MDMA-Assisted Psychotherapy for PTSD Trials Progressing Through Phase 3

The use of MDMA-assisted psychotherapy for the treatment of post-traumatic stress disorder (PTSD) has reached the Phase 3 clinical trial stage and could receive final approval by the US Food and Drug Administration (FDA) by 2022, Rick Doblin, PhD, founder and executive director of the Multidisciplinary Association for Psychedelic Studies (MAPS), told Psych Congress 2020 preconference attendees in a virtual session.

Noting an estimate by the US Department of Veterans Affairs that about 8 million people in the United States, including a little more than 1 million veterans, suffer from PTSD, Dr. Doblin chronicled his organization’s work in developing an MDMA-assisted form of psychotherapy.

“Our system is inner-directed,” Dr. Doblin said. “Once we give someone MDMA, they are the ones who produce the content. We follow and support where they are going. Our hypothesis is there is an inner healing intelligence. We all know that’s true for our bodies. If you get a scratch or break bones, your body has a mechanism to heal itself. … There is this wisdom of the body to try to sustain itself. We think similarly there is something like that for the psyche.”

Therapy is provided in 8-hour sessions, with patients spending half the time reclining and listening to music with headphones and concentrating on their inner focus. The other half of the time is spent speaking with a therapist.

The treatment allows for therapists to implement variations, and there is significant work spent on preparation and integration, Dr. Doblin said. Prior to sessions in which patients are given MDMA, therapists conduct three 90-minute preparation sessions. Another three weekly 90-minute sessions are conducted after the MDMA session as well. Therapy is provided by a two-person team, usually comprised of a male and female.

“A lot of time, we find that people who have developed PTSD have childhood trauma, so having a well-functioning male and female team can be very supportive and useful,” Dr. Doblin said. “It creates wisdom—two people see things differently sometimes—and [having two therapists] creates a sense of safety for the patient.”

The Phase 2 trial for the program, which concluded in 2016, included 105 patients who were given varying amounts of MDMA to identify the most effective dosage. (A dosage between 75 mg and 125 mg was deemed most effective.) At the conclusion of the trial, 56% of patients provided with MDMA no longer had PTSD symptoms compared to 23% of patients who were provided with a placebo. In a 12-month follow-up, 68% of patients reported no PTSD symptoms, and several more reported reduced symptoms.

The MAPS program was given a breakthrough therapy designation by the FDA in 2017, and it is now in a Phase 3 trial. Progress was slowed by the coronavirus pandemic earlier this year, Dr. Doblin said, but FDA allowed MAPS to wrap up the study early, with 90 participants having completed at least one outcome measure. Analysis of data from the study should be completed by later this month, Dr. Doblin said.

Should MDMA-assisted therapy be approved, Dr. Doblin said MAPS proposes four risk evaluation and mitigation strategies:

• The treatment should only be given by certified therapists who are trained by the MAPS or MAPS-certified trainers.
• It should only be administered under direct supervision in a certified clinic.
• It should only be distributed by a centralized pharmacy, with MDMA shipped to prescribers, not patients.
• There will be special safety screenings required for certain patient populations.

MAPS is currently engaged in formal dispute resolution with FDA on the risks/benefits of administering MDMA to therapists as part of training, whether the lead facilitator needs to be an MD or PhD, and whether a physician must be on site or just on call during therapy. Dr. Doblin said these issues should be resolved by the end of the year.

Should MDMA-assisted get final approval from FDA in 2022, Dr. Doblin said up to 6000 psychedelic clinics could open by 2030.

— Tom Valentino

Reference

“MDMA-Assisted Psychotherapy for PTSD: To Phase 3 and Beyond.” Presented at Psych Congress 2020: Virtual; September 9, 2020.