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

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.

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).

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.

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.