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

Mathias E. Jensen, Dea Siggaard Stenbæk, Catharina Messell, Emil Deleuran Poulsen, Tibor V. Varga, Patrick M. Fisher, Marie Katrine Klose Nielsen, Sys Stybe Johansen, Nora D. Volkow, Gitte M. Knudsen, Anders Fink‐jensen

Research Square August 23, 2024 preprint DOI: 10.21203/rs.3.rs-4947184/v1 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Open-label, single-group study Randomized Placebo-controlled
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 Pharmacokinetics Pharmacology
Citations 1
Registration NCT05347849
Key points A single 25 mg dose of psilocybin was associated with significant reductions in heavy drinking days and drinks per day over 12 weeks in adults with severe alcohol use disorder.

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

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