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

Jennifer Mitchell, Marcela Ot’alora G., Bessel Van der Kolk, Scott Shannon, Michael P. Bogenschutz, Yevgeniy Gelfand, Casey Paleos, Christopher R. Nicholas, Sylvestre Quevedo, Brooke Balliett, Scott Hamilton, Michael C Mithoefer, Sarah Kleiman, Kelly Parker-Guilbert, Keren Tzarfaty, Charlotte Harrison, Alberdina De Boer, Rick Doblin, Berra Yazar-Klosinski, Charlotte Harrison, Berra Yazar-Klosinski, Wael Garas, Darrick G. May, Cole Marta, Susan Walker, Elizabeth M. Nielson, Gregory Wells, Randall Brown, Revital Amiaz, Yair Wallach, Ray Worthy, Alia Lilienstein, Amy Emerson

Nature Medicine October 1, 2023 DOI: 10.1038/s41591-023-02565-4 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Placebo-controlled Double-blind Peer reviewed
Sample size 104
Population Adults with moderate to severe post-traumatic stress disorder
Interventions 3 4-methylenedioxymethamphetamine-assisted therapy
Topics MDMA PTSD
Citations 400
Registration NCT04077437
Key findings MDMA-assisted therapy reduced PTSD symptoms and functional impairment more than placebo with therapy in a diverse population with moderate to severe PTSD.

Abstract

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 .

In the evidence

This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.

  • State of the evidence: MDMA for PTSD Supports

    MDMA-assisted therapy reduced CAPS-5 scores more than placebo with therapy (d = 0.7) and improved functional impairment (d = 0.4), with no deaths or serious treatment-emergent adverse events.

    Synthesized

  • State of the evidence: PTSD Supports

    MDMA-assisted therapy reduced CAPS-5 symptoms (d = 0.7) and functional impairment (d = 0.4) more than placebo with therapy, with no deaths or serious treatment-emergent adverse events.

    Synthesized

Comparable studies

Other randomized controlled trials on MDMA for PTSD, most cited first.

Study Year Design Participants
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Patients with severe PTSD, including those with comorbidities such as dissociation,... 2021 Randomized controlled trial n = 90
The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Patients with chronic post-traumatic stress disorder refractory to both psychotherapy... 2010 Randomized controlled trial n = 20
3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. Military veterans and first responders aged 18 or older with chronic PTSD lasting 6... 2018 Randomized, double-blind, dose-response, phase 2 clinical trial n = 26
A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD) Patients with treatment-resistant PTSD 2012 Randomized controlled trial n = 12
3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial. People with chronic posttraumatic stress disorder 2018 Randomized controlled trial n = 28

Citations in the library

Cited by 309

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Cites 17

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