Self-compassion mediates treatment effects in MDMA-assisted therapy for posttraumatic stress disorder

Background: Posttraumatic stress disorder (PTSD) is a severe condition often complicated by co-occurring disorders, such as major depression, alcohol use disorder, and substance use disorders. A well-powered phase 3 randomized, placebo-controlled trial has shown that MDMA-assisted therapy (MDMA-AT)...

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Main Authors: Gabrielle Agin-Liebes, Richard J. Zeifman, Jennifer M. Mitchell
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:European Journal of Psychotraumatology
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Online Access:https://www.tandfonline.com/doi/10.1080/20008066.2025.2485513
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author Gabrielle Agin-Liebes
Richard J. Zeifman
Jennifer M. Mitchell
author_facet Gabrielle Agin-Liebes
Richard J. Zeifman
Jennifer M. Mitchell
author_sort Gabrielle Agin-Liebes
collection DOAJ
description Background: Posttraumatic stress disorder (PTSD) is a severe condition often complicated by co-occurring disorders, such as major depression, alcohol use disorder, and substance use disorders. A well-powered phase 3 randomized, placebo-controlled trial has shown that MDMA-assisted therapy (MDMA-AT) may be an effective treatment for severe PTSD. However, the psychological mechanisms driving the therapeutic effects of MDMA-AT remain unclear. One potential mechanism is self-compassion, which is commonly conceptualized as a balance between compassionate self-responding (CS) – encompassing self-kindness, common humanity, and mindfulness – and uncompassionate self-responding (UCS) – encompassing self-judgment, isolation, and over-identification.Objective: This secondary analysis aimed to explore whether MDMA-AT enhances aspects of self-compassion and if changes in self-compassion mediate the therapy's effectiveness in reducing PTSD severity, depressive, and alcohol and substance use symptoms.Method: Eighty-two adults diagnosed with severe PTSD participated in a double-blind trial comparing three sessions of either MDMA-AT or placebo combined with therapy. Measures of PTSD severity, depressive symptoms, alcohol and substance use, and self-compassion were collected at baseline and 18 weeks later.Results: MDMA-AT led to statistically significant improvements in both UCS and CS. Significant improvements were also observed across all six subscales of the Self-Compassion Scale, including self-kindness, self-judgment, common humanity, isolation, mindfulness, and over-identification, most with large effect sizes. Changes in UCS and CS significantly and fully mediated the effects of MDMA-AT compared to placebo plus therapy in reducing PTSD severity and depressive symptoms. Findings were not significant for alcohol and substance use outcomes.Conclusions: These findings suggest that self-compassion may play a critical role in the therapeutic effects of MDMA-AT. Further research is needed to investigate the role of self-compassion in MDMA-AT to refine and develop more targeted, effective interventions for individuals with PTSD and co-occurring depression.
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spelling doaj-art-f4ddc3d2b1314c89aacd2f6b5e48b53f2025-08-20T02:16:01ZengTaylor & Francis GroupEuropean Journal of Psychotraumatology2000-80662025-12-0116110.1080/20008066.2025.2485513Self-compassion mediates treatment effects in MDMA-assisted therapy for posttraumatic stress disorderGabrielle Agin-Liebes0Richard J. Zeifman1Jennifer M. Mitchell2Department of Psychiatry, Yale School of Medicine, New Haven, CT, USADepartment of Psychiatry, NYU Langone Center for Psychedelic Medicine, NYU Grossman School of Medicine, New York, USADepartment of Neurology, University of California, San Francisco, CA, USABackground: Posttraumatic stress disorder (PTSD) is a severe condition often complicated by co-occurring disorders, such as major depression, alcohol use disorder, and substance use disorders. A well-powered phase 3 randomized, placebo-controlled trial has shown that MDMA-assisted therapy (MDMA-AT) may be an effective treatment for severe PTSD. However, the psychological mechanisms driving the therapeutic effects of MDMA-AT remain unclear. One potential mechanism is self-compassion, which is commonly conceptualized as a balance between compassionate self-responding (CS) – encompassing self-kindness, common humanity, and mindfulness – and uncompassionate self-responding (UCS) – encompassing self-judgment, isolation, and over-identification.Objective: This secondary analysis aimed to explore whether MDMA-AT enhances aspects of self-compassion and if changes in self-compassion mediate the therapy's effectiveness in reducing PTSD severity, depressive, and alcohol and substance use symptoms.Method: Eighty-two adults diagnosed with severe PTSD participated in a double-blind trial comparing three sessions of either MDMA-AT or placebo combined with therapy. Measures of PTSD severity, depressive symptoms, alcohol and substance use, and self-compassion were collected at baseline and 18 weeks later.Results: MDMA-AT led to statistically significant improvements in both UCS and CS. Significant improvements were also observed across all six subscales of the Self-Compassion Scale, including self-kindness, self-judgment, common humanity, isolation, mindfulness, and over-identification, most with large effect sizes. Changes in UCS and CS significantly and fully mediated the effects of MDMA-AT compared to placebo plus therapy in reducing PTSD severity and depressive symptoms. Findings were not significant for alcohol and substance use outcomes.Conclusions: These findings suggest that self-compassion may play a critical role in the therapeutic effects of MDMA-AT. Further research is needed to investigate the role of self-compassion in MDMA-AT to refine and develop more targeted, effective interventions for individuals with PTSD and co-occurring depression.https://www.tandfonline.com/doi/10.1080/20008066.2025.2485513Self-compassionposttraumatic stress disorderMDMAMDMA-assisted therapydepressionMDMA
spellingShingle Gabrielle Agin-Liebes
Richard J. Zeifman
Jennifer M. Mitchell
Self-compassion mediates treatment effects in MDMA-assisted therapy for posttraumatic stress disorder
European Journal of Psychotraumatology
Self-compassion
posttraumatic stress disorder
MDMA
MDMA-assisted therapy
depression
MDMA
title Self-compassion mediates treatment effects in MDMA-assisted therapy for posttraumatic stress disorder
title_full Self-compassion mediates treatment effects in MDMA-assisted therapy for posttraumatic stress disorder
title_fullStr Self-compassion mediates treatment effects in MDMA-assisted therapy for posttraumatic stress disorder
title_full_unstemmed Self-compassion mediates treatment effects in MDMA-assisted therapy for posttraumatic stress disorder
title_short Self-compassion mediates treatment effects in MDMA-assisted therapy for posttraumatic stress disorder
title_sort self compassion mediates treatment effects in mdma assisted therapy for posttraumatic stress disorder
topic Self-compassion
posttraumatic stress disorder
MDMA
MDMA-assisted therapy
depression
MDMA
url https://www.tandfonline.com/doi/10.1080/20008066.2025.2485513
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