Will FDA Block MDMA Stimulate Psychedelic Drug Research? : Gun shoots

The psychedelic drug MDMA is nearing the end of a decades-long effort to enter mainstream medicine, but instead of celebrating, supporters now find themselves wondering if the treatment will hit the market anytime soon.

Last week, advisers to the Food and Drug Administration analyzed the shortcomings and errors in the research and largely dismissed the evidence supporting MDMA as an effective treatment for post-traumatic stress disorder.

It was a stark public account of the future of drugs and an exploitative moment for those involved in psychedelic research.

“It really doesn’t seem like the data were given their due,” says Ingmar Gorman, a psychologist and investigator in the MDMA clinical trials that came under intense scrutiny last week. “The hope was always, if we do the science and we do the science right, the data will speak for itself.”

The advisory committee’s rejection of the drug also raised fears for the future of other psychedelics currently being studied for their therapeutic potential, rocking the market and generating a flood of bad press. Investors and scientists have doubled down on the sector in recent years and poured billions into drugs like psilocybin, ketamine and LSD.

Insiders don’t see the FDA’s powder as an existential threat to the broader psychedelic agenda. But some concerns raised about the research could offer lessons for future efforts to win FDA approval, says Frederick Barrett, director of the Johns Hopkins Center for Psychedelic and Consciousness Research.

“We need to go back in and look at all the studies that are going on now and make sure we’re doubling down on the most rigorous methods,” he says.

More than anything, though, he says the problems at the FDA are an indictment of how the drugmaker, Lykos Therapeutics, ran the trials. “There is a lot of frustration in the commission, but there is also a lot of frustration in [the sponsor] for submitting such a vulnerable application.”

What can happen to MDMA now?

Despite the negative showing, it is not beyond the realm of possibility that the agency will still approve the treatment against the recommendation of its advisory committee.

In fact, Dr. Srinivas Rao thinks there is a “low probability” of an outright rejection.

Instead, the agency could come back with a very strict set of safeguards and requirements to do further research after it goes to market, or the drugmaker could be required to do another clinical trial before FDA approval. .

“It’s a bit like a flip,” says Rao, CEO of Atai Life Sciences, a biotech company invested in mental health and psychedelics. “Going against the committee that is aggressively filled with. On the other hand, there is a lot of pressure to get this approved.”

Gorman says the panel overlooked key points about the research supporting MDMA-assisted therapy and seemed swayed by yet-to-be-proven allegations of ethical misconduct that FDA staff said were not supposed to cover the recommendations. Theirs.

“Now my concern is that it becomes political, doesn’t it?” he says “What is the FDA going to do? Will they oppose the vote taken by the advisory committee?”

Matthew Johnson thinks MDMA will eventually be approved, even if it doesn’t happen by the FDA’s August deadline.

“It seems like a tall order,” says Johnson, senior researcher for the Center of Excellence for Psilocybin Research and Treatment at mental health provider Sheppard Pratt. “You’re sticking your neck out, especially if something goes wrong.”

In the long run, some researchers think this is actually a much-needed level set for the field, lowering the noise and forcing a dialogue about the more dangerous sides of this treatment.

“I don’t see it as an obstacle for the field. It certainly is for Lykos,” says Alan Davis, director of the Center for Psychedelic Drug Research and Education at Ohio State University. “The message from this no vote is that research needs to be done more thoughtfully.”

Where did the MDMA trial go wrong?

The application from Lykos — a drug company incubated by the Multidisciplinary Association for Psychedelic Studies, or MAPS — arrived at the FDA under a cloud of controversy.

Former trial participants had claimed that adverse events were not reported – including suicidal feelings after treatment – and that bias among those running the trials had biased the results. A recent report questioning the validity of the data reinforced these concerns, as did a public hearing in which some accused the study’s sponsor of being a “therapy cult.”

Told that the FDA was actively investigating the claims, committee members were left to draw their own conclusions about their veracity.

“In this day and age, understandably, who wants to be on the side of some sort of argument against people claiming harm in a clinical trial? That’s a bad look,” says Gorman. “I think that was transferred to the FDA advisory panel.”

