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

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posted on 2025-05-07, 14:00 authored by Gabrielle Agin-Liebes, Richard J. Zeifman, Jennifer M. Mitchell

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.

MDMA-assisted therapy significantly improves self-compassion in individuals with severe posttraumatic stress disorder, showing large effect sizes across various aspects, including self-kindness and mindfulness.

Changes in self-compassion play a key role in reducing posttraumatic stress and depressive symptoms, mediating the therapeutic effects of MDMA-assisted therapy.

These findings highlight self-compassion as a potential target for developing more effective treatments for individuals with posttraumatic stress disorder and co-occurring depression.

MDMA-assisted therapy significantly improves self-compassion in individuals with severe posttraumatic stress disorder, showing large effect sizes across various aspects, including self-kindness and mindfulness.

Changes in self-compassion play a key role in reducing posttraumatic stress and depressive symptoms, mediating the therapeutic effects of MDMA-assisted therapy.

These findings highlight self-compassion as a potential target for developing more effective treatments for individuals with posttraumatic stress disorder and co-occurring depression.

Funding

This work was supported by Canadian Institutes of Health Research [grant number 202110MFE-472921-HTB-272687]; National Institutes of Health [grant number T32DA007250]; Lykos Therapeutics ; Multidisciplinary Association of Psychedelic Studies ; Food & Drug Administration; Robert Tod Chubrich; MindMed.

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