(Gray Matter) James D. Stoehr - The Neurobiology of Addiction-Chelsea House (2006)

The Neurobiology
of Addiction
Brain Disorders
Cells of the Nervous System
The Forebrain
The Hindbrain
Learning and Memory
Meditation and Hypnosis
The Midbrain
The Neurobiology of Addiction
Sleep and Dreaming
The Spinal Cord
The Neurobiology
of Addiction
James D. Stoehr
Professor
Colleges of Medicine and
Health Sciences
Midwestern University
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Library of Congress Cataloging-in-Publication Data
Stoehr, James D.
The neurobiology of addiction / James D. Stoehr.
p. cm.—(Gray matter)
Includes bibliographical references and index.
ISBN 0-7910-8574-0
1. Substance abuse—Physiological aspects. 2. Neuropsychology. 3. Brain. I. Title. II.
Series.
RC564.S76 2005
616.86—dc22 2005011989
All links, web addresses, and Internet search terms were checked and verified to be correct at
the time of publication. Because of the dynamic nature of the web, some addresses and links
may have changed since publication and may no longer be valid.
Contents
1. Drug and Alcohol Addiction: Overview . . . . . . . . . . . . . . . . . . . 1
2. The Brain and Our Behavior . . . . . . . . . . . . . . . . . . . . . . . . . . 6
3. Brain Regions Involved in Addiction. . . . . . . . . . . . . . . . . . . . 18
4. Stimulants and Hallucinogens . . . . . . . . . . . . . . . . . . . . . . . . 36
5. Depressants and Marijuana. . . . . . . . . . . . . . . . . . . . . . . . . . 52
6. The Cycle of Addiction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
7. Addiction Treatments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Websites. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Drug and Alcohol Addiction:
1 Overview
The human brain is capable of creating complex and beau-

tiful things. It is capable of undying love and compassion for
others and of true selflessness and generosity. However, the
human brain is also capable of intolerance and cruelty, and
the brain itself is not immune to its own destructive powers.
The needs and wants of the human brain can overcome its
abilities for reason and rational thought to the point of self-
destruction and even death. This can be the case in drug and
alcohol addiction.
To fully understand the problem of drug and alcohol ad-
diction, one must appreciate the processes that occur in the
human brain during the phases of drug use, abuse, depen-
dence, and addiction. Fundamental to this appreciation is the
concept that drug and alcohol addiction is a brain disease. Sci-
entific evidence implicates the human brain as both the un-
derlying cause and ultimate solution to the problem of addic-
tion. Our brains are responsible for all of our thoughts,
motivations, and actions. The human brain is susceptible to
all drugs of abuse. Ultimately these drugs change the chem-
istry and functioning of the human brain and lead to im-
paired judgments and actions that can result in chronic drug
use. Yet the same human brain is capable of understanding its
1
2 The Neurobiology of Addiction
susceptibilities, accepting its limits and, ultimately, striving for

continual self-improvement and health.
The economic cost of drug and alcohol addiction is staggering.
According to estimates from the National Institute on Drug
Abuse (NIDA) and the National Institute on Alcohol Abuse and
Alcoholism (NIAAA), the total annual economic cost of drug and
alcohol abuse exceeds $250 billion. This includes the costs of the
legal consequences of drug abuse (law enforcement, incarceration
of prisoners, drug traffic control), lost work productivity (of both
victims and perpetrators), property damage, and health-related
costs (premature deaths, drug-related illnesses, and healthcare).
Although some of us have not experienced these consequences
first-hand, we may know someone who abuses drugs. They may
smoke or drink too much, misuse prescription medications, or
use illicit drugs occasionally. What they have in common is that
they are all taking risks with their health and safety. Drug and al-
cohol abuse is our number one public health concern.
Nevertheless, the benefits of science-based drug education and
prevention programs are beginning to be realized. Recent trends
in the attitudes and behaviors of high school students indicate
that, in general, drug use is on the decline by school-aged children
and teenagers. Consider the following statistics from the Univer-
sity of Michigan’s annual Monitoring the Future Survey of more
than 48,000 school children from around the country in 2003:
• The use of marijuana and MDMA (Ecstasy) declined in 8th
graders since 2002.
• The use of amphetamines, tranquilizers, and MDMA by 10th
and 12th graders also declined.
• The use of heroin, crack cocaine, and steroids declined
among 10th graders.
• However, inhalant use by 8th graders increased from the
previous year, and the use of Vicodin® and OxyContin® con-
tinues to rise in all age groups.
Drug and Alcohol Addiction: Overview 3
Furthermore, consider the absolute numbers of these chil-

dren who are using these drugs (when 1% roughly equals 40,000
kids nationwide):
• Within the last month 17% of these individuals used to-
bacco products, 33% used alcohol, 15% used marijuana,
and 4% used amphetamines.
• Each day approximately 3,000 teenagers start smoking
cigarettes; one third will become daily smokers.
• Peak lifetime drug use occurs in the young adult age group
(ages 18–25).
• Within the last month non-medical use of prescription
painkillers by young adults jumped by 15%.
• More than 60% of all patients who enter drug treatment
programs started using drugs at age 20 or younger.
Most drug and alcohol use starts at an early age. Recent
studies have also suggested that approximately a third of ado-
lescent alcohol users will progress to alcohol abuse or depen-
dence, and approximately half of adolescent drug users will
make the transition to drug abuse or dependence. Drug and al-
cohol use typically starts as an experiment. Curiosity and peer
pressure may be significant factors during this stage. Recre-
ational or social use may follow as the user increases the fre-
quency of drug or alcohol use. As the user starts to become
adapted to the drug, more (larger doses) will be required to
achieve the same feeling or effect (tolerance). At this point,
drug abuse can rapidly progress to addiction (compulsive drug
use despite harmful consequences). See Table 1.1 for typical
signs and symptoms of drug or alcohol addiction.
Addiction is chronic (persistent and long lasting), progressive
(increasing in severity), and characterized by relapse (regression
or transition into worsening state following partial recovery).
The pace with which abusers may progress through these stages
Table 1.1 Signs and Symptoms of Drug Dependence and Addiction
1 Loss of natural rewards Previously important social or recreational

activities reduced
2 Escalation Drug is taken in larger amounts for longer periods
of time
3 Uncontrolled use Unsuccessful attempts to cut down
4 Time devoted to drug A lot of time spent on getting drug, using drug, or
recovering from drug use
5 Tolerance Using more to achieve same effect; using same
amount and getting reduced effect
6 Withdrawal Characteristic drug withdrawal syndromes (most
often opposite symptoms to that of drug's
effects)
7 Continued harm Drug use despite knowing that physical or
psychological harm is being done
From Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, and Principles of Addiction
Medicine, 3rd Edition.
depends on several factors, including their genetic predisposition

(addiction that runs in their family), their social context
(amount of stress or anxiety in their lives), and the drug in ques-
tion (some drugs are more addicting or potent than others). It is
important to understand that drug and alcohol addiction is
treatable. Addicted individuals should be treated without judg-
ment or stereotypes and will need the support of family, friends,
employers, and health care providers in order to remain drug
free and healthy.
Is drug addiction a brain disease or a matter of choice? Is it de-
termined by the genes you’ve inherited or is it determined by the
environment in which you were raised? Why can’t drug users just
simply stop? Is there something wrong with their brains? What
happens inside the brains of drug users? Answers to these and
other questions concerning drug abuse are being studied and in-
vestigated by counselors, clinicians, teachers, and scientists. In this
Drug and Alcohol Addiction: Overview 5
book we will examine recent scientific evidence that implicates

addiction as a brain disease. We will look at images of a brain that
is damaged by drug use, a brain that is craving cocaine, and the ge-
netics of alcoholism. We will consider what happens in the human
brain as users progress from casual drug use to abuse and addic-
tion, and then discuss how the brain recovers after addiction.
■ Learn more about addiction Search the Internet for teen drug
use, drug addiction defined, or signs of drug addiction.
SUMMARY POINTS
• Drug and alcohol addiction is a chronic and progressive
brain disease.
• Addiction is influenced by genetics, environment, and
drug use.
• Overall rates of drug use by teenagers has declined in recent
years.
• Abuse of inhalants and prescription painkillers is on the rise.
• Addiction is characterized by loss of control, use despite
harm, tolerance, withdrawal, and denial.
2 The Brain and Our Behavior
How drugs affect the human brain determines how they af-
fect human behavior. All drugs of abuse alter specific brain
chemicals located in different areas of the brain. These areas
are also responsible for different functions.
BRAIN STRUCTURE AND FUNCTIONS

One area of the brain may be generally responsible for vision,
or hearing, or controlling muscle movement, or thinking and
reasoning. The more complex functions of the brain, such as
decision making, planning, language, and sensory processing,
are located in the outer surface called the cerebral cortex (Fig-
ure 2.1). The cerebral cortex is sensitive to the immediate, in-
toxicating effects of drugs as well as the long-term effects and
damage that drugs can cause.
The limbic system, located below the cerebral cortex, is re-
sponsible for emotions and some forms of short-term memory.
The limbic system is particularly sensitive to drugs of abuse,
which alter our emotions and the way we feel. It is made up of
several interconnected structures including the hippocampus
(involved with learning and memory), the amygdala (responsi-
ble for negative emotions such as fear and aggression), certain
parts of the thalamus (responsible for relaying sensory informa-
tion to the cerebral cortex and limbic structures), and the hy-
6
Cerebral hemisphere
Frontal lobe
Thalamus Parietal lobe
Midbrain
Hypothalamus
Occipital lobe
Cerebrum
Hippocampus
Brain Stem
Cerebellum
Spinal Cord
Figure 2.1 Different structures of the brain are responsible for different functions.
This diagram shows the locations of important structures that are affected by drugs
of abuse.
pothalamus (which controls body temperature, hunger, thirst,

sleep cycles, and the physical responses to emotional situations).
All of these areas are susceptible to particular drugs of abuse.
Some drugs decrease appetite (the effect of amphetamines in the
hypothalamus), some cause short-term memory problems and
“black-outs” (the effect of alcohol in the hippocampus), and some
may increase aggression (long-term effect of steroid abuse on the
amygdala).
Located below the limbic system is the midbrain (Figure 2.2).
The midbrain contains groups of cells (known as nuclei) that
produce brain chemicals called neurotransmitters that are dis-
tributed throughout other areas of the brain. These will be dis-
cussed in more detail in Chapter 3. These nuclei can be consid-
ered the chemical manufacturing plants in the brain. All drugs
7
Pre-synaptic
nerve ending
Neurotransmitter-containing
vesicle
Neurotransmitter
Synapse
Neurotransmitter
receptor on
post-synaptic neuron
Post-synaptic
neuron
Figure 2.2 Electrical signals are sent using chemicals called neurotransmitters.
Neurotransmitters are released into the synapse, where they make contact with spe-
cial receptors on the neighboring neuron.
of abuse influence the production, release, or elimination of

these neurotransmitters. In addition to the nuclei that produce
neurotransmitters, the midbrain also contains the reticular acti-
vating system (RAS). The RAS is responsible for many functions
including regulation of sleep cycles and consciousness. The RAS
is like a network of highways that transfers information from the
spinal cord and the body to higher centers in the brain such as
the cerebral cortex and limbic system.
The Brain and Our Behavior 9
The RAS is also located in the brain stem—the area just above
the spinal cord. The brain stem also contains nuclei that are re-
sponsible for vital brain functions that are considered automatic,
those that can be done without conscious effort. These functions
include chewing, swallowing, vomiting, sneezing, coughing,
breathing, and regulation of heart rate. An overdose of certain
drugs, such as depressants, can cause death because of their af-
fects on brain stem function (see “Binge Drinking and Alcohol
Poisoning” box).
■ Learn more about general brain functions Search the Internet
for limbic system, prefrontal cortex, or reticular activating system.
FUNCTION OF BRAIN CELLS

Brain cells, known as neurons, are the smallest functional unit in
the central nervous system. There are over 100 billion neurons
in the human brain. The function of a neuron is determined by
its location within the brain and the connections it makes with
other brain cells. Within a neuron, information flows in one di-
rection from one end of the cell to the other. Signals from other
cells enter a neuron in its dendrites and are added together at the
level of the cell body (soma). The cell may then communicate
with other cells by sending a signal (action potential) down its
axon to the terminal endings (Figure 2.3).
Neurons do not make physical contact with one another to
communicate. They are separated by gaps called synapses. Brain
cells communicate through electrochemical signals. When an
electrical signal (action potential) travels down a neuron’s axon,
neurotransmitters are released into the synapse. Electrical sig-
nals traveling in dendrites and axons are converted into chemi-
cal signals released into the synapse. The released neurotrans-
mitter diffuses across the synapse very quickly and contacts the
neighboring (post-synaptic) neuron. The post-synaptic cell will
respond to the neurotransmitter if it expresses receptors on its
cell surface specific for this neurotransmitter. Receptors are

small proteins that recognize specific neurotransmitters. These
receptors lock onto the neurotransmitter in a process called re-
ceptor binding, and subsequently cause an electrical change
Binge Drinking and Alcohol Poisoning

One popular method of drinking alcohol is “chugging” or gulping
large amounts of alcohol in a very short period of time. Some
teenagers have overdosed on alcohol (alcohol poisoning) from this
drinking pattern. When individuals chug large amounts of high
proof alcohol, they can ingest half of a fifth or more of liquor in
the time span of a few minutes. Alcohol is absorbed quickly
through the stomach and intestines, and if a high dose is con-
sumed an individual can rapidly progress from a state of relaxation
to unconsciousness in a matter of minutes. One of the brain’s de-
fense mechanisms for removing poisons in the body is to initiate
vomiting (which is controlled by areas in the brain stem). If an in-
dividual loses consciousness too quickly and anesthetizes these
brain stem areas that control vomiting, he or she may pass out and
continue to absorb the alcohol that remains in the stomach. As
the absorption of alcohol continues, the brain is further sedated
and the individiual may reach a comatose state or death from res-
piratory or circulatory collapse very quickly. If an individual is in-
toxicated prior to drinking heavily or has used other depressants
such as sedative-hypnotics or barbiturates, the likelihood of death
increases significantly. Individuals in this condition must receive
medical treatment as soon as possible. The legal limit of blood al-
cohol concentration (BAC) in most states is 0.08% alcohol by vol-
ume. Death occurs at a BAC of 0.50 or more. Chugging high
amounts of alcohol can rapidly increase BAC from zero to 0.40 or
more in a matter of less than an hour.
Dendrites
Nucleus
Soma (body)
Axon hillock
Initial segment
of axon
Axon
Spines Direction
(sites of various of
types of dendritic impulse
Myelin Sheath
synapse)
Schwann cell
(produces myelin)
Bouton (foot)
Terminal branch
Figure 2.3 The brain has billions of cells called neurons. Each neuron, like the one
shown here, has an axon that transmits information to other cells. Impulses flow in
one direction, from the dendrites to the terminal branch.
known as a potential in the post-synaptic cell. A common anal-

ogy is that of a key and lock. A neurotransmitter may act as a key
that fits into a specific lock (the receptor), which then permits
the turning of the lock and opening of the door (post-synaptic
potential). In this way, a chemical signal in the synapse is trans-

formed into an electrical signal in the post-synaptic cell.
Each neuron may synapse with 10,000 other neurons. Billions
of neurons, each connecting to thousands of other cells, permit
a tremendous amount of information to be processed in the
brain. Electrochemical signaling occurs very quickly in the
brain. Each cell is capable of responding to thousands of neu-
rons simultaneously. Some estimates have suggested that the
human brain can process 100 trillion calculations per second
with a capacity of 100 trillion bytes of memory. Even the fastest
supercomputers cannot do this. The human brain not only pro-
cesses information quickly, but it learns, adapts, creates, and
thinks all while being light and portable.
BRAIN SYSTEMS AND BEHAVIOR

Although the integration of information may occur at the level
of the synapse, complex functions of the human brain occur in
larger areas in the cerebral cortex. In general, anterior (more for-
ward) areas of the cortex are involved with planning and move-
ment, while posterior (near the back) cortical areas are involved
with the processing of sensory information. The cerebral cortex
is further divided into the frontal lobe, parietal lobe, temporal
lobe, and occipital lobe. (See Table 2.1 for a description of the
general functions of each lobe and other brain regions.)
The most anterior area of the frontal lobes is known as the pre-
frontal cortex (the area just behind your forehead). Humans pos-
sess the most developed pre-frontal cortex of all animals. Some
other animals, such as chimpanzees, gorillas, dolphins, and
whales are considered intelligent because they communicate
and have social hierarchies. However, they do not possess large
or well developed pre-frontal cortexes. This highly developed
cortical area provides humans with the ability to plan for events
well into the future. Most animals react on instinct or respond
Table 2.1 Brain Areas and Functions
Frontal lobe Decision-making, reasoning, planning, behavioral inhibition,

and personality
Parietal lobe Sensation and perception of certain senses including touch
Occipital lobe Sensation and perception of visual information
Temporal lobe Sensation and perception of auditory information; language
comprehension
Limbic system Emotions, learning and memory, motivation
Hypothalamus Maintains homeostasis (body temperature, eating, drinking,
sleep, metabolism)
Midbrain Neurotransmitter production
Brainstem Vital body functions (breathing, regulation of heart rate,
consciousness)
Cerebellum Motor coordination and balance, motor learning
to stimuli, but they plan future actions very poorly. Humans can
plan for years in advance, such as planning for college or a career
in a certain field.
The frontal cortex also gives us personality. Human personal-
ities can be quite varied and different from one person to an-
other. For example, we all have different likes and dislikes, such
as hobbies, different senses of humor (sarcastic versus story-
telling style), and different preferences, such as tastes in art or
music. The frontal lobes are also responsible for some forms of
behavioral inhibition. In other words, certain areas in the frontal
cortex are responsible for making decisions and acting appro-
priately based on those decisions. We all know the difference be-
tween what is right and wrong, and we all try not to make the
wrong decisions. Knowing that difference and choosing the
right decisions based on that knowledge are functions of the
frontal lobe.
Unfortunately, the frontal lobes are particularly sensitive to
long-term drug abuse and addiction. The cortical areas in the
frontal lobes may become dysfunctional following chronic drug

use. When this occurs, the individual’s personality may change.
They are not the person you once knew; they don’t care about
the future; they become impulsive and are driven to get their
drug of choice and immediate gratification. They don’t care
about social rules and the difference between right and wrong;
they become ill-mannered and may even commit crimes to sup-
port their drug habit. In this regard, addiction can be considered
dehumanizing. (See “The Infamous Case of Phineas Gage” box.)
Certain areas of the cerebral cortex, including the frontal cor-
tex, normally suppress certain thoughts, actions, and feelings.
The areas of the brain responsible for expressing our emotions
and organizing our movements include areas that lie under-
neath the cerebral cortex. These areas are continually suppressed
by the cerebral cortex. Thought disorders such as schizophrenia,
mood disorders such as depression, and hyperactivity disorders
may occur when these sub-cortical areas are not suppressed by
the cerebral cortex. Prescription amphetamines are one class of
medication that is successful in the treatment of hyperactivity
disorders. Ritalin® is an amphetamine-like medication that is
approved for the treatment of diagnosed and documented at-
tention deficit disorder (ADD). It seems counterintuitive for
someone who is hyperactive to take a stimulant such as Ritalin.
One theory is that the cerebral cortex is not effective in turning
off sub-cortical motor areas in the brains of individuals with
ADD. Ritalin® stimulates their cerebral cortex, which in turn
can effectively inhibit the underlying motor control areas,
thereby allowing the individual to remain calm and focused.
However, these medications must be taken in strict accordance
with the clinician’s orders to be effective.
The human brain is composed of two sides, the left and right
hemispheres, which continuously communicate and share in-
formation with each other. Most functions of the cerebral cor-
tex are found on both hemispheres of the human brain. In
The Infamous Case of Phineas Gage

