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

• DOI: 10.1176/appi.focus.23021011
• Publication Date: 2023-07-14T07:05:36Z
• Authors: Jennifer M. Mitchell; Michael Bogenschutz; Alia Lilienstein; Charlotte Harrison; Sarah Kleiman; Kelly Parker-Guil...; Marcela Ot’alora 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-Klosi...; Amy Emerson; Rick Doblin
• Keywords: MDMA; Clinical endpoint

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test efficacy and safety 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy treatment patients with severe PTSD, including those common comorbidities such as dissociation, depression, history alcohol substance use disorders, childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 receive manualized MDMA or placebo, combined three preparatory nine integrative sessions. PTSD symptoms, measured Clinician-Administered Scale DSM-5 (CAPS-5, primary endpoint), functional impairment, Sheehan Disability (SDS, secondary endpoint) assessed at baseline 2 months after last experimental session. Adverse events suicidality tracked throughout study. was found induce significant robust attenuation in CAPS-5 score compared placebo (P < 0.0001, d 0.91) significantly decrease SDS total 0.0116, 0.43). The mean change scores completing −24.4 (s.d. 11.6) group −13.9 11.5) group. did not adverse abuse potential, QT prolongation. These data indicate that, inactive MDMA-assisted is highly efficacious individuals safe well-tolerated, even comorbidities. conclude that represents potential breakthrough merits expedited evaluation. Appeared originally Nat Med 2021; 27:1025–1033