The Food and Drug Administration on Friday raised concerns about the health effects of MDMA as a treatment for post-traumatic stress disorder, citing flaws in a company's studies that could pose major hurdles to approval of a treatment expected to help people who struggle with the condition.
The agency said bias crept into the studies because participants and therapists were easily able to tell who received MDMA versus a placebo. It also reported “significant increases” in blood pressure and heart rate that could “trigger cardiovascular events.”
The staff analysis was conducted for an independent advisory panel that will meet Tuesday to consider an application from Lykos Therapeutics to use MDMA-assisted therapy. The agency's concerns highlight the unique and complex issues facing regulators as they evaluate the therapeutic value of an illegal drug commonly known as Ecstasy that has long been associated with late-night raves and cuddling puddles.
Approval would mark a sea change in the nation's tortuous relationship with psychedelic compounds, most of which the Drug Enforcement Administration classifies as illegal substances that “have no currently accepted medical use and a high potential for abuse.”
Research such as the current MDMA therapy studies has stalled support from various groups and lawmakers in both parties for the treatment of PTSD, a condition that affects millions of Americans, especially military veterans who are at enormous risk of suicide. No new therapies have been approved for PTSD in more than 20 years.
“What's happening is really a paradigm shift for psychiatry,” said David Olson, director of the Institute for Psychedelia and Neurotherapy at UC Davis. “MDMA is an important step for the industry because there is a real lack of effective treatments, and people need help now.”
Amy Emerson, chief executive officer of Lykos Therapeutics, said the company stood by the data and design of its studies, which were developed in consultation with FDA staff members.
“These are not easy study projects; they are very complicated,” she said.
“Functional unmasking,” in which study participants can determine whether they were given a placebo, often influences research on psychoactive drugs because patients are acutely aware of the effects, he said.
A denial of the application would shake up the nascent field of psychedelic medicine, which has attracted millions of dollars in private investment. Much of this support has been based on the approval of MDMA therapy, which the FDA granted Breakthrough Therapy designation, or accelerated review, in 2017.
The agency gave 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 killed research on a variety of psychoactive compounds that had until then shown therapeutic promise.
In recent years MDMA has fascinated scientists, mental health professionals and patients moved by anecdotes and data suggesting that the drug, when combined with talk therapy, can produce significant improvements in a number of psychiatric conditions, including anxiety , depression, substance abuse and nutrition. disorders.
The drug is not, strictly speaking, a classic psychedelic substance like LSD or psilocybin. In its pure form, MDMA is considered an empathogen or entactogen, meaning it increases an individual's feelings 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 potential cardiac risks, MDMA has a well-established safety profile and is not considered addictive by many in the industry.
The FDA generally follows the recommendations of its advisory panel, and the agency is expected to reach a formal decision by 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 requiring further studies to evaluate its effectiveness as a treatment.
The latest two studies that Lykos submitted to the FDA looked at 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 taking MDMA were given an initial dose of 80 to 120 milligrams, followed by a half dose about two hours later. The sessions were four weeks apart.
Patients also had three appointments to prepare for therapy and another nine where they discussed what they had learned.
The most recent study of the drug found that more than 86 percent of those who received MDMA achieved a measurable reduction in symptom severity. About 71% of participants improved enough to no longer meet the criteria for a PTSD diagnosis. According to the data presented, among those who took the placebo, 69% improved and almost 48% no longer qualify for a diagnosis of post-traumatic stress disorder.
“It's easy enough to point out the cracks in the study, but there's no question that MDMA is helping a lot of people with PTSD,” said Jesse Gould, a former Army Ranger who runs Heroic Hearts, a organization that helps veterans access psychedelic treatments. , most often outside the United States. “With no other drugs in the pipeline and with 17-22 veterans committing suicide every day, we desperately need new treatment options.”
The FDA has scheduled nearly two hours for public comments Tuesday, most likely giving space to a group of MDMA study participants and researchers who have highlighted what they describe as ethical violations and pressure to report positive results during clinical trials conducted by MAPS Public. Benefit Corporation, which changed its name to Lykos Therapeutics this year.
Approval, if granted, would likely have faded. The drug was studied during therapeutic sessions attended by a psychotherapist and by a second therapist who intervened for safety, given the vulnerability of the patients. The FDA staff's analysis proposed some restrictions on approval, including administering the drug in certain healthcare 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 medically certified providers 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 are concerned that the agency's approval could result in marginal treatments by untrained professionals.
To avoid this, the agency's approval “must be accompanied by rigorous regulations, stringent controls over prescribing and dispensing, comprehensive patient education, and ongoing monitoring and surveillance systems,” according to the letter signed by Dr. Saul M. Levin, director doctor of the association. and CEO.
If MDMA were approved, federal health authorities and Justice Department officials would have to follow certain steps to have the drug downgraded from a Schedule 1 controlled substance, similar to the process currently underway with cannabis. The DEA could also set manufacturing quotas for drug ingredients, as it does with stimulant drugs used to treat ADHD.
FDA data released Friday notes that “participants appear to experience rapid, clinically significant, and long-lasting improvement in PTSD symptoms.”
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The agency's 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, released a 108-page report questioning the results of Lykos' study and believing “ the effects of the treatment are inconclusive.
The report notes that some study participants told ICER that ideology shaped the study results, influenced by a close-knit community of therapists interested in psychedelics in reporting good results. Some said they felt they would have been shunned if they had done otherwise.
ICER also described the studies as small and perhaps biased by the fact that around 40% of participants had previous experience of taking MDMA, much more than the general population. Lykos countered the criticism, saying the figure reflects the reality that PTSD patients, desperate for relief, often seek unregulated treatments.
ICER also cited misconduct reported by Meaghan Buisson, an early participant in the study. A video of Ms. Buisson's session with two therapists, a married couple, suggested inappropriate touching.
“The severe post-traumatic stress disorder that led me to participate in this clinical trial has not been addressed or resolved,” Ms. Buisson said at a meeting of ICER consultants on Thursday. “All they did was lay on top of the concrete foundations of new traumas.”
MAPS, the study's original sponsor, addressed the issue in 2019 and again in 2022, saying it had reported the “ethical violation” to the FDA and health officials in Canada, where the conduct occurred.
In an interview on Thursday, Ms. Emerson, Lykos' chief executive, acknowledged the pain felt by Ms. Buisson, but said that rejecting the company's application could produce greater risks given the growing number of people taking illicit drugs or they seek MDMA therapy in clandestine clinics. .
“The voices of injured people must be heard without anyone becoming defensive,” he said. “But people are desperate for treatment, and pushing MDMA outside of a regulatory pathway risks creating more harm.”
Regardless of FDA rules, specialists in the field of psychedelic medicine say there is no turning back, given the growing amount of promising research and broad public and political support that has accompanied and sustained 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 harm your career.
“Psychedelics are now passing the giggle test,” he said. “One notable thing about this moment is that while there are people who criticize aspects of some of these studies, you have to look hard to find people who oppose the substances on the grounds that they are psychedelics.”