European Neuropsychopharmacology 75 (2023) 1–14

www.elsevier.com/locate/euroneuro

REVIEW

Psychedelics in the treatment of eating

disorders: Rationale and potential
mechanisms
Abigail Calder a, Seline Mock a, Nicole Friedli a, Patrick Pasi b,
Gregor Hasler a,∗

a
University Center for Psychiatric Research, University of Fribourg, Chemin du Cardinal-Journet 3, 1752
Villars-sur-Glâne, Switzerland
b
Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich,
University of Zurich, Switzerland

Received 24 March 2023; received in revised form 25 May 2023; accepted 28 May 2023

KEYWORDS Abstract
Eating disorders; Eating disorders are serious illnesses showing high rates of mortality and comorbidity with
Anorexia nervosa; other mental health problems. Psychedelic-assisted therapy has recently shown potential in
Bulimia nervosa; the treatment of several common comorbidities of eating disorders, including mood disorders,
Psychedelic-assisted post-traumatic stress disorder, and substance use disorders. The theorized therapeutic mech-
therapy; anisms of psychedelic-assisted therapy suggest that it could be beneficial in the treatment
Psilocybin; of eating disorders as well. In this review, we summarize preliminary data on the efficacy
MDMA of psychedelic-assisted therapy in people with anorexia nervosa, bulimia nervosa, and binge
eating disorder, which include studies and case reports of psychedelic-assisted therapy with
ketamine, MDMA, psilocybin, and ayahuasca. We then discuss the potential therapeutic mech-
anisms of psychedelic-assisted therapy in these three eating disorders, including both general
therapeutic mechanisms and those which are relatively specific to eating disorders. We find
preliminary evidence that psychedelic-assisted therapy may be effective in the treatment of
anorexia nervosa and bulimia nervosa, with very little data available on binge eating disor-

Glossary of abbreviations: 5-HT, Serotonin; AN, Anorexia nervosa; BED, Binge eating disorder; BN, Bulimia nervosa; DMT,
N,N-Dimethyltryptamine; ED, Eating disorder; LSD, Lysergic acid diethylamide; MDD, Major depressive disorder; MDMA, 3,4-
Methyl enedioxy methamphetamine; MAOI, Monoamine oxidase inhibitor; OCD, Obsessive-compulsive disorder; PAT, Psychedelic-assisted
therapy; PTSD, Post-traumatic stress disorder; SSRI, Selective serotonin reuptake inhibitor.
∗ Corresponding author.

E-mail address: [email protected] (G. Hasler).

https://doi.org/10.1016/j.euroneuro.2023.05.008
0924-977X/© 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/)
 A. Calder, S. Mock, N. Friedli et al.

der. Regarding mechanisms, psychedelic-assisted therapy may be able to improve beliefs about
body image, normalize reward processing, promote cognitive flexibility, and facilitate trauma
processing. Just as importantly, it appears to promote general therapeutic factors relevant to
both eating disorders and many of their common comorbidities. Lastly, we discuss potential
safety concerns which may be associated with these treatments and present recommendations
for future research.
© 2023 The Author(s). Published by Elsevier B.V.
This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/)

1. Introduction Attia, 2017; Attia et al., 2019) Regarding psychotherapy,

cognitive behavioral therapy has the most robust evidence
1.1. Eating disorders base. (Hay, 2020) Family-based therapy, interpersonal
therapy, motivational interviewing, psychoanalytic therapy,
Eating disorders (EDs) are a group of serious conditions char- and some disorder-specific therapies are also sometimes
acterized by abnormal eating behavior which negatively af- used, with varying degrees of efficacy. (Zipfel et al., 2015;
fects physical and mental health. The most prevalent EDs van den Berg et al., 2019; Startup et al., 2021)
in adults include anorexia nervosa (AN), bulimia nervosa Overall, the efficacy of ED treatments is limited, par-
(BN), and binge eating disorder (BED). (Diagnostic and sta- ticularly for AN. Therapy may primarily be effective in
tistical manual of mental disorders: DSM-5TM 2013; Udo and the management of co-morbid diseases or weight, and the
Grilo, 2018) Common symptoms of these three EDs are core symptoms of EDs are not always addressed by cur-
shown in Table 1. EDs are associated with chronic illness rent therapies. (van den Berg et al., 2019; de Vos et al.,
and disability, reduced quality of life, and increased sui- 2014) While up to two thirds of people with AN and BN re-
cide risk, with AN having the highest mortality rate of cover eventually, some remain ill for years or even decades.
any psychiatric disorder. (Diagnostic and statistical man- (Zipfel et al., 2015; Keel and Brown, 2010) There is a need
ual of mental disorders: DSM-5TM 2013; J Arcelus et al., for treatments which can accelerate recovery, and which
2011) EDs additionally show a high degree of comorbid- are effective in treatment-resistant cases.
ity with other psychological disorders, particularly mood
disorders, substance abuse disorders, post-traumatic stress
disorder (PTSD), and obsessive-compulsive disorder (OCD). 1.2. Psychedelic-assisted therapy
(Diagnostic and statistical manual of mental disorders: DSM-
5TM 2013; Brewerton, 2007) Psychedelic-assisted therapy (PAT) shows some efficacy
The pathogenesis of EDs is not completely understood, in the treatment of mood disorders, addiction, and
and it may share etiology with other psychiatric disor- PTSD. (Breeksema et al., 2020) Several different classes
ders. Girls and young women are particularly at risk, al- of psychedelics are commonly used in PAT. The classic
though EDs can affect anyone. (Zipfel et al., 2015) Other psychedelics include lysergic acid diethylamide (LSD), psilo-
likely contributing factors include genetic predisposition, cybin (the principal psychoactive component in magic mush-
hormonal dysregulation, anxious or obsessive temperament, rooms), and N,N-Dimethyltryptamine (DMT, the principal
stress, traumatic experiences in childhood, and environ- psychoactive component in ayahuasca). (Nichols, 2016) Ad-
mental factors, such as an environment that highly values ditionally, the rapid-acting antidepressant ketamine and
thinness. (Zipfel et al., 2015; Brewerton, 2018) Some stud- the empathogen 3,4-Methyl enedioxy methamphetamine
ies have also noted cognitive and neurological abnormalities (MDMA) have some psychedelic properties and are combined
which may constitute risk or maintenance factors for EDs. with psychotherapy in a similar manner. (Smith et al., 2022;
(Zipfel et al., 2015; Kaye, 2008; Kessler et al., 2016) Drozdz et al., 2022) Classic psychedelics have a long history
Therapy for EDs most commonly involves behavior- of use in sociocultural rituals and were first investigated as
centered strategies, sometimes combined with pharma- possible therapeutic agents in the 1950s, though political
cological treatment. (Davis and Attia, 2017; Davis and regulations brought this research to a halt by the 1970s.
Attia, 2019) Antidepressants, particularly selective sero- (Nichols, 2016) Research into the clinical use of psychedelics
tonin reuptake inhibitors (SSRIs), have shown some effi- cautiously recommenced in the 1990s and has rapidly accel-
cacy in people with BN or BED. (Davis and Attia, 2017; erated in the last decade. (Nichols, 2016)
Leombruni et al., 2006) Less commonly, BN may be treated When used in a safe setting, psychedelics can evoke pro-
with other classes of antidepressants or antiepileptic med- found psychological experiences which often have person-
ications, and BED with appetite-suppressing stimulants. ally meaningful content. (Yaden et al., 2022; Roseman and
(Davis and Attia, 2017) AN has proven more difficult to Nutt, 2018) In PAT, these experiences are embedded in
treat with medication, and drugs which improve BN or BED a therapeutic context in order to maximize safety and
symptoms appear to have little efficacy in AN. (Davis and clinical benefits. (Garcia-Romeu and Richards, 2018) PAT
Attia, 2017) Some studies show that the antipsychotic olan- may have some degree of trans-diagnostic efficacy in that
zapine may help people with AN gain weight, but it does it addresses underlying psychological and neurobiological
not appear to improve psychological symptoms. (Davis and pathologies that could contribute to various psychiatric di-

