Rieser Nathalie M, Bitar Raoul, Halm Simon, Rossgoderer Christina, Gubser Ladina P, Thévenaz Maeva, Kreis Yara, von Rotz Robin, Nordt Carlos, Visentini Monika, Moujaes Flora, Engeli Etna J E, Ort Andres, Seifritz Erich, Vollenweider Franz X, Herdener Marcus, Preller Katrin H
Department of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Lenggstrasse 31, Zurich 8032, Switzerland.
EClinicalMedicine. 2025 Mar 14;82:103149. doi: 10.1016/j.eclinm.2025.103149. eCollection 2025 Apr.
Despite the promising therapeutic effects of psilocybin, its efficacy in preventing relapse after withdrawal treatment for alcohol use disorder (AUD) remains unknown. This study aims to assess whether a single dose of psilocybin combined with brief psychotherapy could reduce relapse rates and alcohol use in AUD patients.
This single-center, double-blind, randomized clinical trial was conducted in Switzerland. We recruited participants with AUD between June 8, 2020, and August 16, 2023 who completed withdrawal treatment within six weeks prior to enrollment. Participants were randomized (1:1) to receive either a single oral dose of psilocybin (25 mg) or placebo (mannitol), combined with brief psychotherapy. The primary outcomes were abstinence and mean alcohol use at 4-week follow-up. Participants completed the timeline followback to assess daily alcohol use. The trial is registered on ClinicalTrials.gov (NCT04141501).
We included 37 participants who completed the 4-week follow-up (female:male = 14:23; psilocybin = 18, placebo = 19) in the analysis. There were no significant differences between groups in abstinence duration ( = 0.55, psilocybin mean = 16.80 days, 95% CI: 14.31-19.29; placebo mean = 13.80 days, 95% CI: 10.97-16.63; Cohen's = 0.151) or mean alcohol use per day ( = 0.51, psilocybin: median = 0.48 standard alcohol units, range: 0-3.99, placebo: median = 0.54 standard alcohol units, range: 0-5.96; Cohen's = 0.11) at 4-week or 6-month follow-up (abstinence: Cohen's = 0.10, alcohol use: Cohen's = 0.075). Participants in both groups reported reduced craving and temptation to drink alcohol after the dosing visit, with an additional reduction observed in the psilocybin group. Thirteen adverse events occurred in the psilocybin and seven in the placebo group. One serious adverse event occurred in the psilocybin and four in the placebo group, all related to inpatient withdrawal treatments.
A single dose of psilocybin combined with five psychotherapy sessions may not be sufficient to reduce relapse rates and alcohol use in severely affected AUD patients following withdrawal treatment. However, given the limited sample size of our study, larger trials are needed in the future to confirm these findings.
Swiss National Science Foundation under the framework of Neuron Cofund, Swiss Neuromatrix Foundation, and Heffter Young Investigator Fellowship Award.
尽管裸盖菇素具有良好的治疗效果，但其在酒精使用障碍（AUD）戒断治疗后预防复发方面的疗效仍不明确。本研究旨在评估单剂量裸盖菇素联合简短心理治疗是否能降低AUD患者的复发率和酒精使用量。
本单中心、双盲、随机临床试验在瑞士进行。我们招募了2020年6月8日至2023年8月16日期间患有AUD且在入组前六周内完成戒断治疗的参与者。参与者被随机（1:1）分配接受单剂量口服裸盖菇素（25毫克）或安慰剂（甘露醇），并联合简短心理治疗。主要结局是4周随访时的戒酒情况和平均酒精使用量。参与者完成时间线回溯以评估每日酒精使用情况。该试验已在ClinicalTrials.gov上注册（NCT04141501）。
我们纳入了37名完成4周随访的参与者（女性:男性 = 14:23；裸盖菇素组 = 18人，安慰剂组 = 19人）进行分析。两组在戒酒持续时间（t = 0.55，裸盖菇素组平均 = 16.80天，95%置信区间：14.31 - 19.29；安慰剂组平均 = 13.80天，95%置信区间：10.97 - 16.63；科恩d = 0.151）或4周或6个月随访时的每日平均酒精使用量（t = 0.51，裸盖菇素组：中位数 = 0.48标准酒精单位，范围：0 - 3.99，安慰剂组：中位数 = 0.54标准酒精单位，范围：0 - 5.96；科恩d = 0.11）方面无显著差异（戒酒情况：科恩d = 0.10，酒精使用情况：科恩d = 0.075）。两组参与者在给药访视后报告饮酒渴望和诱惑均有所降低，裸盖菇素组有额外降低。裸盖菇素组发生了13起不良事件，安慰剂组发生了7起。裸盖菇素组发生1起严重不良事件，安慰剂组发生4起，均与住院戒断治疗有关。
单剂量裸盖菇素联合五次心理治疗可能不足以降低严重受影响的AUD患者戒断治疗后的复发率和酒精使用量。然而，鉴于我们研究的样本量有限，未来需要更大规模的试验来证实这些发现。
瑞士国家科学基金会在神经元联合资助框架下、瑞士神经矩阵基金会以及赫夫特青年研究者奖学金。
