美国加州大学旧金山分校Jennifer M. Mitchell等研究人员完成MDMA辅助治疗用于严重PTSD的3期临床评估。2021年5月10日，国际知名学术期刊《自然—医学》在线发表了这一成果。

研究人员报告了一项随机、双盲、安慰剂对照、多中心3期临床试验（NCT03537014）的结果，该试验测试了MDMA（3,4-methylenedioxymethamphetamine）辅助疗法治疗严重创伤后应激障碍（PTSD，）患者的疗效和安全性，也包括了一些常见的合并症，如分裂、抑郁、酒精和药物滥用史以及童年期创伤等。精神药物治疗结束后，将参与者（n=90）1：1随机接受MDMA或安慰剂的手册化治疗，并进行3次准备和9次综合治疗。在基线和2个月时，评估由临床医师管理的DSM-5 PTSD量表（CAPS-5，主要终点）测量的PTSD症状，以及由Sheehan残疾量表（SDS，次要终点）测量的功能障碍。

在最后一次实验之后。在整个研究过程中追踪不良事件和自杀倾向。与安慰剂相比，研究人员发现MDMA诱导CAPS-5评分显著而有力的衰减（P<0.0001，d=0.91），并显著降低了SDS总评分（P=0.0116，d=0.43）。在完成治疗的参与者中，CAPS-5得分的平均变化在MDMA组为-24.4（标准差11.6），在安慰剂组为-13.9（标准差11.5）。MDMA不会引起滥用可能性、自杀倾向或QT延长等不良事件。

这些数据表明，与使用无效安慰剂的手册化疗法相比，MDMA辅助疗法在严重PTSD患者中非常有效，并且即使在合并症患者中，治疗也是安全且耐受性良好的。因此，MDMA辅助疗法是一种潜在的突破性疗法，值得加速临床评估。

据了解，PTSD是一个重大的公共卫生问题，目前可用的治疗方法对此疗效有限。

附：英文原文

Title: MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study

Author: Jennifer M. Mitchell, Michael Bogenschutz, Alia Lilienstein, Charlotte Harrison, Sarah Kleiman, Kelly Parker-Guilbert, Marcela Otalora G., Wael Garas, Casey Paleos, Ingmar Gorman, Christopher Nicholas, Michael Mithoefer, Shannon Carlin, Bruce Poulter, Ann Mithoefer, Sylvestre Quevedo, Gregory Wells, Sukhpreet S. Klaire, Bessel van der Kolk, Keren Tzarfaty, Revital Amiaz, Ray Worthy, Scott Shannon, Joshua D. Woolley, Cole Marta, Yevgeniy Gelfand, Emma Hapke, Simon Amar, Yair Wallach, Randall Brown, Scott Hamilton, Julie B. Wang, Allison Coker, Rebecca Matthews, Alberdina de Boer, Berra Yazar-Klosinski, Amy Emerson, Rick Doblin

Issue&Volume: 2021-05-10

Abstract: Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n=90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P<0.0001, d=0.91) and to significantly decrease the SDS total score (P=0.0116, d=0.43). The mean change in CAPS-5 scores in participants completing treatment was 24.4 (s.d. 11.6) in the MDMA group and 13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.

DOI: 10.1038/s41591-021-01336-3

Source: https://www.nature.com/articles/s41591-021-01336-3