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Psychopharmacology (Berl). 2019 May 7. doi: 10.1007/s00213-019-05249-5. [Epub ahead of print]

MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials.

Author information

1
Medical University of South Carolina, Charleston, SC, USA.
2
MAPS Public Benefit Corporation, 1115 Mission St, Santa Cruz, CA, USA. alli@mapsbcorp.com.
3
MAPS Public Benefit Corporation, 1115 Mission St, Santa Cruz, CA, USA.
4
Private Practice, Charleston, SC, USA.
5
University of British Columbia-Okanagan, Kelowna, BC, Canada.
6
Stanford School of Medicine, Stanford University, Stanford, CA, USA.
7
Multidisciplinary Association for Psychedelic Studies, Santa Cruz, CA, USA.

Abstract

BACKGROUND:

Posttraumatic stress disorder is a prevalent mental health condition with substantial impact on daily functioning that lacks sufficient treatment options. Here we evaluate 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 at five study sites were conducted 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 manualized psychotherapy sessions in two or three 8-h sessions spaced a month apart. Three non-drug 90-min therapy sessions preceded the first MDMA exposure, and three to four followed each experimental session.

RESULTS:

After two blinded experimental sessions, the active group had significantly greater reductions in CAPS-IV total scores from baseline than the control group [MMRM estimated mean difference (SE) between groups - 22.0 (5.17), P < 0.001]. The between-group Cohen's d effect size was 0.8, indicating a large treatment effect. After two experimental sessions, more participants in the active group (54.2%) did not meet CAPS-IV PTSD diagnostic criteria than the control group (22.6%). Depression symptom improvement on the BDI-II was greatest for the active group compared to the control group, although only trended towards significant group differences [MMRM, estimated mean difference (SE) between groups - 6.0 (3.03), P = 0.053]. All doses of MDMA were well tolerated, with some expected reactions occurring at greater frequency for the active MDMA group during experimental sessions and the 7 days following.

CONCLUSIONS:

MDMA-assisted psychotherapy was efficacious and well tolerated in a large sample of adults with PTSD. These studies supported expansion into phase 3 trials and led to FDA granting Breakthrough Therapy designation for this promising treatment.

TRIAL REGISTRATION:

ClinicalTrials.gov Identifier: NCT00090064, NCT00353938, NCT01958593, NCT01211405, NCT01689740, NCT01793610.

KEYWORDS:

Anxiety; MDMA; MDMA-assisted psychotherapy; Posttraumatic stress disorder; Psychedelic

PMID:
31065731
DOI:
10.1007/s00213-019-05249-5

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