry
155(7):960–963
Black DW, Gabel J, Hansen J, Schlosser S (2000) A double-blind comparison o fluvoxamine
versus placebo in the treatment of compulsive buying disorders. Ann Clin Psychiatry
12(4):205–211
Bleuler E (1924) Textbook of psychiatry. McMillan, New York
Burgard M, Mitchell JE (2000) Group cognitive behavioural therapy for buying disorder. In:
Benson AL (ed) I shop, therefore I am: compulsive buying and the search for self. Jason
Aronson, Northvale, pp 367–397
Christenson GA, Faber RJ, de Zwaan M, Raymond NC, Specker SM, Ekern MD, Mackenzie TB,
Crosby RD, Crow SJ, Eckert ED (1994) Compulsive buying: descriptive characteristics and
psychiatric comorbidity. J Clin Psychiatry 55(1):5–11
Claes L, Bijttebier P, Van den Eynde F, Mitchell JE, de Zwaan M, Mueller A (2010) Emotional
reactivity and self – regulation in relation to compulsive buying. Personal Individ Differ
49:526–530
Comings DE, Gade R, Wu S, Chiu C, Dietz G, Muhleman D, Saucier G, Ferry L, Rosenthal RJ,
Lesieur HR, Rugle LJ, MacMurray P (1997) Studies of the potential role of the dopamine
receptor D1 gene in addictive behaviors. Mol Psychiatry 2(1):44–56
De Neve J-E, Fowler JH (2010) The MAOA gene predicts credit card debt. Social
Science Research Network. Disponı́vel em: http://jhfowler.ucsd.edu/maoa_and_credit_card_
debt.pdf
DeSarbo WS, Edwards EA (1996) Typologies of compulsive buying behavior, a constrained
clusterwise regression approach. J Consum Psychol 5:231–262
Devor EJ, Magee HJ, Dill-Devor RM, Gabel J, Black DW (1999) Serotonin transporter gene
(5-HTT) polymorphisms and compulsive buying. Am J Med Genet 88(2):123–125
Dittmar H (2005) Compulsive buying – a growing concern? An examination of gender, age, and
endorsement of materialistic values as predictors. Br J Psychol 96:467–491
Dittmar H, Drury J (2000) Self-image—is it in the bag? A qualitative comparison between
“ordinary” and “excessive” consumers. J Econ Psychol 21(2):109–142
Donahue CB, Odlaug BL, Grant JE (2011) Compulsive buying treated with motivational
interviewing and imaginal desensitization. Ann Clin Psychiatry 23(3):226–227
du Toit PL, van Kradenburg J, Niehaus D, Stein DJ (2001) Comparison of obsessive-compulsive
disorder patients with and without comorbid putative obsessive-compulsive spectrum disorders
using a structured clinical interview. Compr Psychiatry 42(4):291–300
Elliott R (1994) Addictive consumption: function and fragmentation in post-modernity. J Consum
Policy 17(2):159–179
Esquirol JE (1838) Des maladies mentales. Baillière, Paris
Faber RJ, O’Guinn TC (1992) A clinical screener for compulsive buying. J Consum Res 19:459–469
Faber RJ, Vohs KD (2004) To buy or not to buy? Self-control and self-regulatory failure in
purchase behavior. In: Baumeister RF, Vohs KD (eds) Handbook of self-regulation: research,
theory and applications. Guilford, New York, pp 509–524
Fernàndez-Aranda F, Jimenez-Murcia S, Alvarez-Moya EM, Granero R, Vallejo J, Bulik CM
(2006) Impulse control disorders in eating disorders: clinical and therapeutic implications.
Compr Psychiatry 47:482–488
Fernàndez-Aranda F, Pinheiro AP, Thornton LM, Berrettini WH, Crow S, Fichter MM, Halmi KA
et al (2008) Impulse control disorders in women with eating disorders. Psychiatry Res
157:147–157
96 Compulsive Buying Disorder 1541
Filomensky TZ, Tavares H (2009) Cognitive restructuring for compulsive buying. Rev Bras
Psiquiatr 31(1):77–78
Filomensky TZ, Almeida KM, Castro Nogueira MC, Diniz JB, Lafer B, Borcato S, Tavares H
(2012) Neither bipolar nor obsessive-compulsive disorder: compulsive buyers are impulsive
acquirers. Compr Psychiatry 53(5):554–561
Frost RO, Tolin DF, Steketee G, Fitch KE, Selbo-Bruns A (2009) Excessive acquisition in
hoarding. J Anxiety Disord 23:632–639
Glatt MM, Cook CC (1987) Pathological spending as a form of psychological dependence.
Br J Addict 82(11):1257–1258
Grant JE (2003) Three cases of compulsive buying treated with naltrexone. Int J Psychiatry Clin
Pract 7:223–225
Grant JE, Levine L, Kim D, Potenza MN (2005) Impulse control disorders in adult psychiatric
inpatients. Am J Psychiatry 162(11):2184–2188
Grant JE, Odlaug BL, Mooney M, O’Brien R, Kim SW (2012) Open-label pilot study of
memantine in the treatment of compulsive buying. Ann Clin Psychiatry 24(2):119–126
Hanley A, Wilhelm MS (1992) Compulsive buying: an exploration into self-esteem and money
attitudes. J Econ Psychol 13(1):5–18
Hantouche EG, Lancrenon S, Bouhassira M, Ravily V, Bourgeois ML (1997) Repeat evaluation of
impulsiveness in a cohort of 155 patients with obsessive-compulsive disorder: 12 months
prospective follow-up. Encéphale 23(2):83–90
Hollander E, Kwon JH, Stein DJ, Broatch J, Rowland CT, Himelein CA (1996) Obsessive-
compulsive and spectrum disorders: overview and quality of life issues. J Clin Psychiatry
57(Suppl 8):3–6
Kacen JJ, Lee JA (2002) The influence of culture on consumer impulsive buying behavior.
J Consum Psychol 12(2):163–176
Kellett S, Bolton JV (2009) Compulsive buying: a cognitive–behavioural model. Clin Psychol
Psychother 16:83–99
Knutson B, Rick S, Wimmer GE, Prelec D, Loewenstein G (2007) Neural predictors of purchases.
Neuron 53:147–156
Koran LM, Chuang HW, Bullock KD, Smith SC (2003) Citalopram for compulsive shopping
disorder: an open-label study followed by a double-blind discontinuation. J Clin Psychiatry
64(7):793–798
Koran LM, Faber RJ, Aboujaoude E, Large MD, Serpe RT (2006) Estimated prevalence of
compulsive buying in the United States. Am J Psychiatry 163(10):1806–1812
Koran LM, Aboujaoude EN, Solvason B, Gamel NN, Smith EH (2007) Escitalopram for compul-
sive buying disorder: a double-blind discontinuation study. J Clin Psychopharmacol
27(2):225–227
Kraepelin E (1915) Psychiatrie, 8th edn. Verlag Von Johann Ambrosius, Leipzig, p 409
Krueger DW (1988) On compulsive shopping and spending: a psychodynamic inquiry. Am
J Psychother 42(4):574–584
Kyrios M, Frost RO, Steketee G (2004) Cognitions in compulsive buying and acquisition. Cogn
Therapy Res 28(2):241–258
Lee S, Mysyk A (2004) The medicalization of compulsive buying. Soc Sci Med 58(9):1709–1718
Lejoyeux M, Hourtane M, Adès J (1995) Compulsive buying and depression. J Clin Psychiatry 56(1):38
Lejoyeux M, Ades J, Tassain V, Solomon J (1996) Phenomenology and psychopathology of
uncontrolled buying. Am J Psychiatry 153(12):1524–1529
Lejoyeux M, Tassain V, Solomon J, Ades J (1997) Study of compulsive buying in depressed
patients. J Clin Psychiatry 58(4):169–173
McElroy SL, Keck PE Jr, Pope HG Jr, Smith JM, Strakowski SM (1994) Compulsive buying:
a report of 20 cases. J Clin Psychiatry 55(6):242–248
Miltenberger RG, Redlin J, Crosby R, Stickney M, Mitchell J, Wonderlich S, Faber R, Smyth J
(2003) Direct and retrospective assessment of factors contributing to compulsive buying.
J Behav Ther Exp Psychiatry 34(1):1–9
1542 T.Z. Filomensky and H. Tavares
Mitchell JE, Burgard M, Faber R, Crosby RD, de Zwaan M (2006) Cognitive behavioral therapy
for compulsive buying disorder. Behav Res Ther 44:1859–1865
Monahan P, Black DW, Gabel J (1996) Reliability and validity of a scale to measure change in
persons with compulsive buying. Psychiatry Res 64(1):59–67
Mueller A, Mueller U, Silbermann A, Reinecker H, Bleich S, Mitchell JE, de Zwaan M (2008)
A randomized, controlled trial of group cognitive behavioral therapy for compulsive buying
disorder: posttreatment and 6-month follow-up results. J Clin Psychiatry 67:1131–1138
Mueller A, Muhlhans B, Muller U, Mertens C, Horbach T, Michell JE, de Zwaan M (2009)
Compulsive buying and psychiatric comorbidity. Psychother Psychosom Med Psychol
59(8):291–299
Mueller A, Mitchell JE, Crosby RD, Gefeller O, Faber RJ, Martin A, Bleich S, Glaesmer H,
Exner C, de Zwaan M (2010) Estimated prevalence of compulsive buying in Germany and its
association with sociodemographic characteristics and depressive symptoms. Psychiatry Res
180(2–3):137–142
Mueller A, Mitchell JE, Peterson LA, Faber RJ, Steffen KJ, Crosby RD, Claes L (2011) Depres-
sion, materialism, and excessive Internet use in relation to compulsive buying. Compr Psychi-
atry 52(4):420–424
Nataraajan R, Goff BG (1991) Compulsive buying: toward a reconceptualization. J Soc Behav
Personal 6(6):307–328
Ninan PT, McElroy SL, Kane CP, Knight BT, Casuto LS, Rose SE, Marsteller FA, Nemeroff CB
(2000) Placebo controlled study of fluvoxamine in the treatment of patients with compulsive
buying. J Clin Psychopharmacol 20(3):362–366
O’Guinn TC, Faber RJ (1989) Compulsive buying: a phenomenological exploration. J Consum
Res 16:147–157
Potenza MN (2001) The neurobiology of pathological gambling. Semin Clin Neurosci
6(3):217–226
Ridgway NM, Kukar-Kinney M, Monroe KB (2008) An expanded conceptualization and a new
measure of compulsive buying. J Consum Res 35:622–639
Roberts JA, Tanner JF Jr (2002) Compulsive buying and sexual attitudes, intentions, and
activity among adolescents: an extension of Roberts and Tanner (2000). Psychol Rep
90(3 Pt 2):1259–1260
Sansone RA, Chang J, Jewell B, Rock R (2013) Childhood trauma and compulsive buying. Int
J Psychiatry Clin Pract 17(1):73–76
Scherhorn G, Reisch LA, Raab G (1990) Addictive buying in West Germany: an empirical study.
J Consum Policy 13(4):355–387
Schlosser S, Black DW, Repertinger S, Freet D (1994) Compulsive buying. Demography,
phenomenology, and comorbidity in 46 subjects. Gen Hosp Psychiatry 16(3):205–212
Steketee G, Frost R (2003) Compulsive hoarding: current status of the research. Clin Psychol Rev
7:905–927
Tavares H, Gentil V (2007) Pathological gambling and obsessive compulsive disorder: towards
a spectrum of disorders of volition. Rev Bras Psiquiatr 29(2):107–117
Tavares H, Lobo DS, Fuentes D, Black DW (2008) Compulsive buying disorder: a review and
a Case Vignette. Rev Bras Psiquiatr 30(1):16–23
Thornhill K, Kellett S, Davies J (2012) Heterogeneity within compulsive buyers: a Q-sort study.
Psychol Psychother 85(2):229–241
Valence G, D’Astous A, Fortier L (1988) Compulsive buying: concept and measurement.
J Consum Policy 11:419–433
Vissering W (2008) On Chinese currency: coin and paper money. Kessinger Publishing, Whitefish
Sexual Addiction
97
Meyen Hertzsprung and Stephen Amadala
Contents
97.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1544
97.1.1 Relationship with Paraphilias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1547
97.2 Management of Sexual Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1547
97.2.1 Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1547
97.2.2 Etiology and Neurobiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1548
97.2.3 Prevalence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1549
97.2.4 Comorbidity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1549
97.2.5 Treatment Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1550
97.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1552
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1553
Abstract
Excessive sexual behavior or hypersexuality has been documented clinically in
the western world since the eighteenth century. Individuals affected by such
behavior have symptoms akin to those with substance dependence. The concept
of sex addiction share features with substance dependence such as distress due to
negative consequences of compulsive sexual behavior and impulsive sexual
behavior. This chapter reviews the evidence for the concept of sex addiction
and discusses the assessment, etiology, neurobiology, prevalence, comorbidity,
and treatment approaches.
M. Hertzsprung (*)
M Hertzsprung Psychological Services, Calgary, AB, Canada
e-mail: [email protected]
S. Amadala
Foothills Medical Centre, Calgary, AB, Canada
e-mail: [email protected]; [email protected]
Keywords
Sex addiction • Compulsive sexual behaviour • Hypersexuality
97.1 Introduction
when discussing hypersexuality (Kaplan and Krueger 2010). The group of individ-
uals easiest to diagnose with a form of sexual addiction are those (primarily men)
who meet criteria for paraphilia disorders (Kafka 1994). This is due to societal and
legal sanctions that consign these individuals to the legal system for punishment or
medical system for treatment. Outside the paraphilias, sexual addiction typically
presents with specific behaviors that are socially sanctioned but often cause
significant distress with concomitant problems such as substance abuse or mental
disorders (Schneider and Irons 2001; Carnes 1991).
There is a challenge in defining abnormal and pathological practices. Carnes and
Wilson (2002) proposed that sexually addictive behaviors include compulsive
masturbation, affairs and use of prostitutes, pornography, cybersex, voyeurism,
exhibitionism, sexual harassment, and sexual offending. They divided the behav-
iors into three levels, in ascending order of potential serious concern. Level
I behaviors, by far the most controversial category, include behaviors that are
commonplace and widely accepted as being normal and unproblematic
(masturbation, using pornography, visiting strip shows, prostitution). Carnes
noted that these may have “devastating” consequences if compulsive or involving
the “victimization of others.” Level II behaviors “are sufficiently intrusive to
warrant stiff sanctions.” Such behaviors all involve some form of victimization
and include exhibitionism, voyeurism, and indecent phone calls. Level III behav-
iors include the most serious forms of sexual victimization (child molestation,
incest, rape, and violence). Goodman (1992), employing a contemporary definition
of substance addiction (DSM IV Criteria), proposed to replace the word substance
with sexual behavior and formulated criteria to describe sexual addiction disorder.
Kafka (2010) proposed “hypersexual disorder” for consideration in the sexual
disorders section for DSM V. It is conceptualized primarily as a nonparaphilic
sexual desire disorder with an impulsivity component (Kafka 2010). The proposed
diagnostic criteria for hypersexual disorder (American Psychiatric Association
DSM V Development 2010) include recurrent and intense sexual fantasies, sexual
urges, or sexual behaviors over a period of at least 6 months. This is in association
with three or more of the five criteria related to repetitive sexual fantasies, urges, or
behaviors and determined by the following: time consumed interfering with other
important goals, activities, and obligations; engagement in response to dysphoric
mood states or in response to stressful life events; unsuccessful efforts to control or
significantly reduce these fantasies, urges, or behaviors; and disregard for the risk
for physical or emotional harm to self or others.
These fantasies, urges, or behaviors are associated with clinically significant
personal distress or impairment in social, occupational, or other important areas of
functioning, and are not due to the direct physiological effect of a drug of abuse or
a medication.
Kafka formulates “hypersexual disorder” as “a sexual desire disorder” charac-
terized by an increased frequency and intensity of sexually motivated fantasies,
arousal, urges, and enacted behavior in association with an impulsivity
component – a maladaptive behavioral response with adverse consequences.
“Hypersexual disorder” is associated with increased time engaging in sexual
97 Sexual Addiction 1547
97.2.1 Assessment
basic drive required for survival (like feeding, thirst, reproduction) into actions of
craving/seeking behaviors or repetitive out-of-control behaviors may make it plau-
sible that addiction can occur even in the absence of drug taking (Karim and
Chaudhri 2012). Thus, behavioral addictions may share many of the same pathways
associated with chemical dependence. Hence, the theory that “if one can alter
neurocircuitry with illicit drugs and pharmacology, then one can alter it with
behavior as well” (Holden 2001).
97.2.3 Prevalence
97.2.4 Comorbidity
One of the consistent findings of studies of those with sexual compulsion was that
the great majority have lifetime comorbid mood, anxiety, psychoactive substance
use, and/or other impulse disorder diagnoses. ADHD (inattentive subtype) was
identified as a co-occurring psychiatric diagnosis in sexual addicts (Blankenship
and Laseer 2004). There is a high correlation between sex addiction and substance
use disorders, up to 80 % in some studies. This tends to complicate the task of
diagnosis and treatment.
