Effects of MDMA-assisted therapy for PTSD on self-experience

PLoS One. 2024 Jan 10;19(1):e0295926. doi: 10.1371/journal.pone.0295926. eCollection 2024.

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.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III

MeSH terms

  • Anxiety
  • Coping Skills
  • Hallucinogens* / therapeutic use
  • Humans
  • N-Methyl-3,4-methylenedioxyamphetamine* / therapeutic use
  • Stress Disorders, Post-Traumatic* / drug therapy

Substances

  • N-Methyl-3,4-methylenedioxyamphetamine
  • Hallucinogens

Grants and funding

The clinical trial was sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS), a 501(c)(3) non-profit organization. MAPS provided the MDMA and fully funded this study from private donations. Study sponsor responsibilities were fulfilled by MAPS Public Benefit Corporation (MAPS PBC), a subsidiary of MAPS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.