A Phase 3 Program of MDMA-Assisted Therapy for the Treatment of Severe Posttraumatic Stress Disorder (PTSD)
Two Trials: MAPP1 and MAPP2
Study Sponsor: MAPS, a 501(c)(3) non-profit research organization
The MAPP Phase 3 Program Summary
Studies MAPP1 and MAPP2 are randomized, double-blind, placebo-controlled, multi-site clinical trials that assess the safety and efficacy of MDMA-assisted therapy in 200-300 participants with severe posttraumatic stress disorder (PTSD) from any cause, aged 18 and older.
The trials build on the promising results of MAPS’ completed Phase 2 clinical trials, and are the final phase of research required by the U.S. Food and Drug Administration (FDA) before deciding whether to approve MDMA as a legal prescription treatment for PTSD, required to be used in conjunction with therapy in an outpatient setting with a residential stay.
On August 16, 2017, the FDA granted Breakthrough Therapy Designation to MDMA for the treatment of PTSD. The FDA grants this designation for treatments that (1) are intended alone or in combination with one or more other drugs to treat a serious or life-threatening disease or condition; and (2) preliminary clinical evidence indicates may demonstrate substantial improvement over existing therapies. Breakthrough Therapy Designation also means that the FDA will work closely with MAPS to provide guidance on the development of MDMA for post-traumatic stress disorder to design and conduct the development program as efficiently as possible.
On July 28, 2017, MAPS and the FDA reached agreement on the Special Protocol Assessment for Phase 3 clinical trials. This agreement confirms that the protocol design, clinical endpoints, planned conduct, and statistical analyses for the Phase 3 trials (MAPP1 and MAPP2) are acceptable to support regulatory approval by the FDA.
MAPP1: A Randomized, Double-Blind, Placebo-Controlled, Multi-Site Phase 3 Study of the Efficacy and Safety of Manualized MDMA-Assisted Therapy for the Treatment of Severe Posttraumatic Stress Disorder
The Phase 3 trial will take place at 15 research sites in the U.S., Canada, and Israel (see list below). Participants in the main portion of the trial will be randomized to receive three sessions of either MDMA or placebo in conjunction with therapy over a 12-week treatment period, along with non-drug preparatory and integration sessions (three each). MDMA is administered in three single-dose inpatient therapy sessions spaced three to five weeks apart, along with preparatory and integration sessions.
The primary outcome measure for the study is the Clinician-Administered PTSD Scale (CAPS-5), a semi-structured interview used in the majority of clinical trials for PTSD. Additional measures will include the Inventory of Psychosocial Functioning, Beck Depression Inventory, and others. The CAPS-5 will be assessed by a blinded pool of independent raters.
MAPP1 Study Sites
This program will be conducted in following locations:
- Los Angeles, CA | private practice
- San Francisco, CA | research institution
- San Francisco, CA | private practice
- Boulder, CO | private practice
- Fort Collins, CO | private practice
- New Orleans, LA | private practice
- New York, NY | research institution
- New York, NY | private practice
- Charleston, SC | private practice
- Madison, WI | research institution
- Boston, MA | private practice
- Vancouver, Canada | research institution
- Be’er Ya’akov, Israel | research institution
- Tel HaShomer, Israel | research institution
Phase 2 clinical trials have shown that MDMA can reduce fear and defensiveness, enhance communication and introspection, and increase empathy and compassion, enhancing the therapeutic process for people suffering from PTSD.
In MAPS’ completed Phase 2 trials with 107 participants, 61% no longer qualified for PTSD after three sessions of MDMA-assisted therapy two months following treatment. At the 12-month follow-up, 68% no longer had PTSD. All participants had chronic, treatment-resistant PTSD, and had suffered from PTSD for an average of 17.8 years.
MDMA transiently increases heart rate, blood pressure, and body temperature in a dose-dependent manner that is generally not problematic for physically healthy individuals. Serious Adverse Events involving administration of MDMA in MAPS studies have been uncommon and non-life threatening. Phase 2 trial results are currently being prepared for publication.
MAPP2: A Randomized, Double-Blind, Placebo-Controlled, Multi-Site Phase 3 Study of the Efficacy and Safety of Manualized MDMA-Assisted Therapy for the Treatment of Severe Posttraumatic Stress Disorder
This multi-site, double-blind, placebo-controlled, randomized Phase 3 study will assess the efficacy and safety of MDMA-assisted psychotherapy versus psychotherapy with placebo control in participants diagnosed with at least moderate PTSD. The study will be conducted in N ≈ 100 participants. Participants will be randomized into one of two groups (MDMA or placebo) in a 1:1 ratio. A flexible dose of MDMA or placebo, followed by a supplemental half-dose unless contraindicated, will be administered during the Treatment Period with manualized psychotherapy in three monthly Experimental Sessions. This ~12-week Treatment Period will be preceded by three Preparatory Sessions with the participant and therapists. Initial doses in each Experimental Session will be 80 mg or 120 mg of MDMA compounded with mannitol and magnesium stearate or placebo alone (mannitol and magnesium stearate), followed 1.5 to 2 hours later by a supplemental half-dose (40 or 60 mg, respectively). Total amounts of MDMA to be administered per Experimental Session range from 80 mg to 180 mg. Each Experimental Session will be followed by three Integrative Sessions of non-drug psychotherapy to help the participants process and understand their experiences during the Experimental Sessions.
Funding for the research is provided by the Multidisciplinary Association for Psychedelic Studies (MAPS), a 501(c)(3) non-profit research and educational organization. Since its founding in 1986, MAPS has raised over $43.7 million for psychedelic therapy and medical marijuana research and education.
MAPS-sponsored clinical trials are conducted by the MAPS Public Benefit Corporation (MPBC), a wholly-owned subsidiary of MAPS formed in 2014 for the special purpose of balancing social benefits with income from legal sales of MDMA, other psychedelics, and marijuana. For more information, visit mapsbcorp.com.