Journal Article

MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial

Shannon, Scott, van der Kolk, Bessel, Gelfand, Yevgeniy, Tzarfaty, Keren, Kleiman, Sarah, Mitchell, Jennifer M., Ot’alora G., Marcela, Harrison, Charlotte, Hamilton, Scott, Doblin, Rick, Yazar-Klosinski, Berra, Paleos, Casey, Mithoefer, Michael, Parker-Guilbert, Kelly, Bogenschutz, Michael, Balliett, Brooke, Quevedo, Sylvestre, de Boer, Alberdina, Nicholas, Christopher R.

2023

Overview

This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). Changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score (primary endpoint) and Sheehan Disability Scale (SDS) functional impairment score (key secondary endpoint) were assessed by blinded independent assessors. Participants were randomized to MDMA-AT ( n  = 53) or placebo with therapy ( n  = 51). Overall, 26.9% (28/104) of participants had moderate PTSD, and 73.1% (76/104) of participants had severe PTSD. Participants were ethnoracially diverse: 28 of 104 (26.9%) identified as Hispanic/Latino, and 35 of 104 (33.7%) identified as other than White. Least squares (LS) mean change in CAPS-5 score (95% confidence interval (CI)) was −23.7 (−26.94, −20.44) for MDMA-AT versus −14.8 (−18.28, −11.28) for placebo with therapy ( P  < 0.001, d  = 0.7). LS mean change in SDS score (95% CI) was −3.3 (−4.03, −2.60) for MDMA-AT versus −2.1 (−2.89, −1.33) for placebo with therapy ( P  = 0.03, d  = 0.4). Seven participants had a severe treatment emergent adverse event (TEAE) (MDMA-AT, n  = 5 (9.4%); placebo with therapy, n  = 2 (3.9%)). There were no deaths or serious TEAEs. These data suggest that MDMA-AT reduced PTSD symptoms and functional impairment in a diverse population with moderate to severe PTSD and was generally well tolerated. ClinicalTrials.gov identifier: NCT04077437 . Results from the phase 3 placebo-controlled MAPP2 trial show that MDMA-assisted therapy reduces post-traumatic stress disorder (PTSD) symptoms and functional impairment in a diverse population with moderate to severe PTSD.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 692/308/153 / 692/699/578 / Biomedical and Life Sciences / Biomedicine / Cancer Research / Combined Modality Therapy / Double-Blind Method / Ecstasy / Humans / Impairment / Infectious Diseases / MDMA / Mental disorders / Metabolic Diseases / Molecular Medicine / N-Methyl-3,4-methylenedioxyamphetamine - adverse effects / Neurosciences / Placebos / Post traumatic stress disorder / Psychological stress / Stress Disorders, Post-Traumatic - drug therapy / Therapy / Treatment Outcome