MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study

作者：Jennifer Mitchell, Michael P. Bogenschutz, Alia Lilienstein, Charlotte Harrison, Sarah E. Kleiman, Kelly Parker-Guilbert, Marcela Ot’alora G., Wael Garas, Casey Paleos, Ingmar Gorman, Christopher R. Nicholas, Michael C. Mithoefer, Shannon Carlin, Bruce Poulter, Ann T. Mithoefer, Sylvestre Quevedo, G. Beverly Wells, Sukhpreet Klaire, Bessel van der Kolk, Keren Tzarfaty, Revital Amiaz, Ray Worthy, Scott Shannon, Joshua Woolley, Cole J. Marta, Yevgeniy Gelfand, Emma Hapke, Simon Amar, Yair Wallach, Randall Brown, Scott Hamilton, Julie B. Wang, Allison R. Coker, Rebecca Matthews, Alberdina de Boer, Berra Yazar‐Klosinski, Amy Emerson, Rick Doblin · 发表于：FOCUS The Journal of Lifelong Learning in Psychiatry · 年份：2023 · DOI：10.1176/appi.focus.23021011 · 被引用次数：97 · 研究领域：Psychedelics and Drug Studies、Cannabis and Cannabinoid Research、Sleep and Wakefulness Research

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 2 months 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 o...