Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder
In a double‑blind randomised clinical trial of adults with alcohol dependence receiving psychotherapy, two high‑dose psilocybin sessions reduced the percentage of heavy drinking days over 32 weeks to 9.7% versus 23.6% with active placebo (mean difference 13.9 percentage points; 95% CI 3.0–24.7; P = .01). Psilocybin was well tolerated with no serious adverse events, supporting further study of psilocybin‑assisted therapy for alcohol use disorder.
Authors
- Michael Bogenschutz
- Stephen Ross
- Susan Mennenga
Published
Abstract
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, 3 (3.2%) were Asian, 4 (4.2%) were Black, 14 (14.7%) 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; F 1,86 = 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.
Research Summary of 'Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder'
Introduction
Interest in psilocybin and other classic psychedelics for neuropsychiatric disorders, including substance use disorders, has grown over the past two decades. The authors note that these drugs act at serotonin 2A receptors and produce downstream changes that may enhance plasticity at multiple levels (neuronal structure, networks, cognition, affect, and behaviour), while acknowledging that some therapeutic effects may not be solely mediated by serotonin 2A activation. Prior controlled research from the 1960s suggested benefit of LSD for alcohol dependence, and a 2015 open‑label study reported large reductions in drinking after moderately high doses of psilocybin, but controlled evidence for psilocybin in alcohol use disorder (AUD) remained lacking. This multisite randomized clinical trial therefore set out to evaluate whether two administrations of high‑dose psilocybin, given within a manualised psychotherapy programme, would reduce the percentage of heavy drinking days (PHDD) in adults with AUD compared with an active placebo (diphenhydramine) plus the same psychotherapy. The report covers drinking outcomes during the 32‑week double‑blind phase following the first medication session, presenting efficacy and safety data and situating results relative to earlier findings in psychedelic research.
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Study Details
- Study Typeindividual
- Journal
- Compound
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- APA Citation
Bogenschutz, M. P., Ross, S., Bhatt, S., Baron, T., Forcehimes, A. A., Laska, E., Mennenga, S. E., O’Donnell, K., Owens, L. T., Podrebarac, S., Rotrosen, J., Tonigan, J. S., & Worth, L. (2022). Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder. JAMA Psychiatry, 79(10), 953. https://doi.org/10.1001/jamapsychiatry.2022.2096
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