Single-dose psilocybin therapy for alcohol use disorder: Pharmacokinetics, feasibility, safety and efficacy in an open-label study
Journal of Psychopharmacology – February 28, 2025
Source: OpenAlex
Summary
A single dose of the hallucinogen psilocybin significantly reduced alcohol consumption in adults with severe alcohol use disorder. Ten participants saw heavy drinking days drop by 37.5 percentage points and drinks per day decrease by 3.4 drinks over 12 weeks after a 25 mg dosing. Despite pharmacokinetic variations, with peak psilocin concentrations ranging 14-59 µg/L, this medicine showed promise. Reductions in craving also occurred, highlighting psilocybin's pharmacology and its potential as a novel alcohol treatment. This contributes to psychedelics and drug studies exploring neurotransmitter receptor influence on behavior.
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 of 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 10 treatment-seeking adults (8 men and 2 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 using a linear mixed model. Results: Notable between-participant pharmacokinetic variations were observed, with peak plasma psilocin concentrations ranging from 14 to 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 to −13.9, p = 0.005), and drinks per day decreased by 3.4 drinks (95% CI: −6.5 to −0.3, p = 0.03). 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. Clinical trial registration: https://clinicaltrials.gov/study/NCT04718792