Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study
This double-blind, placebo-controlled, randomised pilot study (n=12) found a significant reduction in social anxiety (d=1.4) after MDMA-assisted psychotherapy (75-125mg, 2 sessions). The effects persisted even 6-months later (d=1.1).
Authors
- Berra Yazar-Klosinski
- Lisa Jerome
- Amy Emerson
Published
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 the 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 the 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 the expansion of research into larger samples to further investigate this novel treatment for social anxiety.
Research Summary of 'Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study'
Introduction
Earlier research indicates that 3,4-methylenedioxymethamphetamine (MDMA) produces transient increases in social affiliation, reduces negative responses to social rejection, and promotes release of oxytocin, suggesting potential utility as an adjunct to psychotherapy for disorders of social fear. Danforth and colleagues note that autistic adults experience high rates of social anxiety disorder (SAD) and face limited benefit from standard treatments; biological differences in neurotransmitter systems among autistic people may also alter responses to conventional anxiolytics. Prior epidemiological reports of MDMA/ecstasy use by autistic adults further motivated investigation of MDMA-assisted psychotherapy for social anxiety in this population. This study set out to explore the feasibility and safety of MDMA-assisted psychotherapy for reducing social fear and avoidance in autistic adults with marked to very severe SAD. The trial was designed as a randomized, double-blind, placebo-controlled pilot study to assess change in social anxiety (primary outcome: Leibowitz Social Anxiety Scale, LSAS) from baseline to one month after the second experimental session, with additional follow-up at six months. The investigators emphasise that the intent was remediation of SAD symptoms, not to alter core features of autism itself.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Danforth, A. L., Grob, C. S., Struble, C., Feduccia, A. A., Walker, N., Jerome, L., Yazar-Klosinski, B., & Emerson, A. (2018). Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study. Psychopharmacology, 235(11), 3137-3148. https://doi.org/10.1007/s00213-018-5010-9
References (15)
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Carhart-Harris, R. L., Murphy, K., Leech, R. et al. · Biological Psychiatry (2015)
Danforth, A. L., Struble, C., Yazar-Klosinski, B. et al. · Progress in Neuro-Psychopharmacology and Biological Psychiatry (2016)
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Show all 15 referencesShow fewer
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Oehen, P., Traber, R., Widmer, V. et al. · Journal of Psychopharmacology (2012)
Vizeli, P., Liechti, M. E. · Journal of Psychopharmacology (2017)
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