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.
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State of the evidence: MDMA for PTSD Supports
MDMA-assisted therapy reduced PTSD symptoms (d = 0.7) and functional impairment (d = 0.4) more than placebo with therapy; no deaths or serious treatment-emergent adverse events occurred.
Synthesized
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State of the evidence: PTSD Supports
MDMA-assisted therapy reduced PTSD symptoms and functional impairment more than placebo with therapy in a diverse population with moderate to severe PTSD.
Synthesized
Comparable studies
Other randomized controlled trials on MDMA for PTSD, most cited first.