Phineas Gage was a mid-19th century railroad worker from Ver-
mont. In 1848, while preparing a powder charge in a hole with a
tamping iron, the charge exploded and sent the tamping iron
(which was 2.5-cm in diameter) through his left cheek, left eye,
and the frontal lobes of his brain. After months of recovering from
his injuries, his personality was remarkably different than before
the accident. His friends even said, “Gage was no longer Gage.”
Prior to the accident, Phineas was a well-mannered, calm, and re-
sponsible worker. Following the accident, he was anti-social, ill-
mannered, self-centered, told lies constantly, and could no longer
hold his job or plan for his future. His physician at the time wrote
that “the equilibrium between his intellectual faculties and ani-
mal propensities seems to have been destroyed.” Today we know
that Phineas suffered damage to his prefrontal cortex (a brain area
responsible for emotional control, decision-making, planning, and
inhibition of drives). Other patients with prefrontal cortex damage
have been reported to exhibit the same change in behavioral con-
trol. Drug-addicted individuals also experience the same behav-
ioral changes (drives toward immediate gratifications, loss of long-
term planning, selfishness, and lack of regard for social rules). In
this regard, the prefrontal cortex of the addicted brain is unable
to control behavior including the continued self-administration of
drugs.
other words, both halves of the occipital lobe in the back of the
brain are responsible for vision, both halves of the temporal
lobes are responsible for hearing, and both halves of the frontal
cortex are responsible for planning and decision making. How-
ever, there is one function that is typically unilateral and found
on one hemisphere—language—which is most often located on
the left hemisphere.
Human language is separated in the brain into areas for
comprehension and speech. Wernicke’s area is responsible for
making sense of words that we hear or read, while Broca’s area
is responsible for organizing the necessary muscular activities
required for speech, such as controlling our lips, tongue, and
breathing so that we can make sounds. These areas require a
significant blood supply so that oxygen is constantly deliv-
ered. This blood supply may be disrupted during periods of
very high blood pressure that may occur with drug use. Sev-
eral cases of strokes in young people have been caused by co-
caine or amphetamine overdose. Strokes occur when a blood
vessel ruptures or is blocked in or around the brain, causing
disruption of the blood and oxygen supply to the brain. If the
language areas of the brain are affected, the individual may
lose the ability to understand language (Wernicke’s aphasia)
or the ability to speak (Broca’s aphasia) or both (global apha-
sia). If the person is fortunate, the right side of the brain may
start understanding language or start speaking. However, the
lost functions may take several years to fully return, if they re-
turn at all.
■ Learn more about the function of brain cells Search the Inter-
net for neurons, receptor theory, or drug abuse and frontal cortex.
SUMMARY POINTS
• The cerebral cortex is responsible for complex functions
such as reasoning, thinking, and planning.
• Our emotions and memories are processed in an area of the
brain under the cortex in the limbic system.
• The midbrain produces brain chemicals called neuro-
transmitters.
• Vital functions of the brain, such as controlling breathing
and heart rate, are located in the brain stem.
• The vast number of synapses in the brain allow enormous
amounts of information to be processed.
• The synapse is a favorite target for drugs of abuse.
• The frontal cortex is important for planning, decision
making, impulse control, and personality.
Brain Regions Involved
3 in Addiction
I n the last chapter, we described how the brain’s ability to

complete complex tasks is due to the enormous amount of in-
formation integrated in trillions of synapses in the central
nervous system. All addictive drugs affect synaptic transmis-
sion, neurotransmitters, or receptor systems in the brain,
which will ultimately determine the feelings, thoughts, or ac-
tions of the drug user. In this chapter we will review the spe-
cific neurotransmitters and brain areas that are affected by all
drugs of abuse.
THE MAJOR NEUROTRANSMITTER SYSTEMS

IMPLICATED IN ADDICTION
To be considered a neurotransmitter, a chemical must be syn-
thesized in a neuron, released into a synapse, affect a post-
synaptic neuron or organ, and be inactivated by specific
mechanisms. There are two main classes of neurotransmit-
ters: small molecule transmitters and neuropeptides (Table
3.1). Neuropeptides are short chains of amino acids synthe-
sized from proteins within cells. Small molecule transmitters
are synthesized in the neurons from dietary amino acids.
These neurotransmitters are used in the brain, spinal cord,
and nerves that are distributed throughout the body. We will
discuss the four small molecule transmitters that are most of-
18
Table 3.1 Major Neurotransmitter Systems Implicated in Addiction and Their
Common Functions
NEURO SITE OF COMMON

TRANSMITTER PRODUCTION TARGETS FUNCTIONS
Serotonin (5-HT) Dorsal raphe Widely distributed Regulation of
nuclei in (forebrain, sleep and mood
brain stem midbrain)
Norepinephrine Locus ceruleus Widely Arousal, alertness
(NE) in brain stem distributed
Dopamine (DA) Midbrain Striatum, Movement,
limbic system, pleasure
cerebral cortex
GABA Distributed Neighboring Major
throughout brain neurons inhibitory
in interneurons neurotransmitter
Opioid Midbrain Midbrain, limbic Decrease pain
neuropeptides system signals, behavioral
reinforcement
ten affected by drugs of abuse: serotonin, norepinephrine,

dopamine, and gamma-aminobutyric acid.
Serotonin
Serotonin (5-hydroxytryptamine or 5-HT) is synthesized from
dietary tryptophan in large cells located in distributed brain
stem nuclei called the dorsal raphe system (Figure 3.1). The dor-
sal raphe nuclei project their axons throughout the brain and
spinal cord, including higher centers in the limbic system and
cerebral cortex. A single dorsal raphe cell may project to hun-
dreds of cells that are widely distributed throughout the brain.
The effects of serotonin on complex neural systems and human
behavior depend on the target site of serotonin’s actions. For in-
stance, serotonin released into the pons and midbrain controls
sleep cycles, including rapid eye movement (REM) sleep. The vi-
sual images that occur during dreaming in REM sleep are
19
Corpus striatum (basal nuclei) Thalamus
Hippocampus
Hypothalamus
Amygdala Cerebellum
Dorsal raphe system
Spinal cord
Figure 3.1 Serotonin is a neurotransmitter produced by a cluster of brain

stem nuclei called the dorsal raphe system (red in this figure). Neurons
in the dorsal raphe system project axons throughout the brain. The effect
of serotonin depends upon the brain system into which it is released.
thought to be due to inactivation of specific serotonin cells in the

brain stem. Lysergic acid diethylamide (LSD) is thought to cause
visual hallucinations because of its inhibition of these same sero-
tonin cells in the brain stem.
Serotonin has also been implicated in such mood disorders
as depression. Medications called specific serotonin reuptake
inhibitors (SSRIs), such as Prozac® and Zoloft®, increase sero-
tonin levels in synapses by inhibiting the re-uptake of serotonin
by pre-synaptic raphe neurons that terminate in the limbic sys-
tem and cortex. Symptoms associated with depression are re-
lieved by the continuous elevation of serotonin levels in these
Brain Regions Involved in Addiction 21
synapses, which is achieved through months of treatment with

these medications. However, if a specific drug of abuse is taken
and a sudden release of a large amount of serotonin occurs,
then rebound depression may occur when that drug is elimi-
nated and serotonin levels fall back to normal. This is the case
with use of Ecstasy (MDMA). Rebound sadness and depres-
sion following the use of MDMA is a trigger for continual ad-
ministration of the drug, which may lead to MDMA-induced
toxicity to serotonin cells in the dorsal raphe system.
Norepinephrine
Norepinephrine (NE) is produced in the locus ceruleus (LC), a
group of tightly compacted cell bodies located in the brain stem.
These cells synthesize NE from the essential amino acid tyrosine
and send their projections throughout the brain in a wide distri-
bution pattern similar to that of serotonin (Figure 3.2). The ac-
tions of NE depend upon the particular brain region into which
it is released. For instance, NE released into the lateral hypotha-
lamus can decrease appetite for food. Amphetamines that cause
a large release of NE in the hypothalamus greatly amplify this ef-
fect. Norepinephrine released into the cerebral cortex is respon-
sible for alertness and arousal. The more NE released into the
cerebral cortex, the more alert and attentive an individual be-
comes. The levels of NE released in the cortex from the LC mildly
fluctuate throughout the day. As a result, there are periods of the
day when we feel more awake and alert, while at other times of
the day we are tired and sleepy. Certain drugs of abuse, such as
stimulants or “uppers,” increase alertness and arousal and cause
talkativeness, restlessness, and agitation because of their action
on NE systems. For example, amphetamines can cause profound
insomnia and irritability because of the increased release of NE in
the hypothalamus, cortex, and limbic system.
Cells located outside the central nervous system also use nore-
pinephrine as a chemical signal. Some of these cells are nerves,
Limbic system Amygdala

(basic emotions and learning) (alerts brain to temptation)
Substantia nigra
(source of dopamine)
Prefontal cortex
(judgment and willpower)
Nucleus accumbens
Ventral tegmental area Locus ceruleus
Figure 3.2 Dopamine is a neurotransmitter that is formed in several different sec-

tions of the brain. Two of these, the mesolimbic and mesocortical pathways, are lo-
cated in the ventral tegmental area. Release of dopamine from the ventral tegmen-
tal area into the nucleus accumbens causes feelings of pleasure. Another dopamine
production area, the substantia nigra, is slowly destroyed in patients with Parkin-
son’s disease.
originating in the spinal cord, that stimulate specific target organs

in the body. These organs are activated by emotional states such as
fear and anxiety. For instance, NE will increase heart rate, breath-
ing, blood pressure, glucose release from the liver, sweat secretion
from the palms and feet, and shunt blood from internal digestive
organs to the skeletal muscles during emotional stress. In this case,
NE could be considered a stress signal that prepares the body for
defense or action (known as the “fight or flight response”). NE also
prepares the brain by increasing dilation of the pupils in an at-
tempt to gain more visual information, and activating the cerebral
cortex and limbic system so that a quick assessment of the threat,
a decision, and appropriate action can take place.
Dopamine
Dopamine is a small molecule neurotransmitter that is similar in
structure to norepinephrine. Dopamine is made in four separate
systems in the brain. One system is located between the hypotha-
lamus and pituitary gland that regulates hormone production
and secretion. The other systems are located in the midbrain re-
gion (Figure 3.2). Two of these, the mesolimbic and mesocortical
pathways of the ventral tegmentum, are critical to the addictive
properties of drugs of abuse These systems will be discussed in
greater detail later in this chapter. The fourth system, called the
nigrostriatal system, originates in an area in the midbrain called
the substantia nigra. The nigrostriatal system releases dopamine
into subcortical areas involved with the striatum, which controls
muscle movement. Parkinson’s disease slowly destroys the ni-
grostriatal system in elderly individuals (Figure 3.3). As a result,
they experience shaking extremities (tremors), difficulty with
initiating movements (akinesia), or slow movements (bradyki-
nesia). The reasons for the destruction of the substantia nigra in
Parkinson’s disease may be due to different mechanisms that are
not completely understood. Nevertheless, the fact that medica-
tions that improve dopamine production and release are effective
in treating the symptoms of Parkinson’s suggests that dopamine
does play a role in this movement disorder.
GABA
Gamma aminobutyric acid (GABA) is synthesized from gluta-
mate (an amino acid) and is found in very high concentrations
throughout the brain. When released onto a cell, GABA will de-
crease the chance that a cell will fire an action potential, and is
therefore considered an inhibitory neurotransmitter. GABA is not
synthesized in cells found in specific nuclei in the brain stem or
forebrain (unlike serotonin, norepinephrine, or acetylcholine),
but is synthesized in small interneurons found in all gray matter
throughout the brain.
Cross-section of the
midbrain to reveal
substantia nigra
Substantia nigra
No disease
Substantia nigra is
diminished in
Parkinson's disease
Figure 3.3 A cross-section of the midbrain showing the substantia nigra. In Parkin-
son’s disease, dopamine-producing neurons of the substantia nigra are lost.
Because GABA has inhibitory effects on neurons, any drug

that increases the actions of GABA will decrease general brain
activity and can be considered a “downer” or depressant. De-
pressants that act to increase GABA’s actions include alcohol,
sleeping pills such as Ambien, muscle relaxants such as Valium,
and barbiturates such as Secobarbital. Some depressants are very
powerful GABA agonists (they increase GABA activity) and
cause rapid sedation, coma, and death. Drugs such as GHB and
Rohypnol® are potent GABA agonists that cause a rapid loss of
consciousness (suppression of cortical and NE systems) and suf-

focation due to respiratory failure as a result of suppression of
brain stem centers that drive the diaphragm and breathing mus-
cles in the chest.
Depressant drugs can also be considered amnestic agents that
decrease memory formation and cause forgetfulness. Amnesia
caused by depressants is due to increased GABA activity in areas
normally responsible for memory formation—e.g., the cerebral
cortex and hippocampus in the limbic system. Drug or alcohol
“black-outs” result from suppression of activity in these brain
areas. Black-outs are a symptom of increasing use and abuse of
depressants, particularly alcohol, and are a warning sign of loss
of control.
Depressants are also very potent when mixed with one an-
other because they all activate the GABA systems in slightly dif-
ferent ways. GHB may bind the GABA receptor directly, while
alcohol will bind to a different location on the receptor and
magnify GHB’s effect. This is why depressants are considered a
class of drugs that are synergistic with one another. That is, the
effects of two drugs mixed together might actually appear to
have the effects of more than two drugs. Because of this syner-
gistic effect, overdoses are common when different depressants
are used at the same time.
NEUROPEPTIDES
Peptides are different from small molecule neurotransmitters
in that they resemble proteins and are synthesized as short
chains of amino acids. However, neuropeptides have actions
similar to those of other neurotransmitters: they are released
from neurons into synapses, have inhibitory or excitatory af-
fects on post-synaptic neurons, and are eliminated from the
synapse. Neuropeptides are often co-released into the synapse
with other neurotransmitters. The actions of neuropeptides on
cells are somewhat longer than that of other neurotransmitters.
Therefore, neuropeptides are often considered neuromodulators

and influence the overall activity of networks, as well as indi-
vidual, neurons.
There are several neuropeptides implicated in the behavioral
effects of drugs of abuse. For instance the opioid family of neu-
ropeptides is involved with the actions of opiate drugs such as
heroin, morphine, OxyContin®, and other painkillers. The opi-
oids in the human brain, such as the endorphins and enkephalins,
are considered natural painkillers. These peptides surround
midbrain systems involved with the transmission of sensory
stimuli, especially pain sensations. These pain pathways have
cells that express receptors for the opioid peptides. When opioid
peptides bind these receptors, they block pain signals and there
is a decreased sensation of pain. Medications that are used to
control pain will also bind these receptors and decrease the
transmission of pain signals to higher centers in the brain. Opi-
oid receptors are also located on dopamine cells that are re-
sponsible for behavioral motivation and reward, as well the sub-
jective sensation of pleasure.
■ Learn more about brain chemicals Search the Internet for
neurotransmitters or neuropeptides and addiction.
MOTIVATION, DRIVES, AND THE CHEMISTRY

OF PLEASURE
Human behavior is altered by external stimuli, such as sights and
sounds in our environment, and such internal stimuli as
thoughts, feelings, wants, and needs. These stimuli motivate us
to act in some way or on some thing. Internal motivation signals
tell us to act in a certain way to reach a specific goal or reward.
Simple examples of motivational states include the drives to
maintain body homeostasis, such as eating, drinking, regulation
of body temperature, and sleep. These drives are critical for the
immediate survival of an individual. When drives are not ful-
filled or gratified, we feel uncomfortable and tense. We may de-

sire the goal even more until it is satisfied and we feel subse-
quently relieved. Other drives include the need to reproduce and
care for our offspring, which are important for survival of the
species. More complex drives include personal desires such as
material wealth, social stature, and power, which may not be
considered critical for the survival of an individual or the species,
yet may dominate the needs and wants of many individuals. Ob-
taining the goal or reward of the drive state can be directly plea-
surable and therefore cause us to repeat that behavior when drive
and desire returns. Once the reward is reached, the drive to ob-
tain it and the motivation to act subside. In addition, the stimuli
that predict the goal are ignored until the drive returns.
An example of a drive state and motivation would be the feel-
ing of hunger. Imagine that you are late for school or work one
morning and don’t have time to eat breakfast. Throughout the
morning you experience hunger, and your stomach may growl
in anticipation of food that is overdue. Once you have time to
each lunch you jump in your car to find a restaurant. On the
way, you are irritable, edgy, and experience a little “road rage.”
The internal drive to replenish nutrients is now affecting emo-
tional centers in your limbic system, while you ignore other cor-
tical stimuli—your afternoon plans or traffic laws. You then be-
gin to smell fried fast food, engaging your cerebral cortex and
immediately motivating you to find the food source. You pur-
chase and eat the fast food and are immediately gratified as your
hunger drive subsides despite considerations of its nutritional
value. On the way back to school or work you pass other restau-
rants and smell food, but you can easily ignore these aromas be-
cause the drive to eat has subsided. Drives, as we can see from
this example, are very powerful motivators of human behavior.
Some drives are not the result of the absence of substances
such as food in the body but are a result of external stimuli that
predict reward or pleasure. Pleasure is also a powerful motivator
of human behavior. The areas of the brain responsible for plea-

