Safety and Efficacy of Psilocybin-Assisted Therapy for Alcohol Use Disorder: Open-Label Extension of a Phase II Randomized Controlled Trial
Broc A. Pagni, Stephen Ross, Sarah E. Mennenga, Snehal Bhatt, Richard J. Zeifman, Petros Petridis, Brennan M. Carrithers, Lindsay Worth, Samantha K. Podrebarac, Lindsey T. Owens, Kelley C O'Donnell, Daniel E. Roberts, Yuna Kim, Michael P. Bogenschutz
PsyArXiv March 26, 2026 preprint DOI: 10.31234/osf.io/7xfek_v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label extension of a Phase II randomized controlled trial Double-blind |
|---|---|
| Sample size | 59 |
| Population | Adults with alcohol use disorder |
| Interventions | Psilocybin psilocybin-assisted therapy |
| Dose | 25-40mg/70kg |
| Duration | Four-month follow-up |
| Topics | Addiction Psilocybin |
| Registration | NCT02061293 |
| Key findings | A single open-label psilocybin administration with four hours of therapy was well tolerated and produced short-term reductions in drinking: percent drinking days decreased at one month but returned to baseline by months two through four, with similar transient reductions among heavier baseline drinkers. Craving, abstinence self-efficacy, and treatment readiness improved one week after psilocybin in both prior blinded groups, with variable trajectories over follow-up. The authors suggest these short-term effects may reflect baseline floor effects, treatment resistance, lower treatment readiness and motivation, or fewer medication and therapy sessions. |
Abstract
Background: Psilocybin-assisted therapy (PAT) has shown promise for alcohol use disorder (AUD) in randomized controlled trials (RCTs). However, the effects of open-label administration following blinded treatment are unclear. Here, we present safety and efficacy data from an open-label extension of a Phase II RCT (NCT02061293) examining PAT for AUD.
Methods: Adults with AUD (N = 59) received a single administration of psilocybin (25-40mg/70kg) along with four total hours of therapy. Of this cohort, 30 participants had originally received psilocybin during the blinded phase of the RCT and 29 received active placebo (diphenhydramine). Mixed-Effects Models for Repeated Measures examined the effects of PAT on (a) alcohol consumption (percent heavy drinking [PHDD], drinks per day [DpD], and percent drinking days [PDD]), (b) alcohol craving, (c) abstinence self-efficacy, (d) and treatment readiness across a four-month follow-up.
Results: Psilocybin was well tolerated, with no serious adverse events. Across participants, PDD decreased at 1-month but returned to baseline by Months 2-4. Among those with higher baseline drinking, PHDD, DpD, and PDD showed similar transient reductions. Participants from both double-blind groups demonstrated improvements in craving, self-efficacy, and treatment readiness one week after psilocybin with variable trajectories over follow-up.
Discussion: Results suggest that a single administration of psilocybin in an open-label context may produce short-term improvements in alcohol use and core predictors of clinical change. Given long-lasting efficacy in the double-blind phase, it remains unclear if the short-term durability in the open-label extension is due to baseline floor effects, treatment resistance, lower treatment readiness and motivation, or fewer medication/therapy sessions.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Psilocybin-assisted therapy was safe and associated with sustained reductions in heavy drinking days over 32 weeks.
Synthesized
Comparable studies
Other randomized controlled trials on psilocybin for addiction, most cited first.