With regard to Axis II comorbidity, Raymond et al. (2003) found that the most
commonly co-occurring personality issues are Cluster C personality disorders
(39 %), followed by Cluster B personality disorders (23 %). Reid et al. (2012)
found that men with compulsive sexual behavior exhibited higher levels of
emotional dysregulation, stress vulnerability, and interpersonal sensitivity; these
characteristics generalized to hypersexual women. They concluded that personality
traits associated with emotional problems, difficulties coping with stress, and
interpersonal sensitivity may constitute a precipitating or perpetuating risk factor
in the onset or maintenance of hypersexual behavior in adult men and women and
1550 M. Hertzsprung and S. Amadala
The third category, which Young herself developed, is described as “an integrated
recovery approach that combines cognitive-behavioral and insight-oriented thera-
pies,” which, based solely on her description, was frankly difficult to distinguish
from Carnes’ approach.
Carnes was instrumental in the establishment of the Society for the Advance-
ment of Sexual Health (SASH), a nonprofit multidisciplinary organization “dedi-
cated to scholarship, training, and resources for promoting sexual health and
overcoming problematic sexual behaviors,” such as “sex addiction, hypersexual
disorder, out-of-control sexual behavior, sexual impulsivity, sexual abuse” (SASH
2013). SASH holds a conference yearly and recently started offering a certificate
for “Advanced Training in Problematic Sexual Behavior.”
Carnes also founded the International Institute for Trauma and Addiction Pro-
fessionals (IITAP), which offers “premier training and cutting-edge educational
resources for practitioners who treat people with addictive and compulsive sexual
behaviors” and claims that its CSAT (Certified Sex Addiction Therapist) program is
“one of the most highly regarded programs of its kind, offering a complete group of
training, products and services” (IITAP 2013); Carnes also founded Gentle Path
Press, which publishes many of the materials used for training as well as the books
recommended through his task-centered approach.
While Stefanie Carnes, clinical psychologist and current president of IITAP, has
remarked that the CSAT training is “very strongly research based” (personal
communication, 28 March 2011), Rory Reid, research psychologist at the Depart-
ment of Psychiatry and Biobehavioral Sciences at the University of California, Los
Angeles, asserts that “having reference material that is ‘research based’ is not the
same as having a treatment approach that is empirically supported by research”
(personal communication, 28 March 2011). Indeed, Reid bemoans the fact that as of
early 2011, there were only eight published treatment outcome studies related to the
sex addiction population, half of which were single-subject design studies (personal
communication, 6 February 2011).
When conceptualized as an addiction, there are many possibilities of extending
already established therapies that help with addictive behaviors, such as motiva-
tional enhancement therapy, cognitive-behavioral approaches, emotional aware-
ness, and mindfulness-based approaches. Participation in 12-step recovery groups
is also routinely recommended in conjunction with psychosocial treatment. How-
ever, so far there is a paucity of research evidence to empirically support any
one treatment approach for compulsive sexual behavior.
indicate that SSRIs may be of use in the treatment of sexual addiction. This is based
on the rationale that serotonergic dysfunction may underlie the condition. Madeo
(2008) showed in a randomized control trial with citalopram that in healthy adult
males, 4 weeks of treatment significantly increased the time to orgasm compared to
men on placebo. However, the medications did not dampen sexual desire or penile
tumescence measurements, suggesting that SSRIs may have differential effects on
dampening libido and sexual function in men who are not depressed or who do not
have compulsive sexual behavior. In a randomized control trial, gay and bisexual
men with sexual addiction/compulsivity who were treated for 12 weeks with
citalopram (20–60 mg a day) reported significant reductions in sexual drive,
frequency of masturbation, and viewing of pornography in comparison to those treated
with placebo (Weinberg et al. 2006). In summary there is some evidence supporting
the use of the SSRI citalopram for sex addiction, especially in gay and bisexual men.
Naltrexone is an opioid antagonist approved for use in treating alcoholism and
opioid dependence. It works by dampening dopamine release, thus reducing the
euphorigenic effects of fantasizing and tension building which are considered the
initial steps in compulsive sexual behaviors. There are no randomized trials of
opioid antagonists for sexual addiction. Some open-label trials show that high doses
of naltrexone reduced frequency of masturbation, sexual fantasies, and nocturnal
emission (Bostwick and Bucci 2008).
Antiandrogen medications currently used for treatment of excessive
nonparaphilic sexual behavior are cyproterone acetate (a synthetic steroid similar
to progesterone which acts both as a progesterone and an antiandrogen) and
medroxyprogesterone acetate. Medroxyprogesterone acetate diminishes libido in
men and thus makes it easier to control sexually addictive behavior. The rationale
of using hormone therapies in men with sexual addiction is based on eliminating
sexual compulsivity and obsessions by stopping the production of testosterone. This
approach is usually reserved for treating paraphilias in men that involve sexual
offending involving children and violence (Thibaut et al. 2010; Gottesman and
Schubert 1993). Antiandrogens diminish sex drive in women; hence, the use of
antiandrogens in women to control hypersexuality may be of benefit.
Goodman (1998) has presented a psychotherapeutic stage model integrating
pharmacotherapeutic, behavioral, and psychodynamic approaches. In the first
stage (initial behavior modulation), individuals who engage in addictive sexual
behavior learn how to modulate their behavior through a combination of inner
motivation, psychological support, and affect-regulating medication; the second
stage (stabilization of behavior and affect) addresses the question of relapse pre-
vention, with a distinction between high- and low-risk forms of sexual behavior.
Patients are taught to engage in “healthier” forms of sexual behavior.
97.3 Conclusion
Sex addiction as a concept carries a lot of controversy. In the last two decades, there
has been an effort in defining the features of sex addiction. The proposed inclusion
97 Sexual Addiction 1553
References
American Psychiatric Association (2010) DSM5: proposed revisions: hypersexual disorder. Avail-
able at http://www:dsm5.org/proposed Revisions/pages/ProposedRevision. Accessed 15 April
2010
Anthony S (2012) Just how big are porn sites? Extreme Tech. http://www.extremetech.com/
computing/123929-just-how-big-are-porn-sites. Accessed 14 Feb 2013
Arnow BA, Desmond JE, Banner LL, Glover, GH, Solomon A, Polan ML, Lue TF, Atlas SW
(2002) Brain activation and sexual arousal in healthy heterosexual males. Brain 126 (PT5):
1014–1023
Black DW (2000) The epidemiology and phenomenology of compulsive sexual behavior: CNS
Spectrums 5:26–72
Black C, Tripodi C (2012) Intimate treason: healing the trauma for partners confronting sex
addiction. Central Recovery Press, Las Vegas
Blankenship R, Laaser M (2004) Sexual addiction and ADHD: is there a connection? Sex Addict
Compuls 11:7–20
Bostwick JM, Bucci JA (2008) Internet sex addiction treated with naltrexone. Mayo Clin Proc
83:226–636
Carnes P (1989) Contrary to love. Hazelden, Center City
Carnes P (1991) Don’t call it love: recovery from sexual addiction. Bantam, New York
Carnes P (2005) Facing the shadow: starting sexual and relationship recovery, 2nd edn. Gentle
Path, Carefree
Carnes P, Wilson M (2002) The sexual addiction assessment process. In: Carnes P, Adams K (eds)
Clinical management of sex addiction. Brunner - Routledge, New York, pp 3–20
Carnes PJ et al (2010) The same yet different: refocusing the sexual addiction screening test
(SAST) to reflect orientation and gender. Sex Addict Compuls 12:79–120
Carnes P, Green BA, Merlo LJ, Polles A, Carnes S, Gold MS (2012) A brief screening application
for assessing sexual addiction. J Addict Med 6(1):29–34
Cloud J (2011) The truth about sex addiction. Time (TIME) 177(8):44–48, 50
Di Ciara G (1998) A motivational learning hypothesis of the role of mesolimbic dopamine in
compulsive drug use. J Psychopharmacol 12:54–67
Dryer JA, Lijtmaer RM (2007) Cyber-sex as twilight zone between virtual reality and virtual
fantasy: creative play space or destructive addiction? Psychoanal Rev 94(1):39–61
Fisher WA, Barak A (2001) Internet pornography: a social psychological perspective on internet
sexuality. J Sex Res 38(4):312–323
Gold SN, Heffner CL (1998) Sexual addiction: many conceptions, minimal data. Clin Psychol Rev
18(3):367–381
Goodman A (1992) Sexual addiction: designation and treatment. J Sex Marital Ther 18:303–314
1554 M. Hertzsprung and S. Amadala
Stein DJ et al (1992) Serotonergic medications for sexual obsessions, sexual addictions and
paraphilias. J Clin Psychiatry 53:267–271
Thibaut F, De La Barra F, Gordon H, Cosyns P, Bradford JM (2010) The world Federation of
Societies of Biological Psychiatry (WFSB) guidelines for the biological treatment of
paraphilias. World J Biol Pschiatry 1(4):604–655
van Wormer K (1990) Co-dependency. Women Ther 8(4):51–63
Vilas P, Pont-Sunyer C, Tolosa E (2012) Impulse control disorders. Parkinsonism Relat Disord
18(1):580–584
Weinberg ML, Muench F, Morgenstern J, Hollnder E, Irwin TW, Parsons JT, Allen A, O’Leary A
(2006) A double blind study of citalopram versus placebo in the treatment of compulsive
sexual behaviours in gay and bisexual gay men. J Clin Psychiatry 67(12):1968–1973
Young K (2008) Internet addiction: diagnosis and treatment considerations. J Contemp Psychother
39:241–246
The Association Between Binge Eating,
Obesity and Addiction 98
Stephanie C. Yarnell, Susan Murray, Nicole M. Avena, and
Mark S. Gold
Contents
98.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1558
98.2 Feeding and Reward . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1559
98.3 Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1560
98.4 Binge Eating . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1563
98.5 Screening Individuals for Food Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1565
98.6 Management of Food Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1566
98.7 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1567
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1567
Abstract
Obesity has become a worldwide pandemic with an estimated annual cost in
related illnesses and loss of productivity over $100 billion and rising. Though
not recognized as a psychiatric disorder, obesity has been linked to serious
physical, psychological, and social consequences. Some forms of obesity are
typified by the compulsive consumption of food, difficulty curbing further
intake despite negative consequences, a desire to cut back, as well as needing
increasing amounts of food to reach satiety, resembling a form of tolerance.
These symptoms are remarkably similar to DSM criteria for substance use
disorders. Research in both animals and humans has demonstrated food-related
changes in the brain itself that are very similar to changes caused by drugs of
abuse leading to the hypothesis that some forms of obesity and a related
98.1 Introduction
This chapter seeks to describe the common elements and possible intersection of
binge eating disorder, obesity, and addiction. The Diagnostic and Statistical Manual
of Mental Disorders V (DSM-V) currently recognizes Anorexia, bulimia, binge
eating disorder (BED), and FED-NEC secondary to the serious impairments and
severe negative outcomes associated with these conditions (APA 2013). Unlike
eating disorders, obesity is not currently recognized as a psychiatric disorder.
However, obesity has been linked to serious physical, psychological, and social
consequences. Some forms of obesity are typified by the compulsive consumption
of food, difficulty curbing further intake despite negative consequences, a desire to
cut back, as well as needing increasing amounts of food to reach satiety, resembling
a form of tolerance (Volkow and O’Brien 2007; Taylor et al. 2010). These symp-
toms are remarkably similar to DSM criteria for substance use disorders. These
symptoms are remarkably similar to the DSM-IV criteria for substance abuse and
dependence: preoccupation, escalation, tolerance, denial, and a series of medical,
psychological, and social consequences that relate directly to continued use
(APA 2013; Gold et al. 2009), thereby leading to the hypothesis that some forms
of obesity and a related contributing behavior, binge eating, may manifest second-
ary to or along with a “food addiction.”
The concept of food addiction is a highly debated one (Avena et al. 2012b). One
argument against the notion that food is addictive is, of course, that everyone eats.
How can something that sustains life be considered addictive? It has been proposed,
however, that only certain foods be considered addictive, specifically those high in
sugars and fats. These “forbidden” foods are typically calorie dense, highly palat-
able, and the types of foods that people tend to overconsume most (Corwin and
Grigson 2009). Studies using animal models have provided a great deal of empirical
support for the concept of food addiction. Such studies have found that similar to
substance addictions, the consumption of these types of foods increases dopami-
nergic activity in the brain’s mesolimbic reward circuits and leads to increased
intake over time, and when animals are deprived of these foods, a history of such
consumption can precipitate symptoms of withdrawal (Avena et al. 2008). More
recently, tools have been designed to assess food addiction in humans, and studies
incorporating such tools are beginning to provide additional evidence of this
construct. For example, more than half of obese individuals with binge eating
disorder included in one study met the criteria for food addiction (Gearhardt
et al. 2012). Using fMRI scanning, individuals with greater food addiction scores
have also been shown to have greater activation of motivation-related brain regions
when anticipating highly palatable food, similar to drug-addicted individuals when
viewing cues associated with a drug (Gearhardt et al. 2011).
98 The Association Between Binge Eating, Obesity and Addiction 1559
Disordered eating, such as that seen in binge eating disorder, bulimia nervosa, and
some cases of obesity, poses a number of complications for the medical community.
These conditions can be physically compromising and, in some cases, even fatal;
however, their etiology is not well characterized. Expert speculations regarding the
underlying risk factors for the development of disordered eating include a range of
psychological, biological, and societal influences. Given the growing evidence of
neurochemical and behavioral similarities between overconsumption of certain foods
and substance addiction, and the urgent need to develop effective treatments to
combat obesity and overeating, it may be time to consider food addiction as
a possible contributing factor to these issues, as well as a target for treatment.
release thereby affecting the reward process. Similarly, ACh in the nucleus
accumbens has been associated with satiety, though the precise mechanism of
action needs further investigation (Avena and Rada 2012). 5-HT is also associated
with the sensation of satiety and can be associated with weight loss and fat
intake (Halford and Blundell 2000). Given the interplay between all of these
neurotransmitters and the nucleus accumbens, it is possible that dysfunction at
any of these key points could result in disordered eating. This also explains why
many of the pharmacological therapies for eating disorders have been targeting
these neurotransmitter systems.
98.3 Obesity
Obesity, defined as a body mass index >30, has increased dramatically over the last
three decades and is now estimated to affect over 33 % of the US population. Obesity
is classified as a medical condition as it places a patient at increased risk for
cardiovascular disease, diabetes, cancer, and other diseases resulting in a 5–20-year
reduction in life expectancy, as well as costing $70–$100 billion annually by
conservative estimates. The seriousness of these health consequences highlights the
urgent need for strong prevention efforts and the development of effective treatment
approaches for individuals with this condition (Volkow and O’Brien 2007).
The cause of obesity remains largely unknown, but, similar to eating disorders, is
likely multifactorial (Fig. 98.1). It has been suggested that the behavioral phenotype
of overeating may be influenced by an interplay of genetics, development, and
environmental factors (Brownell and Gold 2012). While separable in theory, the
interplay of one’s genes; the time, place, and culture in which one lives; and the
development of one’s obesity through non-homeostatic mechanisms are likely all
simultaneously involved and thereby relevant to the problem (Devlin 2007).
Within genetic theories, the “thrifty genotype” hypothesis suggests that the
neurocircuitry underlying food procurement and bodily storage evolved at a point
in human history in which food was scarce as a means of promoting survival in
times of famine (Volkow and O’Brien 2007). However, recent advances in tech-
nology have allowed for the creation and modification of foods, which artificially
enhance palatability beyond what would be found in nature, especially with regard
to sugar, fat, and caloric value (Taylor et al. 2010). These calorie-rich, highly
palatable foods are abundant and easily accessible in the typical Western diet.
This combination of factors may lead to the activation of reward circuitry, which
evolved to reinforce feeding behavior, and desires to engage in pathologic
overconsumption, which would have been advantageous in a time of famine but
now, in a context of abundance, appear maladaptive (Brownell and Gold 2012).
In contrast, the “developmental origin” hypothesis suggests that our exposure to
certain nutrients and calorie contents in utero may imprint upon our developing
brain and influence food choices when outside of the womb. Evidence to support
this hypothesis comes from studies investigating the effects of consuming certain
98 The Association Between Binge Eating, Obesity and Addiction 1561
diets during gestation on various outcome measures in the offspring. For example,
recent research has found that the offspring of animals fed a high-fat diet during
gestation are more likely to weigh more and consume more of a high-fat diet
compared to controls (Bocarsly et al. 2012). While one hypothesis takes into
account an evolutionary perspective and the other a more developmental view,
both of these hypotheses may have value for understanding the current issues of
obesity and disordered eating.
In regard to possible cultural and environmental influences of obesity, the past
several decades have seen five major developments that are thought to have tipped
the balance between caloric intake and energy expenditure to an unfavorable
disproportion: (1) expanding labor market opportunities for women, (2) increased
consumption of food outside of the home, (3) rising costs of healthy foods relative
to unhealthy foods, (4) increasing quantities of caloric intake with declining overall
food price, and (5) decreased requirements of occupational and environmental
physical activity (Gold and Gold 2011). Other environmental factors implicated
in the development of patterns of overeating include advertisements, sights, smells,
and sounds, which have all been shown to induce food cravings and can result in
overeating (Blumenthal and Gold 2010). Indeed, eating is more than a physiologic
response; it can serve as a social lubricant, facilitating both personal and profes-
sional interactions, and is a prominent centerpiece for most individuals at holidays
and celebrations (Gold et al. 2009).
