MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study.
Jennifer Mitchell, Michael P. Bogenschutz, Alia Lilienstein, Charlotte Harrison, Sarah Kleiman, Kelly Parker-Guilbert, Marcela Ot'Alora G, Wael Garas, Casey Paleos, Ingmar Gorman, Christopher R. Nicholas, Michael C Mithoefer, Shannon Carlin, Bruce Poulter, Ann T Mithoefer, Sylvestre Quevedo, Gregory Wells, Sukhpreet Klaire, Bessel Van der Kolk, Keren Tzarfaty, Revital Amiaz, Ray Worthy, Scott Shannon, Joshua Woolley, Cole Marta, Yevgeniy Gelfand, Emma Hapke, Simon Amar, Yair Wallach, Randall Brown, Scott Hamilton, Julie B. Wang, Allison R. Coker, Rebecca Matthews, Alberdina De Boer, Berra Yazar-Klosinski, Amy Emerson, Rick Doblin
Nature Medicine June 1, 2021 DOI: 10.1038/s41591-021-01336-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 90 |
| Population | Patients with severe PTSD, including those with comorbidities such as dissociation, depression, history of alcohol and substance use disorders, and childhood trauma |
| Intervention | MDMA-assisted therapy |
| Duration | 2-month follow-up after the last experimental session |
| Topics | MDMA PTSD |
| Keywords | PTSD Treatment MDMA Therapy Clinical trials Mental health breakthrough |
| Citations | 965 |
| Registration | NCT03537014 |
| Key findings | MDMA-assisted therapy produced significantly greater reductions in PTSD symptoms and functional impairment than placebo with no serious adverse events. |
Abstract
Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.
In the evidence
This study is part of the evidence base for 3 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 produced significantly greater reductions in PTSD symptoms (d = 0.91) and functional impairment (d = 0.43) than placebo with therapy, with no serious adverse events.
Synthesized
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State of the evidence: MDMA Supports
MDMA-assisted therapy produced significantly greater reductions in PTSD symptoms and functional impairment than placebo, with no serious adverse events.
Synthesized
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State of the evidence: PTSD Supports
MDMA-assisted therapy produced significantly greater reductions in PTSD symptoms and functional impairment than placebo, with a large effect size on the primary outcome and no serious adverse events.
Synthesized
Comparable studies
Other randomized controlled trials on MDMA for PTSD, most cited first.