Efficacy and Safety Results from the Confirmatory Phase 3 Randomized, Placebo-Controlled Trial of MDMA-Assisted Therapy for Treatment of Chronic PTSD With at Least Moderate Severity

This study was funded by Funded by MAPS and Steven and Alexandra Cohen Foundation, Inc. and organized by MAPS PBC. Background: Posttraumatic stress disorder (PTSD) is a serious neuropsychiatric illness for which novel treatment options are urgently needed. Methods: This multi-site, randomized, double-blind, confirmatory phase 3 trial investigated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy, delivered in three blinded experimental sessions over 3 months, in participants with moderate-to-severe PTSD (baseline Clinician-Administered PTSD Scale for DSM-5 [CAPS-5] score ≥28). Outcome measures included change in PTSD symptoms (CAPS-5 total severity; primary endpoint), change in functional impairment (Sheehan Disability Scale [SDS]; key secondary endpoint), and safety. Endpoints were assessed by a central blinded independent rater pool (baseline through 18 weeks) and analyzed by MMRM. Results: 53 participants were randomized to MDMA-AT and 51 to placebo with therapy. There were nine participants with missing data (one MDMA, eight placebo). Overall, 26.9% (28/104) of participants had moderate PTSD and 73.1% (76/104) had severe PTSD; participants were ethnoracially diverse. LS mean change in CAPS-5 score (95% CI) was –23.7 (–26.94, –20.44) for MDMA-AT versus –14.8 (–18.28, –11.28) for placebo with therapy (P