Single-dose psilocybin therapy for alcohol use disorder: Pharmacokinetics, feasibility, safety and efficacy in an open-label study
Dea Siggaard Stenbæk, Emil Deleuran Poulsen, Marie Katrine Klose Nielsen, Sys Stybe Johansen, Mathias E. Jensen, Catharina Messell, Tibor V. Varga, Patrick M. Fisher, Nora D. Volkow, Gitte M. Knudsen, Anders Fink‐jensen
Journal of Psychopharmacology February 28, 2025 DOI: 10.1177/02698811251319457 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label, single-group study Randomized Placebo-controlled Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | Treatment-seeking adults with severe alcohol use disorder |
| Intervention | Psilocybin |
| Dose | 25 mg |
| Duration | 12-week follow-up |
| Topics | Addiction Psilocybin |
| Keywords | Craving Pharmacokinetics Dosing Placebo Pharmacology Crossover study Hallucinogen |
| Citations | 15 |
| Registration | NCT04718792 |
| Key points | A single 25 mg dose of psilocybin significantly reduced heavy drinking days and drinks per day over 12 weeks in adults with severe alcohol use disorder. |
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