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.
Status
Completed
Results Published
Yes
Start date
29 November 2018
End date
21 August 2020
Chance of happening
100%
Phase
Phase III
Design
Blinded
Type
Interventional
Generation
First
Participants
100
Sex
All
Age
18- 99
Therapy
Yes
Trial Details
Posttraumatic stress disorder (PTSD) is a stress-related psychiatric condition that may occur following a traumatic event such as war, disaster, sexual abuse, violence, terrorism, or accidents. PTSD can negatively impact a person's daily life, resulting in relationship difficulties, difficulty in finding and maintaining a job, reduced cognitive and psychosocial functioning, substance abuse, high-cost healthcare use, and increased depression and suicide risk. Available PTSD treatments, including medications and therapy, effectively treat only a fraction of people who try them for adequate dose and duration. People with PTSD can be treated with psychotherapies and pharmacotherapies. In the past decade, there has been a growing amount of research into medications and other methods that may augment the effectiveness of psychotherapy for PTSD. 3,4-methylenedioxymethamphetamine (MDMA) induces serotonin release and has been shown to enhance fear memory extinction, modulate fear memory reconsolidation, and bolster social behavior in animal models. Pooled analysis of six Phase 2 trials of MDMA-assisted therapy for PTSD have now shown promising safety and efficacy findings. This multi-site, double-blind, randomized Phase 3 study assessed the efficacy and safety of MDMA-assisted therapy versus placebo with therapy in participants diagnosed with at least severe PTSD. The study will be conducted in N ≈ 100 participants. Participants will be enrolled in one of two groups at a 1:1 ratio. A flexible dose of MDMA or placebo, followed by a supplemental half-dose unless contraindicated, is administered 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. Initial doses per Experimental Session include 80 mg or 120 mg of MDMA or placebo followed 1.5 to 2 hours later by a supplemental half-dose (40 or 60 mg). Total amounts of MDMA to be administered per Experimental Session range from 80 mg to 180 mg. The Primary Outcome measure is change in Clinician Administered PTSD Scale for DSM-V (CAPS-5) from Baseline to Primary Endpoint (18 weeks post-Baseline). Drug safety will be assessed by measuring blood pressure, heart rate and body temperature during experimental sessions, collecting adverse events and measuring suicidal thoughts or behaviors with the Columbia Suicide Severity Rating Scale (adapted C-SSRS).NCT Number NCT03537014
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
Pilot study suggests DNA methylation of the glucocorticoid receptor gene (NR3C1) is associated with MDMA-assisted therapy treatment response for severe PTSDThis 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.