MDMA-assisted therapy for posttraumatic stress disorder: A pooled analysis of ethnoracial differences in efficacy and safety from two Phase 2 open-label lead-in trials and a Phase 3 randomized, blinded placebo-controlled trial
This study (2022) analysed data from two Phase II and one Phase III trials from MAPS where MDMA-assisted therapy (MDMA-AT) was used to treat PTSD in order to compare the efficacy and safety of MDMA-AT between Black, Indigenous, and People of Color (BIPOC) and non-Hispanic White participants. No significant ethnoracial difference in CAPS-5 scores was observed while BIPOC participants trended toward greater reductions following MDMA-AT.
Authors
- Rick Doblin
- Berra Yazar-Klosinski
- Lisa Jerome
Published
Abstract
Background
Limited ethnoracial diversity in previous ±3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) trials for posttraumatic stress disorder (PTSD) has prompted questions concerning whether Black, Indigenous, and People of Color (BIPOC) also benefit from this treatment.
Methods
Secondary analysis was conducted using a modified intent-to-treat sample pooled from two Phase 2 open-label trials and a Phase 3 randomized, blinded placebo-controlled trial to compare the efficacy and safety of MDMA-AT for PTSD between BIPOC and non-Hispanic White participants. Four subgroups were of interest: MDMA-AT, BIPOC (n = 20); MDMA-AT, non-Hispanic White (n = 63); Placebo-assisted therapy (Placebo-AT), BIPOC (n = 17); and Placebo-AT, non-Hispanic White (n = 27). Planned comparisons tested subgroup differences in changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) scores from baseline to primary endpoint, controlling for study type and baseline scores. Adverse events (AEs) on the day of (day 0) to 2 days post-dosing were reported for each subgroup.
Results
In the MDMA-AT group, no significant ethnoracial difference in CAPS-5 change scores was observed. In the Placebo-AT group, BIPOC participants trended toward greater reductions in CAPS-5 scores than non-Hispanic Whites. Among non-Hispanic Whites, MDMA-AT was accompanied by significantly greater reductions in CAPS-5 scores than Placebo-AT. No treatment difference emerged among BIPOC participants. AEs were mostly rated as mild or moderate across subgroups.
Conclusions
These findings provide preliminary support for the efficacy and safety of MDMA-AT for treating PTSD across ethnoracial groups. There was also a trend toward greater efficacy with Placebo-AT among BIPOC participants. There was an imbalance in subgroups, highlighting the need for culturally responsive recruitment strategies to diversify future studies.
Research Summary of 'MDMA-assisted therapy for posttraumatic stress disorder: A pooled analysis of ethnoracial differences in efficacy and safety from two Phase 2 open-label lead-in trials and a Phase 3 randomized, blinded placebo-controlled trial'
Introduction
Ching and colleagues situate MDMA-assisted therapy (MDMA-AT) as a promising intervention for severe, treatment-resistant posttraumatic stress disorder (PTSD), on the basis of MDMA's putative pharmacodynamic effects of reducing fear and anxiety while enhancing trust and connectedness. Previous pooled Phase II data have suggested larger effect sizes for MDMA-AT than for existing antidepressant approvals and durable benefits up to 12 months in open-label follow-up, but knowledge about the psychological mechanisms of change remains limited. Qualitative work has suggested benefits beyond symptom reduction—such as increased self-understanding, improved relationships, and reduced substance use—but these studies have limitations including recall bias and low ethnoracial diversity in trial samples; only 12.4% of the pooled Phase II sample identified as individuals of colour, raising uncertainty about whether ethnoracial minority participants benefit similarly. To address this gap, the authors report a mixed-methods single-case study drawn from an open-label lead-in trial to provide a culturally informed lens on recovery from PTSD for a first-generation South Asian American participant. The study aims to describe idiosyncratic cultural content and to characterise immediate, ecologically valid change processes and therapeutic mechanisms by analysing session transcripts from integration sessions following MDMA dosing. The authors acknowledge limited generalisability but propose that detailed case analysis can stimulate deeper consideration of cultural diversity and mechanisms as MDMA-AT research progresses.
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Study Details
- Study Typemeta
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Ching, T. H., Williams, M. T., Wang, J. B., Jerome, L., Yazar-Klosinski, B., Emerson, A., & Doblin, R. (2022). MDMA-assisted therapy for posttraumatic stress disorder: A pooled analysis of ethnoracial differences in efficacy and safety from two Phase 2 open-label lead-in trials and a Phase 3 randomized, blinded placebo-controlled trial. Journal of Psychopharmacology, 36(8), 974-986. https://doi.org/10.1177/02698811221104052
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Barone, W., Beck, J., Mitsunaga-Whitten, M. et al. · Journal of Psychoactive Drugs (2019)
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Feduccia, A. A., Jerome, L., Yazar-Klosinski, B. et al. · Frontiers in Psychiatry (2019)
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Gorman, I., Belser, A. B., Jerome, L. et al. · Journal of Traumatic Stress (2020)
Hendricks, P. S. · International Review of Psychiatry (2018)
Jerome, L., Feduccia, A. A., Wang, J. B. et al. · Psychopharmacology (2020)
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Jungaberle, H., Thal, S., Zeuch, A. et al. · Neuropharmacology (2018)
Mithoefer, M. C., Feduccia, A. A., Jerome, L. et al. · Psychopharmacology (2019)
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Wagner, A. C., Mithoefer, M. C., Mithoefer, A. T. et al. · Journal of Psychoactive Drugs (2019)
Wagner, M. T., Mithoefer, M. C., Mithoefer, A. T. et al. · Journal of Psychopharmacology (2017)
Cited By (3)
Papers in Blossom that reference this study
Black, J. C., Monte, A. A., Dasgupta, N. et al. · Nature Mental Health (2024)
Mitchell, J., Ot’alora G, M., van der Kolk, B. et al. · Nature Medicine (2023)
Jones, J. L. · Frontiers in Psychiatry (2023)
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