Wolfgang Aaron S, Fonzo Gregory A, Gray Joshua C, Krystal John H, Grzenda Adrienne, Widge Alik S, Kraguljac Nina V, McDonald William M, Rodriguez Carolyn I, Nemeroff Charles B
Directorate of Behavioral Health, Walter Reed National Military Medical Center, Bethesda, MD (Wolfgang); Departments of Psychiatry (Wolfgang) and Medical and Clinical Psychology (Gray), Uniformed Services University, Bethesda, MD; Departments of Psychiatry (Wolfgang, Krystal), Neuroscience (Krystal), and Psychology (Krystal), Yale University School of Medicine, New Haven, CT; Center for Psychedelic Research and Therapy, Department of Psychiatry and Behavioral Sciences, The University of Texas at Austin Dell Medical School (Fonzo, Nemeroff); Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, UCLA (Grzenda); Department of Psychiatry & Behavioral Sciences, University of Minnesota, Minneapolis (Widge); Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham (Kraguljac); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (McDonald); Department of Psychiatry and Behavioral Sciences, Stanford University and Veterans Affairs Palo Alto Health Care System, Palo Alto, CA (Rodriguez).
Am J Psychiatry. 2025 Jan 1;182(1):79-103. doi: 10.1176/appi.ajp.20230681.
MDMA (i.e., 3,4-methylenedixoymethamphetamine), commonly known as "Ecstasy" or "Molly," has been used since the 1970s both in recreational and therapeutic settings. The Food and Drug Administration (FDA) designated MDMA-Assisted Therapy (MDMA-AT) as a Breakthrough Therapy for posttraumatic stress disorder (PTSD) in 2017, and the FDA is requiring an additional phase 3 trial after rejecting the initial New Drug Application in 2024. Unlike other psychedelics, MDMA uniquely induces prosocial subjective effects of heightened trust and self-compassion while maintaining ego functioning as well as cognitive and perceptual lucidity. While recreational use in nonmedical settings may still cause harm, especially due to adulterants or when used without proper precautions, conclusions that can be drawn from studies of recreational use are limited by many confounds. This especially limits the extent to which evidence related to recreational use can be extrapolated to therapeutic use. A considerable body of preliminary evidence suggests that MDMA-AT delivered in a controlled clinical setting is a safe and efficacious treatment for PTSD. After a course of MDMA-AT involving three MDMA administrations supported by psychotherapy, 67%-71% of individuals with PTSD no longer meet diagnostic criteria after MDMA-AT versus 32%-48% with placebo-assisted therapy, and effects endure at long-term follow-up. This review primarily aims to distinguish evidence of recreational use in nonclinical settings versus MDMA-AT using pharmaceutical-grade MDMA in controlled clinical settings. This review further describes the putative neurobiological mechanisms of MDMA underlying its therapeutic effects, the clinical evidence of MDMA-AT, considerations at the level of public health and policy, and future research directions.
摇头丸（即3,4-亚甲基二氧甲基苯丙胺），通常被称为“摇头丸”或“莫莉”，自20世纪70年代以来就被用于娱乐和治疗场景。2017年，美国食品药品监督管理局（FDA）将摇头丸辅助疗法（MDMA-AT）指定为创伤后应激障碍（PTSD）的突破性疗法，并且在2024年拒绝了最初的新药申请后，FDA要求进行额外的3期试验。与其他迷幻药不同，摇头丸独特地诱导出增强信任和自我同情的亲社会主观效应，同时保持自我功能以及认知和感知清晰度。虽然在非医疗环境中的娱乐性使用仍可能造成伤害，特别是由于掺假物或在没有适当预防措施的情况下使用，但从娱乐性使用研究中得出的结论受到许多混杂因素的限制。这尤其限制了与娱乐性使用相关的证据可以外推到治疗性使用的程度。大量初步证据表明，在受控临床环境中提供的摇头丸辅助疗法是一种安全有效的创伤后应激障碍治疗方法。在经过一个包括三次摇头丸给药并辅以心理治疗的摇头丸辅助疗法疗程后，67%-71%的创伤后应激障碍患者在接受摇头丸辅助疗法后不再符合诊断标准，而接受安慰剂辅助疗法的患者这一比例为32%-48%，并且这些效果在长期随访中持续存在。本综述主要旨在区分非临床环境中娱乐性使用的证据与在受控临床环境中使用药用级摇头丸的摇头丸辅助疗法的证据。本综述还进一步描述了摇头丸治疗效果背后的假定神经生物学机制、摇头丸辅助疗法的临床证据、公共卫生和政策层面的考虑因素以及未来的研究方向。