sure are believed to be the areas responsible for reinforcement.
In 1954, two scientists, Olds and Milner, discovered areas in rat
brains that when stimulated caused the animals to change their
behavior and learn different tasks. The rats would push levers
and learn to navigate mazes or other new behaviors in order to
receive small electrical stimulation delivered to specific brain ar-
eas (Figures 3.4 and 3.5).
The sensitive brain areas included those that connected the
midbrain and forebrain. It was later discovered that the most
important brain areas for reinforcement and pleasure include
the nucleus accumbens in the forebrain region. The nucleus ac-
cumbens (NA) receives input from dopamine-producing cells in
the midbrain called the ventral tegmental area (VTA). The VTA
contains dopaminergic cells that project to the frontal cortex
and limbic system. Release of dopamine into the frontal cortex
and nucleus accumbens result in the subjective experience of
pleasure. Therefore, dopamine release causes pleasure and
causes us to repeat those behaviors necessary to acquire the re-
ward in the future. Dopamine is released when the reward is ac-
quired (such as the tasty and gratifying fast food in our example)
in addition to the presence stimuli that predict reward (such as
the smell of the food that directed our behavior). In this regard,
the ventral tegmental dopaminergic system is not only responsi-
ble for the pleasurable effects of natural rewards—e.g., food and
artificial rewards—e.g., drugs of abuse but it also predicts ex-
pected rewards (Figure 3.6).
Addictive drugs are reinforcing. They all cause the subjective
experience of pleasure and cause us to repeat drug-taking be-
haviors in order to re-experience the pleasure. Animals, as well
as humans, will work very hard to get infusions of addictive
drugs such as heroin or cocaine. The more addictive a drug is,
the harder animals will work for it. They will endure painful
stimuli and ignore natural rewards in order to get drugs of
Light
Brain stimulator
(computer) activated
by wire
Lever
Water dispenser
Food dispenser
Electric grid
Figure 3.4 In 1954, the scientists James Olds and Peter Milner dis-
covered that rats could be rewarded by stimulating specific areas in the
animals’ brains. The rats would push levers or navigate mazes in order
to receive electrical stimulation to these brain areas.
abuse. Often this leads to malnourishment, dehydration, fa-

tigue, or overdose. In all mammals, these drives to acquire the
dopamine reward can lead to failing health and even death.
If a drug activates the VTA system and increases dopamine in
the nucleus accumbens, it will cause reinforcement and addic-
tion. However, the mechanisms of this effect and the magni-
tude of increased dopamine levels in these areas are often dif-
ferent. For instance, some drugs, such as the amphetamines,
increase release of dopamine from presynaptic terminals in the
nucleus accumbens. Certain drugs, such as cocaine, block the
reuptake of synaptic dopamine into the presynaptic neuron.
Other drugs of abuse, such as alcohol, act on the cell bodies in
the ventral tegmentum that produce dopamine. Addictive opi-
ates, such as heroin and oxycodone, inhibit GABA cells that
surround and normally suppress VTA cell activity. Not all
drugs activate the dopaminergic system to the same extent and,
therefore, they possess different addictive potentials. For in-
stance, cocaine and methamphetamine are much more addicting
than THC because they increase dopamine levels in the nucleus
accumbens more quickly and to a greater extent. In this regard,
Figure 3.5 The positron emission tomography (PET) scans pictured here have been
color-coded to show brain metabolism and the effects of cocaine use. Each brain
scan is axial (horizontal), with the front of the brain at top. The three scans show a
normal, cocaine-free brain (top), the brain of a cocaine user ten days after the last
cocaine dose (middle), and 100 days after the last dose (bottom). Metabolism
ranges are depicted in color, from low (dark to light blue) to high (yellow to red). The
scans show the long-term recovery period, as well as the poor recovery of the front
of the brain after cocaine use.
the most addictive substances are cocaine, particularly smok-

able crack cocaine, amphetamines (especially metham-
phetamine), the opiates such as heroin, morphine, and
painkillers, and nicotine, which is perhaps the most addictive
psychoactive drug. Other drugs of abuse, such as alcohol, Ec-
stasy, Ketamine, and prescription depressants among others,
possess slightly fewer addictive properties but can also lead to
similar self-destructive behaviors and addiction.
Intracranial Self Stimulation
Descending Myelinated Fibers
GABA
Enk
Acc
GABA DA
NE VTA
LC
Barbiturates Opiates Amphetamine

Benzodiazepines Ethanol Cocaine
Barbiturates Opiates
Benzodiazepines THC
Phencyclidine
Ketamine
Nicotine
Figure 3.6 Various drugs affect the different sites along the reward
pathways of the brain.
For a drug to be considered addicting, it must be capable of

producing pleasure, followed by repeated drug taking so that the
pleasure is re-experienced, and it must also lead to tolerance and
dependence. Tolerance is defined as the need to take larger doses
of a drug over time to achieve the same effect. Tolerance may be
due to receptor systems in the brain becoming less sensitive to a
drug over time. For example, someone who uses heroin will
soon develop tolerance and will increase their dose in order to
achieve the same sense of pleasure or high. The opioid receptors
on cells in the midbrain that surround the VTA system may de-
crease in number on the post-synaptic neurons when exposed to
repeated doses of heroin (receptor down-regulation). As a result
there are fewer signals in the post-synaptic cells that ultimately
cause the VTA system to become active. This may lead the user
to take larger doses in order to occupy the remaining opioid re-
ceptors for longer periods of time. Tolerance develops very
quickly with amphetamines and opiates.
Drug dependence occurs when the user must take the drug to
feel normal and to avoid uncomfortable withdrawal symptoms.
Specific withdrawal symptoms for each class of drugs will be dis-
cussed in the next chapter, but all drug withdrawal states include
the sensation of wanting or craving the drug. During drug crav-
ing, certain areas of the reward pathways become activated in
anticipation of rewards. Areas in the prefrontal cortex (dorso-
lateral prefrontal cortex), the amygdala, and temporal lobe be-
come active when cocaine abusers are shown stimuli typically
associated with drug use, such as a video of simulated cocaine
use (Figure 3.7). This state is very powerful in addicted individ-
uals and may lead to extreme and risky behaviors that cause sig-
nificant health, social, and legal consequences.
■ Learn more about addictive pathways in the brain Search the
Internet for dopamine and motivation or nucleus accumbens
and reward.
LOSS OF BEHAVIORAL CONTROL

One of the classic signs of drug or alcohol addition is continued
use despite harmful consequences. Addicted individuals will
continue to use drugs or alcohol despite the mounting harmful
effects to their health, family, employment, legal status, and
quality of life. Earlier we discussed the brain regions and neuro-
transmitters involved with pleasure, drives, and reinforcement.
In this chapter we will discuss the brain areas involved with de-
cision-making and how drugs of abuse alter these areas and lead
to further destructive behavior.
Drugs of abuse can cause immediate feelings of pleasure and
intoxication by activating the ventral tegmental dopaminergic
system. There is mounting scientific evidence that drugs also al-
ter other brain areas that are involved with decision-making,
planning, and behavioral control. Several studies have demon-
strated that chronic drug use alters the brain’s frontal cortex
A
Normal Cocaine addict
B
Noncraving state Cocaine addict
Figure 3.7 (A) These PET scans show brain activity in a normal subject
and in a cocaine addict. The cocaine addict has decreased brain activ-
ity in the orbitofrontal cortex (OFC) when compared to the normal sub-
ject. Low frontal cortex metabolism may cause the loss of behavioral
control in drug addicts. (B) These PET scans show brain activity in a
person who is craving cocaine. The scans on the right show brain ac-
tivity in cocaine addicts who were exposed to cocaine paraphernalia
and videos of people using cocaine. These scans show activity in the
dorsolateral prefrontal cortex (DL), which is important in short-term
memory, and amygdala (AM), which influences emotions and memory.
In volunteers who were not exposed to non-drug-related stimuli, this
brain activity was not seen (scans at left).
where we make decisions about the consequences of our actions.

The frontal cortex decides on which actions to make in a partic-
ular situation by evaluating the risks and benefits of a particular
action. The prefrontal region of the frontal cortex is believed to
be involved in the development of addiction from early stages of
use and abuse to dependence and addiction. Drugs of abuse
cause the prefrontal cortex to overvalue reward, undervalue risk,
and fail to learn from repeated mistakes. The mechanism of this
effect is not completely understood, but there is evidence that
drugs of abuse decrease the influence of the prefrontal cortex on
the nucleus accumbens and other limbic areas. In other words,
addiction can be due to the continuous pursuit of pleasure that
is caused by the drugs affecting the midbrain dopamine systems,
as well as by compulsive drug-taking and loss of behavioral con-
trol due to the drugs disrupting the frontal cortex.
Individuals addicted to methamphetamine have been stud-
ied with various behavioral tests that show that these addicted
individuals made impulsive decisions based on habits and ig-
nored the harm that their decisions can cause. Like these
methamphetamine addicts, individuals with brain damage to
the prefrontal cortex make choices based on the chances for im-
mediate benefit rather than on future consequences. Therefore,
the consequences of prolonged drug use include frontal cortex
dysfunction that leads to choices based on short-term rewards
as well as a hypersensitivity to these rewards. A drug-addicted
frontal cortex is like a car speeding out of control: the driver
can’t hit the brakes (no behavioral control) and the driver’s foot
is planted on the accelerator despite impending danger (hyper-
sensitivity to immediate gratification). It is easy to see how drug
abuse is progressive when brain systems involved with behav-
ioral control are unable to stop drug-taking behavior. (See
Table 3.2 for an overview of major brain systems involved with
drug abuse and addiction.)
Table 3.2 Summary of Brain Areas Implicated in Drug Addiction
ROLE IN EFFECTS OF
BRAIN AREA NORMAL BEHAVIOR DRUGS OF ABUSE
Ventral tegmental Motivational system important Increase system's
dopamine system for survival behaviors activity by various
(eating drinking, mechanisms
reproductive behaviors)
Nucleus Subjective experience of Increase dopamine
accumbens reward and gratification; levels in NA which
anticipation of pleasure causes "high" and
during craving craving during drug
absence
Limbic system Emotional response to Causes agitation and
(amygdala) cues that predict reward; behavioral activation
recalls memories of past during craving;
experiences; activated remembers pleasures
during craving of previous highs
Frontal cortex Weighs risks and benefits of Inactivation leads to
behaviors; controls actions impulsive decisions and
(behavioral inhibition) compulsive behaviors
SUMMARY POINTS
• Neurotransmitters implicated in the effects of drugs of
abuse include serotonin, norepinephrine, dopamine,
GABA, and specific neuropeptides.
• The ventral tegmental dopaminergic system is responsible
for the pleasurable effects of drugs as well as drug craving.
• The frontal cortex is unable to control drives for drugs in
addicted individuals.
4 Stimulants and Hallucinogens
In previous chapters, we saw that each drug of abuse works

a little differently in the brain. Most of the drugs reviewed in
the next two chapters are considered habit forming and ad-
dicting; therefore they are known to affect the chemical mo-
tivation system in the brain (the dopamine system). The way
they influence the brain and other chemical systems, besides
the dopamine system, determines what effect they have on
behavior. Drugs are categorized based on the way they
change behavior.
For instance, stimulants (drugs that increase activity of our
brain and body such as amphetamines) affect chemicals, such
as norepinephrine, that keep us awake, alert, and active. Am-
phetamines fool the brain because their chemical structures
are very similar to our neurotransmitters (Figure 4.1). On the
other hand, depressants (drugs that make us sleepy and de-
crease body functions such as alcohol and GHB) affect brain
chemical systems that normally cause feelings of tiredness or
sleepiness, such as GABA. Drugs that affect our ability to
sense our environment, such as LSD or PCP, alter chemical
systems that may cause distortions of reality or hallucina-
tions. Some drugs can be categorized into more than one
group (such as Ecstasy, which can act like a stimulant as well
as a hallucinogen). However, all of these drugs of abuse have
the ability to change our mood and the way we think and feel.
36
HO NH2
DOPAMINE
HO
OH
NH2
NOREPINEPHRINE
HO
OH
C C H H
C C C C NH2 AMPHETAMINE
C C H CH3
C C H H
C C C C NH CH3 METHAMPHETAMINE
C C H CH3
Figure 4.1 Amphetamines affect the brain by mimicking our neurotransmit-

ters, leading to feelings of alertness.
Let’s review each class of drugs and discuss the impacts they have
on our brain and behavior.
STIMULANTS
Not all stimulants are alike. Although they all increase activity in
the central nervous system and the body, stimulants may have
37
Table 4.1 Effects of Stimulant Abuse (Amphetamines and Cocaine)
SHORT-TERM EFFECTS LONG-TERM

(DURING INTOXICATION) CONSEQUENCES
Behavioral excitation (arousal, Psychosis (extreme paranoia, suspicious,
hyperactivity, excess energy, aggressive)
alertness, confident, talkative)
Acute psychosis (suspicious, Weight loss
paranoid, hallucinations)
Elevation in body temperature Poor hygiene
Increase in blood pressure Skin lesions; hallucinations of bugs on
skin
Irregular heart rhythms Heart disease
Stroke Risks of infections, hepatitis, anemia,
and other diseases if used intravenously
Heart attack Addiction; rebound depression (suicidal)
different addictive potentials. For instance methamphetamine

or crystal meth is one of the most potent stimulants in existence.
On the other hand, caffeine is one of the weakest. They both are
habit forming but to very different degrees. Crystal meth is very
addicting while caffeine is mildly habit forming. Why? It is be-
cause of the way they affect our brain. The quicker a drug
reaches the chemical motivator system in the brain and the more
it stimulates it, the more addicting it is. Let’s consider the most
commonly abused stimulants. (See Table 4.1 for an overview of
the physical and behavioral effects of stimulant abuse.)
Amphetamines
Amphetamines are powerful stimulants and are very addicting.
When abused, they over-stimulate the brain by increasing ac-
tivity of the norepinephrine system (the arousal neurotrans-
mitter). As a result of too much norepinephrine release in the
hypothalamus, amphetamines cause long periods of wakeful-
ness, decreased appetite, agitation, irritability, and increased
Stimulants and Hallucinogens 39
Figure 4.2 This diagram illustrates the effect of cocaine on the dopamine reuptake
channel of the synapse. Cocaine blocks the reuptake of dopamine, leading to in-
creased amounts of dopamine in the synapse.
body temperature. Amphetamines can also cause a large re-

lease of dopamine in the nucleus accumbens, the pleasure cen-
ter (Figure 4.2). As a result, these drugs drive the user to take
more and more of the drug to maintain the artificially high lev-
els of dopamine.
Table 4.2 Behavioral Cycles of Stimulant Abuse
STAGE BEHAVIORAL SIGNS

Intoxication (amphetamine Behavioral excitation
or cocaine use) (energized, aroused, etc.)
Drug elimination (negative Restless, agitated, anxious
feelings, “coming down”
from high)
Repeated use (to relieve Mania (extreme behavioral excitation);
negative feelings); binge higher doses taken in attempt to achieve
use (frequent, high doses initial high
taken)
Crash (worsening negative Depression, despair, intense drug craving,
feelings when drugs wear drug seeking
off); drug withdrawal
Return to use Psychosis and drug toxicity become
more common
Too much dopamine and norepinephrine in the frontal cortex

can also cause paranoia in the user. This is called “amphetamine
psychosis,” which mimics the symptoms of paranoid schizophre-
nia. The paranoid user is suspicious of his or her environment and
friends and may feel as though people are watching or following
them. In some cases the paranoia is so severe that the user becomes
violent and aggressive. Health-care workers and law enforcement
officers are trained to detect the effects of amphetamines. (See
Table 4.2 on the behavioral cycles of stimulant abuse.)
Amphetamines also are dangerous to the body as well as the
brain. High doses of powerful stimulants can cause high blood
pressure, elevated heart and breathing rates, high body temper-
ature, strokes, and heart attacks. For these reasons metham-
phetamine is one of the most dangerous street drugs. It is quick
acting because it is absorbed into the bloodstream and brain
very quickly. It is very addicting and stimulating because it
causes a large release of dopamine and norepinephrine. It is also
very cheap and readily available, and its use is reaching epidemic
proportions in some states. Crystal meth and other am-
phetamines can cause permanent damage to neurons in the
frontal cortex of the brain. This type of damage to brain areas in-
volved with behavioral inhibition makes sobriety and recovery
much more difficult for these individuals. Teenage meth users
with permanent brain damage are some of the most difficult
cases of drug addiction (see “The Story of Skyler” box).
Cocaine
Cocaine is another powerfully addicting stimulant. Cocaine af-
fects the same neurotransmitters as the amphetamines but uses
a slightly different mechanism. While the amphetamines in-
crease release of dopamine from the presynaptic terminals of
dopamine-containing cells in the nucleus accumbens, cocaine
increases the amount of dopamine in the synapse by blocking
its reuptake from these presynaptic terminals (Figure 4.3). Re-
call from Chapter 3 that the addictive nature of certain drugs is
a result of their ability to increase dopamine levels in the
synapse between cells in the pleasure areas of the brain. Some
drugs increase production or release of dopamine from presy-
naptic cells in these areas, while other drugs block the recycling
of dopamine once it is released into the synapses located in
these areas. Cocaine, whether snorted, injected, or smoked, is a
very potent blocker of the recycling, or re-uptake, of dopamine
in the nucleus accumbens. As a result, dopamine remains in the
synapses of cells in the pleasure areas, causes euphoria and leads
to an almost immediate drive to take more and more of the
drug. Crack cocaine is a particularly addicting drug not only be-
cause of its ability to block reuptake of dopamine, but also be-
cause the drug is absorbed so rapidly from the lungs to the
bloodstream and into the brain (see “Dr. Mark” box). The
pharmacological and neurobiological properties of crack co-
caine, in addition to its availability and affordability, have
directly resulted in the social decay of many families and com-

munities. Because cocaine and amphetamines share similar
mechanisms of action in the central nervous system and body
organs, overdoses and toxicity from cocaine and amphetamine
abuse are common occurrences.
The Story of Skyler

