MDMA-assisted therapy appears to be effective in relieving symptoms of post-traumatic stress disorder, according to a study published Thursday.
The research is the latest study by MAPS Public Benefit Corporation, a company that develops prescription psychedelics. It plans to submit the results to the Food and Drug Administration as part of an application for approval to market the psychedelic drug MDMA for the treatment of post-traumatic stress disorder in combination with talk therapy.
If approved, “MDMA-assisted therapy would be the first novel treatment for PTSD in over two decades,” said Berra Yazar-Klosinski, senior author of the study published in Nature Medicine and the company’s chief scientific officer. “PTSD patients can feel hope.”
PTSD affects approximately 5 percent of the adult population in the United States each year. But conventional therapies and medications help about 50 percent 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.
“My clinical experience shows that too many men and women have lost hope in conventional treatments and therapies and feel that the only way out for them is to commit suicide,” said Dr. Xenakis. “We need to do more to help them, and MDMA-assisted therapy offers a new, potentially life-saving option if carried out carefully 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 believes have no medical use and this also do have a high potential for abuse.
Previously, MDMA was administered by an estimated hundreds of therapists in North America and Europe for couples counseling, personal development, and trauma treatment.
“The great tragedy is that by the late 1970s and early 1980s it was pretty clear that MDMA had incredible therapeutic potential,” Rick Doblin, founder of the Multidisciplinary Association for Psychedelic Studies (MAPS), a nonprofit group, told MAPS belongs to 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 the treatment of PTSD since 2001. The Heffter Research Institute, another nonprofit group, is doing the same for psilocybin, the active ingredient in magic mushrooms. Since 1993.
In 2017, the FDA granted “breakthrough therapy” status to MDMA-assisted therapy for the treatment of PTSD. The award enables accelerated development of promising experimental drugs. Psilocybin-assisted therapy for treatment-resistant depression was granted breakthrough status in 2018.
The 104 participants in the new study were diagnosed with moderate to severe PTSD and lived with the condition for an average of 16 years. These included victims of childhood trauma, combat veterans, sexual assault survivors and others. Many have had suicidal thoughts in the past and also suffered from co-morbidities such as depression and alcohol addiction.
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 paired with talk therapy and then participated in three 90-minute talk therapy sessions.
During the experimental sessions, 53 participants received MDMA and 51 received an inactive placebo. Neither the therapists nor the participants were informed which patients had received the MDMA.
According to the research article, participants in the group who received MDMA experienced significantly greater reductions in their PTSD symptoms than those in the group who received a placebo.
At the end of the study, 86.5 percent of people in the MDMA group achieved a measurable reduction in symptom severity, researchers reported. About 71 percent of the MDMA group improved to the point where they no longer met criteria for a PTSD diagnosis. Of those who took the placebo, 69 percent improved and nearly 48 percent no longer qualified for a PTSD diagnosis.
The results were similar to results from the first phase 3 trial of MDMA-assisted therapy for PTSD, published in Nature Medicine in 2021. Of the 90 participants in this study, 67 percent of the group given MDMA no longer qualified for a PTSD diagnosis two months after treatment, compared to 32 percent in the placebo group.
One notable difference in the latest study is the diversity of 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 nonwhite, while about 9 percent of participants in the 2021 study were Hispanic or Latino and 22 percent were nonwhite.
“We have worked long and hard to obtain a study population that is more consistent with the general population with PTSD,” said Dr. Mitchell. “These are not just privileged people with a lot of time and resources.”
The increase in participant diversity was accompanied by 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 stipends to compensate for lost wages or to finance 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: “Given the significant health disparities these groups face, it will be critical that more Black and Indigenous people enroll.”
As in previous studies of MDMA-assisted therapy, treatment was generally well tolerated according to adverse event data presented. Common side effects, particularly 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 severe suicidal ideation during the study, but no suicide attempts were reported.
“People in both groups experienced certain worrisome adverse events, such as suicidality, at comparable rates, although it is notable that most people in the study had previously struggled with these challenges,” said Dr. Garcia Romeu.
In total, seven participants also had cardiovascular problems, including faster heartbeats. According to Dr. According to Paul Summergrad, a professor of psychiatry at Tufts University School of Medicine who was not involved in the research, these events were “generally not serious” but could indicate that a cardiologist is evaluating older patients or patients with known cardiac function should 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 assess 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 something “that the authors recognize and have done everything possible to mitigate,” said Dr. Steven Zalcman, chief of the development division of pathophysiology and biological interventions in adults at the National Institute of Mental Health, was not involved in the research.
The researchers are currently working on a follow-up study that will examine the long-term durability of the effects of MDMA-assisted therapy. Results from Phase 2 trials sponsored by MAPS showed 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 seeking approval for MDMA-assisted therapy. The agency, which does not comment on pending drug trials, could make a decision within a year.
Some outside experts said they did not believe the study’s results would meet the FDA’s approval criteria.
“The benefit in the active group really wasn’t much greater than the benefit in the placebo group,” said Dr. Allen Frances, Professor Emeritus of Psychiatry at Duke University. “Treatment with MDMA would impose enormous costs on the treatment system while providing only small, specific benefits – leading to a massive misallocation of already very scarce resources.”
Dr. However, Akua Prieto Brown, the medical director of the Alchemy Community Therapy Center in Oakland, California, who was also not involved in the study, criticized this “scarcity mentality” and said the focus should be on health care professionals. Instead, it is about “the treatment options for a disease that is known to be difficult to treat.”
Disagreements among mental health professionals are to be expected, said Dr.
Federal approval for MDMA-assisted therapy would also mean that the drug would have to receive a less serious controlled substance designation from the DEA and states.
Another potential bottleneck is therapist training. The company already oversees its own therapist training program and works with other partners, including universities, to improve training.
The specific standards and requirements the FDA might require of prescribers and what the agency would outline for MDMA-assisted therapy labeling instructions are still open questions, said Amy Emerson, executive director of MAPS PBC.
“Medication-assisted therapy hasn’t been approved yet, so there isn’t a lot of precedent,” she said.
The company has not yet set a price for the drug, Ms. Emerson said, and it will not control how much the therapy component will cost.
However, she contacts the insurance companies Medicaid and Medicare to ensure coverage, Ms. Emerson said. The group is also working on patient access programs to help those who lack insurance coverage and cannot pay out of pocket receive discounts or even free treatment.
Given the hurdles that still lie ahead, “it feels a little too early to really celebrate,” said Dr. Doblin. “But it’s been a long, long process and it’s amazing that we’ve gotten this far.”
Source : www.nytimes.com