Cited by 55Psychedelics and Drug StudiesPosttraumatic Stress Disorder ResearchPsychotherapy Techniques and Applications

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

Open access
van der Kolk, Bessel A., Wang, Julie B., Yehuda, Rachel, Bedrosian, Leah, Coker, Allison R., Harrison, Charlotte, Mithoefer, Michael, Yazar-Klosinki, Berra +2 more·2024·PLoS ONE

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.

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  • MDMA enhances metacognitive capacity, promoting self-other differentiation and deeper emotional processing, crucial in working with narcissistic pathology.

    “Additionally, MDMA has demonstrated it enhances metacognitive capacity, promoting self-other differentiation and deeper emotional processing, both of which are crucial in working with narcissistic pathology (137).”

    From Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach (2025) · cites this paper as [137]

    The Discussion reports that MDMA-assisted therapy improved emotional self-awareness and helped participants with PTSD access painful experiences, supporting the emotional-processing part of the claim. The paper does not demonstrate enhanced metacognitive capacity or self–other differentiation. It mentions an association between low self-compassion and narcissism, but does not study treatment of narcissistic pathology. (LLM, conf=0.88)

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  • MDMA-AT improves emotional regulation and strengthens self-experience, particularly in individuals with impaired self-coherence, such as those with PN.

    “MDMA-AT has also been shown to improve emotional regulation and strengthen self-experience, particularly in individuals with impaired self-coherence, such as those with PN (137).”

    From Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach (2025) · cites this paper as [137]

    The Results (Treatment effects on self-experience measures; page not provided) report greater improvements in measures of emotion regulation and self-experience with MDMA-assisted therapy than with therapy and placebo in participants with PTSD. The Discussion suggests benefits may be particularly relevant to people with clinically significant impairments in these areas, but the paper does not establish the effect in people with PN or show that they benefit particularly. (LLM, conf=0.89)

    Experimental — accuracy not yet measured
  • MDMA facilitates emotional disclosure and increases comfort in discussing personal feelings.

    “MDMA also facilitates emotional disclosure and increases comfort in discussing personal feelings (136, 137), which could be particularly important for narcissists with alexithymia, who struggle to identify and express their emotions.”

    From Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach (2025) · cites this paper as [137]

    The Methods (Self-experience measures) describe the alexithymia scale as measuring difficulty verbalizing emotions, and the Results (Treatment effects on self-experience measures) report greater improvement with MDMA-assisted therapy than with therapy plus placebo. This supports a link to expressing feelings, but the paper does not directly report greater comfort discussing personal feelings or measure emotional disclosure during sessions; the Discussion notes that sessions often occurred in relative silence. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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  1. [38]Beck AT, Steer RA, Brown GK. Manual for the beck depression inventory-II. San Antonio, TX: Psychological Corporation. 1996; 1: 82.

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Authors
van der Kolk, B. A., Wang, J. B., Yehuda, R., Bedrosian, L., Coker, A. R., Harrison, C., Mithoefer, M., Yazar-Klosinki, B., Emerson, A., & Doblin, R.
Affiliations
  • James J. Peters VA Medical Center (US)
  • University of California, San Francisco (US)
  • Medical University of South Carolina (US)
  • Multidisciplinary Association for Psychedelic Studies (US)
Venue
PLoS ONE
Published
2024-01-10
Volume
19
Issue
1
Pages
e0295926
ISSN
1932-6203 (ISSN-L)
OpenAlex
W4390693439
Cited by
55
References
81
Citations by year
2026: 17 · 2025: 19 · 2024: 19
FWCI
27.57
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, public-domain)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Multidisciplinary Association for Psychedlic Studies (MAPP1)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
Keywords
MDMA-assisted psychotherapy, post-traumatic stress disorder, self-experience, alexithymia, self-compassion, affect dysregulation, interpersonal conflict, transdiagnostic mechanisms, psychedelic therapy, treatment outcome predictors
MeSH terms
Coping Skills, Anxiety, Hallucinogens, Humans, Stress Disorders, Post-Traumatic, N-Methyl-3,4-methylenedioxyamphetamine

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