1562 S.C. Yarnell et al.
These factors highlight the cultural aspect of obesity, but with them come a new
set of challenges. During the Coronary Artery Revascularization in Diabetes
(CARD) trial, which followed a population of 18–35-year-old patients over
10 years, the average patient showed a weight increase of at least 7 kg regardless
of race and sex. This study demonstrated that significant weight gain over the
course of adult life is now normative, suggesting a strong cultural component
(Norman et al. 2003). In order to be classified as a disease, however, a condition
must clearly differ from the norms of society. This conundrum has led some to
refute claims that obesity should be included in the DSM-V as it may simply be
a behavioral disturbance with an adverse medical outcome, not necessarily
a psychiatric condition (Devlin 2007). While not all individuals who are obese
may fit the existing criteria for food addiction, it is possible that individuals who do
may represent a subcategory of obesity that is characterized in part by significant
distress due to their thoughts and behaviors regarding food and/or exhibit
comprised functioning as a result of these thoughts and behaviors. As such, these
individuals may be recognized as having a psychiatric condition despite being
within a weight range that may be considered relatively “normal” based on current
trends within society. In fact, over- and/or normal-weight individuals also fit the
criteria for food addiction.
Obesity is often described as an imbalance between caloric intake and energy
expenditure. This simplified view has led some to suggest that obesity is the fault of
the person due to excessive consumption, inadequate activity, or a combination of the
two, resulting in much of the stigma that is associated with this condition
(Devlin 2007). While decreased caloric consumption and increased physical
activity can be effective in normalizing weight, these lifestyle modifications have
proven very difficult to sustain (Volkow and O’Brien 2007). The failure of many
lifestyle modifications to reduce obesity over the long term suggests that obesity may
not be entirely a metabolic disorder, but likely has a neuropsychogenic component
(Volkow and O’Brien 2007). While food addiction certainly does not explain all
cases of obesity, the prevalence of people who eat for reasons other than obtaining
energy suggests that other factors may play a role in motivating and/or reinforcing
feeding behaviors. With the rapidly increasing number of cases of obesity, it may be
time to consider new ways of understanding and approaching this problem.
Some hypothesize that obesity, at least in certain cases, is related to
dysregulation of the brain’s reward system. The hypothalamus is accepted as the
primary brain region responsible for managing signals that regulate the intake of
food, primarily through hormones such as ghrelin, leptin, and insulin which effect
both the hypothalamus and the reward neurocircuitry in such areas as the caudate
nucleus, hippocampus, and insula (Taylor et al. 2010). Food, especially when it is
rich in fat and sugars, stimulates brain reward circuitry, in part, through the release
of endogenous opioids, cannabinoids, and DA (Abizaid et al. 2006). Since these are
some of the same neuropathways and neurotransmitters associated with drug
addiction, as mentioned earlier, some have suggested that repeated exposure to
certain foods in vulnerable individuals may result in compulsive food consumption,
poor control, conditioning to food stimuli, and ultimately excess weight gain
98 The Association Between Binge Eating, Obesity and Addiction 1563
Binge eating disorder is now listed in the DSM V as a stand alone diagnosis. Binge
eating is characterized by eating rapidly, eating more than was intended, eating alone,
and feelings of disgust, guilt, or depression secondary to these binges. It has been
reported that 3.5 % of adult women and 2 % of adult men within the US population
suffer from binge eating disorder. These numbers are reported to be slightly lower for
adolescents (2.3 % females, .8 % males) (Smink et al. 2012).
Bingeing has long been associated with bulimia nervosa, as binge eating is one
of the major diagnostic criteria for this disorder, but it is also associated with
obesity (APA 2013). The key difference between binge eating and bulimia
1564 S.C. Yarnell et al.
Studies such as these have also led some to wonder if the dopaminergic system
could provide a target for pharmaceutical intervention of bingeing behaviors.
Indeed, one study using an animal model of binge eating found the D2 antagonist,
raclopride, reduces binge intake of high-fat foods, while having no effect on ad
libitum consumption (Corwin and Wojnicki 2009). Similarly, studies suggest that
naltrexone, an opioid antagonist, can suppress bingeing behaviors (Corwin and
Wojnicki 2009). Further, single-photon emission tomography (SPECT) studies
have demonstrated that when compared to obese controls, decreased 5-HT trans-
porter binding was found among obese binge eaters, suggesting that this may be
another potential pharmaceutical target (Kuikka et al. 2001).
Within the brain, the ventral limbic circuit and the orbitofrontal cortex are
important in the regulation of feeding behaviors as well as identifying emotional
stimuli and facilitating a subsequent response, and atrophy or deregulation within
these regions has been noted in persons with bingeing behaviors (Marsh
et al. 2009). This suggests a link between emotions and binge eating. Indeed, one
study found that 100 % of participants, all of whom were obese women who binge
eat, reported that mood contributed to binge behavior. 68 % reported depression or
sadness and 55 % reported boredom preceding a binge episode (Chua et al. 2004). It
is not surprising, therefore, that the teaching of affect regulation skills through the
use of dialectical behavioral therapy (DBT) has yielded promising results in this
population (Telch et al. 2001).
Given the potential magnitude and severity of food addictions, efforts have been
made to develop screening tools for addictive-like eating. Gearhardt et al. (2009a)
created the Yale Food Addiction Scale (YFAS), which consists of a series of
questions based on the substance addiction criteria as outlined in the DSM-IV. This
tool is designed to identify and better characterize signs and symptoms consistent
with food addiction. Respondents use a yes/no format and 5-point Likert scale for
questions regarding frequency. In early testing, the YFAS exhibited adequate internal
reliability, good convergent validity with other measures of disordered eating, as well
as good discriminant validity relative to related yet dissimilar conditions such as
alcohol consumption and impulsivity (Gearhardt et al. 2009b). A recent study has
shown a link between YFAS scores and mood disorders among obese patients with
binge eating disorder. The YFAS has also been shown to be a good predictor of the
frequency of binge eating episodes in this patient population (Gearhardt et al. 2012).
As noted by the authors, the YFAS may help clinicians better identify disordered
eating habits in their patients as well as allow researchers to better identify potential
candidates for future studies. Future studies in this area may facilitate the development
of screening tests for addiction to specific food ingredients, such as fat or sugar, which
may lead to a better understanding of the types of foods that may be associated with
food addiction, as well as the development of more specific approaches to treatment.
1566 S.C. Yarnell et al.
The study of food addiction is relatively new and specialized treatment approaches
have not yet been developed. However, because of overlaps between binge eating,
obesity, and food addiction, it is possible that strategies that are effective for
treating binge eating and obesity may also prove helpful in the treatment of food
addiction. Certain types of psychotherapy, including cognitive behavioral therapy
(CBT), cognitive behavioral therapy with guided self-help (CBT-gsh), and inter-
personal therapy (IPT), have shown success in the treatment of binge eating
disorder (Devlin et al. 2005; Iacovino et al. 2012). As mentioned earlier, DBT
has also been shown to be effective in treating binge eating behavior (Telch
et al. 2001). Among existing pharmaceuticals, fluoxetine, desipramine, imipramine,
and topiramate have been suggested to be effective in the treatment of binge eating
disorder (Walsh et al. 1997), and phentermine, diethylpropion, and orlistat are often
provided for obesity (Powell et al. 2011). For some, binge eating may become an
ingrained behavior that serves as a form of self-medication in response to negative
emotional states such as depression, anxiety, loneliness, boredom, anger, and
interpersonal conflict. This highlights the role of behavior modification, in addition
to pharmacological interventions, in the treatment of food addictions (Taylor
et al. 2010). It should be noted that treatment of disordered eating can be a long
and arduous process marked by alternating periods of relapse and recovery.
With regard to obesity, some patients turn to invasive procedures such as
bariatric surgical treatments including gastric bypass and gastric banding. While
these procedures do result in dramatic weight loss, they can be expensive and can
have significant risks, including the development of gastric dumping syndrome and
increased risk of bone fractures (Nakamura et al. 2011). As a result, much attention
today is focused on developing better treatment options. Given the rise of obesity
not only in the USA but around the world (Yach et al. 2006), a number of
pharmaceutical companies are looking to develop new treatments for obesity
based on the addiction hypothesis (Blumenthal and Gold 2010). Indeed, a number
of new treatments are in both phase II and phase III clinical trials (Blumenthal and
Gold 2010). The majority of these potential treatment options target the
neuropathways and neurotransmitters discussed in this chapter, including
raclopride, bupropion, and antipsychotics which target dopamine; naltrexone,
naloxone, and nalmefene which target the opioid system; baclofen and topiramate
which target the GABAergic system; SR141716, AM 251, and rimonabant which
target cannabinoid receptors; as well as several new pharmaceuticals (Berner
et al. 2011; Yarnell et al. 2013). However, these medications are not without risk;
many of these drugs carry significant side effects including increased risk for
depression, anxiety, obsessive-compulsive disorder, seizures, suicide, confusion,
or memory deficits (Blumenthal and Gold 2010). Given the risks and side effects
associated with these drugs, physicians will need to exercise great care when
considering whether to prescribe these treatments and should carefully select
their population base prior to prescribing (Blumenthal and Gold 2010).
98 The Association Between Binge Eating, Obesity and Addiction 1567
98.7 Conclusion
As it stands, obesity and binge eating behaviors will continue to be a threat to global
health (Avena et al. 2012c). As such, it is perhaps time to reevaluate the current
food environment from many aspects while taking into consideration both the
individual’s perspective and society as whole. Societal measures may, in fact, be
required at this time as dysfunctional eating behaviors affect not only the current
generation but also its offspring due to the effects that consuming certain highly
palatable foods may have on the developing brain in utero.
Given that some of the cultural factors discussed in this chapter are driven by
economic factors that lie outside the control of the individual, the topic of
obesity cannot simply be relegated to the domain of personal responsibility.
Rather, economic incentives that may encourage people to make unhealthy food
choices may need to be reevaluated on a larger scale. Indeed, any plan to combat
the rise in obesity will need to address the economic, political, social, psycho-
logical, and biological factors that contribute to obesity, as well as factors such
as taste, accessibility, convenience, cost, and level of promotion (Yach
et al. 2006). Moreover, society may need to closely reevaluate the current
state of food marketing. As mentioned earlier, one study has found that food-
addicted persons respond at an even higher level to food cues than their
nonaddicted counterparts (Gearhardt et al. 2011). This finding suggests that
advertising cues may contribute, at least in part, to compulsive eating in
at-risk persons. Further, societal changes such as reevaluating where govern-
ment subsidies are allocated, taxation, publicly enforced well-care programs,
and corporate-driven employee well-being programs may also be needed to
address the issues of disordered eating and obesity. While these efforts are not
expected to cure obesity, binge eating, or food addiction, they may help to
reduce their prevalence and aid prevention efforts.
Acknowledgment The authors would like to thank Paula Edge and Eric Su for their assistance
with the manuscript. Support was provided by the University of Florida and DA-03123 (NMA).
References
Abizaid A, Gao Q et al (2006) Thoughts for food: brain mechanisms and peripheral energy
balance. Neuron 51(6):691–702
American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders
(5th ed.). American Psychiatric Publishing, Arlington, VA
Avena NM, Rada PV (2012) Cholinergic modulation of food and drug satiety and withdrawal.
Physiol Behav 106(3):332–336
Avena NM, Rada P et al (2008) Evidence for sugar addiction: behavioral and neurochemical
effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev 32(1):20–39
Avena NM, Bocarsly ME et al (2012a) Animal models of sugar and fat bingeing: relationship to
food addiction and increased body weight. Meth Mol Biol 829:351–365
1568 S.C. Yarnell et al.
Avena NM, Gearhardt AN et al (2012b) Tossing the baby out with the bathwater after a brief rinse?
The potential downside of dismissing food addiction based on limited data. Nat Rev Neurosci
13(7):514, author reply 514
Avena NM, Gold JA et al (2012c) Further developments in the neurobiology of food and addiction:
update on the state of the science. Nutrition 28(4):341–343
Berner LA, Bocarsly ME et al (2011) Pharmacological interventions for binge eating: lessons from
animal models, current treatments, and future directions. Curr Pharm Des 17(12):1180–1187
Blumenthal DM, Gold MS (2010) Neurobiology of food addiction. Curr Opin Clin Nutr Metab
Care 13:359–365
Bocarsly ME, Barson JR et al. (2012) Effects of perinatal exposure to palatable diets on body
weight and sensitivity to drugs of abuse in rats. Physiol Behav 107(4):568–575
Brownell KD, Gold MS (eds) (2012) Food and addiction: a comprehensive handbook. Oxford
University Press, New York
Chua JL, Touyz S et al (2004) Negative mood-induced overeating in obese binge eaters: an
experimental study. Int J Obes Relat Metab Disord 28(4):606–610
Conason A, Teixeira J et al. (2012) Substance use following bariatric weight loss surgery. JAMA
Surg 148(2):145–150
Corwin RL, Grigson PS (2009) Symposium overview–food addiction: fact or fiction? J Nutr
139(3):617–619
Corwin RL, Wojnicki FH (2009) Baclofen, raclopride, and naltrexone differentially affect intake
of fat and sucrose under limited access conditions. Behav Pharmacol 20(5–6):537–548
Devlin MJ (2007) Is there a place for obesity in DSM-V? Int J Eat Disord 40(Suppl):S83–S88
Devlin MJ, Goldfein JA et al (2005) Cognitive behavioral therapy and fluoxetine as adjuncts to
group behavioral therapy for binge eating disorder. Obes Res 13(6):1077–1088
Gearhardt AN, Corbin WR et al (2009a) Food addiction: an examination of the diagnostic criteria
for dependence. J Addict Med 3(1):1–7
Gearhardt AN, Corbin WR et al (2009b) Preliminary validation of the Yale food addiction scale.
Appetite 52(2):430–436
Gearhardt AN, Yokum S et al (2011) Neural correlates of food addiction. Arch Gen Psychiatry
68(8):808–816
Gearhardt AN, White MA et al (2012) An examination of the food addiction construct in obese
patients with binge eating disorder. Int J Eat Disord 45(5):657–663
Gold J, Gold MS (2011) Exercise for the overweight and obese. Curr Pharm Des
17(12):1193–1197
Gold MS, Graham NA et al (2009) Food addiction? J Addict Med 3(1):42–45
Grucza R, Przybeck TR, Cloninger CR (2007) Prevalence and correlates of binge eating disorder
in a community sample. Compr Psychiatry 48(2):124–131
Halford JC, Blundell JE (2000) Pharmacology of appetite suppression. Prog Drug Res Fortschr
Arzneimittelforschung Progres Rech Pharm 54:25–58
Hasler G, Pine DS et al (2004) The associations between psychopathology and being overweight:
a 20-year prospective study. Psychol Med 34(6):1047–1057
Hudson JI, Hiripi E et al (2007) The prevalence and correlates of eating disorders in the National
Comorbidity Survey Replication. Biol Psychiatry 61(3):348–358
Iacovino JM, Gredysa DM et al (2012) Psychological treatments for binge eating disorder. Curr
Psychiatry Rep 14(4):432–446
Johnson PM, Kenny PJ (2010) Dopamine D2 receptors in addiction-like reward dysfunction and
compulsive eating in obese rats. Nat Neurosci 13(5):635–641
Kales EF (1990) Macronutrient analysis of binge eating in bulimia. Physiol Behav 48(6):837–840
Kampov-Polevoy AB, Ziedonis D et al (2003) Association between sweet preference and paternal
history of alcoholism in psychiatric and substance abuse patients. Alcohol Clin Exp Res
27(12):1929–1936
Koob GF, Volkow ND (2010) Neurocircuitry of addiction. Neuropsychopharmacology
35(1):217–238
98 The Association Between Binge Eating, Obesity and Addiction 1569
Kuikka JT, Tammela L et al (2001) Reduced serotonin transporter binding in binge eating women.
Psychopharmacology (Berl) 155(3):310–314
Leibowitz SF, Hoebel BG (2004) Behavioral neuroscience and obesity. In: Bray G, Bouchard C,
James P (eds) The handbook of obesity. Marcel Dekker, New York
Marsh R, Maia TV et al (2009) Functional disturbances within frontostriatal circuits across
multiple childhood psychopathologies. Am J Psychiatry 166(6):664–674
Merlo LJ, Klingman C et al (2009) Exploration of food addiction in pediatric patients:
a preliminary investigation. J Addict Med 3(1):26–32
Nakamura KM, Haglind EGC et al (2011) Fracture risk after bariatric surgery. Endocr Rev 32:
OR44–OR45, 03_Meeting Abstracts
Norman JE, Bild D et al (2003) The impact of weight change on cardiovascular disease risk factors
in young black and white adults: the CARDIA study. Int J Obes Relat Metab Disord J Int Assoc
Study Obes 27(3):369–376
Pi-Sunyer FX (2002) The medical risks of obesity. Obes Surg 12(Suppl 1):6S–11S
Powell AG, Apovian CM et al (2011) New drug targets for the treatment of obesity. Clin
Pharmacol Ther 90(1):40–51
Rogers PJ (2011) Obesity - is food addiction to blame? Addiction 106(7):1213–1214, discussion
1219–1220
Rolls ET (2007) Sensory processing in the brain related to the control of food intake. Proc Nutr Soc
66(1):96–112
Saper CB, Chou TC et al (2002) The need to feed: homeostatic and hedonic control of eating.
