The Food and Drug Administration raised concerns Friday 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 obstacles to approval of a treatment intended to help people living with this disease.
The agency said bias crept into the studies because participants and therapists were easily able to determine who received MDMA versus a placebo. It also reported “significant increases” in blood pressure and pulse rate that could “trigger cardiovascular events.”
The staff analysis was conducted for an independent advisory committee that will meet Tuesday to review an application from Lykos Therapeutics for the use of MDMA-assisted therapy. The agency’s concerns highlight the unique and complex issues regulators face when assessing the therapeutic value of an illegal drug commonly called Ecstasy, which has long been associated with late-night raves and puddle hugs.
Approval would mark a seismic shift in the nation’s tortuous relationship with psychedelic compounds, most of which are classified by the Drug Enforcement Administration as illegal substances that have “no currently accepted medical use and a high potential for abuse.” “.
Research such as the current MDMA therapy studies have garnered support from diverse groups and lawmakers in both parties for the treatment of PTSD, a disease that affects millions of Americans, particularly veterans who face high risk of excessive suicide. No new treatments have been approved for PTSD in over 20 years.
“What’s happening is truly a paradigm shift for psychiatry,” said David Olson, director of the UC Davis Institute for Psychedelics and Neurotherapeutics. “MDMA is an important step in this area because we really lack effective treatments, period, and people need help now.”
Amy Emerson, chief executive of Lykos Therapeutics, said the company stands behind the data and design of its studies, which were developed in consultation with FDA staff members.
“These are not easy models of study; they are very complicated,” she said.
“Functional unblinding,” in which study participants can determine whether they received a placebo, often influences research on psychoactive drugs because patients are fully aware of their effects, he said. -she declared.
A rejection of the application would shake up the nascent field of psychedelic medicine, which is attracting millions of dollars in private investment. Much of this support hinges on the approval of MDMA therapy, which the FDA granted breakthrough therapy designation, or expedited 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 previously shown great therapeutic promise.
In recent years, MDMA has captivated scientists, mental health professionals and patients moved by anecdotes and data suggesting that the drug, combined with talk therapy, can produce significant improvements in a range of conditions. psychiatric disorders, including anxiety, depression, substance abuse and eating disorders. troubles.
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 sense of empathy and social connectedness. But illicit versions of the drug purchased recreationally are often mixed with other drugs, increasing the risk of adverse effects.
Except for its potential 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 committee, and the agency is expected to make a formal decision by mid-August. But even if it were approved, the agency could heed advice from its staff and outside experts by imposing strict controls on its use and requiring additional studies to assess its effectiveness as a treatment.
The latest two studies Lykos submitted to the FDA looked at about 200 patients who underwent three sessions of eight hours each, during which about half received MDMA and the other half a placebo, according to a report published in Nature Medicine. In each session, the MDMA patients received an initial dose of 80 to 120 milligrams, followed by a dose half as strong about two hours later. The sessions were spaced four weeks apart.
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 who received MDMA achieved a measurable reduction in the severity of their symptoms. About 71 percent of participants improved enough to no longer meet the criteria for a PTSD diagnosis. Among those who took the placebo, 69 percent improved and nearly 48 percent no longer qualified for a PTSD diagnosis, according to the data submitted.
“It’s pretty easy to point out flaws in the study, but there’s no doubt that MDMA helps many 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 to 22 veterans committing suicide every day, we desperately need new treatment options. »
The FDA has scheduled nearly two hours of public comment Tuesday, most 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 qualified. The drug was studied in therapy sessions involving a psychotherapist and a second therapist present for safety reasons, given the vulnerability of patients. The FDA staff’s analysis proposed some restrictions upon approval, including administering the drug in certain health care settings, monitoring patients and tracking adverse reactions.
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 result in marginal treatments by untrained practitioners.
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 signed letter. by Dr. Saul M. Levin, medical director of the association. and general manager.
If MDMA is approved, federal health authorities and Justice Department officials would have to follow certain steps to have the drug downgraded from Schedule 1 controlled substance status, similar to the process currently underway for cannabis. The DEA could also set production quotas for drug ingredients, as it does for stimulant medications used to treat ADHD.
FDA filings released Friday note that “participants appeared to experience rapid, clinically meaningful, and lasting improvement in their PTSD symptoms.”
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The agency staff analysis released Friday echoes concerns raised in recent months. In March, the Institute for Clinical and Economic Review, a nonprofit organization that examines the costs and effectiveness of drugs, released a 108-page report questioning the results of the Lykos study and ruling that the treatment effects “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 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 by about 40 percent of participants having previously taken MDMA – far more than the general population. Lykos countered criticism, saying the figure reflects the reality that PTSD patients, desperate to find relief, often seek unregulated treatments.
ICER also cited reported misconduct by Meaghan Buisson, an early participant in the trial. A video of Ms. Buisson’s session with two therapists, a married couple, suggests inappropriate contact.
“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 advisors on Thursday. “All they did was pour new trauma on top of a concrete base. »
MAPS, the trial’s original sponsor, addressed the issue 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 on Thursday, Ms. Emerson, Lykos’ chief executive, acknowledged the pain Ms. Buisson felt, but said rejecting the company’s application could lead to greater risks given the growing number of people consuming drugs. illicit drugs or seeking MDMA therapy in underground clinics. .
“The voices of people who have been hurt need to be heard without anyone being defensive,” she said. “But people desperately need treatments, and pushing MDMA off the regulatory pathway is likely to create even more harm.”
Whatever the FDA’s decision, experts in the field of psychedelic medicine say there is no going back, given the growing body of promising research and the broad public and political support that has accompanied and supported its growth.
Bob Jesse, a longtime researcher who helped found the psilocybin team at Johns Hopkins University more than 25 years ago, recalled the days when most researchers hid their interest in the compounds psychedelics for fear of harming their careers.
“Psychedelics now pass the laughter test,” he said. “What’s remarkable at this point 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 oppose the substances on the grounds that ‘They’re psychedelic.’