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Table 1 Key symptoms of EDs according to the DSM-V. (Diagnostic and statistical manual of mental disorders: DSM-5TM 2013)
OCD = obsessive compulsive disorder, PTSD = post-traumatic stress disorder.
Anorexia Nervosa Bulimia Nervosa Binge Eating Disorder
Body weight Significantly low body weight Typically normal or overweight Typically overweight
Eating behavior Restriction of energy intake Episodes of binge eating Episodes of binge eating
despite low weight (consuming extremely large (consuming extremely large
amounts of food) amounts of food)
Inappropriate compensatory
behaviors to prevent weight
gain (e.g. vomiting)
Self-image Disturbance in experience of Undue influence of body weight Feelings of depression,
body weight or shape; undue and shape on self-evaluation guilt, or disgust with
influence of body weight or oneself after binge eating
shape on self-evaluation
Other psychological Intense fear of weight gain A sense of a lack of control A sense of a lack of control
symptoms and/or behavior interfering over binge eating episodes over binge eating episodes
with weight gain Marked distress regarding
binge eating
Common comorbidities Bipolar disorder, depression, Depression, bipolar disorder, Bipolar disorder, depression,
anxiety disorders, OCD, anxiety disorders, substance anxiety disorders, substance
substance use disorders, PTSD abuse disorders, personality use disorders
disorders, PTSD

agnoses, including EDs. (Kočárová et al., 2021) Previous BN (Table 2). One 1959 case report describes a patient
authors have named serotonergic mechanisms, changes in with AN who was treated with two doses of psilocy-
functional connectivity, and enhanced cognitive flexibility bin and showed strong therapeutic effects, including im-
as potential mechanisms by which PAT may treat AN in par- proved mood and weight gain. (Verroust et al., 2021) Other
ticular. (Gukasyan et al., 2022) Some have also seen poten- case reports describe therapeutic benefits in people with
tial for serotonergic psychedelics to treat BN, BED, and obe- EDs undergoing ketamine-assisted therapy. (Dechant et al.,
sity, and also name cognitive flexibility as a potential mech- 2020; Ragnhildstveit et al., 2021; Scolnick et al., 2020;
anism. (Borgland and Neyens, 2022) Robison et al., 2022; Schwartz et al., 2021) One expe-
For this review, we searched the PubMed database for rienced lasting remission from BN after ketamine treat-
studies which included people with EDs using the following ment, (Ragnhildstveit et al., 2021) while another recovered
search terms: (Hallucinogen OR Psychedelic OR Ketamine from AN after ketamine combined with a ketogenic diet.
OR Psilocybin OR Mescaline OR Ayahuasca OR "Lysergic Acid (Scolnick et al., 2020) Another patient with AN experienced
Diethylamide") AND ("Anorexia Nervosa" OR “Bulimia Ner- reductions in comorbid suicidality and depression after ke-
vosa” OR “Binge Eating Disorder” OR "Eating Disorder"). tamine treatment, though she did not achieve remission.
The search was first performed in February 2022, and up- (Dechant et al., 2020) A case series of ketamine treatment
dated in May 2023. Further records were identified via ci- in four people with EDs with comorbid treatment-resistant
tation searching. Based on the results of this search, we depression reported improvement in both depression and ED
extracted data from 13 records. We first discuss their find- symptoms in 3 out of 4 patients. (Schwartz et al., 2021)
ings on how psychedelics affect people with EDs, including Finally, a separate series of five people with EDs treated
both improvements in ED symptoms and comorbid disorders. for anxiety and depression reported improvements in both
We then propose therapeutic mechanisms by which PAT may of these comorbid disorders, in addition to some improve-
be helpful in the treatment of AN, BN, and BED, including ments in ED symptoms. (Robison et al., 2022)
both psychological mechanisms and associated neurobiolog- Four cross-sectional studies have also investigated self-
ical changes. Finally, we discuss important safety consider- reported effects of psychedelic use in people with EDs.
ations for future trials with psychedelics in people with EDs. In a prospective survey, 28 participants with a lifetime
We believe these findings provide a clear rationale for more ED diagnosis reported significant improvements in depres-
extensive research into PAT for the treatment of AN, BN, sion and well-being after taking a classic psychedelic.
and BED. (MJ Spriggs et al., 2021) The study also reported moder-
ate evidence for an association between symptom improve-
ment and emotional breakthrough, indicating that emo-
2. Effects of psychedelics in people with tional breakthrough may mediate positive outcomes in EDs
eating disorders after psychedelic experiences. A second survey study inves-
tigated the impact of psychedelic use on symptoms of disor-
Research on the effects of psychedelics in people with dered eating in people with a history of using psychedelics.
EDs has included case reports, cross-sectional research, (Lafrance et al., 2021) They reported that more frequent
and small clinical studies, mostly focusing on AN and psychedelic use was associated with reductions in disor-