Neuron 36(2):199–211
Smink FR, van Hoeken D et al (2012) Epidemiology of eating disorders: incidence, prevalence and
mortality rates. Curr Psychiatry Rep 14(4):406–414
Spangler R, Wittkowski KM et al (2004) Opiate-like effects of sugar on gene expression in reward
areas of the rat brain. Brain Res Mol Brain Res 124(2):134–142
Tanofsky-Kraff M, Cohen ML et al (2006) A prospective study of psychological predictors of
body fat gain among children at high risk for adult obesity. Pediatrics 117(4):1203–1209
Taylor VH, Curtis CM et al (2010) The obesity epidemic: the role of addiction. CMAJ Can Med
Assoc J J Asso Med Can 182(4):327–328
Telch CF, Agras WS et al (2001) Dialectical behavior therapy for binge eating disorder. J Consult
Clin Psychol 69(6):1061–1065
Volkow ND, O’Brien CP (2007) Issues for DSM-V: should obesity be included as a brain
disorder? Am J Psychiatry 164(5):708–710
Walsh BT, Wilson GT et al (1997) Medication and psychotherapy in the treatment of bulimia
nervosa. Am J Psychiatry 154(4):523–531
Wang GJ, Volkow ND et al (2009) Evidence of gender differences in the ability to inhibit brain
activation elicited by food stimulation. Proc Natl Acad Sci U S A 106(4):1249–1254
Wendling A, Wudyka A (2011) Narcotic addiction following gastric bypass surgery–a case study.
Obes Surg 21(5):680–683
Yach D, Stuckler D et al (2006) Epidemiologic and economic consequences of the global
epidemics of obesity and diabetes. Nat Med 12(1):62–66
Yarnell S, Oscar-Berman M et al. (2013) Pharmacotherapies for overeating and Obesity. J Genet
Syndr Gene Ther 4(3):131–148
Section VIII
Medical Disorders and
Complications of Alcohol and Other
Drugs, Pain and Addiction
The health consequences of drugs are major problems throughout the world with
billions of people using legal (tobacco and alcohol) and illegal drugs
(amphetamines, cocaine, opiates, hallucinogens, and marijuana). Drug use is asso-
ciated with burdensome social, economic, and health consequences, the latter
involving almost every physiological/biochemical system. These may include
psychiatric, cardiovascular, metabolic, and hepatic complications and infectious
diseases. Although there is a myriad of problems related to drug use, it is the
medical consequences that are the leading causes of death, and consequently, these
are of great medical concern. It is evident that this section on medical consequences
of drug abuse is an important component of a comprehensive textbook of addiction
medicine that should describe, most if not all, these health effects and their clinical
management. In general, the principles of assessment and management of these
disorders are no different from people who do not abuse drugs or alcohol, but this
section of the textbook describes particular patterns of morbidity and approaches to
management that distinguish this population.
The typical patient with a substance use disorders has multiple problems rather
than single pathology as described above, yet it is not generally feasible for multiple
specialists to become involved. Consequently, the addiction medicine specialist
needs a broad range of clinical skills to adequately manage patients with complex
health problems including pain. Alcohol and other drugs particularly affect the
neurological and gastrointestinal systems but may involve all other systems. The
chief medical comorbidities include infectious diseases, sleep, and pain disorders.
Patients may be infected with infections including human immunodeficiency virus
(HIV) and hepatitis C virus (HCV), tuberculosis, and sexually transmitted infec-
tions individually or in combination. Nutrition is important and nutritional disor-
ders may impact on recovery from other co-occurring illnesses. Patients often
require complex treatment with multiple medications, and consequently, pharma-
cokinetic/pharmacodynamic drug-drug interactions are a particular challenge in
this population. Physicians with a background in mental health will welcome
a concise description of the chief medical disorders to be encountered in their
patients. In many cases with pathology that responds to management as
recommended in this section, further specialist referral can be minimized.
Infectious diseases form the focus of several chapters in this section. An
estimated one third of the global population of seven billion is living with one
or more bacterial or viral infections (United Nations AIDS (UNAIDS) 2008).
There are an estimated 200 million people who abuse illegal drugs regularly
(United Nations Office on Drugs and Crime: World Drug Report 2007) in the
world, and this population is at increased risk of blood-borne viruses and other
infections. Legal and illegal substance abuse alone costs the American society an
estimated 534 billion dollars annually (Office of National Drug Policy 2004),
while diabetes and cancer cost an estimated $174 billion (American Diabetes
Association 2003) and $263 billion (American Cancer 2008), respectively. Infec-
tions that occur in people who use substances lead to enormous social, economic,
and health costs to the society. These infections are associated with inferior
outcomes in drug users compared to nondrug users for a range of reasons
including poor general health, poor engagement with health care, lower rates of
treatment uptake, and higher rates of treatment dropout. Alcohol and drug use are
also associated with impaired immune function that may increase infection risk.
Infectious diseases complicating drug use can affect all systems of the body and
are described throughout this section, but the blood-borne viruses are particularly
important public health problems. There have been striking advances in the
treatment of blood-borne virus infections particularly HCV and HIV. New anti-
virals have transformed HCV treatment and are poised to rapidly develop further
in the coming decade. The complications and management of viral hepatitis in
drug-abusing populations, particularly HCV, have been addressed by Giorgio
Barbarini. HIV treatment continues to improve in efficacy and tolerability. It is
important to note that the problem of drug interactions that appeared earlier
between HIV antiretrovirals and methadone seems to be less with the newly
approved buprenorphine. Khalsa and his colleagues have reviewed the medical
consequences of substance abuse and co-occurring infections and how to clini-
cally manage these health effects.
The cardiovascular complications of alcohol and other drugs have been
addressed by Mori Krantz et al. This group has provided an overview on the
99 Medical Disorders and Complications of Alcohol and Other Drugs 1575
References
American Cancer Society (2008) Cancer facts & figures 2008. Atlanta. http://www.cancer.org/
downloads/STT/2008CAFFfinalsecured.pdf
American Diabetes Association (2003) Economic costs of diabetes in the US in 2002. Diabetes
Care 26:917–932. http://www.ncbi.nlm.nih.gov/pubmed/12610059
Office of National Drug Policy (2004) The economic costs of drug abuse in the United States:
1992-2002. Executive Office of the President, Washington, DC. http://www.ncjrs.gov/
ondcppubs/publications/pdf/economic_costs.pdf
United Nations AIDS (UNAIDS) (2008) Report on the global AIDS epidemic; UNAIDS/08-25E/
JC1510E. ISBN 978 92 9 173711 6; Joint United Nations Programme on HIV/AIDS/WHO,
2008. http://www.unaids.org/en/KnowledgeCentre/HIVData/GlobalReport/2008/
United Nations Office on Drugs and Crime (2007) World drug report 2007. United Nations Office
on Drugs and Crime, vol 1. ISBN 92-1-148214-7. http://www.unodc.org/pdf/research/wdr07/
WDR_2007.pdf
Cardiovascular Consequences of
Addiction 100
Peter K. Moore, David Kao, and Mori Krantz
Contents
100.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1578
100.2 Mechanisms and Cardiovascular Consequences of Abused Drugs . . . . . . . . . . . . . . . . . 1581
100.2.1 Alcohol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1581
100.2.2 Cocaine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1585
100.2.3 Amphetamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1592
100.2.4 Opioids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1594
100.2.5 Nicotine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1599
100.2.6 Cannabis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1601
100.3 Anabolic Steroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1602
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1604
Abstract
Drugs of abuse often have important effects on the cardiovascular system, some
of which are life-threatening. An understanding of the intersection between
addictive and cardiovascular disorders, therefore, is increasingly relevant to
general practitioners and psychiatrists. The effects of illicit drugs vary
depending upon the agent, dose, route of administration, and its potential
interaction with other prescription medications. Cardiovascular consequences
can range from innocuous side effects, such as mild tachycardia and hyperten-
sion, to life-threatening ventricular arrhythmias and myocardial infarction.
P.K. Moore
Department of Internal Medicine, University of California, San Francisco, San Francisco, CA,
USA
e-mail: [email protected]
D. Kao • M. Krantz (*)
Division of Cardiology, School of Medicine, University of Colorado, Aurora, CO, USA
Denver Health Medical Center, University of Denver, Denver, CO, USA
e-mail: [email protected]; [email protected]; [email protected]
Hemodynamic alterations are common with both active drug abuse and with-
drawal and are frequently mediated by the autonomic nervous system.
Sympathomimetic drugs like amphetamines and cocaine often result in an
increase in blood pressure and heart rate. In addition, they may cause substantial
cardiotoxicity including arrhythmia, stroke, myocardial infarction, heart failure,
and death. These stimulant drugs often increase the propensity for developing
atherosclerosis. Some of this is mediated by increases in blood pressure and
lipids, but may also occur due to proinflammatory effects or increased hypercoa-
gulability. By contrast, some drugs such as opioids lead to small reductions in
pulse and blood pressure. Most naturally occurring opioids do not alter cardiac
rhythm; however, synthetic opioids, such as methadone, may result in QTc
interval prolongation and torsades de pointes, a form of life-threatening ventric-
ular arrhythmia. In this chapter we review the cardiovascular effects of common
drugs of abuse including cocaine, amphetamines, nicotine, opioids, alcohol,
marijuana, and anabolic steroids.
100.1 Introduction
Fig. 100.1 (a) Prolonged rate-corrected QT interval (QTc). (b) Torsades de pointes, a type of
polymorphic ventricular tachycardia
100.2.1 Alcohol
Alcohol (ethanol) is widely used throughout the world with an estimated two billion
users representing nearly half of the world’s population. Light to moderate alcohol
consumption has been associated with a reduced risk of atheroembolic vascular
events including myocardial infarction and ischemic stroke, but chronic heavy
alcohol use is clearly cardiotoxic and is associated both directly and indirectly
with a number of cardiovascular consequences including hypertension, atrial fibril-
lation, stroke, and cardiomyopathy. Adverse cardiovascular effects begin to appear
with consumption of two to three standard drinks/day or more and increase there-
after in a dose-dependent fashion (Lange and Hillis 2012). In comparison with
moderate regular drinking, binge drinking is also associated with increased risk of
complications such as atherosclerosis, atrial fibrillation (AF), and stroke (Liang
et al. 2012). Alcohol is directly toxic to cardiomyocytes via a number of mecha-
nisms including uncoupling of the excitation-contraction system, impairment of
calcium sequestration in the sarcoplasmic reticulum, reduction of mitochondrial
respiratory ratio, and increased interstitial protein synthesis (George and Figueredo
2011; Lange and Hillis 2012). In addition, alcohol increases sympathetic tone
producing elevated heart rate and blood pressure (Mandyam et al. 2012), impairs
vagal tone, may precipitate electrophysiologic changes in atrial tissue (Kodama
et al. 2011), and is associated with endothelial dysfunction (Goslawski et al. 2013),
each of which may contribute to adverse cardiovascular outcomes.
Abstinence often results in rapid improvement in many of cardiovascular conse-
quences and in some cases may be the only intervention necessary in the long term to
address alcohol-associated cardiovascular risk. However, acute alcohol withdrawal
delirium tremens in particular can precipitate cardiovascular changes that may be
fatal. Hypertension and tachycardia are classic symptoms of acute alcohol withdrawal,
and though they improve within 3–4 days of alcohol cessation, they may precipitate
ischemic or hemorrhagic stroke, acute decompensated heart failure, or cardiac ische-
mia in the setting of coronary artery disease. Fatal arrhythmias may also be precipi-
tated by adrenergic surge, electrolyte deficiencies, or QT interval prolongation.
Management of patients with acute alcohol withdrawal who have known cardiovas-
cular disease is further complicated by potential exaggerated hemodynamic responses
to beta-blockers, calcium channel blockers, and long-acting nitrates early in the course
of withdrawal (Kahkonen 2006). There is little direct evidence regarding management
of cardiovascular complications of acute alcohol withdrawal in the setting of specific
cardiac conditions, but propranolol and clonidine are most commonly suggested to
treat withdrawal-related autonomic instability as well as aggressive replacement of
potassium, magnesium, and phosphate. Because of the potential exaggerated effects
on cardiac output and peripheral vascular resistance of both medications, particular
caution must be taken in the setting of dilated cardiomyopathy and valvular disease
such as advanced aortic stenosis.
1582 P.K. Moore et al.
thought to contribute to alcohol-related AF. Alcohol and drug abuse have been
associated with a lower likelihood of treatment with warfarin, and it remains
important to risk stratify all patients using a validated risk score such as the
CHADS2 or CH2ADS2-Vasc score when deciding whether to initiate prophylactic
antiplatelet or anticoagulation therapy (Camm et al. 2010). Unlike warfarin, newer
agents such as rivaroxaban, dabigatran, or apixaban offer the advantage of not
requiring routine monitoring, which may be useful in the setting of questionable
compliance (Camm et al. 2012). These agents were associated with lower rates than
warfarin of intracerebral hemorrhage and gastrointestinal bleeding, both of which
occur more frequently in alcoholics than nonalcoholics, but there is no direct
evidence to determine whether they provide a safe alternative for anticoagulation
in AF in the setting of alcohol abuse.
stroke risk within 1–24 h of heavy alcohol use has been observed. This may be due
to reactive thrombocytosis and increased platelet aggregation during alcohol with-
drawal, and we speculate that increased adrenergic activity may also play a role.
Paradoxically, the observed association between alcohol and hemorrhagic stroke
may relate to impaired coagulation function as well as weakening of cerebral
arteries. The increased risk of both stroke and death due to ischemic heart disease
appears to return toward baseline in former heavy drinkers (Hillbom et al. 1999;
Roerecke et al. 2011), and apart from abstinence, there are no specific risk reduction
strategies recommended apart from standard cardiovascular risk reduction. Elimi-
nation of tobacco abuse may be a particularly important risk factor given that it is
often used in the setting of social alcohol consumption and is itself a potent
atherosclerotic risk factor.
100.2.1.3 Cardiomyopathy
Although light to moderate alcohol consumption has been associated with a lower
rate of heart failure than nondrinkers, chronic heavy alcohol use is a well-known
cause of left ventricular diastolic and systolic dysfunction. In fact, alcohol may be
the leading etiology of nonischemic dilated cardiomyopathy in industrialized
nations. Most men who develop alcoholic cardiomyopathy have consumed 8 stan-
dard drinks/day for 5 years. Women appear to be more sensitive to the cardiotoxic
effects of alcohol and may develop cardiomyopathy with a smaller comparative
exposure. Evidence of cardiotoxicity may be apparent long before the emergence of
symptoms, as 30–50 % of alcoholics have echocardiographic evidence of left
ventricular hypertrophy and/or diastolic dysfunction and 30 % of asymptomatic
alcoholics have evidence of systolic dysfunction as measured by reduced left
ventricular ejection fraction (LVEF). Direct myocardial damage may be mediated
by acetaldehyde, the first metabolite of ethanol. Acetaldehyde levels are
particularly elevated in heavy drinkers, in part due to reduce hepatic aldehyde
dehydrogenase activity (Zhang et al. 2004). Chronic activation of the renin-
angiotensin-aldosterone system and sympathetic nervous system and nutritional
deficiency (especially thiamine) may also contribute to progression of myocardial
dysfunction by potentiating alcohol- and acetaldehyde-induced cell death.
Abstinence can result in significant improvement in left ventricular systolic
function if achieved early during the progression of myocardial dysfunction.
It has been shown that “controlled” intake of two to six standard drinks/day has
also been associated with improvement in LVEF within months, but because
controlled drinking is generally not possible for alcoholics, total abstinence remains
the primary recommendation. Long-term survival in patients with alcoholic
cardiomyopathy who achieve abstinence is the same or better than patients with
idiopathic dilated cardiomyopathy, whereas patients who continue to drink have
a lower survival (Prazak et al. 1996). As for all dilated cardiomyopathies, neuro-
hormonal blockade with b-blockers and renin-angiotensin-aldosterone system
inhibitors is the cornerstone of medical therapy. Additional considerations in the
setting of alcoholic cardiomyopathy are nutritional and vitamin supplementation,
particularly vitamin B12 and folate.
100 Cardiovascular Consequences of Addiction 1585
100.2.2 Cocaine
jugular venous pressure and a soft systolic murmur. Lung auscultation is normal.
Urine toxicology is positive for benzoylecgonine. ECG demonstrates ST segment
elevation in leads V2–V5 with peaked T-waves. QRS duration and rate-corrected
QT (QTc) intervals are prolonged. Chest x-ray and serum chemistries (including
cardiac troponin) are unremarkable. Upon sharing these results, the patient con-
fides that he and his girlfriend consumed an “eight-ball” (3.5 grams) of cocaine by
intranasal route.
