Psilocybin-assisted therapy for severe alcohol use disorder: protocol for a double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial.

A proposed clinical trial will test whether adding psilocybin-assisted therapy to inpatient rehabilitation for severe alcohol use disorder is feasible and effective. In a double-blind, randomized, placebo-controlled phase II trial, 62 participants aged 21–64 will receive either a high dose (30 mg) or an active placebo dose (5 mg) of psilocybin alongside a brief psychotherapy based on acceptance and commitment therapy. The main outcome is the difference in heavy drinking days from baseline to four weeks after hospital discharge. Secondary outcomes include drinking behavior up to six months, mental health symptoms, neuroplasticity, and cognitive mechanisms. The trial is registered as EudraCT 2022-002369-14 and NCT06160232.

Study at a glance

Abstract

A significant number of individuals with alcohol use disorder remain unresponsive to currently available treatments, which calls for the development of new alternatives. In parallel, psilocybin-assisted therapy for alcohol use disorder has recently yielded promising preliminary results. Building on extant findings, the proposed study is set to evaluate the feasibility and preliminary clinical efficacy of psilocybin-assisted therapy when incorporated as an auxiliary intervention during inpatient rehabilitation for severe alcohol use disorder. Moreover, it intends to pinpoint the modifications in the two core neurocognitive systems underscored by dual-process models of addiction. In this double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial, 62 participants aged 21-64 years will be enrolled to undergo psilocybin-assisted therapy as part of a 4-week inpatient rehabilitation for severe alcohol use disorder. The experimental group will receive a high dose of psilocybin (30 mg), whereas the control group will receive an active placebo dose of psilocybin (5 mg), both within the context of a brief standardized psychotherapeutic intervention drawing from key elements of acceptance and commitment therapy. The primary clinical outcome is the between-group difference regarding the change in percentage of heavy drinking days from baseline to four weeks posthospital discharge, while safety and feasibility metrics will also be reported as primary outcomes. Key secondary assessments include between-group differences in terms of changes in (1) drinking behavior parameters up to six months posthospital discharge, (2) symptoms of depression, anxiety, trauma, and global functioning, (3) neuroplasticity and key neurocognitive mechanisms associated with addiction, and (4) psychological processes and alcohol-related parameters. The discussion outlines issues that might arise from our design. EudraCT 2022-002369-14 and NCT06160232.