MDMA-assisted psychotherapy for the treatment of PTSD.
Abstract
Background: Post-traumatic stress disorder is a prevalent mental health condition with a substantial impact on daily functioning that lacks sufficient treatment options. Here we evaluated six phase 2 trials in a pooled analysis to determine the study design for phase 3 trials of MDMA-assisted psychotherapy for PTSD.
Methods: Six randomized, double-blind, controlled clinical trials were conducted at five study centers from April 2004 to February 2017. Active doses of MDMA (75-125 mg, n = 72) or placebo/control doses (0-40 mg, n = 31) were administered to individuals with PTSD during manual psychotherapy sessions in two or three 8-hour sessions spaced one month apart. Three 90-minute sessions of non-drug therapy preceded the first exposure to MDMA, and three to four followed each experimental session.
Results: After two blinded experimental sessions, the active group had significantly greater reductions in total CAPS-IV scores from baseline than the control group [estimated mean MMRM difference (SE) between groups - 22.0 (5,17), P <0.001]. The Cohen's d effect size between the groups was 0.8, indicating a large treatment effect. After two experimental sessions, more participants in the active group (54.2%) did not meet the diagnostic criteria for PTSD from CAPS-IV than in the control group (22.6%). The improvement in depression symptoms on the BDI-II was greater for the active group compared with the control group, although it tended only towards significant differences between the groups [MMRM, estimated mean difference (SE) between groups - 6.0 (3.03), P = 0.053]. All doses of MDMA were well tolerated.
Conclusions: MDMA-assisted psychotherapy was effective and well-tolerated in a large sample of adults with PTSD. These studies supported the expansion to phase 3 trials and led the FDA to grant Breakthrough Therapy designation to this promising treatment.
Study record: ClinicalTrials.gov Identifier: NCT00090064 , NCT00353938 , NCT01958593 , NCT01211405 , NCT01689740 , NCT01793610 .
Keywords: Anxiety; MDMA; MDMA-assisted psychotherapy; Post-traumatic stress disorder; Psychedelic.
Declaration of conflict of interest
MCM received salary support from MAPS PBC as a clinical investigator and medical monitor of clinical trials, as well as for training and supervision of research psychotherapists.
AAF received salary support for full-time employment at MAPS PBC.
LJ received wage support for full-time employment at MAPS PBC.
AM received salary support from MAPS PBC as a clinical investigator and for the training and supervision of research psychotherapists.
MW received research support to conduct study assessments.
ZW received research support to conduct study assessments.
SH received salary support from MAPS PBC as a biostatistician.
BY-K. received salary support for full-time employment at MAPS.
AE received wage support for full-time employment at MAPS PBC.
RD received salary support for full-time employment at MAPS.
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