Cocaine (benzoylmethylecgonine) is a crystalline alkaloid, derived from the
coca plant that is among the most widely abused drugs worldwide. It is
a consumed via intranasal insufflation, inhaled vapor from smoking a freebase
combination with sodium bicarbonate, or the intravenous route. Cocaine incites
a wide array of cardiovascular consequences ranging from acute alterations in
hemodynamics to myocardial ischemia, ventricular arrhythmias, and dilated
cardiomyopathy (Table 100.1). The extensive effects on the cardiovascular system
result from its numerous mechanisms of action. Cocaine is a potent sympathomi-
metic that augments central sympathetic outflow and has the ability to increase
peripheral catecholamine concentration. Cocaine also exhibits antiarrhythmic-like
inhibition of voltage-gated sodium channels and potassium channels and has
complex, poorly understood interactions with L-type calcium channels
(Ramirez et al. 2012).
100.2.2.1 Hemodynamics
Cocaine incites a range of hemodynamic alterations. Sympathomimetic activity
dominates at low to moderate doses resulting in tachycardia, systemic vasocon-
striction, and coronary vasospasm. However, at higher doses, cocaine’s sodium and
potassium channel inactivation can lead to cardiodepression, tachy- and bradydysr-
hythmias, and even vasodilation (Egashira et al. 1991a; Schwartz et al. 2010).
When taken at low doses (0.35 mg/kg) through the intranasal route, cocaine
ingestion simply results in slight elevation of systolic blood pressure, while higher
doses (1.3 mg/kg) will cause an increase in systolic and diastolic blood pressure
(30/15 mmHg) and elevation of the heart rate (20 bpm). The onset of these
alterations occurs at 2 min and peaks at 5–10 min (Resnick et al. 1977). Moderate
cocaine doses (2–3 mg/kg) have a positive inotropic effect, resulting in an increase
in left ventricular contractility and cardiac index (Boehrer et al. 1992). In sum, low
to moderate doses of cocaine result in tachycardia and in hypertension via a rise in
both systemic vascular resistance and cardiac output.
The mechanism of catecholamine response is dependent on the route of cocaine
administration. Experimentally, intravenous infusion of cocaine in humans blocks
the reuptake of catecholamines peripherally, thereby increasing available norepi-
nephrine in the heart and vascular smooth muscle (Muscholl 1961; Tuncel
et al. 2002). However, when consumed by the intranasal route, peripheral norepi-
nephrine levels are not elevated (Tuncel et al. 2002). Therefore, the mechanism of
hypertension in acute cocaine intoxication following intranasal is due to an increase
of central sympathetic outflow (Vongpatanasin et al. 1999).
100 Cardiovascular Consequences of Addiction 1587
antagonists, cocaine’s direct effect on the heart is unmasked and left ventricular
contractility is significantly reduced (Kenny et al. 1992).
cocaine users, and the diagnosis of STEMI is challenging in this population due to
baseline ECG abnormalities (Lange and Hillis 2001; McCord et al. 2008). Percu-
taneous coronary intervention is the preferred management of intracoronary throm-
bus, but fibrinolytics can be used in cases of persistent ST segment elevation after
nitroglycerin and calcium channel blockers have been given if there are no contra-
indications and coronary angiography is not available (McCord et al. 2008;
Anderson et al. 2011).
Outcomes are generally better in cocaine-related MI compared to MI not related
to cocaine (McCord et al. 2008). The incidences of ventricular arrhythmias, con-
gestive heart failure, and death are 4–17 %, 5–7 %, and <2 %, respectively (Lange
and Hillis 2001). The better outcomes are presumably due to the overall younger
age of patients experiencing MI while using cocaine. However, those who experi-
ence cocaine-related MI are at high risk for recurrent ischemic events as more than
half will continue to use cocaine and up to 58 % will have recurrence of ischemia
(McCord et al. 2008).
100.2.3 Amphetamines
100.2.4 Opioids
Opioids exert their principal clinical actions of analgesia and euphoria via agonist
activity at the m-opioid receptor in the central nervous system (CNS). Respiratory
depression occurs in a dose-dependent manner and represents the principle cause of
opioid-related mortality. By contrast, cardiovascular effects tend to be relatively mild,
with no direct effect of most opioids on cardiac rhythm or myocardial contractility.
However, orthostatic hypotension may occur, presumably secondary to histamine
release and vasodilation of peripheral arteriolar vessels. In patients with acute coro-
nary syndromes, opioids are often used intravenously for relief of chest discomfort.
Intravenous morphine is most frequently utilized in acute myocardial infarction. It
leads to mild venodilatation, which decreases preload and myocardial oxygen con-
sumption in the setting of left ventricular systolic dysfunction and pulmonary edema.
Intravenous opioids also result in a small decrease in pulse and blood pressure in the
acute coronary syndrome patient. Opioids may also improve myocardial energetics at
the cellular level and have been associated with enhancement of “ischemic
preconditioning.” This phenomenon entails repetitive episodes of noncritical ische-
mia, which may provide myocardial protection to patients chronically treated with
opioids. In support of this theory, an autopsy study evaluated age and gender matched
decedents stratified by the presence of opioid detected at autopsy (Marmor et al. 2004).
100 Cardiovascular Consequences of Addiction 1595
The authors found a lower burden of coronary artery disease among opioid users
and postulated that this may relate to ischemic preconditioning.
By contrast to the potential protective effects of opioids with regard to athero-
sclerotic coronary artery disease, more recent evidence suggests that synthetic
opioids may adversely influence cardiomyocyte electrophysiology and occasionally
lead to malignant arrhythmia. Specifically, synthetic opioids may block the delayed
rectifier potassium ion current known as IKr, which is encoded by the hERG gene.
This blockade may lead prolongation of the QTc interval in vivo, which is the
requisite substrate for drug-induced torsades de pointes, a type of polymorphic
ventricular tachycardia (Fig. 100.1).
Vignette A 34-year-old law school student presents to your psychiatry office with
complaints of fevers, malaise, occasional rigors, and fatigue for 10 days. He has
been previously treated for major depression but takes no prescription drugs. He
has a 7-year history of intermittent recreational opioid abuse. Over the past
6 months he reports escalation in abuse of prescription opioids including oxyco-
done and hydrocodone cough syrup with dextromethorphan. When he is unable to
use opioids, he develops withdrawal symptoms, and 2 weeks ago he admits to
a period of intravenous, black-tar, heroin use. His last opioid consumption was
2 hours ago. The patient is in no acute distress. Examination is notable for
a temperature of 38.5 degrees Celsius. Blood pressure is 135/70 mm Hg, and
pulse is 112 beats per minute. Cardiovascular exam is notable for a grade III
systolic murmur at the lower left sternal border accentuated following inspiration.
He reluctantly rolled up his sleeves, revealing the presence of healed track marks
and a small abscess in the left antecubital fossa. The remainder of his examination
is normal.
100.2.4.1 Heroin
Diacetylmorphine or heroin was originally formulated as an antitussive agent. It is
derived from the opium poppy and was extensively marketed by Bayer Corporation
before its addictive potential was recognized in the early 1900s (Marmor
et al. 2004). Heroin is often injected after heating a liquid solution but increasingly
is smoked or nasally insufflated. Like all opioids, its principal medical complication
is central nervous system (CNS) depression and respiratory depression.
The effects of heroin on the cardiovascular system are not extensive, which may
in part reflect its close derivation from the natural opium poppy. Heroin abuse is
associated with acute pulmonary edema, but this is generally non-cardiogenic in
origin. The typical hemodynamic findings include normal pulmonary-capillary
pressure and a normal or increase cardiac output (Barceloux 2012), suggesting
the absence of direct myocardial toxicity. Although moderately elevated pulmonary
artery pressures have been described, this is most likely due to direct pulmonary
toxicity in the setting of injected impurities or in overdose with hypoxemia leading
to subsequent increased pulmonary-capillary leakage.
1596 P.K. Moore et al.
into ventricular fibrillation and lead to sudden cardiac death. A case of methadone-
induced arrhythmia masquerading as epilepsy has been previously described
(Krantz et al. 2005). This highlights the fact that ventricular arrhythmia if prolonged
may result in marked reduction of cardiac output and cerebral hypoxemia and
subsequent seizures. Thus, seizures are not always due to epilepsy and should alert
clinicians to the possibility of life-threatening arrhythmia.
Many addiction clinicians are unaware of the cardiac arrhythmic properties of
synthetic opioids used in treating opioid dependency (Krantz et al. 2007). However,
a recent registry study found that ventricular arrhythmia and cardiac arrest are now
the most frequent FDA-reported class of methadone-associated adverse events, and
reports of QTc prolongation and torsades de pointes have increased sharply in the
past decade (Kao et al. 2013). In this study, methadone was associated with
a disproportionate signal of torsades de pointes reporting similar to that of drugs
with established proarrhythmic properties (such as dofetilide). By contrast, pro-
poxyphene, which was recently withdrawn from the market due to QTc prolonga-
tion and dysrhythmia, was not associated with disproportional arrhythmia
reporting. Because available evidence definitely suggests that both oral and intra-
venous methadone hydrochloride cause QTc interval prolongation and torsades de
pointes, a consensus guideline suggesting QTc interval screening was developed
(Krantz et al. 2009). The guideline emphasized five recommendations for physi-
cians prescribing methadone (Table 100.3). Because the arrhythmia risk associated
with methadone is a direct consequence of its effect on cardiac repolarization, the
recommendations are applicable to patients either receiving current treatment with
methadone or being considered for initiation of methadone treatment for addiction
or pain management. Because methadone is now considered an essential medica-
tion by the World Health Organization, its utilization is expected to rise, highlight-
ing the need to enhance its cardiac safety.
Table 100.3 Consensus recommendations for QTc interval screening in methadone treatment
(Krantz et al. 2009)
Recommendation Clinicians should inform patients of arrhythmia risk when they
1 (disclosure) prescribe methadone
Recommendation Clinicians should ask patients about any history of structural heart
2 (clinical history) disease, arrhythmia, and syncope
Recommendation Obtain a pretreatment ECG for all patients to measure the QTc
3 (screening) interval and then a follow-up ECG within 30 days and annually.
Additional ECG is recommended if the methadone dosage exceeds
100 mg/d or if patients have unexplained syncope or seizures
Recommendation 4 (risk If QTc interval is >450 ms but <500 ms, discuss potential risks and
stratification) benefits with patients and monitor them more frequently. If the QTc
interval exceeds 500 ms, consider discontinuing methadone or
reducing the methadone dose; eliminating contributing factors, such
as drugs that promote hypokalemia; or using an alternative therapy
Recommendation 5 (drug Clinicians should be aware of interactions between methadone and
interactions) other drugs that possess QT interval-prolonging properties or slow
the elimination of methadone
100 Cardiovascular Consequences of Addiction 1599
100.2.5 Nicotine
Cigarette smoking is the leading risk factor for developing cardiovascular disease,
increasing risk of coronary artery disease by up to 80–100 % (Law et al. 1997).
Secondhand smoke exposure is also harmful, potentially increasing risk of coronary
artery disease by up to 30 % (Whincup et al. 2004). Furthermore, pipe smoking,
smokeless tobacco, and cigars are all associated with increases in cardiovascular
morbidity and mortality (Katsiki et al. 2013). Nicotine is the addictive and primary
active component in tobacco products and causes many of the adverse cardiovas-
cular effects of smoking. Nicotine acts in part by stimulating release of norepi-
nephrine from sympathetic nerves and by release of epinephrine from the adrenal
glands, which produce increases in heart rate and blood pressure shortly after
exposure. Although the precise role of nicotine relative to other components of
cigarette smoke is unclear, cigarette smoking is also associated with vasomotor
dysfunction mediated by reduced availability of nitric oxide, systemic inflammation
that increases adherence of leukocytes to endothelial cells, increases in serum
low-density lipoprotein and triglycerides with decreases in high-density lipopro-
tein, platelet dysfunction, and alteration of thrombotic factors (Ambrose and Barua
2004). Consequently, cigarette smoking is associated with increased rates of
all-cause and cardiovascular mortality, first myocardial infarction, recurrent
infarction or revascularization in patients with coronary artery disease, sudden
death, and stroke (Foody et al. 2001; Prescott et al. 2002; Rodriguez et al. 2002;
Goldenberg et al. 2003).
Cessation of smoking is associated with rapid decreases in cardiovascular events
including myocardial infarction, stroke, and sudden death, with rates returning to
near that of nonsmokers within 3–4 years in many cases (Rea et al. 2002; Gellert
et al. 2013). Although the increased risk of cardiovascular events associated with
smoking appears to increase with age, the benefits of cessation are independent of
age. Despite the clear risks of smoking and benefits of smoking cessation, smoking
rates remain relatively stable, and the rate at which physicians in the United States
advise patients to stop smoking has actually decreased over the last 10 years
(Kruger et al. 2012). Intensive support including structured behavioral modification
counseling and pharmacotherapy with either nicotine replacement therapy and/or
bupropion appears superior to one-time counseling in patients hospitalized for
coronary disease or heart failure, although even a brief statement to outpatients
of the risks associated with smoking can result in increases in smoking cessation
(Lin et al. 2013).
The acute hemodynamic effects of nicotine withdrawal are poorly character-
ized, but appear minimal. Blood pressure and heart rate are likely to decrease
compared with ongoing tobacco use (Morrell et al. 2008), and withdrawal symp-
toms are primarily limited to psychosocial changes including prominent irritabil-
ity. Consequently, abrupt smoking cessation as may occur during hospitalization
for myocardial infarction or heart failure is unlikely to adversely affect an
individual’s hemodynamic status. Theoretical concerns regarding vasoconstrictor
activity of nicotine and rare anecdotal reports of myocardial infarction in patients
1600 P.K. Moore et al.
100.2.6 Cannabis
Anabolic steroids have varying degrees of androgenic properties and are frequently
utilized by athletes, weightlifters, and bodybuilders to enhance athletic perfor-
mance and strength. Anabolic steroids are associated with direct effects such as
left ventricular hypertrophy and myocardial fibrosis and indirect effects, including
dyslipidemia, hypertension, arrhythmia, and myocardial infarction (Higgins
et al. 2012). It is likely that chronic exposure to these agents can result in significant
alterations in the cardiovascular system, beyond the expected increase in salt and
water retention leading to elevations in blood pressure in susceptible patients.
Cardiomyocytes have testosterone receptors, which may explain the propensity
to muscular hypertrophy in the setting of supraphysiologic doses. The most feared
complication of anabolic steroids, however, is the increased risk of ischemic
cardiovascular events. Numerous reports of myocardial infarction have been
described in the literature even among young patients. In addition, there is further
concern that anabolic steroids may accelerate the overall atherosclerotic process
with ongoing abuse. A framework for understanding this risk has been put forward
(Melchert and Welder 1995). Four mechanisms are suggested: (1) atherosclerosis-
dyslipidemia model given marked reductions up to 70 % in high-density lipoprotein
(HDL) cholesterol, which is responsible for reverse cholesterol transport and
>20 % increases in the atherogenic low-density lipoprotein (LDL) cholesterol;
100 Cardiovascular Consequences of Addiction 1603
(2) vasospasm model given alterations in the vascular nitric oxide system;
(3) thrombosis model involving alterations in platelet and clotting function includ-
ing increases in plasminogen activator activity; and (4) direct myocardial injury
model including impaired myocardial relaxation and diastolic dysfunction. Another
factor that enhances the risk of myocardial infarction is polycythemia associated
with anabolic steroids. This increases blood viscosity and the risk of thrombosis.
As such, a complete blood count should be obtained in patients using anabolic
steroids who present with ischemic complications. Beyond the risk of acute
myocardial infarction, these agents have been associated with cerebrovascular
accident (Garcia-Esperon et al. 2013), suggesting that atheroembolic complications
may affect all vascular territories. Furthermore, anabolic steroid use has been
associated with supraventricular and ventricular ectopy, atrial fibrillation, ventric-
ular fibrillation, and ventricular tachycardia, and cardiac pathology has been
frequently observed in deceased anabolic steroid abusers (Thiblin et al. 2000).
Anabolic steroid use should be considered in young athletes with evidence of
hypertension, very low serum HDL and elevated LDL cholesterol levels, atrial or
ventricular arrhythmias, and/or left ventricular hypertrophy by electrocardiogram or
echocardiogram. There is little data regarding cardiovascular risk reduction associ-
ated with anabolic steroid use apart from abstinence. The actual prevalence of
significant coronary artery disease among anabolic steroid users is not known, and
cardiovascular risk reduction should conform to standard age-appropriate guidelines
until additional data is available. Blood pressure and lipid abnormalities will gener-
ally resolve after 6–12 months of abstinence, but there is evidence that pathologic left
ventricular hypertrophy may persist for years after discontinuation of steroid use,
although this persistence may be due to sustained or ongoing strength training (Achar
et al. 2010). If blood pressure abnormalities are particularly severe, or do not resolve
with abstinence, pharmacologic intervention should be considered. Statin therapy
should be initiated for sustained LDL cholesterol levels 160 mg/dL in accordance
with current guidelines. Rosuvastatin in particular appears more effective in raising
HDL levels than other statins. Omega-3 fatty acids and niacin have also been
associated with increases in HDL cholesterol, but their efficacy in reducing risk of
cardiovascular effects is uncertain. Antihypertensive therapy should be considered if
the blood pressure is consistently 140/90 in accordance with currently guidelines.
