MDMA therapy for PTSD moves closer to US approval

MDMA-assisted therapy appears effective in reducing symptoms of post-traumatic stress disorder, according to a study released Thursday.

The research is the latest trial conducted by MAPS Public Benefit Corporation, a company that develops prescription psychedelics. He plans to submit the results to the Food and Drug Administration as part of an application to market MDMA, the psychedelic drug, as a treatment for PTSD, when combined with talk therapy.

If approved, “MDMA-assisted therapy would be the first new treatment for PTSD in more than two decades,” said Berra Yazar-Klosinski, lead author of the study, published in Nature Medicine, and scientific director of the ‘business. . “Patients with PTSD may feel some hope. »

PTSD affects approximately 5 percent of the U.S. adult population each year. But conventional therapies and medications only help about 50% of patients, at best, said Dr. Stephen Xenakis, a psychiatrist and executive director of the American Psychedelic Practitioners Association, who was not involved in the study. .

“In my clinical experience, too many men and women have lost hope in the face of conventional treatments and therapies and feel that their only way out is to commit suicide,” said Dr. Xenakis. “We need to do something more to help them, and MDMA-assisted therapy offers a new, potentially life-saving option when applied thoughtfully and professionally.”

MDMA, also known as Ecstasy or Molly, has been an illegal substance since 1985, when the Drug Enforcement Administration classified it as a Schedule 1 drug, placing it in the highest category of controlled drugs that the agency considers it to be of no medical use and to have a high potential for abuse.

Before that, MDMA was administered by hundreds of therapists in North America and Europe for couples counseling, personal growth, and to treat trauma.

“The big tragedy to point out is that it was pretty clear in the late 1970s and early 1980s that MDMA had incredible therapeutic potential,” said Rick Doblin, founder of the Multidisciplinary Association for Psychedelic Studies. (MAPS), a non-profit group that owns MAPS. PBC. “All the suffering since then, because MDMA was criminalized, is enormous. »

MAPS has advocated for the legalization of MDMA-assisted therapy since 1986 and has supported research into its use in treating PTSD since 2001. The Heffter Research Institute, another nonprofit group, has done the same for psilocybin, the active ingredient in magic mushrooms, since 1993.

In 2017, the FDA granted “breakthrough therapy” status to MDMA-assisted therapy as a treatment for PTSD. This designation helps accelerate the development of promising experimental drugs. Psilocybin-assisted therapy for treatment-resistant depression achieved breakthrough status in 2018.

The 104 participants in the new study had been diagnosed with moderate to severe PTSD and had been living with the illness for an average of 16 years. They included victims of childhood trauma, veterans, survivors of sexual assault and others. Many had a history of suicidal thoughts and also suffered from comorbidities such as depression and alcohol use disorders.

Each participant worked with a two-person therapy team and received three 90-minute preparatory talk therapy sessions, followed by three treatment cycles, spaced one month apart. Each consisted of an eight-hour experimental session in which the participant took either MDMA or a placebo combined with talk therapy, then attended three 90-minute talk therapy sessions.

During the experimental sessions, 53 participants received MDMA and 51 received an inactive placebo. Neither therapists nor participants were informed which patients had received MDMA.

Participants in the MDMA group experienced a significantly greater reduction in their PTSD symptoms compared to those in the placebo group, according to the research article.

At the end of the study, 86.5 percent of people in the MDMA group achieved a measurable reduction in symptom severity, the researchers reported. About 71 percent of patients in the MDMA group improved enough to no longer meet the criteria for a PTSD diagnosis. Among those who took the placebo, 69 percent improved and almost 48 percent no longer qualified for a PTSD diagnosis.

The results were similar to those of the first Phase 3 study of MDMA-assisted therapy for PTSD, published in Nature Medicine in 2021. For the 90 participants in that study, 67% of the group who received MDMA were not more qualified for a PTSD diagnosis. two months after treatment, compared to 32 percent in the placebo group.

One notable difference in the most recent study was the diversity of the participants, said Jennifer Mitchell, a neuroscientist at the University of California, San Francisco and lead author of both studies.

More than a quarter of participants in the new study were Hispanic or Latino and about 34 percent were non-white, while about 9 percent of participants in the 2021 study were Hispanic or Latino and 22 percent were non-white. They weren’t white.