Skyler started experimenting with drugs at age 14. Her brother
introduced her to marijuana, and she soon started smoking pot
occasionally with her friends. By age 16, she stared using co-
caine “casually” and within another year she was using metham-
phetamine and crack cocaine on a daily basis. She moved to an-
other city in an attempt to “start over” and get clean. However,
she was soon back to using regularly and started injecting speed
intravenously every two hours with her friends. Skyler started ex-
periencing black-outs. One day she injected a very large dose of
speed and quickly realized that she had taken too much. “I’m
dead,” she thought. Her eyes rolled back into her head, she con-
vulsed, had seizures, and passed out. The next day, she was still
having convulsions so she called an ambulance and spent the
night in the hospital. After her discharge, she quickly went back
to using. During a domestic violence call, Skyler was arrested for
underage drinking and spent six days in jail where she detoxed.
After her last few experiences, Skyler says that she is done with
drugs. Now at age 20, she holds a job and is a full-time college
student. She is healthy, responsible, and looking forward to her
future. Skyler most likely inherited her compulsive behaviors (all
of her brothers use drugs and her grandfather drank). She is one
of a few young people who was introduced to drugs as a
teenager, had a short but extensive drug use history, but so far
has lived through it. When she thinks about it, she is “amazed
at how ignorant people are about drugs. They’ll give up their
lives for it.”
Figure 4.3 Normally, serotonin is removed from the synapse shortly after being re-
leased. Cocaine and MDMA stops this from happening, leading to increased amounts
of serotonin in the synapse. This diagram shows how MDMA blocks the reuptake of
serotonin.
Ecstasy (MDMA)
Ecstasy (3,4 methylenedioxymethamphetamine, MDMA) is a
drug that has become increasingly popular in the last several
years. As you can see from its chemical name, MDMA is a syn-
thetic amphetamine derivative (a phenylalkylamine) and has
pharmacological and behavioral properties similar to stimulants
as well as hallucinogens. As a result, MDMA is often categorized
Dr. Mark
When Mark was a kid, he thought his family was normal. Later
he learned that he was part of an addictive family (his mother
was anorexic and his father was co-dependent). Mark had early
issues with trust and self-esteem, which he compensated for by
getting good grades and his parent’s admiration. (He says that
he also liked cough syrup—the one with alcohol in it.) After high
school, Mark decided to become a doctor. He drank in college
and smoked pot in med school but felt that he never had a prob-
lem. After graduating, he got his medical license, which allowed
him to purchase morphine, and amphetamines through a cata-
log. He used the drugs occasionally. Mark then met a coke
dealer and started smoking cocaine. His work suffered, but he
and his partner in the medical practice covered for each other.
However, within a few years it was obvious that Mark was pro-
fessionally and personally unreliable and visibly sick. Soon
thereafter, his family and friends held an intervention and sent
him to a nationally recognized treatment center. Upon admis-
sion to the program, Mark thought that he had lost his family,
his friends, and his career. But he realized he was beaten up
enough and didn’t want to use drugs anymore. After eight weeks,
he had a spiritual moment when he finally “got it” and drugs
stopped controlling his life. Mark stayed in the center for four
months. When he returned home, he was pleasantly surprised to
find that his friends and family were still there for him. Today,
Dr. Mark runs a rehab center, is a nationally recognized addic-
tionologist, and gives himself permission to make mistakes. “I
only have to be perfect in my sobriety; I now know its OK to be
human,” he says. “I didn’t plan on becoming a drug addict, but
if I knew what would happen to my life, I wouldn’t have started.”
as a hallucinogen or psychedelic. MDMA not only increases

norepinephrine and dopamine release like a stimulant, but it
also causes a large release of serotonin. This serotonin surge is
believed to cause the sense of warmth, caring, and empathy in its
users. The dopamine release stimulates pleasure areas, and nore-
pinephrine causes behavioral stimulation in MDMA users. The
release of norepinephrine causes an elevation in blood pressure
and heart rate and is believed to underlie the hyperactivity and
energizing effect of MDMA (see Table 4.3 for a summary of the
effects of MDMA). Often this drug is used in group gatherings
or dances (raves) where the users can become dangerously hy-
pertensive (high blood pressure), physically exhausted, and hy-
perthermic (high body temperature). Stimulants also cause
stereotypical behaviors such as lip smacking, chewing, or grind-
ing of teeth. As a result, MDMA users may place objects in their
mouths to satisfy these irresistible urges.
Table 4.3 Effects of MDMA (Ecstasy)
EFFECTS EXAMPLES
Effects on Body Elevated body temperature, heart rate, and blood pres-
sure; risk of heart valve damage; nausea, vomiting,
and chills; muscle cramping, teeth clenching, visual
disturbances; fainting; risk of loss of consciousness;
possible seizures
Behavioral Effects Initial euphoria, behavioral stimulation, empathy; re-
bound depression, anxiety, fatigue, irritability; chronic
users experience impulsiveness, sleep and appetite
problems
Brain Effects Causes large release of serotonin followed by its deple-
tion; chronic users may experience cognitive deficits
such as difficulty with memory, attention, and mood;
heavy use may lead to damage of serotonin cells and
cortical gray matter
Addictive Potential Effects on reward centers not yet completely understood;
most regular MDMA users fit criteria for substance
abuse diagnosis and warrant drug treatment
Tolerance and psychological dependence occur rapidly with

repeated use of MDMA. MDMA has also been reported to be
neurotoxic at chronic, high doses. The toxicity in the brain in-
cludes damage to the serotonin-producing cells in the dorsal
raphe system. Although individuals may not suffer any immedi-
ate consequences to loss of serotonin cells, the long-term effects
of this damage are unknown to researchers. It is hypothesized
that the functions that are served by the serotonin system, in-
cluding mood, appetite, sleep cycles, learning, and memory,
may become altered as the individuals age.
■ Learn more about how stimulants work in the brain Search
the Internet for methamphetamine and brain mechanism,
cocaine and brain mechanism, or MDMA and brain mechanism.
Caffeine
Caffeine is also a psychoactive drug because it has effects on the
brain and on behavior. Although caffeine can be abused and
tolerance does occur, caffeine addiction, as defined by the loss
of control of self-administration and the resulting negative so-
cial, legal, or health consequences, is rare. The mechanism of
action of caffeine in the brain is different from that of all other
stimulants. Caffeine inhibits the action of adenosine, a neuro-
transmitter that normally decreases the activity of nore-
pinephrine cells. As a result, caffeine increases brain activity
and alertness by elevating norepinephrine release in the brain.
Caffeine also increases blood pressure, heart rate, respiration
rate, and metabolic rate, as well as causing blood vessel con-
striction. If people who are tolerant to caffeine and usually
need large doses in order to stay awake stop taking the drug,
they may experience rebound blood vessel dilation and painful
headaches as well as fatigue. (See “Caffeine: The New Drug of
Abuse?” box.)
Nicotine
Nicotine is also a psychoactive stimulant and is one of the most
powerfully addicting drugs in the world. (See Table 4.4 for an
overview of the criteria that classify nicotine as an addictive
chemical.) It is found in preparations of the tobacco leaf and is
often consumed through cigarette smoke and chewing tobacco.
Smoking, or inhalation, is the quickest way drugs can enter the
central nervous system. The cigarette is a very effective drug de-
livery device. Once inhaled, nicotine in tobacco smoke can
Caffeine: The New Drug of Abuse?

The consumption of caffeinated beverages in the last few years
has increased dramatically. Specialty coffee shops and espresso
stands have appeared everywhere. In our homes, we order coffee
beans from all over the world, store them in special containers,
and grind them in expensive machines. The average cup of cof-
fee contains 100 mg of caffeine, and the average soda has 50
mg. It is not uncommon for individuals to consume more than
500 mg of caffeine per day or more. Caffeine is now found in
sport and energy drinks (along with other stimulating herbal ad-
ditives) in very high concentrations. It is even in certain alco-
holic beverages. The long-term effects of high caffeine intake
are not known, but caffeine increases cellular metabolism, heart
rate, blood pressure, and insulin secretion, and has been impli-
cated in cardiovascular and intestinal diseases. Teenagers and
children may take hidden doses of caffeine in candy and sweets
(in the form of chocolate). Tolerance and dependence occur with
caffeine consumption but whether it causes true addiction is de-
batable. The next few years should shed some light on this ques-
tion as marketing campaigns, caffeine extraction devices, and
caffeine preparations become more effective.
Table 4.4 Cigarette Smoking as Addictive Behavior
CRITERIA FOR
NICOTINE AS
ADDICTIVE SUBSTANCE EXAMPLES
Dependence Psychological (craving of cigarettes in particular
setting) and physical dependence (withdrawal
symptoms occur when use stops) develop
rapidly with continual use
Tolerance Increases in doses to achieve same effect (from
one cigarette to one or two packs a day is com-
mon sequence of events)
Addiction Use despite harm (use continues despite educa-
tional campaigns, documented effects on mul-
tiple organ systems, and medical and govern-
mental warnings); denial
Withdrawal Abrupt cessation of use precipitates withdrawal
symptoms (agitation, irritability, craving, drug-
seeking behaviors)
reach the brain’s pleasure areas in less than 10 seconds. Nico-

tine has been reported to increase the release of dopamine in
these areas as well as inhibit the activity of monoamine oxidase
(MAO). MAO is an enzyme that metabolizes dopamine. By de-
creasing MAO activity, nicotine can elevate dopamine levels. As
a result, the user can experience the dopamine-induced eupho-
ria of nicotine and continual need to self-administer the drug.
Nicotine is different from most stimulants because it also acts
on acetylcholine receptors in the central and peripheral nervous
systems. An increase in cholinergic activity in the brain is partly
responsible for the activating, or stimulating, property of the
drug. Nicotine use and dependence can lead to a serious addic-
tion and significant health consequences. Approximately
500,000 Americans die each year from smoking, and more than
3,000 children and teenagers start smoking each day.
THE HALLUCINOGENS
This broad class of drugs includes several different compounds
that alter brain function using different mechanisms of action.
They all, however, have the ability to induce illusions (a mis-
taken perception), delusions (a mistaken idea), hallucinations
(sensing something that does not exist), or to cause severe
breaks with reality. Drugs in this category can affect several dif-
ferent neurotransmitters including serotonin. From Chapter 3,
recall that serotonin controls our mood, appetite, sleep cycles,
and memory, as well as sensation. Inhibiting the serotonin sys-
tems in certain areas of the brain can cause visual, auditory, or
somatosensory distortions.
LSD
Lysergic acid diethylamide (LSD) is a synthetic (man-made)
chemical and is one of the most potent psychoactive drugs. It is
biologically active in the microgram range (one millionth of a
gram). In addition to hallucinations or illusions, the user may
also experience extreme anxiety, breaks with reality, and confu-
sion. LSD also increases heart rate, blood pressure, and respira-
tory rate, and it causes dilation of the pupils because of its effects
on the release of norepinephrine in the brain and body. Inter-
estingly, LSD and most other hallucinogens do not significantly
increase dopamine release in the pleasure areas of the brain. As
a result, the addictive behaviors typically associated with most
drugs of abuse do not occur with some hallucinogens. Most
users take these drugs for their effects on perception and sensa-
tion and not for their reinforcing or rewarding properties.
Psilocybin and Mescaline

Two naturally occurring hallucinogens are psilocybin, found in
certain species of mushrooms, and mescaline, found in peyote
and other cacti. Psilocybin is similar in structure and activity to
LSD. It causes distortions of reality and perception by disturb-

ing the serotonin system and it also causes stimulation of the
brain resulting from norepinephrine release. Psilocybin is not as
potent as LSD and causes less anxiety and fewer panic reactions,
but it may also cause the user to feel nauseated. However, nau-
sea and vomiting is more common with the use of mescaline.
Mescaline is most commonly found in the peyote cactus and has
been used as a hallucinogen for many centuries by Native Amer-
ican cultures in religious ceremonies. Mescaline is chemically re-
lated to amphetamine and norepinephrine and, as a result,
causes stimulation and activation of the central nervous system.
Mescaline causes profound nausea and vomiting and is also be-
lieved to cause disruption of the serotonin systems, which leads
to more visual hallucinations than LSD or psilocybin. Synthetic
mescaline has also been found to be distributed in the form of
pills or capsules and is typically much more potent than the nat-
urally occurring form.
PCP and Ketamine

Phencyclidine (PCP) and its derivative, ketamine, are very
unique hallucinogenic drugs of abuse. PCP was originally mar-
keted as an anesthetic and has been replaced with ketamine for
use in veterinarian practices. These drugs affect a large number
of neurotransmitters including glutamate (an excitatory neu-
rotransmitter) and norepinephrine and cause analgesia, amne-
sia, anesthesia, confusion, excitement, agitation, hallucina-
tions and, in high doses, a psychotic state resembling
schizophrenia. These drugs are also called dissociative anes-
thetics in that they can cause the user to feel separated from his
or her body and environment. These drugs are also believed to
stimulate reward areas in the brain, which leads to repeated
self-administration. Ketamine (also known as “special K”) has
become popular as a “club drug” in the rave subculture. Most
supplies of these drugs are diverted from veterinarian and

medical settings and are often mixed with other hallucinogenic
or cannabinoid substances.
■ Learn more about hallucinogens Search the Internet for club
drug addiction or hallucinogens and brain.
SUMMARY POINTS
• Stimulants increase behavioral arousal and activity by in-
creasing the levels of norepinephrine in brain synapses.
• MDMA (Ecstasy) increases release of serotonin into
synapses and has significant physical effects on the body.
• Nicotine is a powerfully addictive chemical that increases
synaptic dopamine by several different mechanisms.
• Most hallucinogens act on serotonin systems in the brain.
Ketamine affects several different neurotransmitters in-
cluding glutamate.
5 Depressants and Marijuana
All drugs that cause a general slowing of the central nervous

system are most often categorized as depressants. All depres-
sants cause sedation by increasing the activity of inhibitory
neurotransmitters, such as gamma aminobutyric acid
(GABA). GABA is found throughout the central nervous sys-
tem, which is why all depressants cause a general slowing of all
brain functions.
ALCOHOL
Alcohol increases the activity of GABA, as well as the endoge-
nous opioid systems in the brain, which cause euphoria and a
general sense of well-being. Recall that opioid cells surround
dopamine-producing cells in the brain’s motivation systems.
By increasing GABA signals throughout the brain, alcohol
also interferes with muscle coordination (motor cortex and
cerebellum), speech (left hemisphere language areas), vision
(occipital cortex), and planning (frontal cortex), among other
functions. (See Table 5.1 for a description of alcohol intoxica-
tion as well as the common withdrawal symptoms.) Alcohol
also causes relief from anxiety and often releases inhibitions
in users. This, in addition to its legal distribution and socially
acceptable consumption, is one reason that alcoholism and
52
Table 5.1 Signs of Alcohol Intoxication and Withdrawal Symptoms
INTOXICATION SIGNS WITHDRAWAL SYMPTOMS
Initial behavioral stimulation Behavioral agitation; irritability

Relaxation Nervousness
Increased reaction time; driving Nausea; vomiting*
impaired
Poor motor control; unsteady; Increased heart rate;* shortness
imbalanced of breath*
Slurred speech; sedation* Fever;* chills
Coma;* death Hallucinations; seizures*
* Denotes life-threatening sign or symptom that requires medical treatment
Table 5.2 Early Warning Signs of Drinking Problems
Drinking several times per week

More alcohol consumed per event
Gulping drinks; binge drinking
Traffic violation; DUIs
Attempts to cut down drinking fail
Spouse or family complains
Hiding drinking; guilt and shame
Denial when confronted
Continued use despite medical, legal, and social consequences
alcohol-related disorders are so prevalent. (See Table 5.2 for a

list of common warning signs of a drinking problem.)
Physical consequences of alcohol abuse include liver disease,
heart and vascular changes, and esophageal, stomach, and in-
testinal disease. In addition, chronic alcohol abuse can lead to
permanent brain damage. Certain areas of the brain, such as the
thalamus, are very sensitive to the toxic effects of alcohol and are
53
affected by the malnutrition that often occurs in alcoholics. As a

result, alcoholics may suffer from Korsakoff’s syndrome (a neu-
rological disorder that is characterized by memory defects),
cerebral and cerebellar degeneration (which leads to problems
with higher cognitive functions and motor control, respectively)
as well as suffer from physical health problems (see “Buster and
His New Liver” box).
Buster and His New Liver

Buster always associated drinking with having a good time. When
he was a kid, his parents would drink with friends and give him a
sip every so often. When he was 11, his mother died. Buster re-
membered that alcohol was for happiness and soon started drink-
ing to combat his feelings of loneliness and fear. As a teenager,
he drank and had drinking contests with his friends to be cool. By
age 13 he was having black-outs, and by 17 he was using pot and
other drugs. Buster even used some intravenous drugs but his
main drug was alcohol. In his early 20s Buster married an alco-
holic, and was smoking cocaine by his early 30s. After a divorce,
he remarried and went back to school. His non-stop drinking con-
tinued until his second wife moved out. One day after she left, he
had a moment of clarity and realized that if he continued his
lifestyle he might not survive. He went to his first Alcoholics
Anonymous (AA) meeting that day and has been going ever since.
However, while Buster was in recovery his health began to decline.
He was diagnosed with hepatitis C and cirrhosis, and in 2005 he
received a liver transplant. “I’m not sure if my liver failed from
drinking or I.V. drugs or vaccines I got in Vietnam,” says Buster.
“I do know that I learned in recovery that it was OK to have prob-
lems and that I have found new hope in my life.” Buster is thank-
ful every day for his sobriety and grateful for his new lease on life.
Depressants and Marijuana 55
Table 5.3 Effects of Prescription Depressants, GHB, and Rohypnol®
INTOXICATION AND COMPLICATIONS OF

SHORT-TERM EFFECTS CONTINUED USE
Impaired decision-making and Abuse can quickly lead

intellectual functions to dependency
Reduced short-term memory; Insomnia (can't sleep without drug)
blackouts
Lack of coordination and balance Use leads to rapid tolerance; acquiring
from non-medical or illegal sources
Sleepiness; slurred speech Life-threatening withdrawal symptoms
(seizures)
Rapid sedation and overdose Increases risks of falls or motor
vehicle accidents
Death from respiratory failure Elderly are particularly susceptible to
all types of depressants
PRESCRIPTION DEPRESSANTS
Not all addictive drugs are illegal. Some prescription drugs can
cause dependency and addiction if overused or used against the
advice of the prescribing clinician. One class of prescription de-
pressants includes the sedative-hypnotics. This class includes
drugs such as Valium®, Librium®, Xanax®, and other benzodi-
azepines (Valium®-like drugs) and is typically used for anxiety
disorders as well as insomnia. These medications are powerful
GABA agonists (increase GABA activity) and they also affect the
dopaminergic motivational systems in the brain, which can lead
to self-administration and dependence. In addition, these medi-
cations cause general sedative effects that include disruption of
brain circuits involved with balance and motor control, sensation
and perception, and planning and judgment (Table 5.3). In high
doses, sedative-hypnotics can cause overwhelming GABA activa-
tion which leads to loss of consciousness and amnesia. When
mixed with alcohol or other sedatives, this class of drugs can of-
ten lead to respiratory depression, coma, and death.
GHB
Gamma hydroxybutyrate (GHB) was originally sold as a nutri-
tional supplement and marketed as a muscle growth enhancer,
a result of its weak stimulation of growth-hormone release. It
quickly became popular as a depressant and a drug of abuse.
However, GHB is a quick-acting, powerful sedative. It is color-
less, odorless, tasteless, and very potent when mixed with alco-
hol. People under the influence of GHB lose behavioral inhibi-
tions very quickly, become easily manipulated, and often
forget what they did while intoxicated. As a result, it has be-
come popular as a “date-rape” drug. GHB is very similar in
structure to GABA and therefore increases inhibitory signals in
the brain. Users become lethargic, fatigued, and sleepy. They
often slur their speech and their balance becomes unsteady.
Overdoses causing coma and death from respiratory failure are
common because of the quick and powerful effects of the drug.
GHB stimulates the dopaminergic reward pathways and plea-
sure areas and is therefore considered an addictive drug. Phys-
ical dependence, tolerance, and addiction to GHB are com-
mon with chronic use.
ROHYPNOL
Rohypnol® (flunitrazepam; also known as “roofies”) is also a
short-acting, powerful sedative and depressant in the benzodi-
azepine family of drugs (Figure 5.1). It is similar to GHB in its
pharmacological and behavioral effects. It is very powerful
when mixed with alcohol and has also been used as a date-rape
drug. Physical dependence, tolerance, addiction, its mechanism
of action, and the potential for overdose are very similar to that
of GHB. There are no antidotes for overdose from GHB or
O
CH3
C
N C
Rohypnol
C C N
C C C F
C C C C
O2N C C
C C
O
CH3
C
N C
Valium
C C N
C C C
Figure 5.1 The sedatives
C C C C Rohypnol® and Valium®
Cl C C share similar chemical
structures, but Rohypnol®
C C is more powerful.
Rohypnol. There is no safe medication that can be given to re-

verse the respiratory depression or coma that can occur with
acute toxicity of these powerful GABA agonists. The only med-
ical treatment is respiratory support via a ventilator and to wait
for the drug to be metabolized.
INHALANTS
Inhalants are solvents or aerosols that are inhaled and absorbed
through the lungs into the bloodstream. Because of their route of
administration, inhalants have an almost immediate effect on the
brain and body. These chemicals are found in common products
such as spray paint, glue, cement, gasoline, nail polish remover,
and pressurized chemicals (Table 5.4). Because of their easy avail-
ability, this class of drugs is often abused by younger teenagers and
Table 5.4 Commonly Used Inhalants and Their Ingredients
INHALANT INGREDIENTS
Aerosols Freon, toluene, xylene

