Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy
Open accessAbstract
A growing body of research suggests that traumatic events lead to persisting personality change characterized by increased neuroticism. Relevantly, enduring improvements in Post-Traumatic Stress Disorder (PTSD) symptoms have been found in response to 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. There is evidence that lasting changes in the personality feature of "openness" occur in response to hallucinogens, and that this may potentially act as a therapeutic mechanism of change. The present study investigated whether heightened Openness and decreased Neuroticism served as a mechanism of change within a randomized trial of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD. The Clinician-Administered PTSD Scale (CAPS) Global Scores and NEO PI-R Personality Inventory (NEO) Openness and Neuroticism Scales served as outcome measures. Results indicated that changes in Openness but not Neuroticism played a moderating role in the relationship between reduced PTSD symptoms and MDMA treatment. Following MDMA-assisted psychotherapy, increased Openness and decreased Neuroticism when comparing baseline personality traits with long-term follow-up traits also were found. These preliminary findings suggest that the effect of MDMA-assisted psychotherapy extends beyond specific PTSD symptomatology and fundamentally alters personality structure, resulting in long-term persisting personality change. Results are discussed in terms of possible mechanisms of psychotherapeutic change.
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MDMA improves psychological flexibility, reduces fear of negative evaluation, and enhances self-reflection.
“MDMA has been shown to improve psychological flexibility, reduce fear of negative evaluation, and enhance self-reflection (89, 134–136).”
From Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach (2025) · cites this paper as [134]
The Results (Analyses 2; page unavailable) report increased Openness after MDMA-assisted psychotherapy, and the Discussion links Openness with self-examination. These findings are related to flexibility and self-reflection, but the paper does not establish improvements in those specific outcomes or a reduction in fear of negative evaluation. Its findings also concern MDMA combined with psychotherapy in people with PTSD, rather than MDMA alone. (LLM, conf=0.84)
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- Authors
- Wagner, M. T., Mithoefer, M. C., Mithoefer, A. T., MacAulay, R. K., Jerome, L., Yazar-Klosinski, B., & Doblin, R.
- Affiliations
- Medical University of South Carolina (US)
- Private Practice, Mount Pleasant, USA
- University of Maine (US)
- MAPS Public Benefit Corp (MPBC), Santa Cruz, USA
- Multidisciplinary Association for Psychedelic Studies, Santa Cruz, USA
- Multidisciplinary Association for Psychedelic Studies (US)
- Corresponding author
- Wagner, Mark T
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2017-06-21
- Volume
- 31
- Issue
- 8
- Pages
- 967-974
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- PMC
- PMC5544120
- OpenAlex
- W2716623847
- Cited by
- 160
- References
- 51
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 21 · 2023: 14 · 2022: 18 · 2021: 11 · 2020: 49 · 2019: 10 · 2018: 10 · 2017: 4
- FWCI
- 24.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Psychopharmacology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- 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, MDMA, post-traumatic stress disorder, treatment-resistant PTSD, personality change, openness to experience, neuroticism, mechanisms of change, hallucinogens, personality traits
- MeSH terms
- Neuroticism, Adult, Combined Modality Therapy, Female, Hallucinogens, Humans, Male, Personality Inventory, Psychotherapy, Stress Disorders, Post-Traumatic, Treatment Outcome, N-Methyl-3,4-methylenedioxyamphetamine, Young Adult
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