On Friday, the Food and Drug Administration (FDA) raised concerns about the health effects of MDMA as a treatment for post-traumatic stress disorder, and the company's research flaws gave it a major boost in approving a treatment expected to help those struggling. You mentioned that it can be an obstacle.
The agency said bias crept into the study because participants and therapists could easily figure out who received MDMA or a placebo. It also indicated “significant increases” in blood pressure and pulse rate, which “could lead to cardiovascular events.”
The staff analysis was conducted for an independent advisory panel that will meet on Tuesday to consider Lykos Therapeutics' application for the use of MDMA-assisted therapy. The agency's concerns highlight the unique and complex challenges regulators face as they evaluate the therapeutic value of the illicit drug known as ecstasy, which has long been associated with all-night raves and hugs.
Approval would mark a sea change in the drug's warped relationship with the psychedelic compound, which the Drug Enforcement Administration classifies as an illicit substance that “has no currently accepted medical use and has a high potential for abuse.”
Studies like the recent study on MDMA treatment have garnered support from a variety of groups and lawmakers on both sides of the aisle for treatment of PTSD, a condition that affects millions of Americans, especially veterans who face a tremendous risk of suicide. No new treatments for PTSD have been approved in the past 20 years.
“What’s happening is a real paradigm shift in psychiatry,” said David Olson, director of the UC Davis Institute of Psychiatry and Neurotherapy. “MDMA is an important step in the field because effective treatments and durations are lacking and people need help now.”
Amy Emerson, CEO of Lykos Therapeutics, said the company stands behind the data and study design developed in consultation with FDA staff.
“This is not an easy study design. “It’s very complicated,” she said.
“Functional unblinding,” which allows study participants to see whether they received a placebo, often has implications for studies of psychoactive drugs because patients are well aware of their effects, she said.
If the application is rejected, it would shake up the nascent field of psychedelic medicine, which has attracted millions of dollars in private investment. Much of this support is based on the 2017 approval of MDMA treatments, which the FDA granted breakthrough therapy designation or expedited review.
The FDA 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 Nixon administration's criminalization of hallucinogenic drugs in the 1970s effectively halted research into a variety of psychoactive compounds that had until then shown significant therapeutic potential.
MDMA has captivated scientists, mental health professionals, and patients in recent years. I am impressed by the anecdotes and data showing that this medication, when combined with talk therapy, can significantly improve a variety of mental illnesses, including anxiety, depression, substance abuse, and eating disorders. obstacle.
Strictly speaking, this drug is not a classic hallucinogen like LSD or psilocybin. In its pure form, MDMA is considered an empathogen or stimulant. This means increasing a person's empathy and social connectedness. However, illegal drugs purchased recreationally are often mixed with other drugs, increasing the risk of side effects.
Potential cardiac risks aside, MDMA has a well-established safety profile and is not considered addictive by many in the field.
The FDA generally follows the advisory panel's recommendations and is expected to make a formal decision by mid-August. But even if approved, the agency may tightly control its use, listen to the advice of its own staff and outside experts, and require additional studies to evaluate its effectiveness as a treatment.
According to a report published in Nature Medicine, the last two studies Lycos submitted to the FDA involved three sessions (eight hours each) in about 200 patients, about half of whom were given MDMA and the other half a placebo. . In each session, patients were given an initial dose of 80 to 120 mg of MDMA, followed by a half dose approximately two hours later. Sessions were held four weeks apart.
Patients also had three appointments to prepare for treatment and nine more to discuss what they had learned.
The most recent drug trial found that more than 86% of people who took MDMA experienced a measurable reduction in the severity of their symptoms. Approximately 71% of participants improved to the point where they no longer met diagnostic criteria for PTSD. The data submitted showed that 69% of those who took the placebo improved and nearly 48% no longer qualified for a PTSD diagnosis.
“It’s easy to point out problems with 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, an organization that helps veterans get psychedelic treatment. He said. , most of which occur outside the United States. “With no other drugs in the pipeline and 17 to 22 veterans taking their own lives every day, we desperately need new treatment options.”
