The Multidisciplinary Association for Psychedelic Studies (MAPS), a nonprofit organization, is planning to begin the first Phase 3 trials of 3,4-methylenedioxymethamphetamine (MDMA) to treat posttraumatic stress disorder (PTSD) this summer.

Based on positive Phase 2 proof-of-concept results, the Food and Drug Administration (FDA) permitted MAPS to go ahead with large-scale, Phase 3 clinical trials of the drug. In the trials, MDMA will be used as an adjunct to psychotherapy, administered by a doctor on three occasions. Due to its status as a Schedule I drug, all trials require authorization from the Drug Enforcement Agency (DEA) and the Food and Drug Administration (FDA).

MAPS has applied for breakthrough therapy status, and predict, if approved, that MDMA could be available in therapeutic settings by 2021. A recent paper published in the journal, Clinical Pharmacology and Therapeutics, presented information on how the drug works in treating psychiatric disorders and what course the clinical trials may take.

The paper highlights previous MDMA Phase 2 randomized controlled trials (RTCs) which demonstrated efficacy in PTSD patients, including combat veterans, sexual abuse victims and police officers. In one PTSD study, 2 months after two to three active-dose MDMA treatments, 55% of chronic PTSD subjects no longer met the PTSD Diagnostic Criteria (N=100) and 66.2% were in remission at least 12 months post-drug (N=65). 

Other MDMA studies (Neurosci. Biobehav. Rev. 57, 433–446, 2015) have resulted in participants reporting improved self-knowledge, sleep regulation, accuracy in perceiving mental states of others, coping strategies, emotion regulation, and cognitive insights. MDMA works by potentiating “the release of monoamines through reversal of transporter proteins and reuptake inhibition, with the greatest effects on serotonin and norepinephrine.” 

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“One of the first things I said when it kicked in was ‘this is what I’ve been looking for,” said Tony Macie, a retired army sergeant diagnosed with PTSD in 2007, and who took part in a MAPS Phase 2 trial. “I reconnected with myself and did a lot of internal work, and afterwards it was like a huge weight was lifted off my shoulders.”

The authors note that maintenance treatment with MDMA to prevent relapse is unlike most FDA-approved drugs, which may require chronic daily dosing for efficacy. In contrast, the proposed MDMA single-dose treatments have a more favorable risk/benefit profile. The authors of the article point out that Phase 3 study success for any MDMA-assisted psychotherapy would include criteria for statistical superiority over psychotherapy with placebo.

The chances of MDMA meeting the FDA’s accelerated pathway for an unmet medical need are good, as the effect size estimates for PTSD are large, relapse rates are low, and administration would be under strictly controlled conditions. MAPS is taking the lead on MDMA research but the organization says they will need to raise $25 to $30 million to complete the Phase 3 trials. So far they have raised $10 million and lack of funding could potentially slow progress.

MAPS intends to have 230 participants enrolled in their first Phase 3 trial in June of this year. As well as PTSD, MDMA-assisted psychotherapy could be a useful treatment for other disorders, including anxiety, obsessive-compulsive disorder, suicidality, and eating disorders. 

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