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