Goodwin Guy M, Aaronson Scott T, Alvarez Oscar, Carhart-Harris Robin, Chai-Rees Jamie, Croal Megan, DeBattista Charles, Dunlop Boadie W, Feifel David, Hellerstein David J, Husain Muhammad I, Kelly John R, Kirlic Namik, Licht Rasmus W, Marwood Lindsey, Meyer Thomas D, Mistry Sunil, Nowakowska Ania, Páleníček Tomáš, Repantis Dimitris, Schoevers Robert A, Simmons Hollie, Somers Metten, Teoh Emma, Tsai Joyce, Wahba Mourad, Williams Sam, Young Allan H, Young Matthew B, Zisook Sidney, Malievskaia Ekaterina
Compass Pathfinder Ltd (a subsidiary of Compass Pathways plc), London, UK.
The Institute for Advanced Diagnostics and Therapeutics, Sheppard Pratt, Baltimore, Maryland, United States; University of Maryland School of Medicine, Department of Psychiatry, Baltimore, MD, United States.
J Affect Disord. 2025 Mar 1;372:523-532. doi: 10.1016/j.jad.2024.12.061. Epub 2024 Dec 18.
To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression.
For treatment-resistant depression, 233 participants received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a proprietary, pharmaceutical-grade synthesized psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.) with psychological support. The resulting psychedelic experience (Five-Dimensional Altered States of Consciousness questionnaire [5D-ASC] and Emotional Breakthrough Inventory [EBI]) were measured. These proximal variables and outcome 3 weeks post-administration (change in Montgomery-Åsberg Depression Rating Scale [MADRS]) were explored using correlation analysis.
The mean intensity of psychedelic effects was dose-related, but distributions of scores for different doses overlapped considerably. Depression response correlated with select aspects of the psychedelic experience overall and for individual doses. At the 25 mg dose, 5D-ASC dimensions Oceanic Boundlessness (Pearson correlation coefficient r = -0.508) and Visual Restructuralization (r = -0.516), and EBI (r = -0·637) were the variables with the strongest correlation to the Week 3 change from Baseline in MADRS score.
The existence of correlation does not establish causation and exploratory findings require further replication, preferably in larger independent samples.
The intensity of psychedelic experience overlaps widely across doses and mitigates the risk of unblinding to dose. Correlations between psychedelic experience and outcome suggest specificity in psilocybin's mechanism of action. Quality and intensity of psychedelic experience may be a measure of pharmacodynamic effect and reveal an effective dose response phenomenon for single oral doses.
确定在难治性抑郁症中，裸盖菇素剂量、迷幻体验与治疗效果之间的关系。
对于难治性抑郁症患者，233名参与者在心理支持下接受了单次剂量的25毫克、10毫克或1毫克COMP360裸盖菇素（由主办方Compass Pathfinder Ltd.研发的一种专利医药级合成裸盖菇素制剂）。测量由此产生的迷幻体验（五维意识改变状态问卷[5D-ASC]和情感突破量表[EBI]）。使用相关分析探讨这些近端变量与给药后3周的结果（蒙哥马利-奥斯伯格抑郁评定量表[MADRS]的变化）。
迷幻效果的平均强度与剂量相关，但不同剂量的得分分布有相当大的重叠。抑郁反应与迷幻体验的总体及各个剂量的特定方面相关。在25毫克剂量下，5D-ASC维度“海洋般的无限感”（皮尔逊相关系数r = -0.508）、“视觉重构”（r = -0.516）以及EBI（r = -0.637）是与MADRS评分从基线到第3周变化相关性最强的变量。
相关性的存在并不意味着因果关系，探索性研究结果需要进一步重复验证，最好是在更大的独立样本中进行。
迷幻体验的强度在不同剂量间有广泛重叠，降低了因剂量而导致的非盲法风险。迷幻体验与治疗效果之间的相关性表明裸盖菇素作用机制具有特异性。迷幻体验的质量和强度可能是药效学效应的一种衡量指标，并揭示了单次口服剂量的有效剂量反应现象。