“We worked long and hard to get a study population that more closely matches the general population with PTSD,” Dr. Mitchell said. “It’s not just about privileged people with lots of time and resources.”

The increase in participant diversity coincided with an increase in the number of therapists of color, to 28 percent in the new study, up from 11 percent in 2021. MAPS PBC said it also offered participants transportation to and from study sites as well as allowances to compensate for lost wages or cover child or elderly care.

The diversity of participants is “certainly an improvement over previous studies,” said Albert Garcia-Romeu, a psychopharmacologist at Johns Hopkins University School of Medicine who was not involved in the research. But he added that “it will be critical to see more Black and Indigenous people sign up, given the substantial health disparities these groups face.”

As in previous studies of MDMA-assisted therapy, the treatment was generally well tolerated, according to the adverse event data presented. Common side effects, primarily among people in the MDMA group, included muscle tension, nausea, decreased appetite, and sweating.

Two participants in the MDMA group and one in the placebo group had serious suicidal thoughts during the study, but no suicide attempts were reported.

“People in both groups experienced some adverse events that would be concerning, such as suicidality, at comparable rates, although it should be noted that most people in the study already struggled with these challenges before.” , said Dr. Garcia-Romeu.

A total of seven participants also suffered from cardiovascular problems, including a faster heart rate. According to Dr. Paul Summergrad, a psychiatrist at Tufts Medical Center who was not involved in the research, although these events “were generally not serious,” they could indicate that a cardiologist should evaluate older patients or those with known heart problems before treatment with MDMA.

MAPS PBC said it worked closely with the FDA to determine the study methods and number of participants needed to evaluate the safety and effectiveness of the new treatment.

Most participants correctly guessed whether they had received a placebo or MDMA. This is a typical challenge in psychiatric research and is something that “the authors recognize and have done everything possible to mitigate,” said Dr. Steven Zalcman, head of the adult pathophysiology branch. and development of biological interventions at the National Institute of Mental Health, which was not informed. involved in the research.

Researchers are currently working on a follow-up study examining the long-term sustainability of the effects of MDMA-assisted therapy. Results from MAPS-sponsored Phase 2 studies indicated that benefits lasted at least 12 months for most participants who received the drug.

MAPS PBC plans to submit a new drug application to the FDA for approval of MDMA-assisted treatment. The agency, which does not comment on ongoing drug evaluations, could make a decision within a year.

Some outside experts said they did not believe the study results would meet the FDA’s criteria for approval.

“The benefits of the active group were actually not much greater than those of the placebo group,” said Dr. Allen Frances, professor emeritus of psychiatry at Duke University. “MDMA treatment would add enormous costs to the treatment system while providing only a small specific benefit – and thus result in a massive misallocation of already very scarce resources. »

Dr. Akua Prieto Brown, medical director of the Alchemy Community Therapy Center in Oakland, California, who was also not involved in the study, criticized this “scarcity mindset” and said that Instead, the focus for healthcare professionals should be on “increasing treatment options for a notoriously difficult-to-treat disease.”

Disagreements among mental health practitioners are to be expected, Dr.

Federal approval of MDMA-assisted therapy would also mean the drug would have to receive a less serious classification for DEA and state controlled substances.

Therapist training is another potential bottleneck. The company already oversees its own therapist training program and works with other partners, including universities, to increase training.

The specific standards and requirements the FDA might require of prescribers, and what the agency would set for labeling instructions for MDMA-assisted therapies, are still open questions, said Amy Emerson, executive director of MAPS PBC.

“Drug therapy hasn’t been approved before, so there’s not a lot of precedent,” she said.

The company has not yet priced the drug, Ms. Emerson said, and it will not manage the cost of the therapeutic component.

But he contacts insurance companies, Medicaid and Medicare, to try to get coverage, Ms. Emerson said. The group is also working on patient access programs to help those who don’t have coverage and can’t pay out of pocket to receive discounts or even free treatment.

Given the obstacles that remain, “it seems a little too early to really celebrate,” Dr. Doblin said. “But it’s been a very long process, and it’s amazing that we’ve gotten this far.”