MDMA-Assisted Therapy for Social Anxiety Disorder: A Randomized, Open-label, Wait-list Controlled Trial

MDMA-Assisted Therapy (MDMA-AT) produced a large reduction in social anxiety symptoms compared to a waitlist condition in adults with social anxiety disorder. In a randomized open-label trial of 20 participants, those receiving MDMA-AT showed an average decrease of 43.3 points on the Liebowitz Social Anxiety Scale after 16 weeks, while the waitlist group did not. Improvements also occurred in functioning, shame, acceptance, belongingness, self-concealment, and self-compassion. Adverse events were mild to moderate and temporary; no serious adverse events occurred. These preliminary findings suggest MDMA-AT is safe and feasible for social anxiety disorder and warrant further research.

Study at a glance

Abstract

Background: ±3,4-methylenedioxymethamphetamine (MDMA) has positive effects on socio-emotional processing and MDMA-Assisted Therapy (MDMA-AT) showed promise for treating SAD in a previous placebo-controlled trial. Aims: Develop a preliminary estimate of clinical response and safety for MDMA-AT versus waitlist in adults with SAD. Secondary aims included refinement of a standardized psychotherapy manual and assessment of candidate therapeutic processes. Method: This randomized, open-label, wait-list controlled clinical trial recruited and enrolled 20 participants diagnosed with SAD from April, 2022 to March, 2024. They were randomly assigned to either immediate treatment with MDMA-AT or a 16-week waitlist condition followed by MDMA-AT equivalent to the immediate treatment arm. MDMA-AT consisted of three 90-minute preparation sessions, two MDMA sessions, and six 90-minute integration sessions. The preregistered primary outcome was the Leibowitz Social Anxiety Scale; secondary outcomes were functioning, shame, acceptance, belongingness, self-concealment, and self-compassion. Results: Across 20 participants (45% women, 40% men, 15% transgender; 85% White; mean age 38) we observed a mean difference on the Leibowitz Social Anxiety Scale at 16-week primary outcome of −43.3 (SD = 14.7; 95% CI, −29.5 to −57.1; p < .0001; Hedge’s g = 2.8) indicating greater improvement in the MDMA-AT condition. No serious adverse events occurred; adverse events were mild to moderate and transient. Conclusions: MDMA-AT resulted in a significant reduction in social anxiety symptoms and improvement in functioning compared to waitlist. There were no serious adverse events. Findings provide preliminary data for efficacy, safety, and feasibility of MDMA-AT for SAD, supporting the need for further investigation. Trial Registration: https://clinicaltrials.gov/study/NCT05138068 Key words: MDMA, MDMA-AT, social anxiety disorder, clinical trial, RCT, psychedelics