The FDA scheduled nearly two hours for public comment Tuesday, a platform for a vocal group of MDMA study participants and researchers who highlighted what MAPS Public describes as ethical violations in clinical studies conducted and pressure to report positive results. It is likely to provide . Benefit Corporation changed its name to Lykos Therapeutics this year.
If approval is granted, there will probably be nuances. The drug was studied during therapy sessions attended by a psychotherapist and a second therapist present for safety reasons, taking into account the patient's vulnerability. The FDA staff analysis suggested several limitations upon approval, including administering the drug in certain healthcare settings, monitoring patients, and tracking side effects.
One recent example of such approval is Spravato, a ketamine nasal spray that the FDA requires to be given by a certified provider in a healthcare setting and monitored for two hours.
In a letter, the American Psychiatric Association urged the FDA to take a cautious approach. Dr. Jonathan Alpert, chairman of the group's research committee, said doctors were concerned that the agency's approval could lead to untrained practitioners receiving fringe treatments.
To prevent this, according to a letter signed by Dr. Saul M. Levin, the association's medical director, the agency's accreditation “must be accompanied by strict regulations, strict prescribing and dispensing controls, comprehensive patient education, and a continuous monitoring and surveillance system.” . And the CEO.
Once MDMA is approved, federal health and Justice Department officials must follow certain steps to downgrade the drug from a Schedule 1 controlled substance, similar to the process currently underway for cannabis. The DEA may also set production quotas for drug ingredients, as it does for stimulants used to treat ADHD.
“Participants appeared to experience rapid, clinically meaningful, and sustained improvements in PTSD symptoms,” the FDA filing said Friday.
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An analysis of agency staff released Friday reflected concerns raised in recent months. In March, the Institute for Clinical and Economic Review, a nonprofit group that examines the costs and effectiveness of drugs, questioned Lycos' findings and issued a 108-page report deeming the treatment's effectiveness “inconclusive.” A comprehensive report has been published.
The report noted that some study participants told ICER that ideology shaped the study's findings, influenced by a close-knit community of therapists interested in psychedelics to report good results. Some people said they felt they would be turned away if they didn't do so.
ICER also explained that the study was small and may be biased, with approximately 40% of participants having previously taken MDMA. This is much more than the general population. Lycos countered that the figures reflected the reality that PTSD sufferers desperate for relief often turn to unregulated treatments.
ICER also cited misconduct reported by early trial participant Meaghan Buisson. Video footage of Mr Buisson's sessions with two therapists (a married couple) suggested inappropriate touching.
“The severe PTSD that brought me into this trial is unresolved and unresolved,” Mr. Buisson said at an ICER advisory meeting Thursday. “All they did was pour a concrete foundation of new trauma on top of it.”
MAPS, the original trial sponsor, addressed the issue again in 2019 and 2022, saying it had reported “ethical violations” to the FDA and health authorities in Canada where the conduct occurred.
In an interview Thursday, Lykos CEO Emerson acknowledged the pain Buisson has experienced, but said rejecting the company's application could pose greater risks given the growing number of people taking illegal drugs or seeking MDMA treatment in underground clinics. .
“Nobody should be able to hear the voices of those who are hurting without being defensive,” she said. “But people are in desperate need of treatment, and pushing MDMA off the regulatory pathway is likely to cause more harm.”
However the FDA rules, experts in the field of psychedelics say there is no turning back, given the rise in promising research and the broad public and political support that accompanies and fuels it.
Robert Jesse, a longtime researcher who helped found the psilocybin department at Johns Hopkins University 20 years ago, recalled a time when researchers hid their interest in psychedelics for fear of harming their careers.
“Psychedelics are now starting to pass the laugh test,” he said. “What is noteworthy at this moment is that while there are people who criticize aspects of these studies, you have to work hard to find people who are against the drug on the grounds that it is a psychedelic. “The genie is out of the bottle.”