Psilocybin-assisted therapy for relapse prevention in alcohol use disorder: a phase 2 randomized clinical trial
This double-blind randomised clinical trial (n=37) found that a single dose of psilocybin (25mg) with brief psychotherapy did not significantly reduce alcohol relapse rates or consumption compared to placebo in patients with alcohol use disorder (AUD) at 4-week or 6-month follow-up, though psilocybin participants reported additional reductions in craving and temptation to drink, suggesting larger trials are needed to evaluate this approach for severely affected patients.
Authors
- Erich Seifritz
- Franz Vollenweider
- Katrin Preller
Published
Abstract
Background
Despite the promising therapeutic effects of psilocybin, its efficacy in preventing relapse after withdrawal treatment for alcohol use disorder (AUD) remains unknown. This study aims to assess whether a single dose of psilocybin combined with brief psychotherapy could reduce relapse rates and alcohol use in AUD patients.
Methods
This single-center, double-blind, randomized clinical trial was conducted in Switzerland. We recruited participants with AUD between June 8, 2020, and August 16, 2023 who completed withdrawal treatment within six weeks prior to enrollment. Participants were randomized (1:1) to receive either a single oral dose of psilocybin (25 mg) or placebo (mannitol), combined with brief psychotherapy. The primary outcomes were abstinence and mean alcohol use at 4-week follow-up. Participants completed the timeline followback to assess daily alcohol use.
Findings
We included 37 participants who completed the 4-week follow-up (female:male = 14:23; psilocybin = 18, placebo = 19) in the analysis. There were no significant differences between groups in abstinence duration (p = 0.55, psilocybin mean = 16.80 days, 95% CI: 14.31-19.29; placebo mean = 13.80 days, 95% CI: 10.97-16.63; Cohen’s d = 0.151) or mean alcohol use per day (p = 0.51, psilocybin: median = 0.48 standard alcohol units, range: 0-3.99, placebo: median = 0.54 standard alcohol units, range: 0-5.96; Cohen’s d = 0.11) at 4-week or 6-month follow-up (abstinence: Cohen’s d = 0.10, alcohol use: Cohen’s d = 0.075). Participants in both groups reported reduced craving and temptation to drink alcohol after the dosing visit, with an additional reduction observed in the psilocybin group. Thirteen adverse events occurred in the psilocybin and seven in the placebo group. One serious adverse event occurred in the psilocybin and four in the placebo group, all related to inpatient withdrawal treatments.
Interpretation
A single dose of psilocybin combined with five psychotherapy sessions may not be sufficient to reduce relapse rates and alcohol use in severely affected AUD patients following withdrawal treatment. However, given the limited sample size of our study, larger trials are needed in the future to confirm these findings.
Research Summary of 'Psilocybin-assisted therapy for relapse prevention in alcohol use disorder: a phase 2 randomized clinical trial'
Introduction
Harmful alcohol use remains a leading global health risk, and alcohol use disorder (AUD) is typified by repeated cycles of abstinence, withdrawal and relapse. Existing pharmacotherapies such as naltrexone and acamprosate reduce drinking in some patients but relapse rates remain high, with at least 60% of treated individuals returning to drinking within six months in typical samples. Psychedelic compounds, notably psilocybin, have re-emerged in psychiatric research because of early clinical signals and more recent trials suggesting reductions in heavy drinking and improvements in mood when combined with psychotherapy, but no randomized controlled trial (RCT) at current methodological standards had tested psilocybin specifically for relapse prevention after withdrawal treatment in AUD. Rieser and colleagues designed this Phase II RCT to test whether a single oral 25 mg dose of psilocybin, delivered with a brief psychotherapeutic regimen, could prolong abstinence and reduce alcohol consumption in patients who had completed withdrawal treatment. The primary outcomes were duration of abstinence and mean alcohol use during the 4-week period after dosing; secondary outcomes included craving, self-efficacy, psychopathology measures and safety. The trial therefore addresses a distinct clinical question: can a single psilocybin-assisted treatment session prevent relapse in recently withdrawn, moderately to severely affected AUD patients?
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Rieser, N. M., Bitar, R., Halm, S., Rossgoderer, C., Gubser, L. P., Thévenaz, M., Kreis, Y., von Rotz, R., Nordt, C., Visentini, M., Moujaes, F., Engeli, E. J., Ort, A., Seifritz, E., Vollenweider, F. X., Herdener, M., & Preller, K. H. (2025). Psilocybin-assisted therapy for relapse prevention in alcohol use disorder: a phase 2 randomized clinical trial. eClinicalMedicine, 82, 103149. https://doi.org/10.1016/j.eclinm.2025.103149
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Bogenschutz, M. P., Ross, S., Bhatt, S. R. et al. · JAMA Psychiatry (2022)
Rieser, N. M., Herdener, M. ;., Preller, K. H. · Current Topics in Behavioral Neurosciences (2021)
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Griffiths, R. R., Johnson, M. W. · Journal of Psychopharmacology (2016)
Studerus, E., Gamma, A., Vollenweider, F. X. · PLOS ONE (2010)
Meinhardt, M. W., Güngör, C., Skorodumov, I. et al. · Neuropsychopharmacology (2020)
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Jacobs, E., Zahid, Z., Hinkle, J. et al. · BMJ (2026)
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Marsden, J., Kelleher, M., Dunbar, F. et al. · Addiction (2025)
Luquiens, A., Belahda, D., Graux, C. et al. · Addiction (2025)
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