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

• Published in: BMC psychiatry Vol. 24; no. 1; pp. 77 - 15
• Main Authors: Vanderijst, Laetitia, Hever, Felix, Buot, Anne, Dauré, Charles, Benoit, Janaïna, Hanak, Catherine, Veeser, Johannes, Morgiève, Margot, Campanella, Salvatore, Kornreich, Charles, Mallet, Luc, Leys, Christophe, Noël, Xavier
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26.01.2024; BioMed Central; BMC
• Subjects: Abstinence; Acceptance and Commitment Therapy; Addictions; Alcohol Drinking; Alcohol use; Alcoholism; Alcoholism - drug therapy; Care and treatment; Clinical trial; Clinical trials; Clinical Trials, Phase II as Topic; Cognition; Complications and side effects; Development and progression; Double-Blind Method; Drinking behavior; Health aspects; Humanities and Social Sciences; Humans; LSD; Lysergic acid diethylamide; Mental disorders; Mental health; Mushrooms, Hallucinogenic; Neural plasticity; Placebos; Psilocybin; Psilocybin - therapeutic use; Psilocybin-assisted therapy; Psychedelic drugs; Psychic trauma; Randomized Controlled Trials as Topic; Rehabilitation; Serotonergic psychedelics; Severe alcohol use disorder; Treatment Outcome; Switzerland; Serotonergic psychedelics; Clinical trial; Psilocybin-assisted therapy; Severe alcohol use disorder; Psilocybin-assisted therapy Serotonergic psychedelics Clinical trial Severe alcohol use disorder
• ISSN: 1471-244X; 1471-244X
• DOI: 10.1186/s12888-024-05502-y

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.