Psilocybin for alcohol use disorder: Rationale and design considerations for a randomized controlled trial

Area of Science:

• Neuroscience
• Psychiatry
• Clinical Psychology

Background:

• Classic psychedelics, like psilocybin, show potential for facilitating behavior change in substance use disorders.
• Psilocybin acts as a 5-HT2A receptor agonist or partial agonist.
• Alcohol dependence is a significant public health concern with limited effective treatments.

Purpose of the Study:

• To assess the efficacy of psilocybin-assisted psychotherapy in alcohol-dependent individuals.
• To evaluate the safety and tolerability of psilocybin in this population.
• To describe the protocol and rationale for a multi-site, double-blind, randomized controlled trial.

Main Methods:

• A multi-site, double-blind, randomized controlled trial (RCT) involving 96 alcohol-dependent volunteers.
• Participants received a 12-week psychotherapy platform with two dosing sessions of either oral psilocybin (25 mg/70 kg) or an active placebo (diphenhydramine 50 mg).
• Dosing sessions were at weeks 4 and 8, with potential dose adjustments based on initial response. Follow-up extended to week 36.

Main Results:

• The primary outcome was the proportion of heavy drinking days between week 4 and week 36.
• Secondary outcomes included safety, drinking patterns, craving, self-efficacy, and acute effects.
• Exploration of moderators and mediators of treatment outcomes was also planned.

Conclusions:

• This study protocol is designed to rigorously evaluate psilocybin-assisted psychotherapy for alcohol dependence.
• The findings will contribute to understanding the potential of psychedelic-assisted therapies for substance use disorders.
• The trial aims to provide crucial data on the effectiveness and safety of this novel treatment approach.