Aside from the ethics charges, which Lykos denies, some of the top sticking points for advisers may not, in reality, be that big of a deal for federal regulators.

For example, the panel noted “functional bias”—the fact that many trial participants could tell whether they had received the study drug instead of a placebo.

But that’s not necessarily a deal breaker, Johnson says. He points out that this concern is not unique to psychedelics. “This is very common with psychoactive drugs, which are used in psychiatry,” he says. “There will be no perfect solution to this blinding problem.”

Another blow against the app was criticism of the specific form of talk therapy that goes hand in hand with the drug. Councilors were concerned by what some saw as an “experimental” approach.

Dr. Jerry Rosenbaum disputes this characterization, saying the therapy had “core elements” of many evidence-based treatments.

“If anything, it was a generic therapy,” says Rosenbaum, director of the Center for Psychedelic Neuroscience at Mass General Hospital, who advocated on behalf of Lykos for the need for more PTSD treatment.

Gorman admits that Lykos’ therapy protocol is more “open-ended” and not as directed as other approaches such as cognitive-behavioral therapy. However, he says there have been extensive efforts to ensure that therapists adhere to the protocol – a fact that was lost in the committee’s discussion.

The whole idea that the therapy sessions were not standardized, which then undermines the findings, is “simply false,” he says.

Ultimately, Rosenbaum believes all of this is distracted by the fact that the FDA doesn’t even regulate psychotherapy. “People would be free to change therapy to some extent.”

It’s not just the data, it’s the ‘vibe’

In his application, Lykos describes MDMA as a catalyst for the therapeutic process, which is why it received so much attention. However, this is not expected to be as much of a hindrance to other psychedelics.

“Others are studying molecules that don’t require the same degree of therapy,” says Kabir Nath, CEO of Compass Pathways, a biotech company that is conducting phase III clinical trials on psilocybin.

Johnson says the reliance on an “idiosyncratic” form of therapy that may sound more “new” made MDMA-assisted therapy an increasingly tough sell.

In his view, it merely added to a “vibe” that was already creeping into the wider discussion, based largely on widely publicized claims that some involved in the trials had overlooked troubling events and treated the research more as a “movement ” rather than a scientific endeavor.

“There is a concern about the cult-like atmosphere in this field in general … the atmosphere that ‘we are awakening humanity,'” he says.

Although he has no direct knowledge that this has influenced the findings (some participants say it has), perception alone may be enough to sow distrust. “You have to bend over backwards to let people know that you don’t have this kind of religious zeal, that you’re following the data and the evidence.”

The fact that about 40% of those in the trial had tried MDMA before enrolling in the study only fueled speculation about whether the findings could be trusted.

Some lapses in judgment were even harder to ignore. The researchers did not collect data on participants’ experiences with the drug, such as euphoria — information that FDA staff needed to weigh abuse potential — or perform lab work related to the drug’s safety profile.

While these were legitimate mistakes, Barrett was confused by some of the discussion. He says advisers seemed to suggest that not much was known about the drug’s toxicity, although it had been well studied before the trials. And to his mind, they had unfounded concerns that patients would seek illicit drugs like cocaine after taking MDMA.

“It just blew my mind,” he says, “I didn’t understand where comments like that could come from.”

The level of resistance to the Lykos application was not surprising to OSU’s Alan Davis, given all the controversy.

“Personally, I think we still don’t have a full picture and understanding of all those potential issues,” Davis says. “More importantly, we absolutely do not yet have the infrastructure in the United States to address the kinds of specific risks that can arise as part of psychedelic therapy.”

The bumpy ride for Lykos may hold some lessons for others in the psychedelic space.

Nath says his company, Compass, has no plans to change the psilocybin trial design or protocol, but it reinforces the need to show “consistency” with the therapy component and collect relevant data on side effects.

“Obviously it will affect sentiment,” he says, “Over time, it shouldn’t make any difference to our trajectory from a development or regulatory perspective.”