Effects of MDMA-assisted therapy for PTSD on self-experience
Rachel Yehuda, Leah Bedrosian, Charlotte Harrison, Amy Emerson, Rick Doblin, Bessel Van der Kolk, Julie B. Wang, Allison R. Coker, Michael C Mithoefer, Berra Yazar-Klosinski
PLoS One January 10, 2024 DOI: 10.1371/journal.pone.0295926 (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 | Participants with severe PTSD |
| Interventions | MDMA-assisted therapy Therapy with placebo |
| Duration | 3 experimental sessions plus 3 preparation and 9 integration therapy visits; symptoms measured at baseline and 2 months after the last experimental session |
| Topics | Anxiety MDMA PTSD |
| Keywords | Placebo Clinical psychology Randomized controlled trial Exposure therapy Affect linguistics |
| Citations | 52 |
| Registration | NCT03537014 |
| Key findings | MDMA-assisted therapy led to significantly greater improvements in emotional coping and self-experience measures compared to therapy with placebo, which may help explain reductions in PTSD symptoms. |
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.
Comparable studies
Other randomized controlled trials on MDMA for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Gender differences in the subjective effects of MDMA Healthy volunteers with no or minimal MDMA experience | 2001 | Pooled analysis of three double-blind placebo-controlled studies | n = 74 |
| Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study. Autistic adults with marked to very severe social anxiety | 2018 | Randomized controlled trial | n = 12 |
| MDMA-assisted psychotherapy for treatment of anxiety and other psychological distress related to life-threatening illnesses: a randomized pilot study People with life-threatening illnesses and anxiety | 2020 | Randomized controlled trial | n = 18 |
| A randomized controlled trial of 3,4-methylenedioxymethamphetamine (MDMA) and fear extinction retention in healthy adults Healthy adults aged 21–55 from a major metropolitan area | 2022 | Randomized controlled trial | n = 34 |
| Social anxiety and MDMA-assisted therapy investigation: a novel clinical trial protocol Adults with moderate-to-severe generalized social anxiety disorder | 2023 | Randomized open-label delayed treatment pilot study | n = 20 |