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Table 2 Summary of studies describing the effects of psychedelics on eating disorder symptoms, organized by type.
AN = anorexia nervosa, BED = binge eating disorder, BN = bulimia nervosa, MDD = major depressive disorder, MDMA = 3,4-
Methyl enedioxy methamphetamine, OSFED= other specified feeding and eating disorder.
Study Type Eating Disorders Treatment Results
Dechant et al., 2020 Case report AN Ketamine Transient improvement in
suicidality, depression
Ragnhildstveit et al., Case report BN Ketamine Sustained remission >1 year
2021 post-treatment
Scolnick et al., 2020 Case report AN Ketamine Sustained remission from AN, MDD
>6 months post-treatment
Verroust et al., 2021 Case report AN Psilocybin Improved mood, weight gain at 1
month post-treatment
Robison et al., 2022 Case series AN, BN Ketamine Immediate improvement in ED,
mood disorder symptoms; no
long-term follow-up
Schwartz et al., 2021 Case series AN, BN Ketamine Improvements in ED, mood
disorder symptoms
Lafrance et al., 2017 Cross-sectional AN, BN Ayahuasca Self-reported improvement in ED
symptoms
Lafrance et al., 2021 Cross-sectional Not specified Various classic Psychedelic use negatively related
psychedelics to disordered eating
Renelli et al., 2018 Cross-sectional AN, BN Ayahuasca Self-reported improvement in ED
symptoms
MJ Spriggs et al., Cross-sectional Any ED Various classic Self-reported improvements in
2021 psychedelics depression, well-being
Brewerton et al., Clinical trial AN, BN, BED, OSFED MDMA Improvement in ED symptoms 3–4
2022 weeks post-treatment
S Knatz Peck et al., Clinical trial AN Psilocybin Improvement in ED symptoms 1
2022 month post-treatment
Mills et al., 1998 Clinical trial AN, BN Ketamine Sustained reductions in depressive
symptoms, compulsive behaviors
for several months

dered eating, with spirituality and emotional regulation as heterogenous methods make results difficult to evaluate.
mediating factors. Finally, two exploratory studies inter- Nevertheless, there are plausible reasons to hypothesize
viewed people with EDs who partook in ayahuasca cere- that psychedelics could be a particularly effective treat-
monies as a treatment for ED symptoms. These individu- ment for EDs. As we will discuss next, psychedelics may both
als reported subjective improvements in symptoms, partic- activate general therapeutic factors and address symptoms
ularly improvements in negative body perception, and they that are relatively specific to EDs.
contrasted ayahuasca positively with typical ED therapies,
reporting that ayahuasca led to greater improvements and
helped them better understand the roots of their disorder. 3. Potential mechanisms of
(Lafrance et al., 2017; Renelli et al., 2018) psychedelic-assisted therapy in the treatment
Most importantly, some clinical studies with psychedelics of eating disorders
have included people with EDs. An early trial suggested that
ketamine infusions could treat compulsive eating behavior 3.1. Improved body image
in patients with AN, though the concomitant use of opi-
oids makes the results difficult to interpret. (Mills et al., Both AN and BN are associated with a distorted body image,
1998) More recently, a trial of MDMA-assisted therapy for defined as a disturbance in the perception of weight or body
PTSD included 13 patients with clinical ED symptoms, which shape. (Smolak and Levine, 2015) Several mechanisms have
significantly improved after MDMA compared to placebo. been proposed to explain the association between body im-
(Brewerton et al., 2022) Lastly, preliminary data from a pi- age disturbances and these EDs. Firstly, those with AN or
lot study of psilocybin treatment for AN found that 4 out BN frequently evaluate themselves based on their shape,
of 5 patients had significant and persistent reductions in ED weight, and perceived control over their bodies, while ne-
symptoms one month post-treatment. (S Knatz Peck et al., glecting other characteristics. (Diagnostic and statistical
2022) More trials with psilocybin are underway. (S Knatz manual of mental disorders: DSM-5TM 2013) Concerns about
Peck et al., 2022; MJ Spriggs et al., 2021) weight and shape have been shown to predict ED onset,
Many of these studies are limited by open-label designs and over-valuing weight and shape, as well as attempting
and the biases inherent in self-reported symptoms, and the to control them, may be an underlying core psychopathol-

