PMID- 38198456 OWN - NLM STAT- MEDLINE DCOM- 20240112 LR - 20240112 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 19 IP - 1 DP - 2024 TI - Effects of MDMA-assisted therapy for PTSD on self-experience. PG - e0295926 LID - 10.1371/journal.pone.0295926 [doi] LID - e0295926 AB - 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. CI - Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. FAU - van der Kolk, Bessel A AU - van der Kolk BA AUID- ORCID: 0000-0001-5383-957X AD - Trauma Research Foundation, Brookline, MA, United States of America. FAU - Wang, Julie B AU - Wang JB AUID- ORCID: 0000-0001-7039-6061 AD - MAPS Public Benefit Corporation (MAPS PBC), San Jose, CA, United States of America. FAU - Yehuda, Rachel AU - Yehuda R AD - James J. Peters Veterans Affairs Medical Center, Bronx, NY, United States of America. AD - Center for Psychedelic Psychotherapy and Trauma Research, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America. FAU - Bedrosian, Leah AU - Bedrosian L AD - MAPS Public Benefit Corporation (MAPS PBC), San Jose, CA, United States of America. FAU - Coker, Allison R AU - Coker AR AUID- ORCID: 0000-0001-5353-4653 AD - University of California, San Francisco, San Francisco, CA, United States of America. AD - Multidisciplinary Association for Psychedelic Studies (MAPS), San Jose, CA, United States of America. FAU - Harrison, Charlotte AU - Harrison C AD - MAPS Public Benefit Corporation (MAPS PBC), San Jose, CA, United States of America. FAU - Mithoefer, Michael AU - Mithoefer M AUID- ORCID: 0000-0002-4267-6135 AD - MAPS Public Benefit Corporation (MAPS PBC), San Jose, CA, United States of America. AD - Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, United States of America. FAU - Yazar-Klosinki, Berra AU - Yazar-Klosinki B AUID- ORCID: 0000-0001-5972-006X AD - MAPS Public Benefit Corporation (MAPS PBC), San Jose, CA, United States of America. FAU - Emerson, Amy AU - Emerson A AD - MAPS Public Benefit Corporation (MAPS PBC), San Jose, CA, United States of America. FAU - Doblin, Rick AU - Doblin R AD - Multidisciplinary Association for Psychedelic Studies (MAPS), San Jose, CA, United States of America. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial DEP - 20240110 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - 0 (Hallucinogens) SB - IM MH - Humans MH - *N-Methyl-3,4-methylenedioxyamphetamine/therapeutic use MH - *Stress Disorders, Post-Traumatic/drug therapy MH - *Hallucinogens/therapeutic use MH - Anxiety MH - Coping Skills PMC - PMC10781106 COIS- The authors have declared that no competing interests exist. EDAT- 2024/01/10 18:42 MHDA- 2024/01/12 06:42 PMCR- 2024/01/10 CRDT- 2024/01/10 13:33 PHST- 2023/03/27 00:00 [received] PHST- 2023/11/28 00:00 [accepted] PHST- 2024/01/12 06:42 [medline] PHST- 2024/01/10 18:42 [pubmed] PHST- 2024/01/10 13:33 [entrez] PHST- 2024/01/10 00:00 [pmc-release] AID - PONE-D-23-07619 [pii] AID - 10.1371/journal.pone.0295926 [doi] PST - epublish SO - PLoS One. 2024 Jan 10;19(1):e0295926. doi: 10.1371/journal.pone.0295926. eCollection 2024.