Efficacy and safety of psilocybin-assisted therapy for alcohol use disorder: A systematic review and meta-analysis.

Background: Psilocybin-assisted therapy (PAT) has emerged as a promising intervention for alcohol use disorder (AUD), yet contemporary clinical evidence has not been systematically synthesized to validate its clinical utility and safety profile. Methods: Contemporary clinical trials of PAT for AUD were identified systematically from PubMed, PsycINFO, and Scopus by two independent reviewers. Random-effects meta-analyses were conducted to synthesize within-group pre–post changes and between-group differences from randomized controlled trials (RCTs). Primary outcomes included continuous drinking measures and abstinence rates; secondary outcomes included adverse events (AEs). Results: Six trials (N = 202) met inclusion criteria (3 RCTs). PAT produced significant within-group reductions across all drinking outcomes that were sustained at mid- to long-term follow-up (4–28 weeks). Compared to controls, psilocybin demonstrated moderate short-term advantages for drinks per day (standardized mean differences (SMD) = 0.48; p = 0.004), percent drinking days (SMD = 0.50; p = 0.009), and percent heavy drinking days (SMD = 0.39; p = 0.020). At mid- to long-term follow-up, only percent drinking days remained significantly superior (SMD = 0.41; p = 0.032). Psilocybin-treated patients had significantly higher odds of maintaining abstinence compared to controls (OR = 2.78; p = 0.029). AEs were predominantly mild and transient. Conclusions: Current evidence for PAT in AUD is mixed but suggests preliminary signals of efficacy for reducing alcohol consumption and increasing the odds of maintaining long-term abstinence. The intervention was well-tolerated with a favorable safety profile, supporting its potential as a novel treatment option.