Critical review of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for posttraumatic stress disorder: Unanswered questions and future directions

A critical review of six randomized controlled trials of MDMA-assisted therapy for PTSD finds that five show evidence of safety and efficacy. However, the review identifies serious methodological problems: lack of a suitable comparison condition, poor blinding, rigid trial designs, high treatment costs, and no head-to-head comparisons with established PTSD therapies. The sponsoring organization behind all trials may introduce bias. While the results are encouraging, there is not yet enough evidence to recommend widespread adoption of MDMA-assisted therapy over current validated treatments.

Study at a glance

Abstract

AbstractBackground and AimsPost-Traumatic Stress Disorder (PTSD) is a debilitating condition that affects a sizable proportion of U.S. civilians, military personnel, and veterans. 3,4-Methylenedioxymethamphetamine-Assisted Therapy (MDMA-AT) is a novel treatment approach for PTSD that has both stirred media enthusiasm and drawn criticism. This critical review analyzes individual randomized, controlled trials of MDMA-AT and provides a narrative synthesis.MethodsA library search and analysis of extant literature reviews was conducted to identify publications containing original research findings with inter-group statistical comparisons from randomized, controlled trials of MDMA-AT. Seven articles were identified. One pilot study was excluded due to a lack of inter-group comparison.ResultsTo date, six (four Phase II and two Phase III) randomized, controlled trials of MDMA-AT have been published which met criteria for inclusion in this review. Study design, sponsor, recruitment methods, and participant demographics are similar across trials.ConclusionsFive out of six reviewed studies provide evidence for the apparent safety and efficacy of MDMA-AT. However, the lack of suitable comparison condition, poor blinding, and rigid study design across trials make interpretation of results difficult. In addition, the high costs of MDMA-AT and lack of head-to-head comparisons with validated PTSD therapies cast doubt on its potential promise as a treatment. The role of the sponsoring organization behind all trials may further introduce bias into findings. Though research to date is encouraging, there is not yet sufficient evidence to suggest that MDMA-AT should be see widespread adoption over current, validated forms PTSD of treatment.