Degreasing agents; spray Benzene, butyl acetate, heptane, hexane,
paint and paint thinners; methylene chloride, naphthalene,
rubber cement toluene, xylene
Typewriter correction fluid Trichloroethylene
Laughing gas Nitrous oxide
Room deodorizers Amyl nitrite, isobutyl nitrite
Gasoline Gasoline and octane fuel additives
Lighter fluid Butane, isopropane
children. These products contain toluene, propane, butane, ace-

tone, nitrous oxide, or various fluorocarbons. Because these
chemicals are vaporous and very soluble in fat, they are absorbed
very quickly by all biological tissues once inhaled.
Users may experience a brief period of excitation (behavioral
activity) followed by sedation (drowsiness) and disinhibition in
the user. The individual may then experience drowsiness, dizzi-
ness, imbalance, slurred speech, and will appear drunk. The
mechanism of action of this class of drugs is not completely
known but they mimic the effects of anesthetics and alcohol in
the brain. Inhalants may disrupt the membranes that surround
all neurons and thereby cause general sedation and anesthesia.
In addition, these chemicals may directly increase the action of
GABAergic cells in the brain, which may lead to additional se-
dation and drowsiness. Inhalants also increase activation of the
motivational dopaminergic system, which causes euphoria and
may lead to chronic self-dosing and addiction.
Not only do these chemicals disrupt normal activity of brain
cells, but inhalants can quickly disrupt other biologically ex-
citable cells located in other organs such as the heart. There have
been numerous reports of sudden and fatal heart attacks result-

ing from sudden cardiac arrhythmias in children following the
inhalation of volatile solvents and aerosols. Chronic abuse of in-
halants has been shown to cause permanent cell loss in the cen-
tral and peripheral nervous systems, which may lead to muscle
weakness, numbness, and instability.
■ Learn more about the depressants Search the Internet for
CNS depressants and brain, alcohol abuse, date rape drugs, or
inhalant abuse.
OPIATES
The opiates are a separate class of drugs that have very specific
mechanisms of action. All opiates bind to their own separate set
of receptors in the brain (endorphin and enkephalin receptors).
This is unusual for most types of drugs of abuse. Most of the psy-
choactive drugs have their effects on the brain and our behavior
by altering other neurotransmitter systems (the stimulants in-
crease norepinephrine; depressants use GABA; hallucinogens al-
ter serotonin, etc.). Opiates, however, bind specific opioid re-
ceptors in certain areas of the central nervous system as well as
other organ systems.
PRESCRIPTION PAINKILLERS
The most common use for prescription opiates is for analgesia,
to decrease the sensation of pain. These medications block pain
signals from damaged tissue in the body when opioid receptors
in the brain are occupied by these opiates. These drugs are effec-
tive as painkillers. However, opioid receptors are also located on
cells that control the chemical motivational system that uses
dopamine. When drugs like heroin, morphine, codeine, opium,
and prescription painkillers such as OxyContin® and Vicodin®,
turn on these opioid receptors, the user may feel euphoria and
pleasure as well as relief from pain. Because of this effect on the

pleasure pathways, these drugs can be addicting. Indeed, some
of the most addicting substances, such as heroin and fentanyl,
belong to this class of drugs. (See “William’s Story” box.)
HEROIN
Heroin is a very addicting opiate. Chemically, it consists of two
molecules of morphine joined together which make it more
soluble in fat (lipophilic) and is therefore absorbed into the
William’s Story
William was studious as a kid. Quiet and reserved, he preferred
music and sports to partying with friends. In high school, he
started smoking pot mostly just to fit in with his peers. In col-
lege, William had his first experience with painkillers after an
eye injury. Immediately he thought, “now I know what it’s like to
be on heroin.” He felt extremely euphoric, confident, and calm.
Over a five-year period, he had a couple of minor surgeries and
injuries that exposed him to painkillers again. After his wisdom
teeth were pulled the following year, he said he was soon “tak-
ing them at all costs. I lost everything—girlfriends, the trust of
my parents, my health, and thousands of dollars. I spent days
driving around to different doctors, faking injuries, even asking
my friends for their drugs.” If he couldn’t get opiates, he would
drink to keep the withdrawal symptoms away. Finally, William
got help. With the support of his friends, parents, and employer,
William went through intensive in-patient treatment and is now
healthy and productive. He recommends, “breaking out of your
thinking that you want and need things all of the time; improve
yourself. It doesn’t matter if you’re rich or poor, Ivy League grad,
or high school dropout; because if you think you have a prob-
lem—you do.”
bloodstream and brain easily. Heroin is most often intra-

venously injected, but it may also be sniffed or snorted into the
nose. Because of the recent trend in snorting heroin, more
young people who were dissuaded by the stigma associated with
needle use are now trying heroin. Regardless of the route of ad-
ministration, users can progress from experimentation to abuse
and addiction very quickly. Heroin reaches the pleasure path-
ways in the brain rapidly and causes a significant increase in the
production and release of dopamine into the nucleus accum-
bens. (See “The Case of the Frozen Addicts” box.)
The physical effects of opiates are caused when the drugs bind
to opioid receptors in bodily tissues as well as in the brain. When
people are under the influence of an opiate, their pupils become
very constricted, they may experience itching of their skin be-
cause of histamine release, become constipated and feel nause-
ated, and their blood pressure, pulse, and breathing may de-
crease. Overdose from opiates causes respiratory depression,
which occurs when the breathing centers of the brain become
insensitive to carbon dioxide, a normal stimulus to inhale air.
Because overdose is directly due to opioid receptor binding, the
use of opiate receptor blockers (such as naloxone) is an effective
emergency treatment for opiate overdose. Tolerance and depen-
dence also occur rapidly with continual use of opiates. As a re-
sult, individuals can become addicted to prescription opiates as
well as illegal opiates very quickly. (Table 5.5)
THE CANNABINOIDS: MARIJUANA

The cannabinoids are derived from cannabis plants (mari-
juana). Much has been written about the social, legal, medical,
and historical implications of marijuana. However, the neu-
robiology of marijuana and one of its active ingredients, delta-
9-tetrahydocannabinol, or THC, has been studied extensively.
Marijuana preparations are typically smoked or sometimes
ingested in food. THC is very fat soluble and therefore enters

the bloodstream and brain very quickly. Recent scientific evi-
dence suggests that THC does increase dopamine release in
the nucleus accumbens. These data imply that repeated use of
The Case of the Frozen Addicts

In the mid-1980s, several medical reports surfaced about heroin
users who were found in immobile but conscious states in their
homes after using heroin. One by one they were brought into
emergency rooms by friends or family members. For days the doc-
tors were puzzled as to why these individuals suddenly could not
move or speak. One patient had a slight tremor of one of his ex-
tremities so, as a last resort, the doctors tried a Parkinson’s med-
ication to relieve his condition. As the medication took effect, the
patient began to move and speak and explain what had happened
to him. He and all the other “frozen” addicts had bought what they
thought was synthetic heroin from drug dealers. The dealers had
bought the drug from a chemist who made mistakes in the syn-
thesis of the heroin and instead of making meperidine (an opiate),
he made a previously unknown neurotoxin called MPTP. When the
heroin users took the drug, the toxin caused massive damage to
the substantia nigra, a dopamine system in the brain used for
muscle movement. (This system is the same chemical system that
is destroyed over many decades in patients with Parkinson’s dis-
ease.) However, in these drug users, the substantia nigra was al-
most completely destroyed in a few days from a single accidental
exposure to MPTP. While these individuals still suffer from pro-
found Parkinsonism, what was learned from these events is
twofold: MPTP is a useful research tool for the scientific develop-
ment of Parkinson’s medications, and the synthesis of designer
drugs (such as synthetic meperidine, methamphetamine, and
MDMA) is unregulated and extremely dangerous.
Table 5.5 Signs and Symptoms of Opiate Use and Withdrawal (Includes Heroin,
Morphine, and Prescription Painkillers)
PHYSICAL AND PSYCHOLOGICAL WITHDRAWAL SYMPTOMS

EFFECTS OF OPIATES (OPPOSITE OF INTOXICATION EFFECTS)*
Sleepiness Insomnia
Sedation; motor inhibition Agitation; muscle cramps and
exaggerated reflexes
Euphoria (pleasure) Depression; anxiety
Pinpoint pupils Dilated pupils
Slow heart rate; low blood pressure Rapid pulse; high blood pressure
Decreased stomach and intestinal Diarrhea; vomiting
activity (constipation)
Analgesia (pain relief) Bone, joint, and muscle pain
Decreased glandular secretions Yawning, tearing, and runny nose
Respiratory depression (overdose Panting; increased breathing rate
can cause death)
* Withdrawal symptoms are uncomfortable but not typically life threatening
marijuana can be addicting. This increased level of dopamine

release associated with THC is relatively minor, however,
when compared with the increase in dopamine levels caused
by more addicting drugs such as cocaine, crystal meth, and
heroin. Nonetheless, smoking marijuana can become habit
forming and classified as addictive. There have been reports of
physical dependence on THC to the point that individuals
have suffered physical withdrawal symptoms when they stop
using marijuana. These withdrawal symptoms are very similar
to opiate withdrawal symptoms and include irritability, de-
pression, tearing, diarrhea, rapid heart rate, and elevated
blood pressure. Because of this similarity in withdrawal symp-
toms, cannabinoid preparations are sometimes categorized as
opiates and not in a separate class or as hallucinogens or de-
pressants.
Table 5.6 Mechanisms of Health Risks of Marijuana Abuse
RISK OR CONSEQUENCE MECHANISM
Bronchitis, lung irritation, Marijuana smoke; carcinogens

lung damage
Mild analgesia; appetite Binding of THC to opiate-like
stimulation anandamide receptors in midbrain
and hypothalamus
Fatigue, apathy, impaired THC's effects on midbrain, limbic, and
concentration cortical regions of the brain
(amotivational syndrome)
Impaired short-term memory THC's effects on limbic system
(including hippocampus)
Psychological and physical THC activating the ventral tegmental
dependence dopaminergic system
Opiate-like withdrawal symptoms Unoccupied anandamide receptors
during abstinence precipitate withdrawal syndrome
In addition to sharing properties with opiates, THC also has

been shown to possess its own binding sites and receptors in the
brain. This indicates that the brain must have its own, naturally oc-
curring neurotransmitter that can normally occupy these recep-
tors. Scientists have isolated that chemical (anandamide) and
found its receptors in the pleasure areas as well as in the hip-
pocampus, an area of the brain important for memory formation.
Physical effects from marijuana preparations include bloodshot
eyes, drooping eyelids, elevated heart rate, and high blood pres-
sure. Psychological effects include hunger, relaxation, occasional
anxiety or paranoia, internalization and feelings of detachment, and
impaired coordination and perception. These latter effects can dis-
rupt reaction times and interfere with normal decision making.
Long-term effects of marijuana smoking include lung damage and
possible damage to cell layers in the hippocampus (Table 5.6).
Marijuana preparations have been used for medicinal pur-

poses in the treatment of glaucoma, nausea, and poor appetite.
THC decreases ocular pressure (pressure in the eyeball) and
therefore benefited some glaucoma patients. THC also stimu-
lates anandamide receptors in the brain stem and therefore may
help chemotherapy patients suffering from nausea and vomit-
ing. THC also stimulates hypothalamic centers and increases ap-
petite and hunger in chemotherapy patients as well as in patients
suffering from AIDS-wasting syndrome.
■ Learn more about the opiates and marijuana Search the In-
ternet for heroin use, painkiller abuse, or marijuana abuse.
SUMMARY POINTS
• All depressants cause central nervous system sedation by
increasing the actions of the inhibitory neurotransmitter
GABA.
• Opiates act through a specific set of opioid receptors in the
brain normally activated by neuropeptides.
• One of the psychoactive ingredients in marijuana is THC,
which binds to specific receptors in the limbic system and
pathways involved with appetite and the sensation of pain.
6 The Cycle of Addiction
Individuals start using drugs for various reasons including

curiosity, peer pressure, and drug availability. It is very diffi-
cult to predict who will become an addict; certainly nobody
wants to become an addict. The most recent scientific evidence
supports the notion that addiction is a biogenetic, psychoso-
cial brain disease. In other words, whether or not an individ-
ual progresses from casual use to abuse and drug addiction de-
pends on several biological and social variables. Do addiction
or other compulsive behaviors run in an individual’s family?
In what kind of an environment was an individual raised? Was
it loving and nurturing or stressful and isolated? Could the in-
dividual’s possible future addictive tendencies be identified
earlier in life? In this chapter, we will examine how these vari-
ables influence brain areas underlying addictive behavior and
the progression from initial curiosity to compulsive addiction.
NATURE (HEREDITY AND GENETICS)

Our genes not only determine our height, eye, and hair color,
but also our tendency to engage in compulsive behaviors. The
influence of genetics on addictive behaviors has been studied
in genetically identical twins raised in the same family, twins
that have been raised by different families, and even in genet-
ically selected animal models. Overall, the studies suggest that
66
genetics contribute to approximately 50 to 60% of all cases of ad-
diction. These studies have also investigated family histories and
have shown that if one of your parents is an alcoholic, your chances
of becoming an alcoholic increase by one-third. If both parents are
alcoholic, your chances quadruple. If both parents and a grand-
parent are alcoholic, your chances are nine times more likely.
Genetic studies have also identified specific genes associated
with alcoholism. Not surprisingly, these genes encode for pro-
teins in cells located in the ventral tegmental dopaminergic sys-
tem, particularly dopamine receptors. It is hypothesized that in-
dividuals with these genes have exaggerated positive responses
to their initial exposures to drugs or alcohol. This initial positive
response has been associated with drug dependence later in life
(see “Mary’s Honesty” box). These studies have suggested the
same exaggerated response to other potentially compulsive ac-
tivities such as gambling, sexual behavior, and overeating. How-
ever, it is important to remember that one need not have a ge-
netic predisposition to addiction to progress to some type of
addiction. Many individuals whose parents did not drink still
become alcoholics. Therefore, other factors must play a role in
the development of drug or alcohol addiction.
NURTURE (THE ROLE OF THE ENVIRONMENT)

The context or environment in which we are raised can have
tremendous impact on our future behavior as well as our brain
development. Individuals who are raised in environments that
provide emotional support, love, adequate nutrition, and where
learning and healthy lifestyles are encouraged have reduced rates
of drug and alcohol abuse. A common saying is that the brain is
like a muscle—use it or lose it. The more we engage different
areas of our brains in positive, healthy behaviors, such as learn-
ing new information, patience, and delayed gratification, the
greater the likelihood these brain areas will remain vital into
67
68 Neurobiology and Addiction
Mary’s Honesty
Mary’s dad was an alcoholic, and her mom was a social drinker.
There was a lot of drinking in her house while she was growing
up but she didn’t try alcohol until she was 12. One night when
Mary was alone at home for the first time, she raided the liquor
cabinet, and later that night ended up vomiting in a snow bank.
Despite her first negative experience while under the influence
of alcohol, Mary continued to drink. She started drinking small
amounts from each liquor bottle and by age 14, she was having
black-outs. Mary’s mom stayed off her back because she was
mainly worried about Mary’s dad, who was drinking heavily by
this time. By her senior year in high school, Mary was drinking
morning, noon, and night. She knew her problem was worsen-
ing but thought it was because of the stress of her home life.
Mary continued her heavy drinking throughout her college years
(she now admits that her drinking certainly limited her intellec-
tual abilities and opportunities). While Mary was in college, her
dad got sober and told her to stop, too. She slowed down and
“only” binged as a reward for hard school work. In grad school,
she got the “drunkest student” award, and while on a trip over-
seas, Mary experienced her “low point” one night after throwing
up in a bush. So she slowed down again and “only” smoked pot
for a while. Soon she was drinking again and now claims she
had no “off-switch. If I had one drink, I would end up drunk. Ev-
ery day I started counting down to my next drink.” One New
Year’s Day she realized she had to stop. Mary finally made it
through all the years of denial and has been sober for 12 years.
“Don’t wait too long to stop,” warns Mary. “And never forget to
be honest with yourself.”
The Cycle of Addiction 69
adulthood. For some individuals who are raised in emotionally

painful, stressful environments, however, drugs, alcohol, or
some other addicting behaviors or substances may provide an
escape from the emotional pain and stress that they endure
daily. Individuals who are raised in such stressful situations have
much higher rates of addictive behaviors.
■ Learn more about the cause of addictive behaviors Search the
Internet for genetics of alcoholism or addiction and stress.
The mechanism by which stress and addiction interact is be-

ginning to be understood. It is believed that environmental
stress primes the brain for addictive behaviors. Stress can alter
dopamine cells in the VTA to become more responsive to expo-
sure to a drug that affects the system. This may help to explain
why environmental stress causes an individual to progress from
casual drug use to abuse and addiction more quickly than some-
one raised in a less stressful environment.
The rate at which an individual progresses from initial drug
exposure to casual use to abuse and addiction depends not
only on their genetics and environment but also on their psy-
choactive drug use. If an individual has a genetic predisposi-
tion and experiences emotional stress, then they will probably
progress rapidly once psychoactive drug use starts. All three
factors interact with one another. For instance, if an individual
has a lower level of genetic susceptibility, then additional stress
or use of stronger psychoactive drugs would be required for
that individual to progress at a rapid rate. The rate of progres-
sion can vary from person to person. It may take one person
several years of alcohol abuse before they become truly ad-
dicted; it may take another person less than a year if alcoholism
runs in their family. On the other hand, an individual raised in
an abusive environment may quickly progress from cocaine use
once a month, for example, to several times a day in a few weeks.
EARLY BEHAVIOR PREDICTS FUTURE PROBLEMS

Recent scientific studies suggest that problems with behavioral
self-control arising in early childhood are signs that the indi-
vidual may be susceptible to drug abuse later in life. This sug-
gests that areas in the frontal cortex responsible for self-con-
trol, decision-making, and goal-directed behavior exhibit signs
of dysfunction early in life. These signs include irritability and
the expression of intense emotions; these individuals have a
harder time returning to a quiet emotional state after an out-
burst. Other childhood symptoms include lack of behavioral
control such as acting out, being disruptive, defying authority,
and impulsiveness. Studies are being done to investigate a pos-
sibility that a lack of frontal cortical control is responsible for
these behaviors. Future studies may identify ways to practice
improvements in frontal lobe function so as to promote be-
havioral inhibition, self-control, and possibly protect against
future vulnerability to drug abuse.
Mental disorders may also exist with drug and alcohol abuse
later in life. As many as 60% of individuals who abuse drugs
and alcohol also suffer from a mental illness such as depres-
sion, manic depression, and schizophrenia. Since substance
use and mental disorders can co-exist, it is often difficult to de-
termine which comes first. Individuals who suffer from the
symptoms of depression or schizophrenia may start to use
drugs to relieve some of their uncomfortable symptoms. This
may then lead them to drug addiction and further problems
with their mental illness. Other studies have indicated that
substance abuse may start first and then unmask, or lead to,
mental illnesses (Table 6.1).
BRAIN AND BEHAVIOR IN THE PROGRESSION