The optimal antihypertensive agent for steroid-associated hypertension is unclear,
although the stimulation of the renin-angiotensin-aldosterone system observed in
anabolic steroid users suggests that ACE inhibitors or angiotensin receptor blockers
may be particularly effective and are often tolerated well by young patients.
b-blockers are typically not used as monotherapy for hypertension, but may be
considered if coexisting arrhythmias are present. There is currently no evidence or
recommendation for antiplatelet therapy for primary prevention in anabolic steroid
use. There is no clear evidence for pharmacologic treatment of LV hypertrophy,
although dilated cardiomyopathy as a result prolonged steroid use and/or ischemic
events should be treated in accordance with heart failure guidelines using neurohor-
monal blockade with b-blockers and renin-angiotensin-aldosterone system inhibitors
along with vasodilators and/or diuretics according to patient symptoms.
1604 P.K. Moore et al.
References
Achar S, Rostamian A et al (2010) Cardiac and metabolic effects of anabolic-androgenic steroid abuse
on lipids, blood pressure, left ventricular dimensions, and rhythm. Am J Cardiol 106(6):893–901
Ambrose JA, Barua RS (2004) The pathophysiology of cigarette smoking and cardiovascular
disease: an update. J Am Coll Cardiol 43(10):1731–1737
Anderson JL, Adams CD et al (2011) 2011 ACCF/AHA focused update incorporated into
the ACC/AHA 2007 guidelines for the management of patients with unstable angina/
Non-ST-elevation myocardial infarction: a report of the American college of cardiology
foundation/American heart association task force on practice guidelines. Circulation
123(18):e426–e579
Aronow WS, Cassidy J (1974) Effect of marijuana and placebo-marijuana smoking on angina
pectoris. N Engl J Med 291(2):65–67
Bachs L, Morland H (2001) Acute cardiovascular fatalities following cannabis use. Forensic Sci
Int 124(2–3):200–203
Barceloux DG (2012) Heroin and the opium poppy plant (Papaver somniferum L.) (ed) Medical
toxicology of drug abuse synthesized chemicals and psychoactive plants, first edn. Wiley,
Hoboken, p 546
Bennett IL Jr, Walker WF (1952) Cardiac arrhythmias following the use of large doses of central
nervous system stimulants. Am Heart J 44(3):428–431
Benzaquen BS, Cohen V et al (2001) Effects of cocaine on the coronary arteries. Am Heart
J 142(3):402–410
Bertolet BD, Freund G et al (1990) Unrecognized left ventricular dysfunction in an apparently
healthy cocaine abuse population. Clin Cardiol 13(5):323–328
Boehrer JD, Moliterno DJ et al (1992) Hemodynamic effects of intranasal cocaine in humans.
J Am Coll Cardiol 20(1):90–93
Boehrer JD, Moliterno DJ et al (1993) Influence of labetalol on cocaine-induced coronary
vasoconstriction in humans. Am J Med 94(6):608–610
Brogan WC 3rd, Lange RA et al (1992) Recurrent coronary vasoconstriction caused by intranasal
cocaine: possible role for metabolites. Ann Intern Med 116(7):556–561
Cahill PA, Redmond EM (2012) Alcohol and cardiovascular disease–modulation of vascular cell
function. Nutrients 4(4):297–318
Camm AJ, Kirchhof P et al (2010) Guidelines for the management of atrial fibrillation: the task
force for the management of atrial fibrillation of the European Society of Cardiology (ESC).
Eur Heart J 31(19):2369–2429
Camm AJ, Lip GY et al (2012) 2012 focused update of the ESC Guidelines for the management of
atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrilla-
tion. Developed with the special contribution of the European Heart Rhythm Association. Eur
Heart J 33(21):2719–2747
Carty CS, Soloway PD et al (1996) Nicotine and cotinine stimulate secretion of basic fibroblast
growth factor and affect expression of matrix metalloproteinases in cultured human smooth
muscle cells. J Vasc Surg 24(6):927–934, discussion 934–925
Carvalho M, Carmo H et al (2012) Toxicity of amphetamines: an update. Arch Toxicol
86(8):1167–1231
Chakko S, Sepulveda S et al (1994) Frequency and type of electrocardiographic abnormalities in
cocaine abusers (electrocardiogram in cocaine abuse). Am J Cardiol 74(7):710–713
Cuculi F, Kobza R et al (2006) ECG changes amongst patients with alcohol withdrawal seizures
and delirium tremens. Swiss Med Wkly 136(13–14):223–227
Dattilo PB, Hailpern SM et al (2008) Beta-blockers are associated with reduced risk of myocardial
infarction after cocaine use. Ann Emerg Med 51(2):117–125
Diercks DB, Fonarow GC et al (2008) Illicit stimulant use in a United States heart failure
population presenting to the emergency department (from the acute decompensated heart
failure national registry emergency module). Am J Cardiol 102(9):1216–1219
100 Cardiovascular Consequences of Addiction 1605
Durack DT, Lukes AS et al (1994) New criteria for diagnosis of infective endocarditis:
utilization of specific echocardiographic findings. Duke endocarditis service. Am J Med
96(3):200–209
Eagle KA, Isselbacher EM et al (2002) Cocaine-related aortic dissection in perspective. Circula-
tion 105(13):1529–1530
Egashira K, Morgan KG et al (1991a) Effects of cocaine on excitation-contraction coupling of
aortic smooth muscle from the ferret. J Clin Inv 87(4):1322–1328
Egashira K, Pipers FS et al (1991b) Effects of cocaine on epicardial coronary artery reactivity in
miniature swine after endothelial injury and high cholesterol feeding. In vivo and in vitro
analysis. J Clin Inv 88(4):1307–1314
Eisenberg MJ, Grandi SM et al (2013) Bupropion for smoking cessation in patients hospitalized
with acute myocardial infarction: a randomized, placebo-controlled trial. J Am Coll Cardiol
61(5):524–532
Estruch R, Coca A et al (2005) High blood pressure, alcohol and cardiovascular risk. J Hypertens
23(1):226–229
Ettinger PO, Wu CF et al (1978) Arrhythmias and the “holiday heart”: alcohol-associated cardiac
rhythm disorders. Am Heart J 95(5):555–562
Finkel JB, Marhefka GD (2011) Rethinking cocaine-associated chest pain and acute coronary
syndromes. Mayo Clinic proceedings. Mayo Clin 86(12):1198–1207
Fisher BA, Ghuran A et al (2005) Cardiovascular complications induced by cannabis smoking:
a case report and review of the literature. Emerg Med J 22(9):679–680
Fleckenstein AE, Volz TJ et al (2007) New insights into the mechanism of action of amphet-
amines. Annu Rev Pharmacol Toxicol 47:681–698
Flores ED, Lange RA et al (1990) Effect of cocaine on coronary artery dimensions in atheroscle-
rotic coronary artery disease: enhanced vasoconstriction at sites of significant stenoses. J Am
Coll Cardiol 16(1):74–79
Food, U. S. D. O. H. Drug Administration Public Health Service et al (2011) Food and Drug
Administration recommends against the continued use of propoxyphene. J Pain Palliat Care
Pharmacother 25(1):80–82
Foody JM, Cole CR et al (2001) A propensity analysis of cigarette smoking and mortality with
consideration of the effects of alcohol. Am J Cardiol 87(6):706–711
Garcia-Esperon C, Hervas-Garcia JV et al (2013) Ingestion of anabolic steroids and ischaemic
stroke. A clinical case report and review of the literature. Revista de neurologia 56(6):327–331
Gellert C, Schottker B, et al. (2013) Impact of smoking and quitting on cardiovascular outcomes
and risk advancement periods among older adults. Eur J Epidemiol 28(8):649–658
George A, Figueredo VM (2011) Alcoholic cardiomyopathy: a review. J Card Fail
17(10):844–849
Ghuran A, Nolan J (2000) Recreational drug misuse: issues for the cardiologist. Heart
83(6):627–633
Gitter MJ, Goldsmith SR et al (1991) Cocaine and chest pain: clinical features and outcome of
patients hospitalized to rule out myocardial infarction. Ann Intern Med 115(4):277–282
Goldenberg I, Jonas M et al (2003) Current smoking, smoking cessation, and the risk of sudden
cardiac death in patients with coronary artery disease. Arch Intern Med 163(19):2301–2305
Goslawski M, Piano MR, et al. (2013) Binge drinking impairs vascular function in young adults.
J Am Coll Cardiol 62(3):201–207
Haning W, Goebert D (2007) Electrocardiographic abnormalities in methamphetamine abusers.
Addiction 102(Suppl 1):70–75
Heesch CM, Wilhelm CR et al (2000) Cocaine activates platelets and increases the formation of
circulating platelet containing microaggregates in humans. Heart 83(6):688–695
Higgins JP, Heshmat A et al (2012) Androgen abuse and increased cardiac risk. South Med
J 105(12):670–674
Hillbom M, Numminen H et al (1999) Recent heavy drinking of alcohol and embolic stroke.
Stroke J Cereb Circ 30(11):2307–2312
1606 P.K. Moore et al.
Perreault CL, Hague NL et al (1993) Negative inotropic and relaxant effects of cocaine on
myopathic human ventricular myocardium and epicardial coronary arteries in vitro.
Cardiovasc Res 27(2):262–268
Pertwee RG (2006) The pharmacology of cannabinoid receptors and their ligands: an overview. Int
J Obes 30(Suppl 1):S13–S18
Petronis KR, Anthony JC (1989) An epidemiologic investigation of marijuana- and cocaine-
related palpitations. Drug Alcohol Depend 23(3):219–226
Pratap B, Korniyenko A (2012) Toxic effects of marijuana on the cardiovascular system.
Cardiovasc Toxicol 12(2):143–148
Prazak P, Pfisterer M et al (1996) Differences of disease progression in congestive heart failure due
to alcoholic as compared to idiopathic dilated cardiomyopathy. Eur Heart J 17(2):251–257
Prescott E, Scharling H et al (2002) Importance of light smoking and inhalation habits on risk of
myocardial infarction and all cause mortality. A 22 year follow up of 12 149 men and women
in The Copenhagen City Heart Study. J Epidemiol Community Health 56(9):702–706
Prochaska JJ, Hilton JF (2012) Risk of cardiovascular serious adverse events associated with
varenicline use for tobacco cessation: systematic review and meta-analysis. Br Med J 344:e2856
Qureshi AI, Suri MF et al (2001) Cocaine use and the likelihood of nonfatal myocardial infarction
and stroke: data from the third national health and nutrition examination survey. Circulation
103(4):502–506
Ramirez FD, Femenia F et al (2012) Electrocardiographic findings associated with cocaine use in
humans: a systematic review. Expert Rev Cardiovasc Ther 10(1):105–127
Rangel C, Shu RG et al (2010) Beta-blockers for chest pain associated with recent cocaine use.
Arch Intern Med 170(10):874–879
Rea TD, Heckbert SR et al (2002) Smoking status and risk for recurrent coronary events after
myocardial infarction. Ann Intern Med 137(6):494–500
Resnick RB, Kestenbaum RS et al (1977) Acute systemic effects of cocaine in man: a controlled
study by intranasal and intravenous routes. Science 195(4279):696–698
Rodriguez BL, D’Agostino R et al (2002) Risk of hospitalized stroke in men enrolled in the
Honolulu heart program and the framingham study: a comparison of incidence and risk factor
effects. Stroke J Cereb Circ 33(1):230–236
Roerecke M, Greenfield TK et al (2011) Heavy drinking occasions in relation to ischaemic heart
disease mortality– an 11–22 year follow-up of the 1984 and 1995 US national alcohol surveys.
Int J Epidemiol 40(5):1401–1410
Ruidavets JB, Ducimetiere P et al (2010) Patterns of alcohol consumption and ischaemic heart
disease in culturally divergent countries: the Prospective Epidemiological Study of Myocardial
Infarction (PRIME). Br Med J 341:c6077
Samokhvalov AV, Irving HM et al (2010) Alcohol consumption as a risk factor for atrial
fibrillation: a systematic review and meta-analysis. Eur J Cardiovasc Prev Rehabil
17(6):706–712, Official journal of the European Society of Cardiology, Working Groups on
Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology
Schwartz BG, Rezkalla S et al (2010) Cardiovascular effects of cocaine. Circulation
122(24):2558–2569
Shetty KD, DeLeire T et al (2010) Changes in U.S. hospitalization and mortality rates following
smoking bans. J Policy Anal Manage 30(1):6–28
Siegel AJ, Mendelson JH et al (2002) Effect of cocaine usage on C-reactive protein, von
Willebrand factor, and fibrinogen. Am J Cardiol 89(9):1133–1135
Singh KJ, Cohen BE et al (2013) Alcohol consumption and 5-year change in left atrial volume
among patients with coronary heart disease: results from the Heart and Soul study. J Card Fail
19(3):183–189
Snow WM, Murray R et al (2009) Alcohol use and cardiovascular health outcomes: a comparison
across age and gender in the Winnipeg health and drinking survey cohort. Age Ageing
38(2):206–212
100 Cardiovascular Consequences of Addiction 1609
Swalwell CI, Davis GG (1999) Methamphetamine as a risk factor for acute aortic dissection.
J Forensic Sci 44(1):23–26
Sylvester AL, Agarwala B (2012) Acute myocardial infarction in a teenager due to Adderall
XR. Pediatr Cardiol 33(1):155–157
Thiblin I, Lindquist O et al (2000) Cause and manner of death among users of anabolic androgenic
steroids. J Forensic Sci 45(1):16–23
Tuncel M, Wang Z et al (2002) Mechanism of the blood pressure–raising effect of cocaine in
humans. Circulation 105(9):1054–1059
Turnipseed SD, Richards JR et al (2003) Frequency of acute coronary syndrome in patients
presenting to the emergency department with chest pain after methamphetamine use.
J Emerg Med 24(4):369–373
US Food and Drug Administration (2011) FDA drug safety communication: chantix (varenicline)
may increase the risk of certain cardiovascular adverse events in patients with cardiovascular
disease. Silver Spring, Md: US Food and Drug Administration
van Bilsen M, van Nieuwenhoven FA et al (2009) Metabolic remodelling of the failing heart:
beneficial or detrimental? Cardiovasc Res 81(3):420–428
Vongpatanasin W, Mansour Y et al (1999) Cocaine stimulates the human cardiovascular system
via a central mechanism of action. Circulation 100(5):497–502
Wakabayashi I, Araki Y (2010) Influences of gender and age on relationships between alcohol
drinking and atherosclerotic risk factors. Alcohol Clin Exp Res 34(Suppl 1):S54–S60
Wannamethee G, Shaper AG (1992) Alcohol and sudden cardiac death. Br Heart J 68(5):443–448
Ware JH, Vetrovec GW et al (2013) Cardiovascular safety of varenicline: patient-level meta-
analysis of randomized, blinded, placebo-controlled trials. Am J Ther 20(3):235–246
Whincup PH, Gilg JA et al (2004) Passive smoking and risk of coronary heart disease and stroke:
prospective study with cotinine measurement. Br Med J 329(7459):200–205
Wilbert-Lampen U, Seliger C et al (1998) Cocaine increases the endothelial release of immuno-
reactive endothelin and its concentrations in human plasma and urine: reversal by coincubation
with sigma-receptor antagonists. Circulation 98(5):385–390
Wolff V, Lauer V et al (2011) Cannabis use, ischemic stroke, and multifocal intracranial vaso-
constriction: a prospective study in 48 consecutive young patients. Stroke J Cereb Circ
42(6):1778–1780
Wolff V, Armspach JP et al (2013) Cannabis-related stroke: myth or reality? Stroke J Cereb Circ
44(2):558–563
Woolf KJ, Zabad MN et al (2012) Effect of nicotine replacement therapy on cardiovascular
outcomes after acute coronary syndromes. Am J Cardiol 110(7):968–970
Yoshita K, Miura K et al (2005) Relationship of alcohol consumption to 7-year blood pressure
change in Japanese men. J Hypertens 23(8):1485–1490
Zhang X, Li SY et al (2004) Ethanol and acetaldehyde in alcoholic cardiomyopathy: from bad to
ugly en route to oxidative stress. Alcohol 32(3):175–186
Gastrointestinal Disorders Related
to Alcohol and Other Drug Use 101
Guang Chen and Paul S. Haber
Contents
101.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1612
101.2 Alcohol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1612
101.2.1 Parotid Glands and Oral Cavity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1612
101.2.2 Esophagus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1613
101.2.3 Stomach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1614
101.2.4 Alcoholic Pancreatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1615
101.2.5 Alcohol and Gastrointestinal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1623
101.3 Prescription Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1625
101.3.1 Opioids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1625
101.3.2 Laxative Misuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1626
101.3.3 Misuse of Anticholinergics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1627
101.4 Tobacco . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1627
101.4.1 Gastroesophageal Reflux . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1627
101.4.2 Inflammatory Bowel Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1628
101.4.3 Gastrointestinal Malignancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1629
101.5 “Body Packing” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1630
101.6 Psychostimulants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1631
101.7 Cannabis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1631
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1632
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1639
G. Chen
Drug Health Service, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
Discipline of Addiction Medicine, University of Sydney, Sydney, Australia
e-mail: [email protected]
P.S. Haber (*)
Drug Health Service, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
e-mail: [email protected]; [email protected]
Abstract
Acute and chronic gastrointestinal manifestations are common in the setting of
alcohol, tobacco, prescription, and recreational drug use. Excessive alcohol use
is associated with injury to all parts of the gastrointestinal tract. Within the
gastrointestinal tract, alcoholic liver disease, alcoholic pancreatitis, and gastro-
intestinal cancer are important causes of morbidity and mortality related to
excessive alcohol use. Tobacco use is associated with gastroesophageal reflux,
peptic ulceration, and gastrointestinal cancer but appears to protect against
ulcerative colitis. Opioids have important effects on gastrointestinal secretion
and motility. Narcotic bowel syndrome may develop in the setting of escalating
doses of opioid analgesia. Cannabinoid hyperemesis syndrome should be
considered in the setting of heavy cannabis use and recurrent vomiting.
