The Food and Drug Administration on Friday expressed concern about the health effects of MDMA as a treatment for post-traumatic stress disorder, citing flaws in one company’s studies that could pose significant obstacles to approval of a treatment being It anticipates will help people struggling with this condition.
The agency said bias had crept into the studies because participants and therapists could easily determine who received MDMA or who received a placebo. It also noted “significant increases” in blood pressure and pulse rate that could “trigger cardiovascular events.”
The staff analysis was conducted by an independent advisory panel that will meet Tuesday to consider an application by Lykos Therapeutics for the use of MDMA-assisted therapy. The agency’s concerns highlight the unique and complex issues regulators face when weighing the therapeutic value of an illegal drug commonly known as ecstasy that has long been associated with late-night raves and hugging puddles.
Approval would mark a seismic shift in the country’s tortuous relationship with psychedelic compounds, most of which the DEA classifies as illegal substances that “have no currently accepted medical use and have a high potential for abuse.”
Research such as the current studies on MDMA therapy have garnered support from various groups and lawmakers from both parties for the treatment of post-traumatic stress disorder, a disease that affects millions of Americans, especially military veterans who face enormous risk. suicidal. No new therapy has been approved for PTSD in more than 20 years.
“What’s happening is truly a paradigm shift for psychiatry,” said David Olson, director of the Institute for Psychedelics and Neurotherapeutics at UC Davis. “MDMA is an important step for the field because we really lack effective treatments and people need help now.”
Amy Emerson, CEO of Lykos Therapeutics, said the company stood behind the data and design of its studies, which were developed in consultation with FDA staff members.
“These are not easy study designs; They are very complicated,” she said.
“Functional disclosure,” in which study participants can determine whether they have been given a placebo, often influences research on psychoactive medications because patients are so aware of the effects, he said.
A rejection of the application would shake up the nascent field of psychedelic medicine, which has been attracting millions of dollars in private investment. Much of that support has been based on the approval of MDMA therapy, which the FDA granted breakthrough therapy designation, or expedited review, in 2017.
The agency has given the same designation to four other psychedelic compounds, including psilocybin “magic mushrooms” for depression and an LSD-like substance for generalized anxiety disorder.
The criminalization of psychedelics, initiated by the Nixon administration in the 1970s, effectively ended research on a variety of psychoactive compounds that until then had shown significant therapeutic promise.
MDMA in recent years has captivated scientists, mental health professionals and patients moved by anecdotes and data suggesting that the drug, when combined with psychotherapy, can produce significant improvements in a variety of psychiatric conditions, including anxiety , depression, substance abuse and diet. disorders.
The drug is not, strictly speaking, a classic psychedelic like LSD or psilocybin. In its pure form, MDMA is considered an empathogen or entactogen, meaning it increases an individual’s feeling of empathy and social connection. But illicit versions of the drug purchased for recreational purposes are often mixed with other drugs, increasing the risk of adverse effects.
With the exception of its possible cardiac risks, MDMA has a well-established safety profile and is not considered addictive by many in the field.
The FDA generally follows the recommendations of its advisory panel, and the agency is expected to reach a formal decision in mid-August. But even if it were approved, the agency could follow the advice of its staff and outside experts by imposing strict controls on its use and require additional studies to evaluate its effectiveness as a treatment.
The last two studies Lykos submitted to the FDA examined about 200 patients who underwent three sessions (eight hours each) in which about half received MDMA and the other half a placebo, according to a report published in Nature Medicine. . In each session, patients receiving MDMA received an initial dose of 80 to 120 milligrams, followed by a dose half as strong about two hours later. The sessions were separated by four weeks.
The patients also had three appointments to prepare for therapy and nine more in which they discussed what they had learned.
The most recent drug trial found that more than 86 percent of those given MDMA achieved a measurable reduction in the severity of their symptoms. About 71 percent of the participants improved enough to no longer meet the criteria for a PTSD diagnosis. Of those who took the placebo, 69 percent improved and nearly 48 percent no longer qualified for a diagnosis of post-traumatic stress disorder, according to the data presented.
