Social anxiety and MDMA-assisted therapy investigation: a novel clinical trial protocol

An open-label pilot study will test MDMA-assisted therapy for social anxiety disorder. Twenty participants with moderate-to-severe generalized social anxiety will be randomly assigned to immediate or delayed treatment. The immediate group receives three preparation sessions, two MDMA medicine sessions, and six integration sessions over about 16 weeks. The primary outcome is symptom reduction measured by the Liebowitz Social Anxiety Scale at post-treatment and 6-month follow-up. Secondary outcomes include changes in functional impairment, safety, and processes like shame, belongingness, self-concealment, and self-compassion. Results will inform the design of larger randomized controlled trials.

Study at a glance

Abstract

BackgroundSocial anxiety disorder (SAD) is a serious and prevalent psychiatric condition that heavily impacts social functioning and quality of life. Though efficacious treatments exist for SAD, remission rates remain elevated and a significant portion of those affected do not access effective treatment, suggesting the need for additional evidence-based treatment options. This paper presents a protocol for an open-label pilot study of MDMA-assisted therapy (MDMA-AT) for social anxiety disorder. The study aims to assess preliminary treatment outcomes, feasibility and safety, and psychological and physiological processes of change in the treatment of SAD with MDMA-AT. A secondary aim includes the development of a treatment manual for MDMA-AT for SAD.MethodThe outlined protocol is a randomized, open-label delayed treatment study. We will recruit 20 participants who meet criteria with moderate-to-severe social anxiety disorder (SAD) of the generalized subtype. Participants will be randomly assigned to an immediate treatment (n = 10) or delayed treatment condition (n = 10). Those in the immediate treatment condition will proceed immediately to active MDMA-AT consisting of three preparation sessions, two medicine sessions in which they receive oral doses of MDMA, and six integration sessions over approximately a 16-week period. The delayed treatment condition will receive the same intervention after a 16-week delay. Our primary outcome is SAD symptom reduction as measured by the Liebowitz Social Anxiety Scale administered by blinded raters at post-treatment and 6 month follow up. Secondary outcomes include changes in functional impairment, feasibility and safety measures, and novel therapeutic processes of change including shame and shame-related coping, belongingness, self-concealment, and self-compassion at post-treatment. Exploratory outcomes are also discussed.DiscussionThe results of this pilot trial advance the field’s understanding of the acceptability and potential effectiveness of MDMA-AT for social anxiety disorder and provide an overview of relevant therapeutic mechanisms unique to SAD. We hope findings from this protocol will inform the design of subsequent larger-scale randomized controlled trials (RCT) examining the efficacy of MDMA-AT for SAD.Clinical trial registrationhttps://clinicaltrials.gov/, NCT05138068.