Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder that can develop after a traumatic life experience that severely reduces the quality of life. This multi-site, double-blind, placebo-controlled, randomized Phase 3 study assessed the efficacy and safety of MDMA-assisted psychotherapy compared to psychotherapy with placebo in participants diagnosed with at least moderate PTSD.
The study will be conducted in up to N ≈ 100 participants. Participants will be randomized to receive a flexible dose of MDMA or placebo, followed by a supplemental half-dose, unless contraindicated, during the Treatment Period with manualized therapy in three monthly Experimental Sessions. This ~12-week Treatment Period is preceded by three Preparatory Sessions. During the Treatment Period, each Experimental Session is followed by three Integrative Sessions of non-drug psychotherapy.
Trial Details
Trial Number
Sponsors & Collaborators
MAPSMAPS stands for Multidisciplinary Association for Psychedelic Studies, it's the front runner in making psychedelics a legal way to use (and improve) in therapy.
Papers
Self-compassion mediates treatment effects in MDMA-assisted therapy for posttraumatic stress disorderThis secondary analysis (n=82) of a Phase III RCT of MDMA-assisted therapy found significant improvements in both uncompassionate self-responding and compassionate self-responding across all six Self-Compassion Scale subscales, most with large effect sizes. Changes in self-compassion fully mediated the reductions in PTSD severity and depressive symptoms observed with MDMA-AT versus placebo plus therapy, though no significant effects were seen for alcohol or substance use outcomes.
Pilot study suggests DNA methylation of the glucocorticoid receptor gene (NR3C1) is associated with MDMA-assisted therapy treatment response for severe PTSD
This pilot sub-study (MDMA, n=16; placebo, n=7) examined epigenetic changes in three hypothalamic-pituitary-adrenal (HPA) genes before and after MDMA-assisted therapy for post-traumatic stress disorder (PTSD). Methylation changes at 37 out of 259 CpG sites predicted symptom reduction, with one site in the NR3C1 gene showing greater methylation change in the MDMA treatment group compared to placebo.
Effects of MDMA-assisted therapy for PTSD on self-experience
This re-analysis of an RCT of MDMA-assisted therapy for PTSD finds that study participants (n=90) had significant improvements in the measures of self-experience (e.g. alexithymia - the inability to identify & describe emotions experienced by oneself). The change in scores of self-experience correlates with recovery from PTSD.
The Costs and Health Benefits of Expanded Access to MDMA-assisted Therapy for Chronic and Severe PTSD in the USA: A Modeling Study
This study (2022) uses a decision-analytic model to assess the cost and health benefits of expanded access to MDMA-assisted therapy (MDMA-AT) in the phase III clinical trials from MAPS. Expanding access to MDMA-AT to 25-75% of eligible patients was projected to avert 43,618-106,932 deaths and gain 3.3-8.2 million quality-adjusted life-years (QALYs).
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study
This double-blind, placebo-controlled study (n=90) finds that MDMA-assisted therapy (3x 80-120mg) is effective (d=.91, large effect size) in the treatment of PTSD. 67% of those in the MDMA-group no longer qualified for PTSD (vs 32% for the therapy-only group). This study is part of the Phase III trial to get MDMA approved by the FDA.
The Effects of MDMA-Assisted Therapy on Alcohol and Substance Use in a Phase 3 Trial for Treatment of Severe PTSD
This trial (n=90) assessed patterns of alcohol and substance use in patients receiving MDMA-assisted therapy. MDMA was associated with a significant reduction in Alcohol Use Disorder Identification Test (AUDIT) scores when compared to placebo. Changes in Drug Use Disorder Identification Test (DUDIT) scores did not significantly differ between groups.
Measures Used
Clinician-Administered PTSD Scale for DSM-5The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is often considered the gold standard in PTSD assessment. The 30-item structured interview was developed by staff at the U.S. Department of Veterans Affairs National Centre for PTSD. CAPS can be used to make a current diagnosis, lifetime diagnosis or assess PTSD symptoms over the past week in accordance with DSM-5 criteria.