MDMA-Assisted Psychotherapy for Social Anxiety in Adults with Autistic Spectrum Disorder: A Randomized, Double-Blind, Placebo-Controlled Longitudinal Study
Irina Dell'Orto
2026 preprint DOI: 10.17605/osf.io/tqmr6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Clinical protocol Randomized Placebo-controlled Double-blind Longitudinal |
|---|---|
| Sample size | 44 |
| Population | English-speaking autistic adults aged 21–55 with clinically significant social anxiety (LSAS > 60), recruited across the UK, USA, Australia, and Canada |
| Interventions | MDMA-assisted psychotherapy MDMA Placebo |
| Dose | 80–120 mg MDMA or matched placebo; optional 40 mg booster |
| Duration | 12-month trial; 11-session intervention with primary outcomes at 3-month (T1) and 6-month (T2) follow-up |
| Measures | Liebowitz Social Anxiety Scale (LSAS), Social Functioning Scale (SFS), WHOQOL-BREF, Toronto Alexithymia Scale (TAS-20), Self-Compassion Scale–Short Form (SCS-SF), Working Alliance Inventory–Short Revised (WAI-SR), Camouflaging Autistic Traits Questionnaire (CAT-Q) |
| Topics | Anxiety MDMA Psychedelic-assisted therapy |
| Key points | Proposes a 12-month randomized, double-blind, placebo-controlled trial (N = 40–44) testing whether MDMA-assisted psychotherapy reduces social anxiety in autistic adults, with primary outcome change in LSAS total score at 3- and 6-month follow-up. The authors contend that CBT and SSRIs show limited and inconsistent efficacy in autistic individuals because they were developed within neurotypical frameworks and target behaviour rather than relational and affective roots of distress. |
Abstract
Social anxiety is among the most disabling comorbidities in autistic adults, affecting approximately 50% of this population (Spain et al., 2018). Current first-line treatments — cognitive-behavioural therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) — demonstrate limited and inconsistent efficacy in autistic individuals, partly because they were developed within neurotypical frameworks and address behaviour rather than the relational and affective roots of distress. This pre-registered study proposes a 12-month, parallel-group, randomised, double-blind, placebo-controlled longitudinal trial (N = 40–44) evaluating the efficacy, durability, and psychological mechanisms of MDMA-assisted psychotherapy (MDMA-AP) for social anxiety in autistic adults. Participants are English-speaking adults aged 21–55 with clinically significant social anxiety (LSAS > 60), recruited across four English-speaking countries (UK, USA, Australia, Canada). The intervention consists of an 11-session integrative psychotherapy protocol: three preparatory sessions, two supervised dosing sessions (80–120 mg MDMA or matched placebo, spaced four weeks apart; optional 40 mg booster), and six integration sessions. The primary outcome is change in Liebowitz Social Anxiety Scale (LSAS) total score at 3-month (T1) and 6-month (T2) follow-up. Secondary outcomes include social functioning (SFS), quality of life (WHOQOL-BREF), and alexithymia (TAS-20). Pre-specified mediators are plasma oxytocin reactivity, self-compassion (SCS-SF), and therapeutic alliance (WAI-SR). Autistic masking (CAT-Q) is a pre-specified moderator. The primary analysis uses linear mixed-effects models under the intent-to-treat principle. Causal mediation analyses and reflexive thematic analysis of qualitative interview data will supplement quantitative findings. The study is grounded in a neurodiversity-affirming ethical framework: its goal is to reduce suffering and support self-acceptance, not to normalise autistic traits.