Phase 2 Pilot Safety Study of MDMA-assisted Therapy for Social Anxiety in Autistic Adults

Studies suggest that autistic adults are at greater risk for social anxiety. Social anxiety is a condition characterized by fear of scrutiny and avoidance of social interactions. Social anxiety frequently compounds the considerable social challenges experienced by autistic adults. There are currently no FDA-approved pharmacologic treatments for autistic adults, although off-label prescription of selective serotonin reuptake inhibitors (SSRIs) are on the rise in this population.

Based on the known effects of MDMA, as well as individual reports from autistic adults, this exploratory study focused on enhancing functional skills in this underserved population, who tend to experience greater anxiety, depression and victimization than typically developing adults. This double-blind, randomized, placebo-controlled exploratory pilot study assessed the safety and feasibility of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for social anxiety in MDMA-naïve adults on the autism spectrum.

The main objective of this study was to collect safety data to examine whether MDMA-assisted therapy was tolerated and to estimate symptom reduction in social anxiety and other psychiatric symptoms that are common in the adult autistic population as evaluated by standard clinical measures. The primary outcome measure was change in social anxiety symptoms as measured by the Liebowitz Social Anxiety Scale (LSAS) [Heimberg et al., 1999].

Each of the 12 subjects participated in two blinded experimental sessions, assisted by either MDMA or placebo, which lasted seven hours. Before experimental sessions, participants underwent three separate hour-long preparatory sessions to learn what to expect and complete pre-treatment assignments. After each experimental session, participants underwent three separate hour-long integrative sessions to help integrate their experiences and insights from the experimental sessions.

This study was designed as a dose escalation study to assist with the exploration of safety and finding the most effective dose in this population. Upon enrollment, the first six subjects (Group 1) was randomized to receive one dose of either placebo (N=2) or 75 mg of MDMA (N=4). In the second experimental session one month later, Group 1 subjects randomized to MDMA escalated to 100 mg of MDMA, unless contraindicated. The second six subjects enrolled (Group 2) were randomized to receive one dose of either placebo (N=2) or 100 mg of MDMA (N=4). In the second experimental session one month later, Group 2 subjects randomized to MDMA escalated to 125 mg of MDMA, unless contraindicated.

The blind was maintained through the six-month follow-up. In Stage 2 after the blind was broken, subjects who received placebo in Stage 1 were offered an open-label extension with two experimental sessions of MDMA scheduled one month apart. Subjects received 75 mg of MDMA in the first session and escalated to 125 mg of MDMA in the second session, unless contraindicated.