Fonzo Gregory A, Wolfgang Aaron S, Barksdale Bryan R, Krystal John H, Carpenter Linda L, Kraguljac Nina V, Grzenda Adrienne, McDonald William M, Widge Alik S, Rodriguez Carolyn I, Nemeroff Charles B
Department of Psychiatry and Behavioral Sciences (Fonzo, Barksdale, Nemeroff) and Center for Psychedelic Research and Therapy (Fonzo, Nemeroff), University of Texas at Austin Dell Medical School, Austin; Institute for Early Life Adversity Research, University of Texas at Austin, Austin (Fonzo, Nemeroff); Department of Behavioral Health, Walter Reed National Military Medical Center, Bethesda, MD (Wolfgang); Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD (Wolfgang); Department of Psychiatry, Yale University School of Medicine, New Haven, CT (Wolfgang, Krystal); Butler Hospital, Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI (Carpenter); Department of Psychiatry and Behavioral Neurobiology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham (Kraguljac); Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, UCLA, Los Angeles (Grzenda); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (McDonald); Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis (Widge); Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA (Rodriguez); Veterans Affairs Palo Alto Health Care System, Palo Alto, CA (Rodriguez).
Am J Psychiatry. 2025 Jan 1;182(1):54-78. doi: 10.1176/appi.ajp.20230682.
The authors critically examine the evidence base for psilocybin administered with psychological support/therapy (PST) in the treatment of psychiatric disorders and offer practical recommendations to guide future research endeavors.
PubMed was searched for English-language articles from January 1998 to November 2023, using the search term "psilocybin." A total of 1,449 articles were identified and screened through titles and abstracts. Of these, 21 unique open-label or randomized controlled trials (RCTs) were identified that examine psilocybin for the treatment of obsessive-compulsive and related disorders (N=2), anxiety/depression associated with a cancer diagnosis (N=5), major depressive disorder (MDD; N=8), substance use disorders (N=4), anorexia (N=1), and demoralization (i.e., hopelessness, helplessness, and poor coping) in AIDS survivors (N=1).
The most developed evidence base is for the treatment of MDD (three double-blind RCTs with positive signals spanning a range of severities). However, the evidence is tempered by threats to internal and external validity, including unsuccessful blinding, small samples, large variability in dosing and PST procedures, limited sample diversity, and possibly large expectancy effects. Knowledge of mechanisms of action and predictors of response is currently limited.
The evidence is currently insufficient to recommend psilocybin with PST as a psychiatric treatment. Additional rigorously designed clinical trials are needed to definitively establish efficacy in larger and more diverse samples, address dosing considerations, improve blinding, and provide information on mechanisms of action and moderators of clinical response. Head-to-head comparisons with other evidence-based treatments will better inform the potential future role of psilocybin with PST in the treatment of major psychiatric disorders.
作者批判性地审视了在心理支持/治疗（PST）辅助下使用裸盖菇素治疗精神疾病的证据基础，并提供实用建议以指导未来的研究工作。
在PubMed数据库中检索1998年1月至2023年11月期间的英文文章，检索词为“裸盖菇素”。共识别出1449篇文章，并通过标题和摘要进行筛选。其中，确定了21项独特的开放标签或随机对照试验（RCT），这些试验研究了裸盖菇素用于治疗强迫症及相关障碍（N = 2）、与癌症诊断相关的焦虑/抑郁（N = 5）、重度抑郁症（MDD；N = 8）、物质使用障碍（N = 4）、厌食症（N = 1）以及艾滋病幸存者的士气低落（即绝望、无助和应对能力差，N = 1）。
最完善的证据基础是关于MDD的治疗（三项双盲RCT显示出在不同严重程度范围内的积极信号）。然而，证据受到内部和外部效度威胁的影响，包括盲法失败、样本量小、给药和PST程序的巨大变异性、样本多样性有限以及可能存在的大期望效应。目前对作用机制和反应预测因素的了解有限。
目前的证据不足以推荐在PST辅助下使用裸盖菇素作为精神疾病的治疗方法。需要进行更多严格设计的临床试验，以在更大、更多样化的样本中明确确定疗效，解决给药问题，改善盲法，并提供关于作用机制和临床反应调节因素的信息。与其他循证治疗方法进行直接比较，将更好地说明在PST辅助下使用裸盖菇素在治疗主要精神疾病方面未来可能发挥的作用。