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ogy in AN and BN. (Smolak and Levine, 2015; McLean and cluding body image, and a greater motivation to treat them-
Paxton, 2019; A Kearney-Cooke and Tieger, 2015) Secondly, selves and their bodies with more care. (Lafrance et al.,
many people with EDs internalize culturally promoted body 2017; Renelli et al., 2018) In people with EDs, temporary
objectification, such as body shape and weight ideals or the dissolution of the self – and its associated beliefs about the
sexualization of certain body types. (Davenport et al., 2015; body – could allow for more flexibility in these beliefs.
A Kearney-Cooke and Tieger, 2015) Finally, people with EDs
struggle with emotional regulation, and behaviors such as
bingeing, over-exercising, or starving oneself provide tem- 3.2. Normalized reward processing
porary relief from negative feelings about physical appear-
ance. (A Kearney-Cooke and Tieger, 2015) People with EDs show dysfunctional reward processing
PAT is thought to help people break down maladaptive which can be observed in both behavior and brain activity.
beliefs and thought patterns, which could include nega- BN and BED are characterized by a bias towards food re-
tive beliefs about one’s own body and shape. (Carhart- wards over other types of rewards, as well as steeper dis-
Harris and Friston, 2019; Ho et al., 2020) Ordinarily, the counting of monetary rewards and altered reinforcement
brain continuously constructs a first-person concept of the learning. (Leenaerts et al., 2022) People with EDs also show
body and its environment (the ‘bodily self’) by predictive altered activity in the striatum, insula, and anterior cingu-
coding. (Apps and Tsakiris, 2014) This involves dynamic late cortex (ACC) in response to food images. (Zipfel et al.,
optimization of beliefs about the self via bottom-up up- 2015; Leenaerts et al., 2022; Bohon and Stice, 2011;
dating, which results from the comparison between exist- Foldi et al., 2020; Haynos et al., 2021; Keating et al., 2012)
ing beliefs, or priors, and new sensory inputs. (Ho et al., This may also extend to social stimuli, such as feedback
2020) Within this framework, distorted body image could from others. (El-Deredy et al., 2015; Wagner et al., 2010)
result from distorted high-level priors which are resistant In BN and BED, reduced structural and functional connec-
to bottom-up updating (for example, “My body is not thin tivity between frontal regions and the striatum is associ-
enough”). (Ho et al., 2020) As psychedelics disrupt top- ated with binge frequency and compulsive reward seeking.
down predictive networks, prior beliefs about the body (Leenaerts et al., 2022; Haynos et al., 2021) AN is also some-
can weaken, allowing sensory input to influence them once times characterized by anhedonia, a state in which response
more. (Ho et al., 2020) In line with this, people often to rewards is globally reduced. (Keating et al., 2012)
report alterations in how they perceive themselves and AN in particular can be viewed as a disease of “reward
their bodies while under the influence of psychedelics. contamination,” in which maladaptive conditioning causes
(Breeksema et al., 2020; Preller and Vollenweider, 2018; normally punishing stimuli to be rewarding (e.g. starva-
Girn and Kalina, 2018) In an appropriate therapeutic set- tion) and normally rewarding stimuli to be punishing (e.g.
ting, enabling bottom-up signals to disrupt maladaptive pri- high-calorie foods). (Keating et al., 2012) This contamina-
ors could help people with EDs reinstate healthier beliefs tion is relatively specific to disease-related stimuli, such
about their body and its shape. (Carhart-Harris and Fris- as food, exercise, and body shape. (Keating et al., 2012;
ton, 2019; Ho et al., 2020) This is also in line with the finding O’Hara et al., 2015; Kogel et al., 2021) Consistent with
that providing bottom-up information about a healthy body this theory, people with AN show increased activity in re-
size via virtual reality can improve body image distortions ward regions when viewing moldy food and reduced activ-
in people with AN. (Keizer et al., 2016) ity after eating or consuming sugar. (Keating et al., 2012;
Neurobiologically, psychedelic effects on the bodily self O’Hara et al., 2015) They also show reductions in gray mat-
may particularly involve the insula, a key region for inte- ter in the striatum and somatosensory cortex, which may
roceptive awareness, self-referential processing, and self- underlie their abnormal responses to food. (Titova et al.,
recognition. (Craig, 2009; Damasio et al., 2000) Insula func- 2013)
tion is known to be disrupted in EDs. (Zipfel et al., 2015; People with AN also often have a favorable view of their
Bulik et al., 2022; Frank et al., 2019) Psilocybin generally disorder, believing that it helps them feel safe, communi-
appears to increase activity in the insula, (Lewis et al., cate distress, and deal with strong emotions. (Schmidt and
2017) and its acute effects in this region are also correlated Treasure, 2006) One maladaptive “reward” obtained from
with reduced self-referential processing. (Smigielski et al., disordered eating is control over negative emotions and
2020) Reduced self-referential processing is a typical phe- other undesirable experiences. People with EDs show high
nomenon in PAT, culminating in the complete dissolution of levels of experiential avoidance, defined as the unwilling-
the self in the most extreme cases. (Mason et al., 2020; ness to have particular private experiences, including diffi-
Nour et al., 2016; Lebedev et al., 2016) cult emotions, memories, and thoughts. (Rawal et al., 2010;
Participants with EDs in previous studies have reported Frank et al., 2018) Many people with AN report using control
effects on self-referential processing and body image while over food to help cope with emotions they find overwhelm-
under the influence of psychedelics. For example, one in- ing. (Startup et al., 2021; Schmidt and Treasure, 2006) Binge
dividual with AN saw herself first as a “rotting, decay- eating is also mediated by experiential avoidance, and tar-
ing skeleton” and later as a “full-bodied, just beautiful geting avoidance with therapy can reduce the frequency of
woman” under the influence of ayahuasca, which moti- episodes. (Lillis et al., 2011)
vated her to “start gaining some weight.” (Lafrance et al., PAT may help normalize reward processing. As discussed
2017) A second person reported that she “experienced [her] above, psychedelics are thought to weaken the influence of
body as a gift”, motivating her to nourish it more properly. high-level priors and allow bottom-up information to update
(Lafrance et al., 2017) Other participants had similar ex- beliefs. (Carhart-Harris and Friston, 2019) This may also ap-
periences, in which they reported improved self-image, in- ply to beliefs about what is rewarding and what is not. In

