The Food and Drug Administration raised concerns Friday about the health effects of MDMA used to treat post-traumatic stress disorder, citing flaws in a company’s studies that could significantly hinder approval of a treatment intended to help people with the disease.
The agency said bias entered the studies because participants and therapists could easily figure out who was receiving MDMA or a placebo. It also pointed to a “significant increase” in blood pressure and pulse rate that “could trigger cardiovascular events.”
The staff analysis was conducted for an independent advisory panel that will meet Tuesday to review an application from Lykos Therapeutics to use MDMA-assisted therapy. The agency’s concerns highlight the unique and complex issues regulators face as they weigh the therapeutic value of an illegal drug commonly known as ecstasy, which has long been associated with late-night raves and cuddles.
The approval would mark a sea change in the country’s difficult relationship with psychedelic compounds, most of which the Drug Enforcement Administration classifies as illegal substances that “currently have no recognized medical use and have a high potential for abuse.”
Research such as the current studies on MDMA therapy have confirmed the support of various groups and lawmakers from both parties for the treatment of PTSD, a condition that affects millions of Americans, particularly military veterans who are at outsized risk of suicide. No new treatment for PTSD has been approved for more than 20 years.
“What’s happening is really a paradigm shift for psychiatry,” said David Olson, director of the UC Davis Institute for Psychedelics and Neurotherapeutics. “MDMA is an important step for this field because we are really lacking effective treatments 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.
“These are not simple study designs; They’re very complicated,” she said.
“Functional unblinding,” which allows study participants to determine whether they have been given a placebo, often influences psychoactive drug research because patients are highly aware of the effects, she said.
Rejecting the proposal would devastate the emerging field of psychedelic medicine, which has attracted millions of dollars in private investment. Much of this support was based on the approval of the MDMA therapy, which the FDA granted fast-track designation 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 virtually halted research on a variety of psychoactive compounds that had previously shown significant therapeutic success.
MDMA has captivated scientists, mental health professionals and patients in recent years, moved by anecdotes and data suggesting that the drug, when combined with talk therapy, can lead to significant improvements in a range of psychiatric disorders, including anxiety, depression, substance abuse and eating disorders.
Strictly speaking, the drug is not a classic psychedelic like LSD or psilocybin. In its pure form, MDMA is considered an empathogen or entactogen, meaning it increases a person’s feelings of empathy and social connectedness. But illegal 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 potential cardiac risks, MDMA has a well-established safety profile and is not considered addictive by many experts.
The FDA generally follows the recommendations of its advisory panel and is expected to make a formal decision by mid-August. But even if it were approved, the agency could heed the advice of its staff and outside experts by imposing strict controls on its use and requiring additional studies to evaluate its effectiveness as a treatment.
The last two studies Lykos submitted to the FDA looked at about 200 patients who underwent three sessions – eight hours each – with about half given MDMA and half a placebo, according to one in Nature Medicine published report. In each session, patients receiving MDMA received an initial dose of 80 to 120 milligrams, followed by a half-strength dose about two hours later. The meetings were four weeks apart.
Patients also had three appointments to prepare for therapy and nine more to discuss their findings.
The most recent drug study 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 to the point where they no longer met criteria for a PTSD diagnosis. Of those who took the placebo, 69 percent had their condition improved and nearly 48 percent were no longer eligible for a diagnosis of PTSD, according to the data presented.
“It’s easy to point out gaps in the study, but there is no doubt that MDMA helps many people with PTSD,” said Jesse Gould, a former Army Ranger and head of Heroic Hearts, an organization that provides access to veterans Psychedelic treatments are facilitated, most commonly outside the United States. “With no other drugs in the pipeline and 17 to 22 veterans taking their own lives every day, we urgently need new treatment options.”
The FDA scheduled nearly two hours for a public comment Tuesday, most likely giving a platform to a vocal group of MDMA trial participants and researchers who have highlighted what they see as ethical violations and pressure to produce positive results in clinical trials conducted by MAPS Public Studies report Benefit Corporation, which changed its name to Lykos Therapeutics this year.
A permit, if granted, would likely be nuanced. The drug was studied during therapy sessions involving a psychotherapist and a second therapist who were present for safety reasons given the risk to the patients. FDA staff’s analysis suggested some restrictions on approval, including administering the drug in certain health care facilities, monitoring patients and tracking side effects.
A recent example of such approval is Spravato, a ketamine nasal spray that the FDA says must be administered by certified providers in a medical setting, followed by two hours of monitoring.
In a letter, the American Psychiatric Association called on the FDA to take a measured approach. Dr. Jonathan Alpert, chairman of the group’s research council, said doctors are concerned that regulatory approval could lead to side treatments by untrained doctors.
To prevent this, the agency’s approval “must be accompanied by strict regulations, rigorous prescribing and dispensing controls, comprehensive patient education and ongoing surveillance and monitoring systems,” says the statement from Dr. Saul M. Levin, the association’s medical director, signed the letter and executive director.
If MDMA is approved, federal health officials and Justice Department officials would have to follow certain steps to allow the drug to be downgraded from a Schedule 1 controlled substance, similar to the process currently underway with cannabis. The DEA could also set production quotas for drug ingredients, as is the case with stimulant medications used to treat ADHD.
FDA documents released Friday said that “participants appeared to experience rapid, clinically meaningful, and lasting improvement in their PTSD symptoms.”
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The agency staff’s analysis released Friday reflected concerns raised in recent months. In March, the Institute for Clinical and Economic Review, a nonprofit that studies the cost and effectiveness of drugs, released a 108-page report questioning Lykos’ trial results and calling the treatment’s effects “inconclusive.” classified.
The report noted that some study participants told ICER that ideology shaped the study results and that a close community of therapists interested in psychedelics reported good results. Some said they felt like they would be shunned if they didn’t.
ICER also described the studies as small and potentially biased, as about 40 percent of participants had previous experience using MDMA – far more than the general population. Lykos countered the criticism, saying the figure reflected the reality that PTSD patients desperate for relief often seek unregulated treatment.
ICER also cited misconduct reported by Meaghan Buisson, an early litigant. A video of Ms. Buisson’s session with two therapists, a married couple, suggested inappropriate contact.
“The severe post-traumatic stress disorder that landed me in this clinical trial remained untreated and unresolved,” Ms. Buisson said during a meeting of ICER advisers on Thursday. “All they did was pour a concrete foundation of new trauma over it.”
MAPS, the study’s original sponsor, looked into the matter in 2019 and again in 2022 and said it reported the “ethical breach” to the FDA and health authorities in Canada, where the behavior occurred.
In an interview on Thursday, Ms. Emerson, Lykos’ chief executive, acknowledged the pain Ms. Buisson felt but said the rejection of the company’s request was a reflection of the growing number of people taking illegal drugs or receiving MDMA in underground clinics. Seeking therapy could lead to greater risks.
“The voices of hurting people need to be heard without anyone becoming defensive,” she said. “But people are desperate for treatments, and pushing MDMA out of a regulatory path is likely to cause even more harm.”
Whatever the FDA decides, 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 fueled its rise.
Bob Jesse, a longtime researcher who helped establish the psilocybin team at Johns Hopkins University more than 25 years ago, recalled the days when most researchers kept their interest in psychedelic compounds secret for fear of damaging their careers.
“Psychedelics now pass the giggle test,” he said. “The remarkable 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 reject the substances on the grounds that they are psychedelics.”
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2024-06-01 23:12:23
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