Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study

Alicia L Danforth, Charles S Grob, Christopher Struble, Allison A Feduccia, Nick Walker, Lisa Jerome, Berra Yazar-Klosinski, Amy Emerson, Alicia L Danforth, Charles S Grob, Christopher Struble, Allison A Feduccia, Nick Walker, Lisa Jerome, Berra Yazar-Klosinski, Amy Emerson

Abstract

Rationale: Standard therapeutic approaches to reduce social anxiety in autistic adults have limited effectiveness. Since 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy shows promise as a treatment for other anxiety disorders, a blinded, placebo-controlled pilot study was conducted.

Objectives: To explore feasibility and safety of MDMA-assisted psychotherapy for reduction of social fear and avoidance that are common in the autistic population.

Methods: Autistic adults with marked to very severe social anxiety were randomized to receive MDMA (75 to 125 mg, n = 8) or inactive placebo (0 mg, n = 4) during two 8-h psychotherapy sessions (experimental sessions) in a controlled clinical setting. Double-blinded experimental sessions were spaced approximately 1 month apart with 3 non-drug psychotherapy sessions following each. The primary outcome was change in Leibowitz Social Anxiety Scale (LSAS) Total scores from Baseline to one month after the second experimental session. Outcomes were measured again six months after the last experimental session.

Results: Improvement in LSAS scores from baseline to the primary endpoint was significantly greater for MDMA group compared to the placebo group (P = 0.037), and placebo-subtracted Cohen's d effect size was very large (d = 1.4, CI - 0.074, 2.874). Change in LSAS scores from baseline to 6-month follow-up showed similar positive results (P = 0.036), with a Cohen's d effect size of 1.1 (CI - 0.307, 2.527). Social anxiety remained the same or continued to improve slightly for most participants in the MDMA group after completing the active treatment phase.

Conclusions: This pilot trial demonstrated rapid and durable improvement in social anxiety symptoms in autistic adults following MDMA-assisted psychotherapy. Initial safety and efficacy outcomes support expansion of research into larger samples to further investigate this novel treatment for social anxiety.

Trial registration: clinicaltrials.gov identifier, NCT02008396.

Keywords: 3,4-Methylenedioxymethamphetamine; Anxiety; Asperger’s; Autism; Liebowitz Social Anxiety Scale; MDMA; MDMA-assisted psychotherapy; Psychedelics; Social anxiety.

Conflict of interest statement

Alicia Danforth and Charles Grob received research funds from MAPS Public Benefit Corporation as clinical investigators.

Allison Feduccia, Lisa Jerome, and Amy Emerson received salary support for full-time employment with MAPS Public Benefit Corporation.

Berra Yazar-Klosinski received salary support for full-time employment with Multidisciplinary Association for Psychedelic Studies.

Nick Walker received payment for independent consultant services from Multidisciplinary Association for Psychedelic Studies.

Figures

Fig. 1
Fig. 1
CONSORT diagram
Fig. 2
Fig. 2
Change over time in LSAS total scores (MDMA n = 8 at baseline, n = 7 at all other time points; placebo n = 4). The primary endpoint occurred 1 month after the second experimental session. The 6-month follow-up visit was 6 months after the primary endpoint. The MDMA group had a greater mean change from baseline than the placebo group at the primary endpoint (P = 0.037) and at the 6-month follow-up (P = 0.036). The line at LSAS score of 60 represents inclusion criteria minimum score

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