MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study
- PMID: 33972795
- PMCID: PMC8205851
- DOI: 10.1038/s41591-021-01336-3
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study
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.
Conflict of interest statement
The authors declare the following financial competing interests: A.E., R.M., C.H., A.D.B., S.C., A.C. and J.B.W. received salary support for full-time employment with MAPS PBC for this study and other work; A.L., B.Y.-K. and R.D. received salary support for full-time employment with MAPS for this study and other work; M.M., A.M., M.O.G., B.P. and K.T. received support as contractors from MAPS PBC for training and supervision of research psychotherapists for this study and other work; S.K., K.P.-G. and S.H. received support as contractors of MAPS PBC for their contributions to this study and other work; and study investigators and researchers, J.M.M., M.B., M.O.G., W.G., C.P., I.G., C.N., B.P., S.Q., G.W., S.S.K., B.V.D.K., K.T., R.A., R.W., S.S., J.D.W., C.M., Y.G., E.H., S.A., Y.W. and R.B., received funding from MAPS PBC during the conduct of the study for this study as well as other studies. The following authors disclose receipt of personal fees or grants from companies in the field, but unrelated to the present work: M.B. (Heffter Research Institute, Turnbull Family Foundation, B. More, Mind Medicine, Fournier Family Foundation, Bill Linton, George Sarlo Foundation, RiverStyx Foundation, Dr. Bronners Family Foundation, and National Institutes of Health), C.P. (Fluence and Mindbloom), J.D.W. (Filament Ventures and Silo Pharmaceuticals), and J.M.M. and A.C. (Usona Institute). The following authors disclose non-financial relationships with organizations in the field: M.M. and A.M. serve on the Scientific Advisory Board for Awaken Life Sciences, C.P. co-founded Nautilus Sanctuary and Nautilus Psychiatric Services, S.S. serves on the advisory board for Maya Health, and I.G. serves on the Scientific Advisory Board of Journey Clinical and co-founded Fluence.
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Comment in
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Putting the MD back into MDMA.Nat Med. 2021 Jun;27(6):950-951. doi: 10.1038/s41591-021-01385-8. Nat Med. 2021. PMID: 34031606 No abstract available.
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Psychotherapy-supported MDMA treatment for PTSD.Cell Rep Med. 2021 Aug 17;2(8):100378. doi: 10.1016/j.xcrm.2021.100378. eCollection 2021 Aug 17. Cell Rep Med. 2021. PMID: 34467253 Free PMC article.
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Reply to: Caution at psychiatry's psychedelic frontier and Challenges with benchmarking of MDMA-assisted psychotherapy.Nat Med. 2021 Oct;27(10):1691-1692. doi: 10.1038/s41591-021-01526-z. Epub 2021 Oct 11. Nat Med. 2021. PMID: 34635856 No abstract available.
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Challenges with benchmarking of MDMA-assisted psychotherapy.Nat Med. 2021 Oct;27(10):1689-1690. doi: 10.1038/s41591-021-01525-0. Epub 2021 Oct 11. Nat Med. 2021. PMID: 34635857 No abstract available.
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Caution at psychiatry's psychedelic frontier.Nat Med. 2021 Oct;27(10):1687-1688. doi: 10.1038/s41591-021-01524-1. Epub 2021 Oct 11. Nat Med. 2021. PMID: 34635858 No abstract available.
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