Effects of MDMA-assisted therapy for PTSD on self-experience
This re-analysis of an RCT of MDMA-assisted therapy for PTSD finds that study participants (n=90) had significant improvements in the measures of self-experience (e.g. alexithymia -; the inability to identify & describe emotions experienced by oneself). The change in scores of self-experience correlates with recovery from PTSD.
Authors
- Rick Doblin
- Berra Yazar-Klosinski
- Michael Mithoefer
Published
Abstract
Introduction
There is a resurgence of interest in the therapeutic potential of psychedelic substances such as 3,4-methylenedioxymethamphetamine (MDMA). Primary findings from our randomized, double-blind, placebo-controlled, multi-site Phase 3 clinical trial of participants with severe PTSD (NCT03537014) showed that MDMA-assisted therapy induced significant attenuation in the Clinician-Administered PTSD Scale for DSM-5 compared to Therapy with placebo. Deficits in emotional coping skills and altered self-capacities constitute major obstacles to successful completion of available treatments. The current analysis evaluated the differential effects of MDMA-assisted therapy and Therapy with placebo on 3 transdiagnostic outcome measures and explored the contribution of changes in self-experience to improvement in PTSD scores.
Methods
Participants were randomized to receive manualized therapy with either MDMA or placebo during 3 experimental sessions in combination with 3 preparation and 9 integration therapy visits. Symptoms were measured at baseline and 2 months after the last experimental session using the 20-item Toronto Alexithymia Scale (TAS-20), the 26-item Self Compassion Scale (SCS), and the 63-item Inventory of Altered Self-Capacities (IASC).Results 90 participants were randomized and dosed (MDMA-assisted therapy, n = 46; Therapy with placebo, n = 44); 84.4% (76/90) had histories of developmental trauma, and 87.8% (79/90) had suffered multiple traumas. MDMA-assisted therapy facilitated statistically significant greater improvement on the TAS-20, the SCS, and most IASC factors of interpersonal conflicts; idealization disillusionment; abandonment concerns; identity impairment; self-awareness; susceptibility to influence; affect dysregulation; affect instability; affect skill deficit; tension reduction activities; the only exception was identity diffusion.
Conclusion
Compared with Therapy with placebo, MDMA-assisted therapy had significant positive effects on transdiagnostic mental processes of self-experience which are often associated with poor treatment outcome. This provides a possible window into understanding the psychological capacities facilitated by psychedelic agents that may result in significant improvements in PTSD symptomatology.
Research Summary of 'Effects of MDMA-assisted therapy for PTSD on self-experience'
Introduction
Van Der Kolk and colleagues place this study within the recent resurgence of clinical research into psychedelic-assisted psychotherapy, noting that substances such as psilocybin, ketamine and MDMA have re‑opened interest in pharmacologically facilitated therapy. Earlier Phase II pooled analyses and a recently completed Phase III multisite trial demonstrated substantial and sustained reductions in PTSD symptoms with MDMA‑assisted therapy (MDMA‑AT), and the FDA granted MDMA‑AT breakthrough therapy designation for PTSD. At the same time, the authors note that outcomes from standard trauma‑focused psychotherapies remain limited for many patients: substantial dropout rates and residual problems with emotion regulation, interpersonal functioning, alexithymia and low self‑compassion are common and predict poorer treatment response. This paper reports exploratory analyses from the Phase III trial that examine whether MDMA‑AT produces changes in transdiagnostic self‑experience constructs thought to impede successful PTSD treatment. Specifically, the investigators evaluate measures of altered self‑capacities, alexithymia and self‑compassion collected alongside the primary PTSD outcome, and ask whether baseline deficits on these measures predict differential PTSD benefit from MDMA‑AT versus protocolised therapy with placebo. The study therefore aims to illuminate psychological change processes that may underlie the clinical advantages of MDMA‑AT compared with therapy alone.
Expert Research Summaries
Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.
Full Text PDF
Full Paper PDF
Pro members can view the original manuscript directly in the browser.
Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
van der Kolk, B. A., Wang, J. B., Yehuda, R., Bedrosian, L., Cooker, A., Harrison, C., Mithoefer, M., Yazar-Klosinki, B., Emerson, A., & Doblin, R. (2023). Effects of MDMA-assisted therapy for PTSD on self-experience. https://doi.org/10.1101/2023.01.03.23284143
References (9)
Papers cited by this study that are also in Blossom
Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T. et al. · Journal of Psychopharmacology (2012)
Mitchell, J., Bogenschutz, M. P., Lilienstein, A. et al. · Nature Medicine (2021)
Carhart-Harris, R. L., Erritzoe, D., Haijen, E. C. H. M. et al. · Psychopharmacology (2017)
Brouwer, A., Carhart-Harris, R. L. · Journal of Psychopharmacology (2020)
Carhart-Harris, R. L., Wall, M. B., Erritzoe, D. et al. · International Journal of Neuropsychopharmacology (2013)
Bedi, G., Hyman, D., De Wit, H. · Biological Psychiatry (2010)
´dric, C., Hysek, M., Schmid, Y. et al. · Social Cognitive and Affective Neuroscience (2013)
Oehen, P., Traber, R., Widmer, V. et al. · Journal of Psychopharmacology (2012)
Jerome, L., Feduccia, A. A., Wang, J. B. et al. · Psychopharmacology (2020)
Cited By (2)
Papers in Blossom that reference this study
Kvam, T. M., Goksøyr, I. W., Rog, J. et al. · British Journal of Psychiatry (2025)
Agin-Liebes, G. I., Zeifman, R. J., Mitchell, J. · European Journal of Psychotraumatology (2025)
Your Personal Research Library
Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.