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the right therapeutic context, psychedelics may help peo- AN is also associated with reduced self-reported cognitive
ple to reevaluate their beliefs about their own bodies, food, flexibility, as well as impaired perceptual flexibility, both of
and the utility of their unhealthy behaviors. Furthermore, which may constitute risk or maintenance factors for the
psychedelics may restore responses to naturally rewarding disorder. (Miles et al., 2020)
stimuli and counteract anhedonia. (Hesselgrave et al., 2021) Like other maladaptive priors, rigid ways of thinking
In people with depression, psilocybin therapy increased and behaving could become loosened in the psychedelic
scores on the Snaith-Hamilton Pleasure Scale, which mea- state, allowing for revision. (Gukasyan et al., 2022; Carhart-
sures one’s self-reported ability to feel pleasure. (Carhart- Harris and Friston, 2019) Relatedly, the psychedelic state of-
Harris et al., 2016) LSD has also been shown to increase ten requires people to give up some degree of control over
reward responses and reward-based reinforcement learn- what is happening, and therapists commonly advise clients
ing, without also increasing responses to negative feed- to “trust, let go, and be open.” (Wolff et al., 2020) Volun-
back. (Glazer et al., 2022; Kanen et al., 2022) Addition- tary surrender of control under psychedelics may serve as a
ally, psychedelics may be able to adjust reward responses useful foil for people with a high need for control, as often
to social stimuli by re-opening a critical period of social re- seen in AN. When properly handled in a safe and supportive
ward learning. (Nardou et al., 2019) MDMA, LSD and psilocy- therapeutic context, these individuals may be able to ex-
bin have all been shown to increase oxytocin, which evokes perience a positively valenced loss of control that does not
a period of synaptic plasticity necessary for social reward come with expected negative consequences. (Wolff et al.,
learning. (Nardou et al., 2019; Holze et al., 2019; F Holze 2020) In this vein, previous research suggests that psilocy-
et al., 2021; Schmid et al., 2015; F Holze et al., 2022) Peo- bin might be able to improve symptoms of OCD, which is
ple with EDs often struggle in social situations and show mal- often comorbid with EDs and shares control-related symp-
adaptive emotional responses to social events, which then toms. (Palmieri et al., 2021; Moreno et al., 2006)
feed into their avoidant coping behavior. (Startup et al., People with BN and BED may not benefit from this
2021) PAT may present an opportunity for re-learning pos- aspect of PAT as much, because they show a different
itive interactions with other people. kind of behavioral rigidity. Rather than excessive control,
PAT has also been shown to reduce experiential avoid- lack of control over binge episodes is a central feature.
ance, thought to be an underlying factor in maladaptive (Diagnostic and statistical manual of mental disorders: DSM-
reward processing. (Zeifman et al., 2020; Watts et al., 5TM 2013) Binge eating is a compulsive behavior that shows
2017) Under normal circumstances, avoidant coping strate- some similarities with addiction: people feel compelled to
gies can “work” in the short-term via negative reinforce- persist in unhealthy behaviors despite severe consequences.
ment. In the psychedelic state, however, this is no longer (O’Hara et al., 2015) Because of this commonality, peo-
the case: attempts to avoid unpleasant experiences often ple with BN and BED may instead benefit from the anti-
only intensify those experiences. (Wolff et al., 2020) By addictive properties of psychedelics. Participants in trials of
contrast, accepting difficult emotions can make them seem psilocybin for alcohol use disorder reported greater control
less frightening and ultimately lead to relief; acceptance over their choices and behaviors, including but not limited
is thus negatively reinforced in a type of operant condi- to their drinking, and many remained abstinent from alco-
tioning. (Wolff et al., 2020; Wolff et al., 2022) People thus hol for years after treatment. (Bogenschutz et al., 2018;
learn that they can withstand even very intense negative Bogenschutz et al., 2015; Bogenschutz et al., 2022) If this
emotions, and that accepting these emotions is more re- effect generalizes to people with BN and BED, it is possible
warding than avoiding them. Moreover, the brain may be that PAT could help them resist the impulse to binge.
particularly receptive to learning experiences at this time
because psychedelics promote neuroplasticity in cortical
regions, including regions important for emotional regula- 3.4. Trauma processing
tion. (Calder and Hasler, 2022; Barrett et al., 2020) In the
abovementioned study of people with EDs who consumed Traumatic experiences, particularly in childhood, are com-
ayahuasca, several individuals describe shifts away from un- mon in people with EDs and are considered a risk factor
healthy coping mechanisms, as well as greater ability to ac- for developing an ED. (Solmi et al., 2021; Brewerton, 2019;
cept negative emotions. (Lafrance et al., 2017) Molendijk et al., 2017; Tagay et al., 2010; Dansky et al.,
1997; Brewerton et al., 2021) EDs have been linked to
many types of potentially traumatic events, including a
3.3. Reduced behavioral and cognitive rigidity history of sexual, physical, or emotional abuse, as well
as neglect and bullying. (Brewerton, 2007) Consequently,
AN in particular is characterized by a rigid style of think- EDs are frequently accompanied by trauma-related symp-
ing and behaving, including but not limited to rigidity toms, including a lower tolerance to distress and trauma,
in eating behavior, which may also be a risk factor that heightened threat perception, and heightened emotional
appears before the disease itself. (Startup et al., 2021; reactivity and avoidance, all of which may drive maladap-
Wollburg et al., 2013) Rigid thinking styles are also associ- tive eating behaviors. (Brewerton, 2007; Brewerton, 2019;
ated with a greater need for control and fear of losing self- Brewerton et al., 2021; Rijkers et al., 2019; Holzer et al.,
control. (Froreich et al., 2016; Palmieri et al., 2021) OCD, 2008) Between 9.4% and 24.3% of people with an ED also
which is characterized by rigid, uncontrollable patterns of fulfill clinical criteria for PTSD at some point in their lives.
thought and behavior, is comorbid in 15–29% of people with (Brewerton, 2007) More specifically, some studies report
AN, and up to 79% of people with AN will experience com- that up to 47% of people with AN and 62% in people with BN
pulsions or obsessions in their lifetime. (Zipfel et al., 2015) fulfill clinical criteria for PTSD. (Rijkers et al., 2019) Trauma