FROM ADDICTION TO RECOVERY
There are several identifiable behaviors that typically occur in
the progression towards drug addiction. It is important to
Table 6.1 Where to Get Help
WHO OR WHERE WHAT TO EXPECT
Your primary care clinician Screening questionnaires

(family doctor) Diagnosis
Referrals to specialists
Overall medical management of recovery
Specialty clinicians Certified to treat addictions;
(addictionists) knowledgeable of local resources and
steps in recovery; can treat withdrawal
symptoms
Hospital or crisis center Assess extent of problem
Recommend treatment plan
Local yellow pages or Location of community resources
behavioral health directory (crisis centers, detox, or rehab facilities,
• under “Drug Abuse and counselors, group meetings, etc.)
Addiction Information
and Treatment”
• or “Alcoholism Information
and Treatment"
Internet Useful information about substance abuse
• Alcoholics Anonymous and treatment; review of neural
• National Institute on mechanisms and drug information
Drug Abuse
Individual therapist Identification of risk factor
Cognitive behavioral therapy
Group therapy Sharing experiences and hope with
similar individuals
understand the changes that occur in the brain during this

progression so that these changes can be treated and reversed
during the recovery stage. Addiction and recovery stages were
first developed by E. M. Jellinek in the early 1940s in order to
categorize different types of alcoholics and to underscore the
notion that drug and alcohol addiction are the results of a brain
disorder and are not due to weaknesses of will or moral charac-
ter. The medical community has since accepted the concept that
addiction is a brain disease.
In the progression from initial drug use to abuse to addiction

and recovery, there are several key steps that occur in the brain
that coincide with behavioral changes. Let’s follow a hypotheti-
cal individual (Bill) through various stages of substance abuse
and recovery and outline some of the brain changes that may
underlie his behavior.
Bill didn’t start using drugs or alcohol until he was in his 20s;
early experimentation didn’t lead to immediate compulsive be-
havior. None of his family members were alcohol or drug users;
he didn’t have a strong genetic predisposition, but Bill liked the
effects. Bill drank more often as he got older and started drink-
ing more at parties. Alcohol made him feel relaxed and at ease
as a result of ethanol’s action at GABA receptors in the cortex
and limbic system. It also made him happy as ethanol caused
dopamine release in the nucleus accumbens; neuropeptide re-
lease reinforces this effect. Occasionally alcohol made him
more social, confident, and talkative from the ethanol’s seda-
tion of the cerebral cortex, which resulted in a release of emo-
tions from limbic system—cortical disinhibition. Bill found
that if he had a particularly bad day or was stressed at work that
he would have a couple of drinks on his way home. His envi-
ronmental stress increased use; repeated stress signals prime re-
ward pathways. He noticed that he started to look forward to
the pleasure that alcohol would give him and was a little edgy
until he had his first drink. The prediction of reward increased
dopamine release which caused behavioral stimulation to lo-
cate and acquire the reward.
At this point, Bill’s behavior was becoming more patterned
and he was transitioning from recreational use to habituation.
When he stopped at the bar after work, he noticed that he was
increasing the amount that he was drinking and that he started
to like the effects more and more. He needed to have more alco-
hol to improve his mood and feel relaxed. Bill was developing
tolerance; neurotransmitter adaptation was occurring in the

brain; and his liver enzymes were also becoming more effective
in metabolizing ethanol. Over the last couple of months he
gained weight and ate less nutritional meals. Alcohol is high in
calories, which caused his weight gain and meal skipping. Bill
felt worse throughout the day, which caused him to drink more
in the evenings. Habitual alcohol use alters serotonin systems,
which leads to mood instability. Bill also noticed that he was get-
ting more headaches and feeling unusually tired the mornings
after he drank. (Alcohol disrupts normal sleep cycles.)
On several occasions, Bill’s family and friends reminded him
of things he did while he was drinking. Bill laughed along with
the stories but only remembered some things that he did. Bill
was experiencing black-outs: short-term memory systems in the
limbic system are sedated by alcohol’s GABAergic and anes-
thetic properties. These experiences caused Bill to feel guilty
about his behavior and, for a short period of time, he cut down
on his drinking. However, continued stress at work and at home
caused Bill to start returning to the bar after work. Within weeks
he was drinking more than when he stopped before. He was ex-
periencing more black-outs and his efforts to control his drink-
ing failed. Bill lost interest in things that he used to enjoy, even
his hobbies. He tried to avoid his family and friends and tended
to isolate himself whenever he could. The natural rewards in
Bill’s life were ignored and he has cognitive control over his
drinking. His frontal cortex was unable to suppress the
dopaminergic and limbic drives to consume his drug of choice.
His habit had become a compulsion and he transitioned into
drug abuse—using despite negative consequences.
After a period of a few months, Bill drank every night and
thought about drinking during the day. His physical health got
worse and he couldn’t sleep unless he drank before bed. Some
mornings on the weekends he had a drink to calm his nerves. He
realized that he probably drinks too much but he thought he

could control it and stop whenever he wanted to. Bill’s tolerance
increased and he became physically dependent on alcohol. Sleep
centers in the hypothalamus and brain stem became adapted
and he required alcohol to sleep. He used alcohol to suppress the
withdrawal symptoms he experienced on some mornings. Bill
used denial to defend his behavior.
Bill’s poor performance at work was noticed by his supervi-
sors, and Bill’s wife told him that he must stop drinking or face
the consequences of their separation. Bill slowed down his
drinking for a few weeks, but he still drank in secret and mini-
mized the amount he drank. His thinking was impaired
throughout the day, he felt unable to find a solution to his prob-
lems, and he felt defeated and hopeless. Bill was an alcoholic. He
drank despite consequences, he was tolerant and dependent on
alcohol, and drank compulsively. If Bill did not stop drinking he
would most likely cause significant harm to himself—physically,
mentally or legally, or to someone else. There was a strong pos-
sibility that Bill would even die if he didn’t quit.
Bill’s wife, family, and friends all noticed that he had a drink-
ing problem and decided to confront him. They researched lo-
cal treatment facilities, talked to a couple of experts, and
planned a course of recovery for him. They took Bill to a family
meeting and expressed their love and support. They asked him
to be willing to be assessed by a professional and enter treat-
ment. Bill was acting completely on his motivational and drive
systems in his brain. He no longer responded to rational thought
and was incapable of suppressing these drives. Bill’s family at-
tempted to reach past these self-centered drives and appeal to
him on the basis of their love. Bill’s denial was met with firm re-
solve and support. Bill’s family had conducted an intervention.
Bill agreed to be interviewed and assessed by a trained profes-
sional at a treatment center. He was subsequently admitted.
Many social stigmas associated with addiction and the judg-

ments placed on these individuals are unnecessary, inappropri-
ate, and may lead to further compulsive behaviors. In our ex-
ample, Bill responded to the care and support that his family and
friends were willing to provide him. He had an honest desire to
receive help and was willing to learn about his illness and take
responsibility for his recovery.
KEY STEPS IN RECOVERY FROM ADDICTION

For individuals to experience successful recovery from drug and
alcohol addiction, they should have a treatment plan that is
matched to their individual needs. These depend on factors such
as their level of dependence upon the drug, their drug of choice,
and their willingness to change (Table 6.2).
The initial medical treatments are highly dependent upon the
abused drug. The first step is chemical detoxification (detox).
The main objective in detox is medical management. Individu-
als should be treated in a controlled medical setting where their
symptoms of drug withdrawal and any other medical conditions
can be properly treated. Detox procedures typically last from
two to seven days and depend on the overall health of the indi-
vidual and the drug of choice. During this time, they may be
given medications to help them cope with the withdrawal symp-
toms. For example, heroin users may be given anti-diarrhea
medication. Cocaine or amphetamine users may start antide-
pressant treatment. It is particularly important that individuals
who are dependent on alcohol or any other depressants are
detoxified in an in-patient hospital setting to protect against the
occurrence of life-threatening seizures. The alcohol-dependent
brain is accustomed to continuous sedation from alcohol’s effect
on inhibitory neurotransmitters. When the alcohol is suddenly
removed, as in early detox, the brain is easily overexcited and is
unable to control its own electrical activity; seizures may occur.
Table 6.2 Neurobiological Correlates of Steps in Drug Addiction and Recovery
BRAIN BEHAVIOR
Genetic predisposition; May determine rate of progression from

environmental stress; initial drug use to abuse
drug exposure
Dopamine surge in nucleus Euphoria; drug seeking
accumbens
Limbic drives supersede Abuse progresses into drug dependence
cortical control and compulsiveness
Internal or external signals Honest desire for change;
force or compel behavior “hitting bottom;” sobriety sought
to change
Drug free state; anti-craving Drive cycles broken; recovery starts
medications
Natural rewards are reinforcing Interests in food, sleep, and family
nurturing return
Hypothalamic balance Sleep cycles and appetite return
Frontal cortex control Emotional and impulse control
Cognitive development Contentment in sobriety
Drug craving during the initial detox period can be very in-
tense for certain individuals and is specific for each class of drugs
of abuse. Anti-craving compounds, discussed in Chapter 7, are
used to combat these symptoms. In opiate withdrawal, individ-
uals may be given a substitute opiate and then slowly weaned off
the substitute to control their discomfort and cravings.
Methadone and LAAM® (levo-alpha-acetyl-methadol) are used
successfully in detox and early in-patient rehabilitation pro-
grams as substitute opiates. These agents are agonists at opiate
receptors in the brain. The binding of these receptors in cells
that surround the ventral tegmentum is believed to reduce their
cravings. The methadone doses are then tapered in the con-

trolled detox and rehab environments.
The overall general physical and mental health of the individ-
ual is addressed in detox settings. Serious diseases or conditions
such as high blood pressure, malnourishment, diabetes, and de-
hydration are treated. Adequate diet and rest are also encour-
aged. Co-existing mental disorders are addressed and treated in
these settings as well. However, completion of the detoxification
stage is not enough for individuals to successfully remain drug-
free. Individuals who return home to daily living at this stage are
extremely vulnerable to relapse. In this stage the brain is very
sensitive to stress and environment. If emotional or physical
stress is sensed by the brain (particularly the frontal cortex and
limbic areas), the chances of relapse are very high. The amygdala
and nucleus accumbens respond to sensory stimuli that predict
reward and may elicit immediate sensations of drug-craving. In
this respect, the brain needs to be free from these triggers as
much as possible during this period.
At this point the individual may enter an extended in-patient
rehabilitation program. A typical stay at an in-patient facility is
between two weeks and six months. A minimum of a three-
month stay in these treatment programs has been shown to be
very successful for long-term sobriety. During rehabilitation,
individuals identify their initial reasons for drug use and the ar-
eas of their lives that need work and improvement, and take
part in individual and group counseling. They also acknowl-
edge their addictive problems, address and commit to working
on their weakness, reach out to others they may have harmed
or to those from which they would like support, and commit to
continually work on themselves and others struggling with
similar problems. It is essential that individuals learn to accept
that their addictions are chronic, progressive, and fatal if left
untreated.
In Bill’s case, he will enter a detox facility, either in a hospital

or treatment center, where his physical and mental status will be
assessed. His level of alcohol dependence will be determined and
treated accordingly. He will be given medications to prevent
seizures, multivitamins to protect his brain from any further
damage from vitamin deficiencies, and other medications to
control his blood pressure, heart rate, and anxiety. His will be
discharged within 10 days and enter an in-patient rehab pro-
gram. Unfortunately, Bill will need to determine which program
his health insurance will cover or which one he can afford. Dur-
ing this time period, Bill’s neurotransmitter balance will return
to normal. His drives for drug-taking will subside and he will re-
gain cortical control over his impulses. A proper balance be-
tween limbic and frontal cortical system will continue to im-
prove if he remains drug free and healthy.
Upon release from rehab, Bill can return home or stay in a res-
idential treatment facility such as a half-way house, where he can
go to work during the day and at night stay in the drug-free, con-
trolled, and supportive environment. The length of stay in these
settings typically varies between one month and one year. Upon
returning to his family and home, Bill may enroll in a three-
month intensive out-patient program (IOP) in the evenings
where he will continue to learn stress-management and self-
improvement techniques. Bill can use these techniques for re-
lapse prevention by controlling stress, minimizing drug-taking
cues, and using other coping mechanisms to deal with his life.
■ Learn more about the cause of addictive behaviors Search the
Internet for genetics of alcoholism or addiction and stress.
SUMMARY POINTS
• Having an alcoholic parent or grandparent significantly in-
creases an individual’s chances of developing compulsive
behaviors, including addiction.
• Critical steps in recovery from addictions include admit-

ting the problem, professional assessment, detoxification,
rehabilitation, minimization of drug-associated stimuli
and stress, and group and individual therapy.
7 Addiction Treatments
There are treatments for drug and alcohol addiction, but

there are no cures. Group and individual counseling are crit-
ical for maintaining sobriety for most individuals. One be-
havioral treatment strategy involves cognitive behavioral ther-
apy (CBT). In CBT, therapists teach their clients to recognize
how their thoughts and feelings translate into actions that
may threaten their sobriety and abstinence. Clients are taught
how to avoid specific situations that may lead to drug use and
relapse, how to recognize thoughts that lead to craving, and
how to control their emotions in situations that may lead to
drug use. The patients analyze their thoughts, plan appropri-
ate actions, and control their impulses. In other words, pa-
tients learn how to gain cognitive, cortical control of their
drug-seeking urges and drives. CBT takes several months to
learn and use successfully. Unfortunately, studies have found
that individuals who have suffered cortical damage or have
cognitive deficits (such as those from amphetamine or co-
caine abuse) struggle with learning and remaining in CBT
programs. However, the longer a patient remains in behav-
ioral therapy, the greater their chance of remaining abstinent.
Other experimental techniques have employed the use of
incentives as rewards for continued sobriety. Clients are given
small prizes and even supportive words of encouragement or
80
praise to remain drug-free. Other studies have examined the use
of vouchers earned in exchange for drug free urine samples. The
vouchers may be exchanged for community goods or services
that provide pleasurable alternatives to drug use. Early data
from these studies suggest that incentives and vouchers act as
positive, non-pharmacologic reinforcement strategies that can
be learned by individuals who were once engaged in very impul-
sive and high-risk behaviors. Future therapies may use addi-
tional techniques to teach patience and the value of legal alter-
natives to drug use.
Learning behavioral control is very difficult for individuals in
early recovery. Recent experimental therapies include behav-
ioral training to block the learned associations between drug
cues, drug craving, and drug rewards (known as extinction).
This type of extinction training in laboratory animals has re-
sulted in increased frontal cortex control of the nucleus accum-
bens and subsequent drug-seeking behavior. Researchers state
that in the future, computer simulation or video games may
train the addicted individual that particular environments or
cues no longer predict reward or pleasure. However, for most
individuals, patience, dedication to long-term goals, and behav-
ioral control are very difficult in early recovery. These patients
may benefit from medications as well as behavior therapies.
MEDICATIONS
While cognitive therapies and behavioral strategies are very ef-
fective in prevention of relapse and maintenance of abstinence,
recent advances have also been made in the development of
medications that are used in various stages of recovery. These
medications are used for management of early withdrawal
symptoms, the treatment of drug craving, and the long-term
maintenance of sobriety (Table 7.1).
81
Table 7.1 Some Medications Used for Addictive Disorders
MEDICATION BEHAVIORAL EFFECT MECHANISM OF ACTION
Nicotine replacement Reduce nicotine Nicotinic receptor

preparations withdrawal agonist; increases
symptoms (cravings) synaptic levels of
dopamine
Bupropion (Zyban, Reduce nicotine Dopamine, norepinephrine,
Wellbutrin) cravings and serotonin reuptake
blocker
Buprenorphine/ Reduce opiate cravings; Combination of opiate
naloxone relapse prevention receptor agonist/
antagonist
GVG; D3 receptor Reduces cocaine-induced Reduces dopamine surge
blockers euphoria and caused by drugs of abuse
drug-seeking behavior
Cocaine antibodies Prevents drug of abuse Recognition, binding, and
from reaching brain inactivation of drug in
blood
Anti-craving Compounds
Anti-craving medications designed to replace the drug of abuse
have been used for decades. These medications are used to slowly
taper the dose of a drug over time. In this way, withdrawal symp-
toms are minimized. However, for some preparations of these re-
placement drugs, the users are left to determine their dosing sched-
ule for themselves. They must then adhere to this schedule during
the taper. Nicotine replacement devices are used in this manner.
Nicotine replacement patches, gum, and inhalers are available on
the market without a prescription. As we know, nicotine is a very
powerful drug of abuse and is very difficult to quit once depen-
dence has occurred. The individual who uses nicotine replacement
preparations must be extremely dedicated to the ultimate goal of
abstinence. For these individuals, group and individual therapy are
recommended in conjunction with taper regimens.
Addiction Treatments 83
One of the first anti-craving medications that targeted the neu-

rotransmitters involved with reinforcement and craving was
bupropion (also known as Zyban® or Wellbutrin®). Bupropion is
a relatively weak presynaptic re-uptake blocker of dopamine,
norepinephrine, and serotonin in the brain. For these reasons,
buproprion was originally marketed as an antidepressant. By
slightly increasing the level of dopamine in synapses in dopamin-
ergic reward pathways, craving is reduced in some individuals.
Although bupropion is not effective for all smokers, it was the
first medication in a new class of anti-craving compounds that
involved targeting the dopaminergic reward systems.
More recent medications designed to alter the dopaminergic
system include compounds that have been used for other neuro-
logical diseases that involve dopaminergic systems. For individu-
als who are unsuccessful at abstinence from nicotine, a Parkin-
son’s disease medication may provide benefit. Craving from
nicotine withdrawal is associated with sharp declines in
dopamine in the reward pathways. Selegiline has been shown to
increase synaptic levels of dopamine because it inhibits the en-
zyme monoamine oxidase-B (MAO-B). This enzyme is normally
present in dopaminergic synapses and is responsible for the
metabolism of dopamine following presynaptic release. In early
trials, selegiline has been shown to combat nicotine cravings and
lead to prolonged abstinence in heavy smokers. Future studies
will determine if selegiline has widespread therapeutic potential.
Opiate Addiction Medications

In 2002, the Food and Drug Administration (FDA) approved
a combination medication for the treatment of opiate addic-
tion. The medication is a mixture of buprenorphine (an opiate
receptor agonist) and naloxone (an opiate receptor antago-
nist). The buprenorphine is believed to bind to opiate recep-
tors and decrease the intense cravings that opiate-addicted
individuals experience. The naloxone prevents other opiates

of abuse from having effects. This combination therapy has
been very successful in the treatment of opiate withdrawals
and the prevention of relapse. This combination medication
was formerly available only in treatment centers, but is now
available for use in the doctor’s office setting. A new, longer-
lasting preparation of the medication is becoming available,
which will require only one dose per month.
Relapse Prevention Medications

