Single-Dose Psilocybin Therapy for Alcohol Use Disorder: Pharmacokinetics, Feasibility, Safety, and Efficacy in an Open-Label Study

A single 25 mg dose of psilocybin, given with preparation and integration sessions, reduced alcohol consumption in ten adults with severe alcohol use disorder. Heavy drinking days dropped by 37.5 percentage points over 12 weeks, and drinks per day decreased by 3.4 units. Participants also reported rapid and lasting reductions in craving and increased self-efficacy. Blood levels of the active metabolite psilocin varied widely between individuals, peaking from 14 to 59 µg per liter. The open-label study, which lacked a placebo group, suggests that even a single psilocybin session may be safe and effective, but larger randomized controlled trials are needed.

Study at a glance

Abstract

Abstract Background Psilocybin, a serotonin 2A receptor agonist with psychedelic properties, shows promise as a novel treatment for alcohol use disorder (AUD). While current studies involve two dosing sessions, the effects a single dose have not been investigated. Aims To investigate the pharmacokinetics, feasibility, safety, and efficacy of single-dose psilocybin therapy in AUD. Methods This open-label, single-group study investigated single-dose psilocybin therapy in ten treatment-seeking adults (eight men and two women; median age 44 years) with severe AUD. The treatment involved two preparation sessions, a high-dose psilocybin session (25 mg), and two integration sessions. Pharmacokinetics were determined by noncompartmental analysis, and changes in alcohol consumption, craving and self-efficacy, were assessed with a linear mixed model. Results Notable between-participant pharmacokinetic variations were observed, with peak plasma psilocin concentrations ranging from 14-59 µg/L. Alcohol consumption significantly decreased over the 12 weeks following psilocybin administration. Heavy drinking days were reduced by 37.5 percentage points (95% CI, -61.1, -13.9, p = 0.005), and drinks per day decreased by 3.4 units (95% CI: -6.5, -0.3), p = 0.035). This was corroborated by reports of rapid and sustained reductions in craving and increases in self-efficacy. Conclusions Despite pharmacokinetic variations, a single 25 mg psilocybin dose was safe and effective in reducing alcohol consumption in AUD patients. Larger randomised, placebo-controlled, single-dose AUD trials are warranted. Funding This work was supported by The Novo Nordisk Foundation (NNF19OC0058412), The Lundbeck Foundation (R-355-2020-945), The Health Foundation(21-B-0358) and The Ivan Nielsen Foundation. Clinical trial registration: NCT05347849