Journal Article

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

Zeifman, Richard J., Mitchell, Jennifer M., Agin-Liebes, Gabrielle

2025

Overview

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. 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. 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. 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. 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.

• Publisher: Taylor & Francis Ltd,Taylor & Francis Group
• Subject: Adult / Alcohol / depression / Double-Blind Method / Drug use / Empathy - drug effects / Female / Humans / Male / MDMA / MDMA-assisted therapy / Mental depression / Middle Aged / Mindfulness / N-Methyl-3,4-methylenedioxyamphetamine - pharmacology / N-Methyl-3,4-methylenedioxyamphetamine - therapeutic use / Post traumatic stress disorder / posttraumatic stress disorder / Psychiatry / Self compassion / Stress Disorders, Post-Traumatic - drug therapy / Stress Disorders, Post-Traumatic - psychology / Stress Disorders, Post-Traumatic - therapy / Treatment Outcome