PMID- 30371148 OWN - NLM STAT- MEDLINE DCOM- 20191210 LR - 20240403 IS - 1461-7285 (Electronic) IS - 0269-8811 (Print) IS - 0269-8811 (Linking) VI - 32 IP - 12 DP - 2018 Dec TI - 3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial. PG - 1295-1307 LID - 10.1177/0269881118806297 [doi] AB - BACKGROUND: Posttraumatic stress disorder often does not resolve after conventional psychotherapies or pharmacotherapies. Pilot studies have reported that 3,4-methylenedioxymethamphetamine (MDMA) combined with psychotherapy reduces posttraumatic stress disorder symptoms. AIMS: This pilot dose response trial assessed efficacy and safety of MDMA-assisted psychotherapy across multiple therapy teams. METHODS: Twenty-eight people with chronic posttraumatic stress disorder were randomized in a double-blind dose response comparison of two active doses (100 and 125 mg) with a low dose (40 mg) of MDMA administered during eight-hour psychotherapy sessions. Change in the Clinician-Administered PTSD Scale total scores one month after two sessions of MDMA served as the primary outcome. Active dose groups had one additional open-label session; the low dose group crossed over for three open-label active dose sessions. A 12-month follow-up assessment occurred after the final MDMA session. RESULTS: In the intent-to-treat set, the active groups had the largest reduction in Clinician-Administered PTSD Scale total scores at the primary endpoint, with mean (standard deviation) changes of -26.3 (29.5) for 125 mg, -24.4 (24.2) for 100 mg, and -11.5 (21.2) for 40 mg, though statistical significance was reached only in the per protocol set ( p=0.03). Posttraumatic stress disorder symptoms remained lower than baseline at 12-month follow-up ( p<0.001) with 76% ( n=25) not meeting posttraumatic stress disorder criteria. There were no drug-related serious adverse events, and the treatment was well-tolerated. CONCLUSIONS: Our findings support previous investigations of MDMA-assisted psychotherapy as an innovative, efficacious treatment for posttraumatic stress disorder. FAU - Ot'alora G, Marcela AU - Ot'alora G M AD - 1 Aguazul-Bluewater, Inc., Boulder, CO, USA. FAU - Grigsby, Jim AU - Grigsby J AD - 2 Department of Psychology, University of Colorado, Denver, CO, USA. FAU - Poulter, Bruce AU - Poulter B AD - 1 Aguazul-Bluewater, Inc., Boulder, CO, USA. FAU - Van Derveer, Joseph W 3rd AU - Van Derveer JW 3rd AD - 3 Integrative Psychiatric Healing Center, Boulder, CO, USA. FAU - Giron, Sara Gael AU - Giron SG AD - 4 Multidisciplinary Association for Psychedelic Studies (MAPS), Boulder, USA. FAU - Jerome, Lisa AU - Jerome L AUID- ORCID: 0000-0001-6209-8750 AD - 5 MAPS Public Benefit Corporation, Boulder, CO, USA. FAU - Feduccia, Allison A AU - Feduccia AA AD - 5 MAPS Public Benefit Corporation, Boulder, CO, USA. FAU - Hamilton, Scott AU - Hamilton S AD - 6 Stanford School of Medicine, Stanford, CA, USA. FAU - Yazar-Klosinski, Berra AU - Yazar-Klosinski B AD - 4 Multidisciplinary Association for Psychedelic Studies (MAPS), Boulder, USA. FAU - Emerson, Amy AU - Emerson A AD - 5 MAPS Public Benefit Corporation, Boulder, CO, USA. FAU - Mithoefer, Michael C AU - Mithoefer MC AD - 7 Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA. FAU - Doblin, Rick AU - Doblin R AD - 4 Multidisciplinary Association for Psychedelic Studies (MAPS), Boulder, USA. LA - eng PT - Clinical Trial, Phase II PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20181029 PL - United States TA - J Psychopharmacol JT - Journal of psychopharmacology (Oxford, England) JID - 8907828 RN - 0 (Hallucinogens) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Adult MH - Aged MH - Combined Modality Therapy MH - Cross-Over Studies MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Female MH - Follow-Up Studies MH - Hallucinogens/*administration & dosage/adverse effects MH - Humans MH - Male MH - Middle Aged MH - N-Methyl-3,4-methylenedioxyamphetamine/*administration & dosage/adverse effects MH - Pilot Projects MH - Psychiatric Status Rating Scales MH - Psychotherapy/*methods MH - Stress Disorders, Post-Traumatic/physiopathology/*therapy MH - Treatment Outcome MH - Young Adult PMC - PMC6247454 OTO - NOTNLM OT - 3,4-Methylenedioxymethamphetamine (MDMA) OT - depression OT - oxytocin OT - posttraumatic stress disorder OT - serotonin OT - sleep disturbance COIS- Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M Ot'alora G received research funds from MAPS Public Benefit Corporation (MPBC) as the clinical trial principal investigator as well as for training and supervision of research psychotherapists. J Grigsby received research funds from MPBC as a clinical trial sub-investigator. B Poulter received research funds from MPBC as a clinical trial sub-investigator and as study administrator. JW Van Derveer III received research funds from MPBC as a clinical trial sub-investigator and as a study physician. SG Giron received research funds from MPBC as a clinical trial sub-investigator and from MAPS for directing the Zendo Project. S Hamilton received research funds from MPBC as a biostatistician. A Feduccia, A Emerson and L Jerome received salary support for full-time employment with MPBC. B Yazar-Klosinski and R Doblin received salary support for full-time employment with MAPS. M Mithoefer received research funds from MPBC as clinical trial medical monitor as well as for training of research psychotherapists. EDAT- 2018/10/30 06:00 MHDA- 2019/12/18 06:00 PMCR- 2018/11/21 CRDT- 2018/10/30 06:00 PHST- 2018/10/30 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2018/10/30 06:00 [entrez] PHST- 2018/11/21 00:00 [pmc-release] AID - 10.1177_0269881118806297 [pii] AID - 10.1177/0269881118806297 [doi] PST - ppublish SO - J Psychopharmacol. 2018 Dec;32(12):1295-1307. doi: 10.1177/0269881118806297. Epub 2018 Oct 29.