Other dopaminergic compounds are currently being investi-
gated as potential agents to decrease the possibility of relapse in
recovery. Vigabatrin® (GVG) is a GABAergic drug that is used to
treat epilepsy. GVG has been shown in laboratory experiments
to reduce the dopamine surge caused by cocaine and other stim-
ulants. As a result, animals demonstrate less addictive behavior
when pre-treated with GVG. Clinical trials of GVG on humans
are underway and have shown promising results. These data
suggest that medications that modulate the response of the
dopaminergic system to drugs of abuse may be beneficial for the
treatment of relapse.
Medications have also been developed to interact directly
with dopaminergic receptors in the ventral tegmental reward
pathways. The nucleus accumbens and frontal cortex are two ar-
eas of the brain that are sensitive to the pleasurable effects of
drugs of abuse that possess different receptors for dopamine.
Three types of dopamine receptors have been studied in these
areas as potential targets for medications (the D1, D2, and D3
dopamine receptors). Some laboratory studies have shown that
agonists that bind and activate the D1 and D2 receptors are too
rewarding and pleasurable and would end up being abused as
much as cocaine or amphetamine. Yet, blockers or antagonists
to these receptors have been shown to cause depression. Antag-
onists at the D3 receptor have shown the most promise as po-
tential therapeutic agents. Experimental D3 receptor blockers

reduce the pleasurable effects of cocaine and reduce drug-seek-
ing behaviors during abstinence in laboratory studies. Addi-
tional studies have demonstrated similar effects on behaviors in-
duced by heroin and nicotine use. Future experiments will
investigate the safety of these compounds for human use.
Future treatments may also include the use of antibodies to
inactivate drugs of abuse in the bloodstream before they reach
the brain. Current studies are investigating the possibility of syn-
thetic antibodies that catalyze enzymatic reactions when they
recognize and attach to molecules of cocaine, metham-
phetamine, or other drugs of abuse. Future experiments will
continue to address the possible development and use of blood
detoxification agents in relapse-prevention programs as well as
the possibility of immunizing certain populations of individuals
against the effects of specific drugs of abuse.
Other medications being investigated as treatments for addic-
tive disorders include other Parkinson’s disease agents (which
affect dopaminergic transmission and muscle spasticity),
antiepileptic and antiseizure medications, and medications used
to treat narcolepsy. The research involved with the development
of medications to treat addictive disorders is in its infancy. Un-
doubtedly, future treatment strategies will be highly dependent
upon the individual in recovery, their drug(s) of choice, and the
presence of any residual brain damage that occurred during
their drug use. Perhaps the most successful strategies will em-
ploy a combination of medications (anti-craving compounds
and receptor blockers) and behavioral therapies (such as indi-
vidual and group therapy, and 12-step recovery programs)
matched to individuals and their treatment expectations.
■ Learn more about treatments for addictions Search the Inter-

net for addiction and behavioral therapies or drug addiction
treatment medications.
CONCLUSION
The human brain is susceptible to all drugs of abuse. Our chem-
ical motivational systems are easily hijacked resulting in dys-
functional behavioral control mechanisms. The brain is also sus-
Behavioral Addictions
Several lines of evidence implicate that the same brain areas in-
volved with drug addiction (ventral tegmental dopaminergic sys-
tem, the nucleus accumbens, the limbic system, and the frontal
cortex) are also altered in those with behavioral addictions (such
as gambling, sex addictions, and overeating). The classic hall-
marks of addictive behaviors (compulsiveness, impulsiveness,
tolerance, dependence, and withdrawal) are also present in indi-
viduals with behavioral addictions. Chronic gamblers, food ad-
dicts, and sex addicts all state that they engage in these behav-
iors because it makes them feel good (provides a feeling of
pleasure) but that it also removes the negative feelings of agita-
tion or tension when the behavior is absent (reduction of with-
drawal symptoms). For some individuals, recovery from these
compulsive behavioral addictions is very difficult. While it is easy
to recognize that we don’t need cocaine or methamphetamine to
survive, we do need food, for example. Recovery programs mod-
eled after Alcoholics Anonymous are some of the most success-
ful strategies for regaining behavioral control. Certain medica-
tions useful in obsessive-compulsive disorders, such as
serotonin-type drugs, have also shown beneficial in behavioral
control. High risk/high reward behaviors are becoming more com-
monplace in society today. Gambling on television, on the Inter-
net, and on computer games will undoubtedly lead to new gen-
erations of individuals who struggle with behavioral addictions.
ceptible to behavioral addictions that result in compulsions (see

“Behavioral Addictions” box). The recent rise in these behaviors
is no surprise given that we are exposed to fast-paced technolo-
gies (computers, televisions, means of travel, even food prepara-
tion) that set the stage for immediate gratification and the reset-
ting of behavioral control thresholds. We possess the material
wealth, the means to acquire psychoactive chemicals, and the ac-
cess to behaviors that can overcome our normal biological
drives and control mechanisms. Yet the technological age has
also brought us a better understanding of the human brain. It
has led to better medications, diagnostic tools, and novel behav-
ioral therapies with which to diagnose and treat addictive disor-
ders. Public recognition of the impact and causes of addiction
has led to the acceptance that addiction is a treatable disease. In
this regard, the human brain can be considered not only the
cause, but the ultimate solution to problem of addiction.
SUMMARY POINTS
• Successful treatment programs include behavioral therapy
in which the individual learns to cope with problems with-
out using drugs or alcohol.
• Some therapies incorporate the use of incentives or prizes
to encourage drug-free lifestyles in their clients.
• Medications for treating drug addictions include drug-re-
placement medications, anti-craving compounds, and
other dopaminergic drugs.
Glossary
Action potential Electrical signal that travels down a nerve cell.
Acetylcholine Neurotransmitter used between cells in the brain
and between cells and muscles in the body.
Addiction Progressive, chronic brain disease characterized by loss
of control; drug use despite harm and denial.
Adenosine Neurotransmitter that normally inhibits norepineph-
rine release in the brain.
Amnestic Any drug that causes memory loss.
Amphetamine Stimulating drug that increases the action of norepi-
nephrine and dopamine and causes alertness.
Amphetamine psychosis Drug-induced paranoia and suspicious-
ness resulting from excess dopamine in frontal lobes.
Amygdala Nuclei located in the temporal lobes of the brain that
process emotion and anticipation of drug delivery.
Anandamide Neurotransmitter involved with pain control whose
receptors also bind chemicals in marijuana.
Analgesia State of decreased pain sensation.
Anesthesia State of loss of consciousness.
Anti-craving compounds Medications used to block the craving for
drugs during withdrawal.
Antidote Any drug that blocks another; typically used in medical
emergencies.
Aphasia Loss of language comprehension or production skills.
Arousal State of behavioral alertness; very awake and attentive.
Behavioral inhibition Control of emotions and urges to act.
Black-out Temporary state of drug-induced amnesia.
Brain stem Brain area above spinal cord that regulates automatic
and vital function such as breathing and heart rate.
Buprenorphine Drug that binds opiate receptors in the brain; used
for pain control and treatment of heroin users.
88
Bupropion Anti-craving drug that increases dopamine, norepi-
nephrine, and serotonin levels in brain.
Cannabinoid Any drug that acts on marijuana-like receptors in the
brain.
Cerebellum Area in the back of the brain responsible for muscle
balance, coordination, and some forms of learning.
Cerebral cortex Outer surface of the brain involved with higher
intellectual functions such as planning, logic, reasoning, and emo-
tional control.
Cognitive Mental activities such as thinking and learning.
Cognitive behavioral therapy Drug counseling that uses thinking
and acting to solve problems and change bad behaviors.
Compulsive Irresistible urge to perform an act repeatedly.
D3 dopamine receptor Dopamine receptor in pleasure center and
potential target for future medications.
Date-rape drug Illegal drug that is secretly given to an unsuspecting
individual so they won’t resist non-consensual sex.
Dependence State of drug use when individual will become physi-
cally sick or emotionally anxious without drug; closely associated
with addiction.
Depression Medical illness characterized by sadness; responds to
antidepressant medications.
Dendrite Part of nerve cell that receives information from other
cells.
Detoxification Earliest stage of recovery from drug addiction that
involves elimination of drug from the body.
Disinhibition Lack of control over emotions by the highest brain
centers.
Dopamine Neurotransmitter involved with feelings of pleasure,
drug seeking, and also muscle movement.
Dorsal raphe system Groups of cells in the base of the brain that
produce neurotransmitter serotonin.
89
Drug Any chemical found outside the body that can change
thoughts, feelings, or actions in the user.
Dynorphin Chemical signal in brain that acts to normally suppress
pain; shaped like a small protein.
Endorphin Small protein-like brain chemical involved with pain
suppression.
Enkephalin Chemical signal in the brain that acts to normally sup-
press pain; shaped like a small protein.
Fentanyl Very powerful medication used to suppress pain; typically
used in hospital setting.
Fight or flight responseBehavioral state in which fear has caused
activation of hormones and neurotransmitters to prepare for quick
action.
Frontal lobe Furthest forward area of the brain behind the fore-
head responsible for controlling emotions and behaviors.
Gamma-aminobutyric acid (GABA) Neurotransmitter in the brain
that suppresses activity of other cells.
GHB Drug that causes rapid sedation and sleepiness.
Glutamate Neurotransmitter in the brain that increases the activity
of other cells.
GVG Experimental medication to treat drug craving.
Half-way house Long-term residential facility that houses individu-
als recovering from drug addiction.
Hallucinogen Drug that causes distortions of senses (such as
vision).
Hemisphere One-half of the brain.
Hippocampus Structure located deep inside the sides of the
brain.
Homeostasis In multicelled organisms; the capacity for maintain-
ing the internal environment when conditions change.
Hyperthermic Very high body temperature.
90
Hypothalamus Brain structure involved with controlling body tem-
perature, eating, drinking, sleep cycles, and emotions.
Inhalant Vapor or aerosol that contains a drug which is inhaled.
Inhibitory neurotransmitter A neurotransmitter that prevents or
inhibits action potential to be fired by a neuron.
Internalization Attending to stimuli within the brain instead of
stimuli located in outside world.
Interneurons Small nerve cells located throughout brain that typi-
cally decrease the activity of other cells.
Intervention A strategy or approach by a group that intends to
change the actions or behavior of an individual.
Ketamine Drug typically used in veterinarian practices but can be
drug of abuse.
Korsakoff’s syndrome Brain disease in malnourished alcoholics;
characterized by poor memory.
Limbic system Area of the brain responsible for emotions and
memory.
Lipophilic Dissolvable in fat.
Locus ceruleus Group of nerve cells in the base of brain that pro-
duce norepinephrine.
LSD (Lysergic Acid Diethylamide) Drug that cause distortions of reality.
Marijuana Drug made from the dried flowers and leaves of the
hemp plant. When smoked or eaten, causes intoxication.
MDMA (Ecstasy) Drug that causes release of serotonin that leads to
pleasurable feelings followed by depression.
Mescaline Drug found in cacti that causes distortions of senses and
reality.
Mesolimbic and mesocortical pathways Neurotransmitter pathways
in the brain that deliver dopamine to pleasure centers.
Methamphetamine Stimulant drug that acts by increasing
dopamine and norepinephrine release in brain.
91
Midbrain Area in the center of brain that produces neurotransmit-
ters for other parts of the brain.
Monoamine oxidase Enzyme that breaks down neurotransmitters
and some drugs of abuse.
Motor Brain systems involved with control of muscle movement.
Naloxone Blocker of pain suppressing drugs; used in medical situa-
tions to prevent overdose.
Neuron Smallest functional unit in brain; nerve cell.
Neuromodulator Small protein that acts as neurotransmitter to
change activity of groups of neurons.
Neuropeptide Small protein in the brain; usually acts like neuro-
transmitter.
Neurotransmitter Chemical signal in the brain; main means of cel-
lular communication.
Nicotine replacement Medication strategy whereby a nicotine-
addicted individual is given smaller and smaller doses of nicotine in
gum, skin patch, or inhaler.
Dopamine system involved with controlling
Nigrostriatal system
muscle movement; damaged in Parkinson’s disease.
Norepinephrine Neurotransmitter that causes arousal and alertness
when released.
Nuclei Group of cell bodies in the brain.
Nucleus accumbens Area of the brain that is very sensitive to
drugs of abuse; when activated causes pleasure.
Occipital lobe Area of the back of the brain involved with vision.
Opioid Drug or chemical that blocks pain signals in the brain.
OxyContin® Pain medication that is often abused.
Overdose Emergency medical situation resulting from ingestion of
large doses of drug.
Painkiller Any drug or medication that blocks pain signals.
92
Parietal lobe Part of the brain responsible for processing informa-
tion about sense of touch.
PCP (Phencyclidine) Drug that causes distortions of reality and
feelings of separation from body.
Pons Area in base of brain responsible for transferring signals
between the spinal cord and the brain’s higher centers.
Predisposition Tendency to develop a disease; a susceptibility aris-
ing from a hereditary or other factor.
Prefrontal cortex Area of the brain responsible for planning, deci-
sion making, and controlling emotions and drives; implicated in the
loss of control associated with addiction.
Psilocybin Active ingredient in mushrooms that cause distortions
of reality.
Psychoactive Any drug that affects the brain and behavior.
Raves Large parties of young dancers; can be associated with drug use.
Receptor Protein on the brain cell surface that recognizes a brain
chemical or drug.
Receptor binding Act of drug or brain chemical binding to a recep-
tor that leads to a change in the activity of a cell.
Recreational or social drug use Stage of drug taking when a user
seeks out drug for effects but is not using in a consistent pattern.
Relapse Returning to drug/substance use after a period of not
using drugs or other substances.
REM sleep Dream sleep during which rapid eye movement occurs.
Reticular activating system (RAS) Network of brain cells in base of
brain responsible for consciousness, alertness, and reflexes such as
sneezing, vomiting, and swallowing.
Re-uptake Cellular mechanism of inactivation of neurotransmit-
ters in synapse.
Reward A stimulus that causes pleasure and increases the likeli-
hood that the reward will be sought again.
93
Rohypnol® Strong drug that causes sleepiness and forgetfulness;
very powerful when mixed with alcohol.
Schizophrenia Brain disease characterized by irrational thoughts.
Sedative-hypnotic Drugs that produce sleep or drowsiness—e.g.,
sleeping pills and tranquilizers.
Selegiline Medication used for patients with Parkinson’s disease
that may provide benefit in addiction treatment.
Sensory Relating to one of five senses (sight, hearing, taste, smell,
or touch).
Serotonin Brain neurotransmitter involved with controlling mood,
sleep, and eating.
Soma Body of nerve cell; processes incoming signals from other
neurons; contains nucleus.
SSRIs Specific serotonin re-uptake inhibitors used for treatment
of depression (such as Prozac® and Zoloft®).
Stimulants Class of drugs characterized by behavioral alertness,
wakefulness, and muscular activity.
Stroke Rupturing or blocking of blood vessel in or around the
brain; causes lack of oxygen and possible brain damage.
Sudden cardiac arrhythmias Fatal skipping of heart beats.
Synapse Gap between nerve cells; point of integration of informa-
tion in the brain.
Synergistic Combined effects of drugs that exceeds the sum of
their individual effects.
Temporal lobe The sides of the brain just behind the ears; involved
with hearing and language.
Thalamus Area deep inside the center of the brain that is responsi-
ble for transmitting signal to and from different parts of the brain.
Tolerance Loss of reduction in the normal response to a drug or
other substance, following prolonged use.
Toxicity Point at which drug dose causes damage.
94
Tranquilizers Class of drugs that induce sleep and muscle relax-
ation.
Ventral tegmentum (VTA) Area in the middle of the brain that pro-
duces dopamine, which is released into pleasure centers.
Vicodin® Medication used for pain control; becoming more popu-
lar as drug of abuse.
Vouchers Prizes or words of praise given to individuals in drug-
treatment programs to encourage a drug-free lifestyle.
Withdrawal Unpleasant behavioral and physical state induced by
the absence of drug.
95
Bibliography
American Psychiatric Association. Diagnostic and Statistical Manual
of Mental Disorders, 4th Ed. Washington, DC: American Psychiatric
Association, 2000.
Diaz, J. How Drugs Influence Behavior: A Neuro-Behavioral Approach.
Upper Saddle River, NJ: Prentice Hall, 1997.
Falkowski, C. Dangerous Drugs: An Easy to Use Reference for Parents
and Professions. Center City, MN: Hazelden, 2000.
Graham, A. W., et al. Principles of Addiction Medicine, 3rd Ed. Chevy
Chase, MD: American Society of Addiction Medicine, 2003.
Inaba, D. S., and W. E. Cohen. Upper, Downers, All Arounders, 5th Ed.
Ashland, OR: CNS Publications, Inc.
Julien, R. M. A Primer of Drug Action. New York, NY. Henry Holt and
Company, 2001.
Kandel, E. R., J. H. Schwartz, and T. M. Jessell. Principles of Neural
Science, 4th Ed. New York, NY. McGraw Hill, 2000.
National Institute on Drug Abuse. 2003 Monitoring the Future Survey.
www.nida.nih.gov/Infofax/HSYouthtrends.html
Olive, M. Designer Drugs. Philadelphia, PA: Chelsea House
Publishers, 2004.
Stimmel, B. The Facts About Drug Use. Binghamton, NY: Haworth
Medical Press, 1993.
96
Further Reading
Fields, R. Drugs in Perspective, 5th Ed. New York, NY: McGraw Hill
Publishers, 2004.
Kuhn, C, S Swartzwelder, and W Wilson. Buzzed: The Straight Facts
about the Most Used and Abused Drugs. New York, NY: W.W.
Norton & Company, 1998.
Twerski, A. The Spiritual Self: Reflections on Recovery and God. Center
City, MN: Hazelden, 2000.
97
Websites
National Institute on Alcohol Abuse and Alcoholism.
www.niaaa.nih.gov
National Institute on Drug Abuse.
www.nida.nih.gov
Substance Abuse and Mental Health Services Administration.
www.health.org
National Institute on Drug Abuse, website designed specifically for
teenagers.
http://teens.drugabuse.gov/
98
Index
Acetylcholine, 48, 88 psychosis, 40, 88
Action potential, 9, 23, 88 use of, 2–3
Addiction, cycle of withdrawal, 75–76
early behavior, 70–75 Amygdala
environment, 67, 69–70, 76 functions, 6, 88
heredity and genetics, 66–67, and reward pathway, 33, 35, 77
69, 72, 76, 78 steroid abuse in, 7
progression, 71–75 targets of addiction, 7, 32
recovery steps, 72, 75–87 Analgesia, 50, 59, 88
Addiction, drug, 1, 88 Anandamide, 64–65, 88
and the brain, 5–36, 41, Anesthesia, 50, 58, 88
49, 86 Anti-craving compounds
economic cost, 2 and recovery, 76–77, 82–83, 85,
signs and symptoms, 3–4, 32 87–89
statistics, 2–3 Antidote, 56, 88
and stress, 68–69, 72–73, Aphasia, 88
78 types, 16
treatment, 4 Arousal, 21, 88
Adenosine, 46, 88
Barbiturates
Alcohol addiction, 1, 44
effects of addiction, 24
economic cost, 2
overdose, 10
effects of addiction, 5, 7, 24–25,
Behavior
29–30, 36, 52–54, 58,
and addiction, 36, 59, 67, 72–75,
68–69, 72
79, 86
and genetics, 5, 67, 69, 71, 75,
early, 70
78 and inhalants, 58
and other drugs, 56 inhibition, 13, 41, 56, 88
poisoning and overdoses, and loss of control, 15, 32,
10, 53, 91 34–35, 70, 78, 87
signs and symptoms, 3, 33, 53 motivation, 26, 45
tolerance and dependence, risky, 32
73–75 and stimulant abuse, 38, 40–41,
treatment, 4, 54, 74–87 45
use, 3 therapies, 80–81, 85, 87
withdrawal symptoms, 52–53, Benzodiazepines, 55
74–75 Binge drinking, 10
Amnestic properties, 88 Black-outs. 7, 25, 42, 54, 73, 88
of depressants, 25 Brain
Amphetamine destructive powers of, 1
abuse effects, 7, 21, 29–32, disease and injury, 1, 4–5, 34,
36–42, 44, 50, 80, 84 46, 53, 71, 78, 88, 91
and hyperactivity disorders, 14 functions, 1, 6–12, 22–24, 30,
overdose, 16, 42 49, 52
99
Brain (continued) Craving, 32, 34–35, 91
processes with abuse and addic- treatments, 76–77, 80–83
tion, 1, 5, 29–34, 36, 38, 41,
49, 55–56, 62, 64, 66–75, 82, D3 dopamine receptor, 82, 84–85,
86–89 89
structures, 6–14, 16–17, 33, 67, “Date-rape” drug, 56, 89
90–91 Dependence, drug and alcohol, 1,
Brain stem 3, 67, 86, 89
nuclei, 9, 19–21, 23 on depressants, 55–56, 73–75
vital functions of, 9, 17, 25, 65, signs and symptoms, 4
74, 88 on stimulants, 46–48, 82
Buprenorphine, 82–83, 88 Depressants
Bupropion, 82–83, 89 effects on brain processes, 30,
36, 52, 59, 63, 65
Caffeine overdose, 9
addiction, 38, 46–47 types, 24, 52–59
tolerance, 46–47 withdrawal, 75
Cannabinoid, 51, 61–65, 89 Depression, 14, 89, 95
Cerebellum, 52, 89 manic, 70
Cerebral cortex, 8
rebound, 21, 38
amphetamines in, 21
role of serotonin and, 20–21
functions, 6–7, 12, 14, 17,
Detoxification, 75–79, 89
20–22, 25, 54, 89
Disinhibition, 58, 89
structures, 12, 19
Dissociative, 50
targets of addiction, 6–7, 14, 19,
Dopamine
27, 72
Cocaine functions, 19, 22–25
abuse effects, 29–30, 32–33, production, 19, 22–24, 28, 35,
38–42, 54, 63, 69, 80, 82, 49, 67, 72, 89, 93
84–85 reuptake, 29, 39, 41, 83
addiction, 5, 28–30, 32–33, 44 targets of addiction, 19, 22–24,
antibodies, 82 26, 28–29, 32, 34–36, 39–41,
crack, 2, 30, 41–42 45, 48–49, 51–52, 55–56, 58,
overdose, 42 61–63, 69, 72–73, 76, 82–88,
withdrawal, 75–76 92
Cognitive functions Dorsal raphe system
and addictive behavior, 45, 54, and serotonin production,
66–67, 73, 76 19–21, 46, 89
behavioral therapy, 80–81, 89 Drives
deficits, 80 and addictive behavior, 26–32,
Compulsive, 89 74
behaviors, 42, 73–75, 78, inhibition, 15
86–87 Drug treatment programs, 44
drug use, 3 future considerations, 80–87
100
inpatient, 60, 75–78 Glutamate, 23, 50–51, 90
medications, 75–78, 81–87, GVG, 82, 84, 90
89
types, 54, 74–87 Half-way house, 78, 90
Drug use and abuse, 1, 5, 88, 90 Hallucinogens, 45, 90
adolescents, 2–3 effects of addiction, 36, 43,
effects on brain processes, 6–36, 49–51, 59, 63
86 types, 36, 43, 49–51
legal consequences, 2 Hemisphere, 90
statistics, 2–3 functions, 14–16, 52
Heroin
Ecstasy. See MDMA effects of addiction, 2, 26,
Education programs, 2 28–31, 59–63, 85
Endorphin, 26, 59, 90 overdose, 61
Enkephalin, 26, 59, 90 tolerance and dependence, 32
withdrawal, 60, 63, 75, 89
Fentanyl, 60, 90 Hippocampus, 90
alcohol effects, 7
Fight or flight response, 22, 90
functions, 6, 25, 64
Forebrain
targets of addiction, 7
targets of addiction, 19, 23, 28
Homeostasis, 26, 90
Frontal cortex
Hyperactivity disorders
impulse and personality control
causes, 45
of, 13–14, 16–17, 34–35, 52, 70 treatment, 14
targets of addiction, 13–14, 28, Hyperthermic, 45, 90
34–35, 40, 73, 76, 78, 84, 86 Hypothalamus, 91
Frontal lobe, 12 amphetamines in, 7, 21, 38
functions, 13–16, 88, 90 functions, 6–7, 13, 21, 23, 65
targets of addiction, 13–14, 70 targets of addiction, 6–7, 74, 76
GABA. See Gamma-aminobutyric Incentives, 80–81