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exposure and PTSD may also be associated with more severe sion and anxiety disorders, including in treatment-resistant
ED symptoms, (Molendijk et al., 2017; Rijkers et al., 2019; cases. (Gasser et al., 2014; F Holze et al., 2022; Carhart-
Backholm et al., 2013) and there is some evidence that the Harris et al., 2021; Griffiths et al., 2016; Ross et al., 2016;
relationship between trauma and EDs may partly be medi- Davis et al., 2021) In a small pilot study of psilocybin for
ated by PTSD symptoms. (Dansky et al., 1997; Holzer et al., the treatment of AN, two individuals showed meaningful
2008; Dubosc et al., 2012; Mitchell et al., 2016; KS Mitchell reductions in comorbid anxiety symptoms. (S Knatz Peck
et al., 2021) Consequently, integrating trauma therapy into et al., 2022) Additionally, ketamine is an effective antide-
the treatment of EDs is essential in people with previous pressant and may be particularly useful in reducing suici-
exposure to trauma. (Brewerton, 2007; Brewerton, 2019; dality, one of the main causes of death in people with EDs.
Molendijk et al., 2017; Brewerton et al., 2021; Holzer et al., (Reinstatler and Youssef, 2015; Surjan et al., 2022) In people
2008) with EDs, ketamine has already been seen to reduce anxiety
Most psychotherapies applied in those with PTSD are and depression, (Scolnick et al., 2020; Robison et al., 2022;
exposure-based and aim to extinguish conditioned fear Schwartz et al., 2021) as well as suicidality. (Dechant et al.,
to trauma-related cues, which can be aversive enough 2020)
that clients terminate therapy. (Krediet et al., 2020) Interestingly, both EDs and mood disorders are often co-
Psychedelics have an advantage in that they may pro- morbid with gastrointestinal symptoms and reduced diver-
vide some protection against re-traumatization in psy- sity of the gut microbiome. (Lam et al., 2017) A dysregu-
chotherapy, and MDMA may provide the best protection. lated microbiome may constitute a development or main-
(Hasler, 2022) During PAT, people may re-experience painful tenance factor for AN in particular. (Butler et al., 2021) It
memories, but they are often able to face and work through has been suggested that psychedelics exert some of their
these difficult experiences rather than being simply over- long-term effects via the microbiome. (Kuypers, 2019) Psilo-
whelmed. (Sessa, 2017) This has been dubbed the “helio- cybin has been shown to diversify the intestinal micro-
scope” effect. (Hasler, 2022) Neurobiologically, this effect biome in mice, and this diversification appeared to be re-
may arise from the fact that MDMA, LSD, and psilocybin sponsible for lasting antidepressant-like behavioral effects.
acutely reduce the activity and responsiveness of the amyg- (Cordner et al., 2022) Normalization of the gut microbiome
dala. (Bedi et al., 2009; Gamma et al., 2000; Mueller et al., may thus assist with recovery from both EDs and comorbid
2017; Kraehenmann et al., 2015) They also have strong mood disorders, and presents an intriguing avenue for fu-
prosocial and anxiolytic effects, which may counteract ture research. (Kleiman et al., 2015)
trauma-related avoidance and hyperarousal in psychother- EDs are also commonly comorbid with substance use dis-
apy sessions. (Brewerton et al., 2021; Krediet et al., 2020; orders, and they may share some underlying neurobiology.
Dolder et al., 2016; Preller et al., 2016) EDs are associated with abnormalities in the dopamine sys-
MDMA-assisted psychotherapy has been shown to be par- tem, including altered dopamine receptor binding in re-
ticularly effective in the treatment of PTSD, (JM Mitchell ward regions, D2 receptor polymorphisms, and abnormal
et al., 2021; Mithoefer et al., 2018) and though there are dopaminergic reactions to food, starvation, and exercise.
no controlled studies on EDs specifically, preliminary re- (Leenaerts et al., 2022; Keating et al., 2012; O’Hara et al.,
sults from people with comorbid EDs show promising results. 2015) Particularly for BN and BED, these changes are sim-
(Brewerton et al., 2022; Brewerton et al., 2021) Ketamine ilar to those seen in addiction. (Avena and Bocarsly, 2012)
and classic psychedelics may also act as “helioscopes” and Psychedelics have thus far shown promising results in tri-
show some potential in the treatment of trauma-related als focused on alcoholism and smoking cessation, and they
psychopathology. (Feder et al., 2021; Anderson et al., 2020) are theorized to help with addiction recovery in gen-
Relatedly, people with EDs who attended ayahuasca cer- eral. (Bogenschutz et al., 2015; Bogenschutz et al., 2022;
emonies have reported positive effects on trauma-related Johnson et al., 2017; Sessa et al., 2021)
symptomatology. Several participants reported more insight One small trial suggested that psilocybin might be useful
into the root causes of their psychological problems, includ- in the treatment of OCD, (Moreno et al., 2006) another
ing previous traumatic experiences. (Lafrance et al., 2017; common comorbidity with EDs. There is also some ev-
Renelli et al., 2018) They also reported that ayahuasca idence for ketamine’s efficacy in OCD. (Sharma et al.,
helped them to deal with difficult emotions. (Renelli et al., 2020; Rodriguez et al., 2013) One case report of ketamine
2018) treatment for BN also described resolution of compulsory
symptoms. (Ragnhildstveit et al., 2021) However, these
results are very preliminary and it remains to be seen
3.5. Improvements in co-morbid disorders and whether psychedelics truly have the potential to treat OCD
general therapeutic factors symptoms.
The potential for treating multiple co-morbid disorders
Comorbid disorders are more common than not in peo- suggests that psychedelics have some degree of trans-
ple with EDs, and they are strong predictors of mortal- diagnostic efficacy, similar to psychotherapy. (Kočárová
ity. (J Arcelus et al., 2011; Hambleton et al., 2022) Apart et al., 2021) It is thus plausible that they facilitate general
from trauma history and PTSD, discussed above, EDs are processes of therapeutic change, in addition to mechanisms
often comorbid with depression and anxiety, and PAT may specific to EDs. Based on data from in-person psychother-
be able to address these disorders in addition to spe- apy, Klaus Grawe proposed five general mechanisms of
cific ED symptoms. (Gukasyan et al., 2022; Borgland and therapeutic change which have been widely influential and
Neyens, 2022) Several clinical trials with psilocybin and LSD map particularly well onto PAT. (Grawe, 1997) Grawe con-
have shown promising results in the treatment of depres- cluded that the therapeutic alliance, resource activation,

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 A. Calder, S. Mock, N. Friedli et al.

