PMID- 30196397 OWN - NLM STAT- MEDLINE DCOM- 20181231 LR - 20181231 IS - 1432-2072 (Electronic) IS - 0033-3158 (Print) IS - 0033-3158 (Linking) VI - 235 IP - 11 DP - 2018 Nov TI - Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study. PG - 3137-3148 LID - 10.1007/s00213-018-5010-9 [doi] AB - 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. FAU - Danforth, Alicia L AU - Danforth AL AD - Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Box 498, 1000 West Carson Blvd., Torrance, CA, 90509, USA. FAU - Grob, Charles S AU - Grob CS AD - Department of Psychiatry, Harbor-UCLA Medical Center, Box 498, 1000 West Carson Blvd., Torrance, CA, 90509, USA. cgrob@labiomed.org. FAU - Struble, Christopher AU - Struble C AD - Department of Psychiatry, Harbor-UCLA Medical Center, Box 498, 1000 West Carson Blvd., Torrance, CA, 90509, USA. FAU - Feduccia, Allison A AU - Feduccia AA AD - MAPS Public Benefit Corporation, 1115 Mission Street, Santa Cruz, CA, 95060, USA. FAU - Walker, Nick AU - Walker N AD - School of Undergraduate Studies, California Institute of Integral Studies, 1453 Mission Street, San Francisco, CA, 94103, USA. FAU - Jerome, Lisa AU - Jerome L AD - MAPS Public Benefit Corporation, 1115 Mission Street, Santa Cruz, CA, 95060, USA. FAU - Yazar-Klosinski, Berra AU - Yazar-Klosinski B AD - Multidisciplinary Association for Psychedelic Studies, 1115 Mission Street, Santa Cruz, CA, 95060, USA. FAU - Emerson, Amy AU - Emerson A AD - MAPS Public Benefit Corporation, 1115 Mission Street, Santa Cruz, CA, 95060, USA. LA - eng SI - ClinicalTrials.gov/NCT02008396 GR - NA/Multidisciplinary Association for Psychedelic Studies/ PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial DEP - 20180908 PL - Germany TA - Psychopharmacology (Berl) JT - Psychopharmacology JID - 7608025 RN - 0 (Serotonin Agents) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Adult MH - Anxiety/epidemiology/psychology/*therapy MH - Autistic Disorder/epidemiology/psychology/*therapy MH - Combined Modality Therapy/methods MH - Double-Blind Method MH - Fear/drug effects/psychology MH - Female MH - Humans MH - Male MH - Middle Aged MH - N-Methyl-3,4-methylenedioxyamphetamine/*administration & dosage MH - Pilot Projects MH - Psychotherapy/*methods MH - Serotonin Agents/*administration & dosage MH - Treatment Outcome PMC - PMC6208958 OTO - NOTNLM OT - 3,4-Methylenedioxymethamphetamine OT - Anxiety OT - Asperger's OT - Autism OT - Liebowitz Social Anxiety Scale OT - MDMA OT - MDMA-assisted psychotherapy OT - Psychedelics OT - Social anxiety COIS- 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. EDAT- 2018/09/10 06:00 MHDA- 2019/01/01 06:00 PMCR- 2018/09/08 CRDT- 2018/09/10 06:00 PHST- 2018/06/12 00:00 [received] PHST- 2018/08/20 00:00 [accepted] PHST- 2018/09/10 06:00 [pubmed] PHST- 2019/01/01 06:00 [medline] PHST- 2018/09/10 06:00 [entrez] PHST- 2018/09/08 00:00 [pmc-release] AID - 10.1007/s00213-018-5010-9 [pii] AID - 5010 [pii] AID - 10.1007/s00213-018-5010-9 [doi] PST - ppublish SO - Psychopharmacology (Berl). 2018 Nov;235(11):3137-3148. doi: 10.1007/s00213-018-5010-9. Epub 2018 Sep 8.