Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder

This double-blind, active placebo-controlled study (n=95) finds that psilocybin (2x, 25-40mg/70kg) significantly reduced the number of heavy drinking days (10% versus 24% in the placebo group) in the 32-week follow-up period. The trial is the first to test psilocybin for alcoholism (alcohol use disorder, AUD) in a double-blind study.


Importance Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown.

Objective To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy.

Design, Setting, and Participants In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following the first dose of study medication. The study was conducted at 2 academic centers in the US. Participants were recruited from the community between March 12, 2014, and March 19, 2020. Adults aged 25 to 65 years with a DSM-IV diagnosis of alcohol dependence and at least 4 heavy drinking days during the 30 days prior to screening were included. Exclusion criteria included major psychiatric and drug use disorders, hallucinogen use, medical conditions that contraindicated the study medications, use of exclusionary medications, and current treatment for AUD.

Interventions Study medications were psilocybin, 25 mg/70 kg, vs diphenhydramine, 50 mg (first session), and psilocybin, 25-40 mg/70 kg, vs diphenhydramine, 50-100 mg (second session). Psychotherapy included motivational enhancement therapy and cognitive behavioral therapy.

Main Outcomes and Measures The primary outcome was percentage of heavy drinking days, assessed using a timeline followback interview, contrasted between groups over the 32-week period following the first administration of study medication using multivariate repeated-measures analysis of variance.

Results A total of 95 participants (mean [SD] age, 46 [12] years; 42 [44.2%] female) were randomized (49 to psilocybin and 46 to diphenhydramine). One participant (1.1%) was American Indian/Alaska Native, 5 (5.3%) were Black, 16 (16.8%) were Hispanic, and 75 (78.9%) were non-Hispanic White. Of the 95 randomized participants, 93 received at least 1 dose of study medication and were included in the primary outcome analysis. Percentage of heavy drinking days during the 32-week double-blind period was 9.7% for the psilocybin group and 23.6% for the diphenhydramine group, a mean difference of 13.9%; (95% CI, 3.0–24.7; F1,86 = 6.43; P = .01). Mean daily alcohol consumption (number of standard drinks per day) was also lower in the psilocybin group. There were no serious adverse events among participants who received psilocybin.

Conclusions and Relevance Psilocybin administered in combination with psychotherapy produced robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy. These results provide support for further study of psilocybin-assisted treatment for AUD.

Authors: Michael P. Bogenschutz, Stephen Ross, Snehal Bhatt, Tara Baron, Alyssa A. Forcehimes, Eugene Laska, Sarah E. Mennenga, Kelley O’Donnell, Lindsey T. Owens, Samantha Podrebarac, John Rotrosen, J. Scott Tonigan & Lindsay Worth

Study details

Compounds studied

Topics studied
Alcohol Use Disorder Addiction

Study characteristics
Original Placebo-Controlled Active Placebo Double-Blind Randomized

95 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.


Institutes associated with this publication

NYU Langone Health
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.

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

Compound Details

The psychedelics given at which dose and how many times

Psilocybin 25 - 40
mg | 2x

Linked Research Papers

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Linked Clinical Trial

A Double-Blind Trial of Psilocybin-Assisted Treatment of Alcohol Dependence
Several lines of evidence suggest that classic hallucinogens such as psilocybin can facilitate behaviour change in addictions such as alcohol dependence. The investigation is a multi-site, double-blind, active-controlled trial (n=95, 47 per group) contrasting the acute and persisting effects of psilocybin to those of diphenhydramine (placebo) in the context of outpatient alcoholism treatment.

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