The sponsor of the MDMA treatment, Lykos Therapeutics, conducted two late-stage clinical trials showing that patients treated with the drug experienced a significant improvement in their PTSD symptoms relative to those who got a placebo. The data, however, is uncommonly messy. Participants in the clinical trials also received various forms of psychotherapy, whose role wasn’t specifically measured in the results. The consciousness-distorting properties of MDMA also complicate the gold standard for clinical trials, which requires that participants not know whether they received a drug or a placebo.
An approval would mark a watershed moment for advocates who believe psychedelic drugs best known for mind-bending trips or partying can successfully treat an array of mental health disorders. MDMA’s potential has been championed by veterans and others who suffer from PTSD, a condition afflicting an estimated 13 million in the United States but for which there are few drugs approved for treatment.
Should the drug fail to win approval, it would be a monumental setback for the field of psychedelic medicine and investors who have poured hundreds of millions of dollars into companies developing psychedelics to treat mental health conditions.
Ahead of Tuesday’s advisory meeting, the FDA’s own staff raised extensive questions about the potential skewing of pivotal late-stage trials because patients figured out whether they had actually received the drug. The agency also highlighted cardiovascular and substance abuse risks.
An FDA official, Tiffany R. Farchione, told the panel Tuesday that while the agency had asked Lykos to report impacts associated with abuse, the company failed to note effects such as “euphoria” or “elated mood. ” That will make it challenging for the FDA, if it approves the drug, to describe MDMA’s effects for labeling or for treatment recommendations, said Farchione, director of the agency’s psychiatry division.
Farchione said the lack of data collection “may have the greatest impact” on the agency’s decision.
Lykos’s senior medical director, Alia Lilienstein, acknowledged Tuesday the company didn’t record euphoria and related effects because researchers did not interpret them to be “adverse events.” She said the company is prepared to study that data if MDMA-assisted therapy is approved.
“We recognize more can be learned in the real-world setting,” Lilienstein said.
The federal government categorizes MDMA as a Schedule I controlled substance with no accepted medical use and a high risk of abuse, in the same class as heroin and LSD.
Lilienstein stressed that while MDMA has a “moderately high” abuse potential, it remains lower than drugs such as methamphetamine and produces no withdrawal symptoms.
Committee member Maryann Amirshahi, a professor of emergency medicine at Georgetown University School of Medicine, said she is seeing more cases of MDMA overdoses — and asked about study patients who went on to use illicit doses.
Lilienstein said most patients did not use illicit MDMA after their sessions, but among the few that did, “no one used MDMA to satisfy a craving.”
Farchione also raised concerns about the effectiveness of the psychotherapy itself — which the FDA does not regulate. She added that while the agency could not label MDMA for use on its own, “we also don’t have strong evidence therapy is necessary.”
Committee members pressed Lykos officials on the company’s manual for therapy and how therapists were evaluated. They also raised concerns about the case of a female trial patient who said that in 2015 she was sexually abused by a male therapist, whose wife was also a therapist during sessions that crossed ethical boundaries.
“Let’s try to not gloss over this misconduct — it was sexual misconduct,” said Elizabeth Joniak-Grant, a University of North Carolina at Chapel Hill sociologist and panel member who serves as a patient representative.
A nonprofit affiliated with the American Psychological Association said in a letter to FDA on Monday that it determined there is “insufficient evidence” for the advisory panel to recommend MDMA-assisted therapy for PTSD, citing concerns that the results may have been biased by participants who knew whether they received the actual drug or a placebo. That echoed concerns from the influential nonprofit Institute for Clinical and Economic Review, which published a draft report this year voicing “substantial concerns” about the research supporting the drug’s approval.
Lykos officials said that rollout of the drug would be limited and that the FDA’s proposed restrictions would include that the drug could be dispensed only in certain health-care settings — with a doctor available while the drug is administered, and at least two health-care providers to monitor a patient’s physical and psychological state for at least eight hours.