Safety and Efficacy of Psilocybin-Assisted Therapy for Alcohol Use Disorder: Open-Label Extension of a Phase II Randomized Controlled Trial

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.