The body packing syndrome is rare but challenging when encountered.
101.1 Introduction
101.2 Alcohol
The relative risk of alcohol-related GI toxicity appears to differ between affected tissues
and between benign and neoplastic disorders. Similarly the pattern and type of beverage
have not been consistently shown to predispose to any specific GI effects of alcohol.
enlarged parotid glands. Sialosis is characterized by the triad of acinar cell hyper-
trophy, myoepithelial degeneration, and neural degeneration. Salivary secretion is
reduced in experimental animals given alcohol. These effects may contribute to
progressive dental caries and poor oral mucosal health. The effect of alcohol abuse
on salivary function in humans is controversial with reports of increased, unaltered
(Silver et al. 1986), and decreased salivary flow (Proctor and Shori 1996). More-
over, alcoholics may suffer from inflammation of the tongue (i.e., glossitis) and the
mouth (i.e., stomatitis). It is unclear, however, whether these changes result from
poor nutrition or reflect a direct effect of alcohol on the mucosa.
101.2.2 Esophagus
Both acute and chronic alcohol consumption are associated with symptomatic
gastroesophageal reflux disease (GERD). Dysfunction of the lower esophageal
sphincter (LES) and esophageal peristalsis and abnormal gastric acid secretion may
be involved in the pathogenesis of alcohol-related GERD. Exposure of the esophagus
and stomach to alcohol may cause direct damage to esophageal and gastric mucosa.
In addition, acetaldehyde generated from alcohol may affect the function of the
esophagus and stomach. Systemic investigations concerning this matter are still
inadequate and further well-designed prospective studies are needed to clarify the
effect of alcohol on GERD. An Irish study concluded that alcohol consumption in
early adulthood may lead to the development of reflux esophagitis. More recent
alcohol consumption does not appear to confer any increased risk of reflux esopha-
gitis, Barrett’s esophagus, or esophageal adenocarcinoma. In fact, wine consumption
may reduce the risk of these esophageal disorders (Anderson et al. 2009).
Reflux episodes were increased by 60 g of ethanol given with a meal to healthy subjects
without alcohol dependence (Kaufman and Kaye 1978). These episodes were measured
by measurement of esophageal pH for three hours after a standard meal and most were
asymptomatic. A number of mechanisms have been identified that may contribute to
these effects of alcohol (Lieber 1992b). Direct application of 30 % ethanol, but not lower
concentrations, causes injury to the esophageal mucosa. An acute dose of alcohol reduces
lower esophageal sphincter pressure (LESP) (Hogan et al. 1972) and reduced maximal
LESP stimulated by a meal (Mayer et al. 1978). Chronic excessive alcohol use is also
associated with manometric abnormalities relevant to GERD that recover with a month of
abstinence (Keshavarzian et al. 1987; Silver et al. 1986). These abnormalities were found
regardless of the presence or absence of peripheral neuropathy. These studies provide
evidence to support the time-honored advice to reduce alcohol consumption in the
presence of symptomatic GERD.
Upper gastrointestinal bleeding (UGIB) is more frequent in alcoholics, espe-
cially those with cirrhosis. In a 2007 UK audit of 6,750 patients with acute UGIB,
9 % had known cirrhosis and 26 % a history of alcohol excess (Hearnshaw
et al. 2011). A Czech prospective study of 137 cirrhotic patients presenting with
acute UGIB found the following causes: esophageal varices (57.7 %), peptic gastric
and duodenal ulcers (18.2 %), portal hypertension gastropathy (9.5 %), gastric
1614 G. Chen and P.S. Haber
varices (5.1 %), reflux esophagitis (2.9 %), Mallory–Weiss syndrome (2.9 %), and
erosive gastropathy (1.5 %). The mortality in all bleeding cirrhotic patients was
14.6 % (Svoboda et al. 2012). Mallory–Weiss syndrome is characterized by mas-
sive bleeding caused by tears in the mucosa at the cardio-esophageal junction after
vomiting. The syndrome accounts for 5–15 % of all cases of bleeding in the upper
GI tract. Mallory–Weiss syndrome prevalence varies; it is uncommon in China (Yin
et al. 2012). In one series, almost 50 % of these patients, the disorder was caused by
increased gastric pressure resulting from repeated retching and vomiting following
excessive acute alcohol consumption (Kortas et al. 2001).
101.2.3 Stomach
101.2.4.1 Definitions
The term acute pancreatitis refers to an acute inflammatory process of the pancreas,
with variable involvement of other regional tissues or remote organ systems. Chronic
pancreatitis is characterized by chronic inflammation, glandular atrophy, and fibrosis.
Clinically, it manifests pain with exocrine or endocrine insufficiency. The revised
classification of acute pancreatitis identified two phases of the disease: early and late.
Severity is classified as mild, moderate, or severe. Mild acute pancreatitis, the most
common form, has no organ failure and local or systemic complications and usually
resolves in the first week. Moderately severe acute pancreatitis is defined by the
presence of transient organ failure, local complications, or exacerbation of comorbid
disease. Severe acute pancreatitis is defined by persistent organ failure, that is, organ
failure >48 h. Local complications are peripancreatic fluid collections, pancreatic
and peripancreatic necrosis (sterile or infected), pseudocyst, and walled-off necrosis
(sterile or infected) (Banks et al. 2013).
101.2.4.2 Etiology
The most common associations of acute pancreatitis in Western societies are
gallstones and heavy alcohol use which together account for approximately 75 %
cases. A Danish cohort study showed gallstones as the most common cause (up to
34 %) for acute pancreatitis and alcohol was the most common cause (up to 68 %)
for chronic pancreatitis (Nøjgaard et al. 2010). Yadav et al. (2011) found that while
alcohol was the most common etiology in men (59 %), it was a less common
etiology in women (28 %). In women, both nonalcoholic and idiopathic etiologies
were more common (37 % and 35 %, respectively). Nonetheless, only a minority of
heavy drinkers develop clinically evident pancreatic disease.
The association between alcohol and pancreatitis appears to be dose related.
Pancreatitis typically occurs in subjects who have consumed greater than 100 g alcohol
per day for at least 5–10 years and rarely if ever follows an isolated alcoholic debauch.
1616 G. Chen and P.S. Haber
Kristiansen et al. (2008) reviewed 17,905 Danish men and women with pancreatitis
and found hazard ratios associated with drinking 1–6, 7–13, 14–20, 21–34, 35–48,
and >48 drinks/week were 1.1 (95 % confidence interval (CI): 0.8, 1.6), 1.2 (95 %
CI: 0.8, 1.8), 1.3 (95 % CI: 0.8, 2.1), 1.3 (95 % CI: 0.7, 2.2), 2.6 (95 % CI: 1.4, 4.8),
and 3.0 (95 % CI: 1.6, 5.7). The risk of pancreatitis may be increased in developing
countries as impurities within country-made alcoholic products may cause pancre-
atic injury (Barreto et al. 2010). In a Swedish cohort study, the risk of acute
pancreatitis was associated with the amount of spirits consumed on a single occa-
sion but not with wine or beer consumption (Sadr Azodi 2001). Acute gallstone
pancreatitis occurs more often in women, while alcoholic pancreatitis occurs more
often in men. Once the disease is established, episodic heavy drinking often pre-
cipitates relapses. Relapses have been described after only 1 day of recurrent
drinking. Pancreatitis is common among people with HIV particularly in associa-
tion with heavy alcohol use (Dutta et al. 1997; Whitfield et al. 1997). Many patients
with acute alcoholic pancreatitis progress to chronic pancreatitis, with continued
alcohol abuse being a key prognostic factor (Ammann 1996).
Other than gallstones, relatively common causes for pancreatitis that should be
considered include hypercalcemia of any cause and severe hypertriglyceridemia.
Hypertriglyceridemia (greater than 10 mmol/l (approximately 1,000 mg/dl) with
lipemic serum) of any cause is associated with recurrent attacks of pancreatitis
(Greenberger et al. 1966). Although alcohol abuse is a known cause of hypertrigly-
ceridemia, the majority of cases of alcoholic pancreatitis are not associated with
marked hyperlipidemia (Haber et al. 1994). Other causes include pancreatic trauma,
duct pathology, and a number of drugs. In most series, about 10 % of cases are
idiopathic.
These two studies support the concept that genetic factors influence susceptibility to
pancreatitis, but given that only 6 % and 3 % of the subjects carried these mutations,
respectively, individual susceptibility to this disease remains largely unexplained.
Two other important genetic mutations are linked to pancreatitis, but not the
alcoholic form. Gain-of-function mutations in the serine protease 1 gene (PRSS1)
on chromosome 7q35, which encodes cationic trypsinogen, results in an autosomal
dominantly inherited form of hereditary pancreatitis. Mutations in the cystic
fibrosis gene (CFTR) have been associated with an autosomal recessive form of
pancreatitis.
101.2.4.4 Pathogenesis
Two important factors leading to tissue injury in pancreatitis are autodigestion
and oxidant stress. Several lines of evidence indicate that activated digestive
enzymes play an important role in pancreatitis (Haber et al. 1997):
(a) Mutations of the cationic trypsinogen gene that increase pancreatic content
of trypsin underlie hereditary pancreatitis (Whitcomb et al. 1996). (b) Activated
digestive enzymes are found in both clinical and experimental pancreatitis and
can produce cellular necrosis when instilled into pancreatic tissue. (c) Protease
inhibitors reduce the incidence of post-ERCP and experimental pancreatitis.
Oxidant stress is characterized by the production of reactive oxygen species that
are atoms or molecules containing oxygen with an unpaired electron in the outer
shell (free radicals). Free radicals are highly reactive and bind to lipids, proteins,
and nucleic acids leading to cellular injury (Freeman and Crapo 1982). Free
radicals are generated during experimental pancreatitis (Nonaka et al. 1989)
from infiltrating leukocytes (Slater 1984) or possibly within acinar cells
(Braganza et al. 1995).
Several mechanisms have been proposed to explain why alcohol-induced
pancreatitis occurs only after many years of alcohol abuse and not after a single
binge in humans. These include the role of progressive pancreatic fibrosis related to
activation of pancreatic stellate cells by acetaldehyde and oxidative stress (Haber
et al. 1999) and the potential for endotoxin to precipitate pancreatitis in the alcohol-
exposed gland (Vonlaufen et al. 2007). Chronic alcohol intake is associated with
increased gut permeability and translocation of Gram-negative bacteria across the
mucosal barrier. Thus, bacterial components (endotoxins) can enter the circulation
and reach the pancreas. Plasma LPS levels have been shown to be significantly
higher in drinkers (either after chronic alcohol intake or a single binge) compared to
nondrinkers and in patients with alcoholic liver disease compared to those with liver
disease of other etiologies (Bode and Bode 2005).
101.2.4.5 Diagnosis
A confident diagnosis of pancreatitis can often be made on the basis of an attack of
severe abdominal pain and tenderness with elevation of the serum amylase more
than three times the upper limit of normal and with imaging studies suggestive of
inflammation in and around the pancreas.
1618 G. Chen and P.S. Haber
101.2.4.7 Treatment
Overall, about 20 % of patients with acute pancreatitis have a severe course, and
10–30 % of those with severe acute pancreatitis die. Despite improvements in intensive
care treatment during the past few decades, the rate of death has not significantly
declined (McKay and Imrie 2004). Severe cases, particularly those associated
with respiratory or renal failure, require treatment in an intensive care unit.
101 Gastrointestinal Disorders Related to Alcohol and Other Drug Use 1619
Initially, patients are treated with bed rest, analgesics, intravenous fluids, and
fasting. Adequate pain control requires the use of intravenous opiates, usually in
the form of a patient-controlled analgesia pump. Fentanyl is being increasingly used
due to its better safety profile, especially in renal impairment.
Meperidine (pethidine) has been favored over morphine for analgesia in pan-
creatitis because studies showed that morphine caused an increase in sphincter of
Oddi pressure. However, there are no clinical studies to suggest that morphine can
aggravate or cause pancreatitis or cholecystitis. It is important to note that meper-
idine has a short half-life and repeated doses can lead to accumulation of the
metabolite normeperidine that causes neuromuscular irritation and, rarely, seizures.
Morphine is more effective analgesic, is less susceptible to abuse, and is usually the
drug of choice.
Ebbehøj et al. (1985) showed the use of indomethacin suppositories (50 mg
twice daily) reduced opioid requirements in 30 patients with acute pancreatitis
without risk of gastrointestinal bleeding. An Iranian double-blind randomized
control trial showed that rectal indomethacin given immediately before ERCP
reduced the incidence and severity of post-ERCP pancreatitis (Sotoudehmanesh
et al. 2007).
Intravenous fluids are given aggressively to restore vascular volume and renal
perfusion and hour by hour monitoring is required. Patients are initially fasted,
partly for symptomatic reasons but also because early refeeding seems to cause
clinical relapse. Nutritional support is required if oral intake is not likely to be
restored within several days. Total parenteral nutrition (TPN) and enteral feeding
(nasogastric or nasojejunal) have been evaluated. Enteral feeding is safer and less
expensive and there is some evidence it may be more effective than TPN (Pandol
et al. 2007). Provision of early enteral nutrition is therapeutic, changing the
patient’s hospital course in a favorable manner (McClave 2013).
Protease inhibitors may limit the damage done by activated digestive enzymes.
In clinical practice, it is not possible to commence treatment early enough in the
attack of pancreatitis for protease inhibitors to be effective, except for post-ERCP
pancreatitis, where some benefit has been reported. Peritoneal lavage might
improve the outcome by removing toxic inflammatory products from the perito-
neum but the results of controlled studies have been conflicting (Mayer et al. 1985;
Stone and Fabian 1980). Other approaches that may prove more effective include
extended lavage (Ranson and Berman 1990) and retroperitoneal lavage using
operatively placed cannulas (Pederzoli et al. 1990). Antibiotics have not been
shown to be beneficial for unselected cases of acute pancreatitis for which the
prognosis is already excellent (Bradley 1989). In severe pancreatitis, infectious
complications contribute to morbidity and mortality, and several controlled trials of
prophylactic antibiotic therapy have been undertaken, (Pandol et al. 2007). The
results have been inconsistent and the use of antibiotics in acute pancreatitis
remains controversial.
A number of antioxidant therapies have been evaluated for both acute and
chronic pancreatitis given the role of oxidative stress in the pathogenesis of these
diseases and encouraging results from early small trials. However, a well-conducted
1620 G. Chen and P.S. Haber
101.2.4.10 Treatment
Complete abstinence from alcohol is essential to minimize progression of the
disease. Reassurance that the disorder is benign with a tendency to slowly remit
is helpful. In patients who continue to drink alcohol, a Japanese study of 12 patients
101 Gastrointestinal Disorders Related to Alcohol and Other Drug Use 1621
Small Intestine
Diarrhea is common among those who drink alcohol excessively, both acutely and
chronically. Multiple factors contribute to this problem including altered motility,
permeability, and nutritional disorders. Small intestinal mucosal injury can occur
after acute or chronic administration of alcohol. Perfusion of the hamster jejunum
with 4.8 % ethanol caused separation of the tip of the villus epithelium forming
blebs (Beck 1996). These blebs may rupture leading to denudement of the epithe-
lium. The villus core contracts and loses height within 1 min of ethanol exposure.
This effect is independent of any action on the microcirculation (Dinda et al. 1994)
and may be mediated by leukocytes (Dinda et al. 1996) via release of histamine
from mast cells and by oxidant stress (Dinda et al. 1994).
Mucosal blood flow is acutely increased with increased endothelial permeability
(Beck 1996). Acute administration of alcohol leads to increased gut permeability
resulting both in abnormal absorption of luminal content (such as endotoxin, which
contributes to the pathogenesis of alcoholic liver disease; see previous chapter) and
abnormal leakage of mucosal contents (such as albumin). Ethanol also inhibits
absorption of actively transported sugars, dipeptides, and amino acids. Many
defects in absorption have been reported in people with alcohol problems, including
water (Krasner et al. 1976a, b), carbohydrate, lipid, vitamins (notably thiamine,
folate), and minerals (calcium, iron, zinc, and selenium) (Beck 1996). Folate
deficiency, common among people with alcohol problems, causes intestinal injury
leading to malabsorption and diarrhea and further loss of folate. Ethanol may
exacerbate lactase deficiency, especially in non-Caucasians (Perlow et al. 1977).