Table 3 Typical aspects of three categories of eating disorders which may cause safety concerns or contraindicate psychedelic-
assisted therapy.
Average age of onset Anorexia Nervosa Bulimia Nervosa Binge Eating Disorder
Under 18 Under 18 –
Body weight Low body weight or – Obesity-related
refeeding syndrome may be hypertension,
present cardiovascular disease may
be present
Common comorbidities Bipolar disorder Bipolar disorder, personality Bipolar disorder
(Diagnostic and statistical disorders
manual of mental
disorders: DSM-5TM 2013)
Medication interactions Serotonergic medications Serotonergic medications Serotonergic medications
Common psychedelic side – Nausea and vomiting –
effects

clarification (understanding the root of one’s psychological in addition to general safety guidelines for clinical use
problems), problem actuation (emotional experience of of psychedelics (see Johnson et al., 2008 for a review
one’s problems), and mastery (reinforcement of appropri- (Johnson et al., 2008)).
ate coping methods) were important drivers of therapeutic One of these considerations is the typical age of peo-
change. Their importance has been supported by studies ple with EDs. ED prevalence increases by the age of 14,
with diverse patient groups, including those which included with a median age of onset of 17 for AN, 16 for BN, and
people with EDs. (Mander et al., 2013) 21 for BED, and early intervention is critical. (Udo and
Introducing psychedelics into therapy may both pro- Grilo, 2018) According to preliminary data from a survey of
mote these general mechanisms of change and solidify naturalistic psychedelic use, younger age may be a risk fac-
their impact via effects on neuroplasticity. The first mech- tor for persisting perceptual symptoms in the weeks after a
anism, the therapeutic alliance, can be strengthened by psychedelic experience. (Zhou et al.) Though psychedelics
psychedelics via positive effects on empathy, trust, and so- may be no more harmful than alternative psychiatric med-
ciality. (Dolder et al., 2016; Oehen and Gasser, 2022) Re- ications given to younger age groups, the lack of data on
garding resource activation, people have often described their long-term effects on cognitive development should
discovering new personal strengths and motivations after warrant caution.
psychedelic experiences, (Mander et al., 2013; Oehen and Additionally, dangerously low or high body weight may in-
Gasser, 2022) and this theme has appeared in interviews crease the risk for certain adverse effects. People with AN
with people with EDs as well. (Lafrance et al., 2017) Re- in particular may have a dangerously low body weight, rais-
flecting Grawe’s concept of clarification, many people de- ing concerns about medical stability and dosing. Medical in-
scribe an improved understanding of their problems fol- stability can result from low body weight or from refeeding
lowing psychedelic experiences, and this is thought to be syndrome, comprising abnormal electrolyte concentrations
a key mechanism of PAT. (Peill et al., 2022) Additionally, and cardiac, hepatic, or renal dysfunction. (Zipfel et al.,
people commonly report extremely emotional experiences 2015) Recent, rapid weight loss can also be a sign of
of their problems during PAT, often accompanied by the re- instability. Medical stability should be closely monitored
lease of suppressed or “forbidden” emotions; this is akin to due to the risk that psychedelics could exacerbate some
Grawe’s idea of problem actuation. (Roseman et al., 2019; of these problems, with some substances perhaps riskier
Gasser et al., 2015) Finally, PAT may be able to reinforce than others. On the other hand, people with BED are 3–
appropriate coping strategies by promoting acceptance of 6 times more likely to suffer from obesity than the gen-
difficult experiences over avoidance. (Wolff et al., 2020) It eral population, and this brings other challenges. (McCuen-
may thus be particularly suited to disorders characterized Wurst et al., 2018) Obesity raises the risk for hyperten-
by avoidance-related behaviors, which would include EDs sion and other cardiovascular problems, which are often
and many of their common comorbidities. an exclusion criterion in clinical trials with psychedelics
due to concerns about increased heart rate and blood pres-
sure. (Borgland and Neyens, 2022; Johnston et al., 2022)
4. Safety considerations Additionally, while classic psychedelics do not need to be
dosed according to body weight, MDMA effects do depend
Psychedelics have a favorable safety profile when used in on weight. (Studerus et al., 2021; Spriggs et al., 2022) Many
controlled settings, and toxicity is rare even in uncon- studies with MDMA have thus far used a standard dose with-
trolled settings. (Nichols and Grob, 2018; AC. Parrott, 2012; out accounting for body weight, which could result in un-
AC. Parrott, 2012; Thomas et al., 2017; Mithoefer et al., expectedly intense effects for those who are underweight
2019) Nevertheless, there may be specific safety consid- or relatively weak effects for those who are overweight.
erations relevant to treating people with EDs (Table 3), (JM Mitchell et al., 2021; Mithoefer et al., 2018)

