NBC News
The Food and Drug Administration (FDA) refused to approve MDMA, commonly known as ecstasy or molly –a laboratory-produced (synthetic) drug that has effects similar to those of methamphetamine – as a treatment for post-traumatic stress disorder, the pharmaceutical company Lykos Therapeutics reported on Friday.
Experts and advocates said the decision is a minor setback in the growing movement to use psychedelics to treat certain mental health conditions.
There was intense political pressure on the FDA to approve the drug. Friday’s decision was the first time the agency considered a Schedule 1 psychedelic for medical use. If approved, it would have been the first new treatment for post-traumatic stress disorder in more than two decades.
Lykos Therapeutics had asked the FDA to approve the drug as part of a treatment regimen that includes talk therapy.
The agency’s decision came after an independent advisory committee in June declined to recommend approval of the drug, saying there was insufficient evidence that the therapy was safe and effective.
The committee cited a host of concerns, including poorly designed studies, allegations of sexual misconduct during a mid-stage clinical trial and the potential for serious health risks after taking the drug, including heart problems and abuse.
A review by FDA scientists, released before the June meeting, also raised concerns about how the trials were conducted, including that several patients and therapists were likely able to guess who was given the drug and who received the placebo.
Despite the pushback, experts say they hope psychedelic therapies will eventually win FDA approval. There are about four dozen MDMA trials in various stages of clinical development, according to ClinicalTrials.gov.
“I think this is a temporary setback,” said Holly Fernandez Lynch, an assistant professor of medical ethics at the University of Pennsylvania. “The advisory committee and the FDA have given very clear directions of what they are looking for in terms of study design and adverse event reporting, so Lykos and other companies need to have a clear idea of how to proceed going forward if they want psychedelics to be approved.”
Scrutiny of psychedelics
The agency’s rejection highlights the high level of study and scrutiny that psychedelics must undergo as proponents of the treatment seek approval for medical use in the United States.
According to Lykos, the FDA has asked the company to complete an additional Phase 3 clinical trial to further study the safety and efficacy of MDMA. Lykos said the agency raised concerns similar to those raised during the advisory committee meeting in June. The drugmaker said it plans to ask the FDA to reconsider the decision.
“The FDA’s request for additional studies is deeply disappointing, not only to all who dedicated their lives to this pioneering effort, but most importantly to the millions of Americans with PTSD, along with their loved ones, who have not seen any new treatment options in more than two decades,” Lykos CEO Amy Emerson said in a statement.
An agency spokesperson said in a statement that the FDA recognizes there is a “significant need” for additional treatment options for PTSD.
However, “as discussed at the advisory committee meeting, there are significant limitations in the data contained in the application that prevent the agency from concluding that this treatment is safe and effective for the proposed indication,” the spokesperson said.
Around 13 million people in the United States, many of whom are veterans, have PTSD, according to data shared by the FDA at the June meeting.
Talk therapy, as well as antidepressants, are the main treatments, but patients may not stick with the therapy, and less than a third report complete remission of their symptoms with the drugs, according to the FDA.
David Olson, director of the UC Davis Institute for Psychedelics and Neurotherapeutics, said he does not believe the FDA’s decision will hinder the development of psychedelics for mental health disorders, including PTSD.
He also noted that the FDA has already approved a version of ketamine to treat treatment-resistant depression. That version, sold under the name Spravato, uses a modified drug called esketamine that does not produce the same dissociative and psychedelic effects as natural psychedelics.
Olson hopes that within the next five years there may be another psychedelic-based treatment for PTSD.
“Psychedelics like psilocybin are showing great promise, and hopefully the groups developing these compounds will learn from each other’s mistakes and become more rigorous,” Olson wrote in an email.
He also noted that there is a new and emerging class of drugs called neuroplastogens that he says have been designed to preserve the therapeutic effects of MDMA while minimizing side effects such as hallucinations.
“All of this means that the future is very promising for this type of therapy,” he said.
Dr. Brian Barnett, a psychiatrist who heads psychedelic research at the Cleveland Clinic in Ohio, also said he believes MDMA will eventually be approved for PTSD, despite the FDA’s decision.
“I think it will be another arrow in the quiver of psychiatry,” Barnett said. “We have some good treatments for PTSD. But they don’t work for everyone.”
He acknowledged the concerns of the FDA and the advisory committee, although he noted that some of the questions they raised about the trials are not unique to MDMA.
“The advisory committee was very focused on what was called functional blinding, where participants knew whether they had received MDMA or not,” she said. “I was very surprised that they focused so much on that, because functional blinding is a problem that affects essentially all pharmacological treatments in psychology.”
Pressure on the FDA
In July, nearly 800 veterans sent a letter asking President Joe Biden, a Democrat, to consider using MDMA for PTSD, saying they were “confident” the therapy would prove to be “one of the most valuable treatments to combat the epidemic of veteran suicides.”
Politicians also had their say.
Earlier this month, a bipartisan group of 80 lawmakers sent letters to Biden and FDA Commissioner Robert Califf urging them to consider approving the treatment, writing that “we cannot allow our veterans to continue to suffer in silence.”
Lynch, of the University of Pennsylvania, said she had been “dismayed to see politicians lobbying the FDA” over the decision, adding that it could hurt future approvals of psychedelics.
While agency decisions cannot be based solely on science, and questions about safety and efficacy require some “judgment” decisions, “when politicians interfere on behalf of specific products, it can reduce confidence in FDA decisions,” he said.
The Institute for Clinical and Economic Review, a nonprofit group that evaluates the cost and effectiveness of drugs, has criticized the development of the treatment, saying in a report published in late March that patients and trial providers treated psychedelics “more like a religious movement than pharmaceuticals.”