Colon
Portal hypertension may manifest uncommonly with hemorrhoids and rarely with
colonic varices. Colonic varices appear as filling defects on barium enema and may
occur in any part of the colon, most commonly in the rectum (Feinman et al. 1992).
Alcohol has also been reported to cause non-ulcerative inflammatory changes in
101 Gastrointestinal Disorders Related to Alcohol and Other Drug Use 1623
human colonic epithelium (Brozinsky et al. 1978). These changes resolved during
a 2-week period of abstinence and were not explained by folate deficiency. This
form of colitis has the potential to contribute to diarrhea but is not usually recog-
nized clinically as pathology elsewhere in the gut tends to dominate the clinical
picture.
Inappropriate alcohol enema has been reported to cause a chemical colitis
(Herrerias et al. 1983) and this may result from a toxic effect similar to the direct
toxicity of alcohol on the gastric mucosa. Alcohol use has a recognized association
with colorectal cancer as indicated below. Finally, alcohol consumption may have
at least one beneficial effect on the colon in that it has been linked to a reduced
incidence of ulcerative colitis in one study (Boyko et al. 1989).
ALDH2 mutation develop severe side effects with small amounts of alcohol and
hence are protected against alcohol-related disorders and alcohol overuse. In Japan,
heterozygosity is prevalent in alcoholics and is significantly associated with
oropharyngolaryngeal (OR 11.14), esophageal (OR 12.50), and esophageal cancer
concomitant with oropharyngolaryngeal and/or stomach cancer (OR 54.20)
(Yokoyama et al. 1998).
101.2.5.2 Stomach
The association between gastric cancer and alcohol consumption appears to be
mild. Tramacere et al..’s (2012) meta-analysis of 34,557 patients provided defini-
tive evidence of a lack of association between moderate alcohol drinking and
gastric cancer risk. There was, however, a positive association with heavy alcohol
drinking (RR 1.14 (95 % CI 1.08–1.21) for 50 g/day). Gastric noncardia adenocar-
cinomas were more common than gastric cardia cancers. This is supported by the
European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study
which also showed beer but not wine or spirits to be positively associated with
gastric cancer (Duell et al. 2012). Genetic susceptibility also appears to be impor-
tant, especially in Asian populations. A Korean study showed ALDH2 polymor-
phisms were found to modify the susceptibility to the development of gastric cancer
associated with alcohol intake, especially in case of ALDH2 *1/*2 genotype
(Shin et al. 2011).
101 Gastrointestinal Disorders Related to Alcohol and Other Drug Use 1625
101.2.5.3 Colonic
A large pooled analysis found that those who consumed 30 to less than 45 g per
day of alcohol had a relative risk (RR) of colorectal cancer of 1.16 (95 % CI
0.99–1.36) and those who consumed more than 45 g per day had an RR of 1.41
(CI 1.16–1.72); the relative risks in men and women appeared similar, and the
association was seen for cancers of all portions of the colon and rectum (Cho
et al. 2004). This data is reflected in the Netherlands Cohort Study which showed
alcohol consumption 30 g/day or more was associated with a hazard ratio of 1.3
(hazard ratio: 1.32, 95 % CI: 1.06–1.65) [46]. Of note, cancer risk appeared to
increase from proximal colon through rectum (hazard ratio: 1.29, 95 % CI:
0.85–1.96 for proximal colon cancer; hazard ratio: 1.41, 95 % CI: 0.94–2.11
for distal colon cancer; hazard ratio: 2.07, 95 % CI: 1.03–4.18 for rectosigmoid
cancer; and hazard ratio: 1.69, 95 % CI: 1.08–2.64 for rectal cancer)
(Bongaerts et al. 2008).
101.2.5.4 Pancreatic
The role of alcohol in pancreatic cancer pathogenesis appears to be significant.
Retrospective analysis of the Swedish Inpatient Register suggested that excess risk
for pancreatic cancer among alcoholics is small and could conceivably be
attributed to confounding by smoking (Ye et al. 2002). High lifetime ethanol intake
from spirits/liquor tends to be associated with a higher risk, but no associations
were observed for wine and beer consumption (Rohrmann et al. 2009;
Gapstur et al. 2011).
101.3.1 Opioids
It has long been recognized that opioids affect gastrointestinal motility. Opioids act
on gut function in a complex fashion via all three receptor classes in the brain,
spinal cord, and enteric nervous systems. Low doses act at enteric nervous system
sites and higher doses also act within the CNS. These effects usually are manifest as
constipation, but bloating, early satiety, and pain are possible. Occasionally,
patients develop ileus or a syndrome characterized by a relatively high level of
abdominal pain. When pain is significant, the term “narcotic bowel syndrome” has
sometimes been applied (Fig. 1). It is attributed to the effects of opioid drugs on
bowel function and opioid-induced hyperalgesia (Grunkemeier et al. 2007). A US
survey of 98 patients with chronic non-cancer pain treated with opioids revealed
constipation prevalence was 46.9 %, nausea 27 %, vomiting 9 %, and gastroesoph-
ageal reflux disease 33 %. Chronic abdominal pain was reported by 58.2 % and
6.4 % fulfilled the criteria of NBS. Prevalence of constipation increased with
duration of treatment. Health-related quality of life was low in patients with chronic
abdominal pain (Tuteja et al. 2010).
1626 G. Chen and P.S. Haber
Surreptitious laxative misuse is among the more common causes for unexplained
chronic diarrhea. It represents an intriguing form of substance misuse but is rare and
is typically observed in people without other substance misuse issues. These
patients present to family physicians and gastroenterologists. Some are associated
with bulimia. Others tend to be older women and the disorder can be viewed as
a form of Munchausen’s syndrome. The diagnosis rests on identification of
laxatives by stool alkalinization, osmolality studies, or a bag search in the hospital
(Fine 1998).
101 Gastrointestinal Disorders Related to Alcohol and Other Drug Use 1627
In high doses, anticholinergic drugs alter mood and are occasionally misused,
particularly when prescribed to relieve extrapyramidal symptoms in the mentally
ill (Caplan et al. 2007) and among those with limited access to other drugs of abuse.
Amitriptyline and other tricyclic antidepressant drugs are commonly misused by
people on opioid maintenance treatment (Peles et al. 2008). Clonidine and/or
buscopan prescribed for opioid withdrawal may also be misused. Patients develop
marked constipation and abdominal pain as well as dry mouth and blurred vision. In
the author’s experience, patients have had previous drug-dependence problems and
have welcomed an explanation of their symptoms and participated in structured
withdrawal.
101.4 Tobacco
Tobacco use is associated with a number or benign and malignant disorders of the
gastrointestinal tract.
Patients with ulcerative colitis who begin smoking after the diagnosis of their
disease present a significant reduction in the number of recurrences (Fraga
et al. 1997), and hospitalization and surgical procedure occur most frequently in
heavy smokers who quit smoking before the onset of ulcerative colitis (Boyko
et al. 1988). This suggests nicotine may have a therapeutic potential for this disease.
Nicotine influences immune cellular function, increases mucin production, relaxes
colonic smooth muscle, increases endogenous glucocorticoids, and influences
rectal blood flow and intestinal permeability (Thomas et al. 2005). Less toxic
approaches to this form of therapy have been sought and include topical colonic
administration of nicotine. These approaches remain experimental at this time
(Lunney and Leong 2012). McGrath et al.’s Cochrane Review (2004) of transder-
mal nicotine patches for the treatment of mild to moderate ulcerative colitis has
suggested that these agents can improve ulcerative colitis compared to placebo but
have significant adverse events and have not been shown to be more effective than
other effective treatments.
Smoking has been strongly linked to cancers of the upper gastrointestinal tract and
pancreas as discussed above. The link between smoking and stomach cancer is
weaker but is present in most studies (Neugut et al. 1996; Trédaniel et al. 1997).
A Swedish population-based prospective cohort of 17,118 twins with up to 30 years
of follow-up showed long-term heavy smoking was associated with a statistically
significant threefold increased risk of colorectal cancer compared with never
smoking (relative risk 3.1, 95 % CI 1.4–7.1). Examining colorectal cancer
sub-sites separately, a nonsignificant 60 % increased risk of colon cancer was
observed only for heavy smokers and a statistically significant fivefold increased
risk was observed for rectal cancer (Terry et al. 2001).
The risk is related to total number of cigarettes smoked and the duration of
smoking. Pipe and cigar smoking have a higher risk compared with cigarette
smokers (Franceschi et al. 1990). Interestingly, a recent meta-analysis of smokeless
tobacco (snus or snuff) available in Scandinavia has shown to be not associated with
cancers of the oropharynx, esophagus, stomach, and pancreas once the effects of
smoking are removed (Lee 2011).
Tobacco smoke contains multiple mutagenic and carcinogenic compounds
including nicotine, nitrosamines, and polycyclic hydrocarbons. Mouse and cell
models reveal a direct promoting action of nicotine on the growth of gastric
tumor and neovascularization through sequential activation of the ERK/COX-2/
VEGF signaling pathway (Shin et al. 2004). The effects of tobacco and alcohol
appear to be synergistic. Smoking increases the acetaldehyde burden following
alcohol, and alcohol enhances the activation of various procarcinogens via cyto-
chrome P450 induction.
1630 G. Chen and P.S. Haber
Persons smuggling illicit drugs may ingest large amounts of cocaine, heroin, or
other drugs aiming to retrieve the packages after reaching their destination (Traub
and Kohn et al. 2003a). This is referred to body packing, cocaine packing, or body
stuffing syndrome (Malbrain et al. 1994). Multiple packages made from latex
condoms, wax, or plastic bags are either swallowed or placed retrogradely into
rectum or vagina. The incidence of this practice is unknown. Most cases present in
police custody raising ethical and potentially funding challenges of managing an
involuntary patient. Some people may be coerced to smuggle drugs. Cases involv-
ing children and pregnant women have been described (Traub et al. 2003a, b).
Hospitals close to international airports may encounter these cases and should
consider developing a management policy for this challenging problem. An early
report describes 10 cases diagnosed only after death in which as many 147 packages
were found (Wetli and Mittlemann 1981). Lethal drug absorption through rubber
condoms may occur without rupture. The body packer may present with
life-threatening symptoms of intoxication, including seizures and cardiorespiratory
collapse, as well as mechanical obstruction from the ingested drug packets. The
distal ileum was the most common site of obstruction, whereas rupture tended to
occur in the upper gastrointestinal tract (East 2005). The largest series comprises
61 cases from Milan, Italy, of which only two cases required laparotomy, one each
for obstruction and nonfatal drug toxicity (Aldrighetti et al. 1996).
Plain X-ray is the method of choice to detect drug-filled packets within the
gastrointestinal tract of body packers (Hergan et al. 2004). Dilute contrast has been
reported to assist identification of the packages (Gherardi et al. 1990). In some
cases, CT is required, with potential concerns regarding radiation exposure if
repeated examinations are needed. Extensive dose reduction makes low-dose CT
a valuable alternative imaging modality for the examination of suspected body
packers and might replace conventional abdominal radiographs as the first-line
imaging modality (Maurer et al. 2011).
Clinical monitoring comprises frequent clinical and neurological assessment and
abdominal examination daily to the detected complications of acute drug intoxica-
tion or bowel obstruction or perforation. The patient should be kept in hospital until
all drug packages have cleared due to the risk of life-threatening overdose if any
rupture. Traub et al. (2003) presented a detailed review and clinical approach to
management. A light solid diet with free liquids may be given. Oily or polyethylene
glycol laxatives can be given repeatedly to accelerate passage of packages
(Hoffman et al. 1990). Symptomatic cases may require early surgery (Silverberg
et al. 2006). The risk of careful endoscopic removal from the esophagus is probably
exaggerated, and in any case, the risk of endoscopic removal is almost certainly less
than that of any other surgical approach to the esophagus. The rigid esophagoscope
appears to have an advantage over the flexible instrument because of the wide
lumen which will accommodate most average-sized pellets. Intact pellets in stom-
ach and small bowel may be retrieved endoscopically or are evacuated through
a single gastrotomy and/or enterotomy. Non-obstructing pellets in the colon pose an
101 Gastrointestinal Disorders Related to Alcohol and Other Drug Use 1631
interesting dilemma. Removal through a colotomy will expose the patient to the risk
of sepsis. The risk of rupture of pellets already in the colon must be very low as
there are no noxious enzymes here and the pellets are subject to less turbulence
within formed stool than they would be in the small intestine (East 2005).
Methamphetamine body stuffers have similar demographics to those of body
stuffers of other stimulants but tended to ingest fewer baggies with larger masses
and had a higher percentage of severe outcomes (29 %) than previously reported
with other stimulants. Increases in presenting pulse rate and temperature (pulse rate
120 beats/min or 38.0 C) are common in patients who will develop end-organ
damage (West et al. 2010).
101.6 Psychostimulants
101.7 Cannabis
Our understanding of cannabis and cannabinoid substances has changed since the
discovery of the endocannabinoid system (ECS). Cannabinoid receptors are widely
expressed throughout both the upper and lower GI tract and are also expressed on
hepatic stellate cells. Consequently, cannabinoids may influence a range of GI
functions in health and disease (Pertwee 2001). Cannabinoids have been implicated
in the pathophysiology of satiety, nausea/emesis, gastrointestinal secretion, gastro-
intestinal motility, gastrointestinal sensation, as well as inflammation (Izzo and
Sharkey 2010). Nausea and vomiting are side effects of many chemotherapeutics
and reduce the quality of life of patients with diabetes, cancer, and acquired
immune deficiency syndrome. Cannabis (marijuana) and other cannabinoids appear
to be effective antiemetics. The antiemetic effect has been demonstrated in an
animal model and is related to the expression of CB1 receptors in the dorsal
vagal nucleus (Van Sickle et al. 2001). Cannabinoids are also involved in inhibition
of gastric emptying and gastric acid secretion.
Cannabis has also been linked to a series of cases with hyperemesis (Allen
et al. 2004). Cessation of cannabis, as confirmed by a negative urine drug screen for
1632 G. Chen and P.S. Haber
cannabinoids, led to cessation of the cyclical vomiting illness and a return to regular
cannabis use heralded a return of the hyperemesis weeks to months later. The
hyperemesis is often relieved by frequent hot showers (Sontineni et al. 2009).
The mechanism is not understood. A further similar case was described in the
UK (Roche and Foster 2005) and a small series has now been reported in the USA
(Soriano-Co et al. 2010). Most recently, a series of 98 cases was reported from the
Mayo Clinic (Simonetto et al. 2012). Cannabinoid hyperemesis should be consid-
ered in younger patients with long-term cannabis use and recurrent nausea,
vomiting, and abdominal pain.
References
Abelson DC, Mandel ID, Karmiol M (1976) Salivary studies in alcoholic cirrhosis. Oral Surg Oral
Med Oral Pathol 41(2):188–192
Adamu MA et al (2011) Incidence and risk factors for the development of chronic atrophic
gastritis: five year follow-up of a population-based cohort study. Int J Cancer
128(7):1652–1658
Aldrighetti L et al (1996) Conservative management of cocaine-packet ingestion: experience in
Milan, the main Italian smuggling center of South American cocaine. Panminerva Med
38(2):111–116
Allen JH et al (2004) Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic
cannabis abuse. Gut 53(11):1566–1570
Ammann RW (1996) Alcoholic chronic pancreatitis: its relation to alcoholic acute pancreatitis.
Gastroenterol Clin Biol 20(3):312–314
Anderson LA et al (2009) The association between alcohol and reflux esophagitis, Barrett’s
esophagus, and esophageal adenocarcinoma. Gastroenterology 136(3):799–805
Aro P et al (2010) Use of tobacco products and gastrointestinal morbidity: an endoscopic
population-based study (the Kalixanda study). Eur J Epidemiol 25(10):741–750
Banks PA et al (2013) Classification of acute pancreatitis – 2012: revision of the Atlanta
classification and definitions by international consensus. Gut 62(1):102–111
Barreto SG et al (2010) Can by-products in country-made alcohols induce acute pancreatitis?
Pancreas 39(8):1199–1204
Battaglia B et al (1990) Alcohol intake and acute duodenal ulcer healing. Am J Gastroenterol
85(9):1198–1199
Beck IT (1996) Small bowel injury by ethanol. In: Preedy VR, Watson RR (eds). CRC Press, Boca
Raton, pp 163–202
Bhandarkar PV et al (2000) Effect of acute and long-term oral tobacco use on oesophageal
motility. J Gastroenterol Hepatol 15(9):1018–1021
Bhardwaj P et al (2009) A randomized controlled trial of antioxidant supplementation for pain
relief in patients with chronic pancreatitis. Gastroenterology 136(1):149–159.e2
Blot WJ et al (1988) Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res
48(11):3282–3287
Bode C, Bode JC (200