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Certain comorbidities of EDs also present challenges and 5. Conclusion and outlook
may make PAT unwise, or at least justify extreme caution.
There is some concern that psychedelics could exacer- Preliminary evidence suggests that PAT could be bene-
bate mania in bipolar disorder due to its partially shared ficial in the treatment of AN and BN, as well as sev-
etiology with psychosis. (Bosch et al., 2022) Additionally, eral common comorbidities, presenting a clear rationale
people with comorbid personality disorders may not be for future research. Specifically, preliminary studies sup-
able to benefit from PAT without specialist care because of port more research into therapy with psilocybin, ke-
difficulty maintaining trust and a stable therapeutic al- tamine, and ayahuasca for AN, ketamine and ayahuasca
liance. (Bender, 2005) for BN, and MDMA for EDs associated with trauma-related
Medication interactions must also be considered. Though pathology.
clinical trials often exclude people who are taking addi- PAT may improve symptoms of EDs by both addressing
tional medications, real-world clinical practice (currently specific ED symptoms and promoting general therapeutic
limited to restricted medical use programs (Oehen and factors. Previous accounts of psychedelic use in people
Gasser, 2022)) must consider the risks and benefits of con- with EDs suggest that psychedelics may improve distorted
tinuing or stopping medications. The risk of serotonin tox- body image, normalize maladaptive reward processing, re-
icity, in particular, may be substantial and has not yet duce behavioral and cognitive rigidity, and aid in trauma
been fully explored. Classic psychedelics share activa- processing. Furthermore, psychedelics may promote gen-
tion of 5-HT2A receptors, and MDMA also has serotoner- eral therapeutic factors that are helpful in recovering from
gic activity. (Nichols, 2016) EDs and many of their com- avoidance-related psychological disorders, including both
mon comorbidities are often managed with psychotropics EDs and common comorbidities. Psychedelics’ ability to re-
that affect serotonergic neurotransmission, including SSRIs, lax higher order beliefs may account for some of this, as may
serotonin norepinephrine reuptake inhibitors, tricyclic an- their ability to promote acceptance of difficult thoughts
tidepressants, monoamine oxidase inhibitors (MAOIs), bus- and emotions. Changes arising during or shortly after a
pirone, trazodone, mirtazapine and atypical antipsychotics. psychedelic experience may additionally have a lasting im-
(Davis and Attia, 2017) While SSRIs appear to be safe pact on the brain via psychedelics’ effects on cortical neu-
when combined with classic psychedelics, (Becker et al., roplasticity.
2021) many other drug combinations have not been ade- Given preliminary results and plausible therapeutic
quately tested. In general, serotonin agonists such as classic mechanisms, there is a clear rationale for future studies
psychedelics, appear to have a lower risk for development into PAT for EDs. Future research would benefit from larger,
of serotonin toxicity. (Malcolm and Thomas, 2021) However, controlled trials investigating the safety and efficacy of PAT
serotonin releasing agents such as MDMA can precipitate with different substances for different ED diagnoses. In par-
serotonin toxicity when combined with other drugs, for ex- ticular, it is still unclear whether specific psychedelic sub-
ample MAOIs. (Pilgrim et al., 2012) stances are better suited to certain patient groups. It is pos-
Because of this potential risk, careful monitoring of sible, for example, that MDMA may be particularly suitable
diagnostic criteria for serotonin toxicity should be con- for those with a history of trauma. There is also a rationale
sidered with people with EDs on serotonergic medica- for better inclusion of people with BED, because despite
tions. Serotonin-related adverse reactions occur along commonalities with BN, BED has been far less researched in
a spectrum from mild symptoms to a severe and connection with PAT. Future trials should also make a point
life-threatening reaction encompassing neuroexcitation, to record safety-related outcomes, taking into considera-
changes in mental status, and instability in the car- tion that safety concerns may vary with different ED diag-
diovascular system. (Buckley et al., 2014; Ellahi, 2018) noses. Specifically, it would be useful to record data on the
Typical psychedelic drug effects may overlap with signs presence and impact of gastrointestinal side effects (e.g.
of mild serotonin toxicity, including altered mental sta- vomiting), weight-related side effects, and any lasting per-
tus, mydriasis, mild hyperthermia, changes in tempera- ceptual abnormalities, particularly in younger patients. Fi-
ture sensation, mild tremors or shaking, and gastroin- nally, trials comparing PAT to other ED treatments would be
testinal distress. (Nichols and Grob, 2018; AC. Parrott, valuable in order to determine the relative safety and effi-
2012; Mithoefer et al., 2011; F Holze et al., 2021) cacy of psychedelic treatments.
Transient signs of serotonergic drug ingestion which fol-
low the psychological trajectory of the psychedelic ex-
perience are to be expected, but these somatic symp- Role of funding source
toms are more persistent and intense with serotonin
toxicity. The study for supported by the University of Fribourg.
Finally, common side effects of psychedelics should be This research did not receive any specific grant from
considered in light of ED symptoms. Vomiting is a common funding agencies in the public, commercial, or not-for-profit
effect of ayahuasca in particular, though it can also occur sectors.
with other psychedelics. (Rossi et al., 2022) Though peo-
ple with BN in ayahuasca studies thus far have not found
this problematic, (Lafrance et al., 2017) samples have been Contribrutors
small and other psychedelics with lower rates of nausea and
vomiting may be more suitable for those with bingeing and Design of the study: GH and SM
purging behavior. Collection of data: AC, SM, NF, PP, GH
Interpretation of the data: AC, SM, NF, PP, GH

9
 A. Calder, S. Mock, N. Friedli et al.

Writing of the paper: AC, SM, NF, PP, GH cybin-assisted psychotherapy for alcohol use disorder. Front.
Pharmacol. 9, 100.
Bogenschutz, M.P., Ross, S., Bhatt, S., et al., 2022. Percentage of
heavy drinking days following psilocybin-assisted psychotherapy
Conflict of interest vs placebo in the treatment of adult patients with alcohol use
disorder: a randomized clinical trial. JAMA Psychiatry.
GH does not have a conflict of interest regarding the content Bohon, C., Stice, E., 2011. Reward abnormalities among women
of the paper. with full and subthreshold bulimia nervosa: a functional mag-
SM does not have a conflict of interest regarding the con- netic resonance imaging study. Int. J. Eat. Disord. 44 (7),
tent of the paper. 585–595.
AC does not have a conflict of interest regarding the con- Borgland, S.L., Neyens, D.M., 2022. Serotonergic psychedelic treat-
ment for obesity and eating disorders: potential expectations
tent of the paper.
and caveats for emerging studies. J. Psychiatry Neurosci. 47 (3),
NF does not have a conflict of interest regarding the con-
E218–E221.
tent of the paper. Bosch, O.G., Halm, S., Seifritz, E., 2022. Psychedelics in the treat-
PP does not have a conflict of interest regarding the con- ment of unipolar and bipolar depression. Int. J. Bipolar Disord.
tent of the paper. 10 (1), 18.
Breeksema, J.J., Niemeijer, A.R., Krediet, E., Vermetten, E., Scho-
evers, R.A., 2020. Psychedelic treatments for psychiatric dis-
orders: a systematic review and thematic synthesis of patient
Acknowledgements experiences in qualitative studies. CNS Drugs 34 (9), 925–946.
Brewerton, T.D., Lafrance, A., Mithoefer, M.C., 2021. The poten-
None. tial use of N-methyl-3,4-methylenedioxyamphetamine (MDMA)
assisted psychotherapy in the treatment of eating disorders co-
morbid with PTSD. Med. Hypotheses 146, 110367.
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