Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study

This open-label study (n=10) combined therapy with two psilocybin (21-28mg) sessions and showed a significant reduction in (heavy) drinking days up to 36 weeks later.


“Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants’ responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5–8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms.”

Authors: Michael P. Bogenschutz, Alyssa A. Forcehimes, Jessica A. Pommy, Claire E. Wilcox, P. C. Riberio Barbosa & Rick J. Strassman


This proof-of-concept study shows what promise psychedelics offer for the treatment of addiction. Many studies (with thousands of participants) were done in the 1960s. Now in 2020, we are awaiting the publication of an even more impressive report on MDMA and alcohol dependence by Ben Sessa and colleagues.

A qualitative content analysis of clinical sessions in this study was done by Nielson and colleagues (2018).

Participants received psilocybin on two occasions. The first time it was 0.3mg/kg (21mg/70kg), the second time this was raised to 0.4mg (28mg) unless otherwise indicated.

This study was supported, in part, by the Heffter Research Institute.



In the 1950s and early 1970s there was extensive research on the use of LSD and other classic hallucinogens in the treatment of addiction, existential distress in dying patients, pain, and other conditions. A recent meta-analysis showed that LSD treatment of alcoholism was effective.

Psilocybin, a classic hallucinogen, has shown promising results in clinical trials in patients with anxiety related to advanced cancer.

Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. A proof-of-concept study of psilocybin in alcohol-dependent participants showed that abstinence increased significantly following psilocybin administration and was largely maintained at follow-up to 36 weeks.

Biological mechanisms

Although classic hallucinogens bind to many serotonin receptor subtypes and other receptors, their psychoactive effects appear to depend primarily on their actions at 5HT2A receptors.

The relationship between 5HT2A receptor activity and alcoholism or alcohol exposure is less clear, but increased activity in 5HT2A-mediated pathways increases cue response and impulsivity in rat models of cocaine addiction. However, two large trials of the 5HT2A antagonist ritanserin failed to demonstrate beneficial effects in people with alcohol dependence.

Animal studies suggest that acute activation of 5HT2A receptors could activate intracellular signaling pathways resulting in persisting changes in cellular structure and synapses.

Psychological models of psychedelic treatment

Clinical work with hallucinogens has emphasized the central role of the altered state of consciousness experienced during the drug’s acute effects.


The psychosocial intervention consisted of 12 sessions: seven sessions of Motivational Enhancement Therapy (MET), three preparation sessions, two debriefing sessions, and four sessions after the second psilocybin session. Three of the authors served as study therapists.

Participants ingested a single gelatin capsule of psilocybin followed by 4 ounces of water, and remained under observation for at least 8 hours following psilocybin administration. They completed questionnaires and assessments, and a brief clinical interview was performed, including mental status exam.

For the first psilocybin session, participants received 0.3 mg/kg. For the second session, the dose was increased to 0.4 mg/kg unless the participant was unwilling to increase the dose, experienced adverse effects during the first session, or reported a “complete” mystical experience during the first session.

Safety assessment was performed at each visit and frequent readings were taken during psilocybin sessions. Adverse events were collected on an AE case report form.

Statistical analysis and power

This open-label pilot study tested two hypotheses about changes in drinking behavior, consequences of drinking, and psychological outcomes. The study had power of 0.803 to detect prepost changes of effect size d = 1.0, with 0.05 (2-tailed) prior to correction for multiple comparisons.


70 individuals were screened for the study, of whom 10 were included. Improvement in drinking consequences, craving, self-efficacy, and motivation were not significant during the first 4 weeks of participation, but were significantly lower at all follow-up points following the first psilocybin session.

treatment response

Acute effects of psilocybin were quite variable, and correlations were observed between acute effects and changes in drinking behavior, craving, and self-efficacy.

Treatment-related adverse events

Five participants reported mild headaches, one participant had nausea and diarrhea, and one participant reported insomnia following a psilocybin session. No participant required medication for blood pressure, anxiety, or other psychiatric symptoms.


The response of our alcohol-dependent participants to psilocybin was qualitatively similar to that reported in other samples, although subjective response was highly variable among participants and numerically weaker on average for some of the measures than that reported in normal volunteers at comparable doses.

Participants showed significant improvement in drinking and psychological measures relevant to drinking following the administration of psilocybin. The relationship between intensity of the acute drug effects and clinical outcomes supports the concept that psilocybin may produce lasting benefits in alcohol use disorder.

Study details

Compounds studied

Topics studied
Addiction Alcohol Use Disorder

Study characteristics
Original Open-Label Within-Subject

10 Humans


Authors associated with this publication with profiles on Blossom

Michael Bogenschutz
Dr. Michael P. Bogenschutz is a Professor in the Department of Psychiatry at NYU Grossman School of Medicine who specializes in treating addiction and anxiety disorders.

Rick Strassman
Rick Strassman is an associate professor of psychiatry and best known for his DMT research in the late 1990s and his subsequent book DMT: The Spirit Molecule.


Institutes associated with this publication

University of New Mexico
This company doesn't have a full profile yet, it is linked to a clinical trial.

Heffter Research Institute
The Heffter Research Institute has been advancing psychedelics (psilocybin) as medicines since 1993.

Compound Details

The psychedelics given at which dose and how many times

Psilocybin 21 - 28
mg | 2x

Linked Research Papers

Notable research papers that build on or are influenced by this paper

Clinical interpretations of patient experience in a trial of psilocybin-assisted psychotherapy for alcohol use disorder
This study describes the treatment trajectories of (n=3) participants administered with psilocybin (25-40mg/70kg) in a double-blind placebo-controlled clinical trial investigating the treatment of alcoholism (AUD). These participants experienced acute and lasting alterations in their perceptions of self, in the quality of their baseline consciousness, and in their relationship with alcohol. Increased mindfulness, and control over choices, were also reported following the treatment. 

The psychedelic debriefing in alcohol dependence treatment: illustrating key change phenomena through qualitative content analysis of clinical sessions
This open-label pilot study (n=10) of psilocybin-assisted treatment of alcohol dependence (21mg/70kg) presents a qualitative content analysis of the 17 debriefing sessions conducted in the pilot study, which occurred the day after corresponding psilocybin medication sessions. Participants articulated a series of key phenomena related to change in drinking outcomes and acute subjective effects of psilocybin.

Linked Clinical Trial

Effects and Therapeutic Potential of Psilocybin in Alcohol Dependence
This trial is an open-label pilot study (N = 10) designed to assess the effects of psilocybin in alcohol dependent participants, demonstrate the feasibility of the integrated behavioral/pharmacologic intervention, and provide preliminary outcome and safety data.

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