Single-dose psilocybin therapy for alcohol use disorder: Pharmacokinetics, feasibility, safety and efficacy in an open-label study

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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.

OriginalsprogEngelsk
TidsskriftJournal of psychopharmacology (Oxford, England)
Antal sider13
ISSN0269-8811
DOI
StatusE-pub ahead of print - 2025

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