acid Inhalants, 91
Gage, Phineas, 15 effects of, 57–59
Gamma-aminobutyric acid use and abuse, 2, 5, 57–59
(GABA), 90 Inhibitory neurotransmitter, 23,
and depressants, 52, 55–57, 59 25, 75, 91
functions, 19, 23–25, 84 Internalization, 64, 91
and inhalants, 58 Interneurons, 23, 91
production, 19 Intervention, 74, 91
targets of addiction, 19, 29,
35–36, 52, 65, 72–73 Jellinek, E.M., 71
GHB, 90
effects of addiction, 24, 36, Ketamine, 91
55–56 effects of addiction, 30, 50–51
overdose, 56 Korsakoff ’s syndrome, 54, 91
101
Limbic system, 8 structures, 8, 23, 28
amphetamines in, 21 targets of addiction, 19
emotions and memories, 6–7, Milner, Peter, 28–29
13, 17, 25, 27, 35, 73, 91 Monoamine oxidase, 48, 83, 91
structures, 7, 19–20 Morphine
targets of addiction, 19, 22, 28, addiction, 26, 30, 44, 59–60
65, 72–73, 76, 78, 86 withdrawal 63
Lipophilic, 60, 91 Motivation,
Locus ceruleus, 91 and addictive behavior, 26–32,
and norepineprine production, 35, 38, 52, 58, 74, 86
21 Motor, 92
LSD (Lysergic acid diethylamide), 91 areas in the brain, 14, 52, 55, 62
effects on brain, 36, 49–50 MPTP, 62
Lysergic acid diethylamide. See LSD
Naloxone, 61, 83–84, 92
Marijuana (THC), 89 National Institute on Alcohol Abuse
dependence, 63 and Alcoholism (NIAAA), 2
and health risks, 64 National Institute on Drug Abuse
medical uses, 65 (NIDA), 2
use of, 2–3, 29, 44, 54, 60–65, Neuron
68, 88, 91 damage to, 41, 58–59
MDMA (Ecstasy) functions, 7–9, 11–12, 18, 20, 25
effects on brain, 30, 36, 43, structures, 8–9, 11, 29, 31, 92
45–46, 51, 91 targets of addiction, 19
tolerance and dependence, 46 Neuromodulator, 26, 92
toxicity, 21, 46 Neuropeptides, 92
use of, 2 functions, 18–19, 25–26
Mescaline, 49–50, 91 opioid, 19, 26
Mesolimbic pathway production, 19
and the addictive properties of targets of addiction, 19, 35, 65, 82
drugs, 22–23, 91 Neurotransmitter
Mesocortical pathway classes, 18, 22
and the addictive properties of functions, 9, 17–19, 78, 90–92
drugs, 22–23, 91 production, 7–11, 22–26
Methadone, 76 targets of addiction, 8, 18–25,
Methamphetamine, 38, 91 32, 35–38, 41, 46, 51–52, 59,
addiction, 29–30, 33–34, 40–42, 64–65, 73, 75, 83, 88, 94
63 NIAAA. See National Institute on
Midbrain, 91 Alcohol Abuse and
and dopamine production, 19, 34 Alcoholism
and opiod neuropeptide Nicotine
production, 19, 26, 31 effects of addiction, 30, 47–48,
and production of neurotrans- 51, 85
mitters, 7–8, 13, 17, 19 replacement, 82–83, 92
102
withdrawal, 82–83 Pituitary gland
NIDA. See National Institute on functions 23
Drug Abuse Pleasure chemistry, 22, 34–35, 93
Nigrostriatal system, 92 and addictive behavior, 26–32,
and the addictive properties of 45, 56, 61, 64, 72, 84, 86, 92
drugs, 23 and depressants, 56, 60
Norepinephrine and stimulants, 39, 41, 48
functions, 19, 21–23, 89 Pons, 19, 93
production, 19, 21, 92 Predisposition, 4–5, 93
targets of addiction, 19, 35–36, Prefrontal cortex, 93
38, 40, 45, 49–51, 59, 82–83, damage and behavior, 15
88 function, 12–13
Nucleus accumbens targets for addiction, 32–34
stimulant effects on, 29, 39, 41 Prescription medications
and dopamine, 22, 28–29, 35, abuse of, 2–3
39, 61–62, 72, 76, 84, 86 depressants, 55–56
and reward pathway, 24, 28, painkillers, 59–60
34–35, 77, 84, 92
Prevention programs, 2, 78
Psilocybin, 49–50, 93
Occipital lobe, 12, 92
Psychoactive, 59, 87, 93
functions, 13, 16, 52
drug use, 69
Olds, James, 28–29
Psychosis
Opiates, 52, 92
causes, 38, 40
addiction medications, 83–84
effects of addiction, 26, 29–31,
59–63 RAS. See Reticular activation
overdose, 61 system
tolerance, 32, 61 Raves, 45, 93
use, 63 Receptors, 31
withdrawal, 63, 76, 82 anandamide, 64–65
OxyContin® binding, 9–10, 48, 59, 61, 63, 93
use and abuse, 2, 26, 59, 92 dopamine, 67, 84–85
and neurotransmitters, 9–11,
Painkiller, 92 59, 64, 67
use, 2–3, 5, 26, 30, 59–60 opiod, 59–61, 64, 77, 82–83, 89
withdrawal, 63 Recovery
Parietal lobe, 12, 92 brain and behavior, 71–75
functions, 13 early, 81
Parkinson’s disease, 22, 62 steps in, 75–79, 81, 86–87
symptoms and causes, 23–24 Recreational (social) drug use, 3,
treatments, 83, 85, 94 93
PCP (Phencyclidine), 92 Relapse, 3, 93
effects on brain, 36, 50–51 prevention medications, 77,
Phencyclidine. See PCP 81–82, 84–85
103
REM sleep, 19, 93 abuse effects, 21, 36–48, 59
Reticular activating system stereotypical behaviors, 45
(RAS), 93 Striatum
functions, 8–9 and movement, 23
Reward, 93 targets of addiction, 19
and addictive behavior, 26–29, Stroke, 94
31–35, 49, 56, 68, 72, 76–77, deficits, 16
81, 83–84 drug causes of, 16
Rohypnol®, 93 Substantia nigra
effects of addiction, 24, 56–57 structures, 22–24, 62
overdose, 56–57 Sudden cardiac arrhythmias, 59, 94
Synapse, 31, 94
Schizophrenia, 14, 50, 70, 93 functions, 8–9, 17–18, 21, 25
symptoms, 40 targets for addiction, 39, 51
Sedative-hypnotics, 94 Synergistic properties, 94
dependence and addiction, 55 of depressants, 25
effects on brain processes,
55–57, 65 Temporal lobe, 12, 94
overdose, 10, 56 functions, 13, 16, 32, 88
types, 55 Thalamus, 94
Selegiline, 83, 94 functions, 6, 53
Sensory, 94 THC. See Marijuana
information, 6–7, 12 Tobacco
stimuli, 26 use, 3, 47
Serotonin, 94 Tolerance, 3, 31, 86, 94
functions, 19–21, 23, 89–90 on depressants, 56
production, 21, 92 on stimulants, 46–48
re-uptake, 20, 43, 82–83, 94–95 Toxicity, 94
targets of addiction, 19–21, 35, Tranquilizers, 2, 94
43, 45–46, 49–50, 59, 73
Serotonin reuptake inhibitors. See Ventral tegmentum
SSRIs and the addictive properties of
Sleeping pills, 24 drugs, 22–23, 28–29, 31, 35,
Spinal cord 67, 69, 86
structures of, 8–9, 18–19, 22, and craving and pleasure,
88, 93 28–29, 35, 76, 84, 94
SSRIs (Serotonin reuptake and motivation, 34
inhibitors), 20, 94 Vicodin®, 2, 59, 95
Steroids Vouchers, 81, 95
effects of abuse, 7
use, 2 Withdrawal, 5, 48, 86, 95
Stimulants, 94 symptoms, 4, 32, 75–77, 81–82
104
About the Author
James D. Stoehr, originally from Pittsburgh, Pennsylvania,
received his B.S. in Biology from the University of Pittsburgh at
Johnstown in 1987 and his Ph.D. in Physiology from
Dartmouth Medical School in 1993. He was a National Institute
of Mental Health Postdoctorate Fellow in the Division of
Neural Systems, Memory, and Aging at the University of
Arizona until 1996 when he joined the faculty of Midwestern
University in Glendale, Arizona. He currently teaches neuro-
science and physiology and supervises student research projects
as a professor in the Colleges of Medicine and Health Sciences.
Dr. Stoehr is the author of publications in the fields of addic-
tion medicine, neurobiology of memory, psychopharmacology,
and health professions education. He recently completed a five-
year grant from the White House Office of National Drug
Control Policy that funded his teaching of the neurobiology of
addiction to more than 15,000 high school teenagers in the
greater Phoenix area.
105
Picture Credits
page:
7: ©Peter Lamb 31: Philip Ashley Associates
8: ©Peter Lamb 33: National Institutes of Health
11: ©Peter Lamb 37: Philip Ashley Associates
15: National Institutes of Health 39: Philip Ashley Associates
20: ©Peter Lamb 43: ©Peter Lamb
22: ©Peter Lamb 57: Accurate Art
24: Philip Ashley Associates
29: Greg Gambino / 20•64 Design
30: Brookhaven National
Laboratory / Science Photo
Library
LAAM® is a registered trademark of Roxane Laboratories, Inc.;

Librium® is a registered trademark of Hoffman-LaRoche
Pharmaceuticals; OxyContin® is a registered trademark of Purdue
Pharma; Prozac® is a registered trademark of Eli Lilly and Company;
Ritalin® is a registered trademark of Novartis Pharmaceuticals
Corporation; Rohypnol® is a registered trademark of Hoffman-
LaRoche Incorporated; Valium® is a registered trademark of Roche
Pharmaceuticals; Vicodin® is a registered trademark of Knoll
Pharmaceutical; Vigabatrim® is a registered trademark of Aventis
Pharma; Wellbutrin® is a registered trademark of GlaxoSmithKline;
Xanax® is a registered trademark of Pfizer Inc.; Zoloft® is a registered
trademark of Pfizer Inc.; Zyban® is a registered trademark of
GlaxoSmithKline.
106

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The Neurobiology

STAFF FOR THE NEUROBIOLOGY OF ADDICTION

©2006 by Chelsea House Publishers,

Library of Congress Cataloging-in-Publication Data

2. The Brain and Our Behavior . . . . . . . . . . . . . . . . . . . . . . . . . . 6

3. Brain Regions Involved in Addiction. . . . . . . . . . . . . . . . . . . . 18

4. Stimulants and Hallucinogens . . . . . . . . . . . . . . . . . . . . . . . . 36

5. Depressants and Marijuana. . . . . . . . . . . . . . . . . . . . . . . . . . 52

6. The Cycle of Addiction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

The human brain is capable of creating complex and beau-

susceptibilities, accepting its limits and, ultimately, striving for

Furthermore, consider the absolute numbers of these chil-

Table 1.1 Signs and Symptoms of Drug Dependence and Addiction

1 Loss of natural rewards Previously important social or recreational

depends on several factors, including their genetic predisposition

book we will examine recent scientific evidence that implicates

BRAIN STRUCTURE AND FUNCTIONS

pothalamus (which controls body temperature, hunger, thirst,

of abuse influence the production, release, or elimination of

FUNCTION OF BRAIN CELLS

cell surface specific for this neurotransmitter. Receptors are

Binge Drinking and Alcohol Poisoning

known as a potential in the post-synaptic cell. A common anal-

potential). In this way, a chemical signal in the synapse is trans-

BRAIN SYSTEMS AND BEHAVIOR

Table 2.1 Brain Areas and Functions

Frontal lobe Decision-making, reasoning, planning, behavioral inhibition,

frontal lobes may become dysfunctional following chronic drug

The Infamous Case of Phineas Gage

I n the last chapter, we described how the brain’s ability to

THE MAJOR NEUROTRANSMITTER SYSTEMS

NEURO SITE OF COMMON

ten affected by drugs of abuse: serotonin, norepinephrine,

Corpus striatum (basal nuclei) Thalamus

Dorsal raphe system

Figure 3.1 Serotonin is a neurotransmitter produced by a cluster of brain

thought to be due to inactivation of specific serotonin cells in the

synapses, which is achieved through months of treatment with

Limbic system Amygdala

Ventral tegmental area Locus ceruleus

Figure 3.2 Dopamine is a neurotransmitter that is formed in several different sec-

originating in the spinal cord, that stimulate specific target organs

Because GABA has inhibitory effects on neurons, any drug

consciousness (suppression of cortical and NE systems) and suf-

Therefore, neuropeptides are often considered neuromodulators

MOTIVATION, DRIVES, AND THE CHEMISTRY

filled or gratified, we feel uncomfortable and tense. We may de-

of human behavior. The areas of the brain responsible for plea-

abuse. Often this leads to malnourishment, dehydration, fa-

the most addictive substances are cocaine, particularly smok-

Intracranial Self Stimulation

Descending Myelinated Fibers

Barbiturates Opiates Amphetamine

For a drug to be considered addicting, it must be capable of

LOSS OF BEHAVIORAL CONTROL

where we make decisions about the consequences of our actions.

Table 3.2 Summary of Brain Areas Implicated in Drug Addiction

In previous chapters, we saw that each drug of abuse works