MDMA-assisted therapy for social anxiety disorder: A randomized, open-label, wait-list controlled trial

±3, 4-methylenedioxymethamphetamine (MDMA) has positive effects on socio-emotional processing and MDMA-Assisted Therapy (MDMA-AT) showed promise for treating Social Anxiety Disorder (SAD) in a previous placebo-controlled trial.

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.

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-min preparation sessions, two MDMA sessions, and six 90-min integration sessions. The preregistered primary outcome was the Liebowitz Social Anxiety Scale; secondary outcomes were functioning, shame, acceptance, belongingness, self-concealment, and self-compassion.

Across 20 participants (45% women, 40% men, 15% transgender; 85% White; mean age 38) we observed a mean difference on the Liebowitz Social Anxiety Scale at 16-week primary outcome of -43.3 (SD = 14.7; 95% CI, -29.5 to -57.1; p < .0001; Hedges' g = 2.8) indicating greater improvement in the MDMA-AT condition. No serious adverse events occurred; adverse events were mild to moderate and transient.

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 clinical response, safety, and feasibility of MDMA-AT for SAD, supporting the need for further investigation. Trial Registration https://clinicaltrials.gov/study/NCT05138068.