“It’s pretty easy to point out flaws in the study, but there’s no doubt that MDMA is helping a lot of people with PTSD,” said Jesse Gould, a former Army soldier who runs Heroic Hearts, an organization that helps veterans to access psychedelic treatments. , most often outside the United States. “With no other medications in the pipeline and 17 to 22 veterans committing suicide each day, we desperately need new treatment options.”
The FDA has scheduled nearly two hours of public comment on Tuesday, likely giving a platform to a vocal group of MDMA study participants and researchers who have highlighted what they describe as ethical violations and pressure to report positive results during clinical studies conducted by MAPS. Public. Benefit Corporation, which this year changed its name to Lykos Therapeutics.
Approval, if granted, would likely be nuanced. The drug was studied during therapy sessions attended by a psychotherapist and a second therapist who came for safety, given the vulnerability of the patients. The FDA staff analysis proposed some restrictions upon approval, including administering the drug in certain health care settings, monitoring patients, and monitoring for adverse effects.
A recent example of such approval is Spravato, a ketamine nasal spray that the FDA requires to be administered by certified providers in a medical setting followed by two hours of monitoring.
In a letter, the American Psychiatric Association urged the FDA to take a measured approach. Dr. Jonathan Alpert, chairman of the group’s research council, said doctors were concerned that the agency’s approval could lead to marginal treatments by untrained professionals.
To avoid this, the agency’s approval “must be accompanied by rigorous regulations, strict prescribing and dispensing controls, comprehensive patient education, and ongoing monitoring and surveillance systems,” according to the letter signed by Dr. Saul M. Levin, director association doctor. and executive director.
If MDMA is approved, federal health authorities and Justice Department officials would have to take certain steps to convert the drug from being a Schedule 1 controlled substance, similar to the process currently underway with cannabis. The DEA could also set production quotas for drug ingredients, as it does for stimulant medications used to treat ADHD.
FDA records released Friday note that “participants appear to experience rapid, clinically significant, and long-lasting improvement in their PTSD symptoms.”
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The agency staff analysis released Friday echoed concerns raised in recent months. In March, the Institute for Clinical and Economic Review, a nonprofit that examines the costs and effectiveness of drugs, issued a 108-page report questioning the results of Lykos’ study and calling the treatment effects ” inconclusive”.
The report noted that some study participants told ICER that ideology shaped the study’s results, influenced by a tight-knit community of therapists interested in psychedelics to report good results. Some said they felt they would be rejected if they did otherwise.
ICER also described the studies as small and possibly biased because about 40 percent of participants had prior experience taking MDMA, much more than the general population. Lykos has responded to the criticism, saying the figure reflects the reality that PTSD patients, desperate for relief, often seek unregulated treatments.
ICER also cited reported misconduct by Meaghan Buisson, one of the trial’s first participants. A video of Ms. Buisson’s session with two therapists, a married couple, suggested inappropriate contact.
“The severe post-traumatic stress disorder that led me to this clinical trial was not addressed or resolved,” Ms. Buisson said during an ICER advisors meeting on Thursday. “All they did was lay a concrete foundation of new traumas.”
MAPS, the original sponsor of the trial, addressed the matter in 2019 and again in 2022, saying it reported the “ethical violation” to the FDA and health officials in Canada, where the conduct occurred.
In an interview Thursday, Emerson, Lykos’ chief executive, acknowledged the pain Buisson experienced but said rejection of the company’s application could lead to greater risks given the growing number of people using illicit drugs or seeking MDMA therapy. in clandestine clinics. .
“The voices of people who have been hurt must be heard without anyone becoming defensive,” he said. “But people are desperate for treatments, and removing MDMA from a regulatory pathway is likely to cause more harm.”
No matter which way the FDA rules, specialists in the field of psychedelic medicine say there is no turning back, given the growing trove of promising research and the broad public and political support that has accompanied and fueled its rise.
Bob Jesse, a longtime researcher who helped create the psilocybin team at Johns Hopkins University more than 25 years ago, recalled the days when most researchers hid their interest in psychedelic compounds for fear of damaging their careers. .
“Psychedelics are now passing the laugh test,” he said. “What’s notable about this moment is that while there are people who are critical of aspects of some of these studies, you have to look hard to find people who are opposed to these substances because they are psychedelics.”