Can MDMA still win FDA approval? Supporters rally as time runs out

It’s a crucial moment for the future of psychedelic medicine.

By August 11, the Food and Drug Administration is expected to decide whether MDMA – the chemical found in ecstasy or molly – can be prescribed as a treatment for post-traumatic stress disorder.

And supporters have launched an all-out push to convince the agency to greenlight the therapy, despite the fact that advisors to the agency overwhelmingly rejected the evidence supporting MDMA in combination with psychotherapy in June.

The push includes bipartisan support from Congress. On Monday, a group of 19 Senators from both parties sent a letter to the head of the FDA, drawing attention to MDMA's promise for treating PTSD, with signatures that included Democrats John Fetterman and Cory Booker, and Republicans Rand Paul and Thom Tillis, among others.  As of Friday, more than 60 House Democrats and Republicans had signed onto their own letter addressed to President Biden, voicing support for the treatment and pushing back on some of the recent criticism.

Military veteran groups helped rally this Congressional support. Veterans have emerged as some of the most visible advocates, arguing it fills a much-needed gap in effective treatments for PTSD.

Rogers Masson, an Army veteran, was skeptical when his wife broached the idea.

“I blew it off as that’s a bunch of woo woo,” recalls Masson, who is 55 and suffered from PTSD for years after his military service, “No way.”

Working in the music industry, he’d traveled in circles where ecstasy made an appearance, but had never been interested in taking the drug himself.

So it’s with a touch of irony that he now describes himself as a believer. The treatment rid him of chronic nightmares and dramatically “turned down the volume” on his other symptoms. He’s even planning to travel to Washington D.C in the coming days to meet with lawmakers and lobby with other veterans.

“I'm a complete newbie at this stuff,” says Masson, “I feel the need to say something and hope that somebody will listen.”

Recently, some prominent figures in mental health and psychedelics, plus a few billionaires on social media, have joined the fight, too.

The drugmaker, Lykos Therapeutics, is also putting resources into the effort to build public support. The company wants to ensure “the voices of the patients weren’t lost,” says Amy Emerson, Lykos’ CEO. “The unmet need is clear.”

Can the FDA go against its advisers?

The downvote in June – not to mention controversy about the trials that spilled into full view during a public hearing — has put the FDA in a tough spot.

Heed its advisors’ recommendation and deny approval? Or greenlight the long-awaited decision on psychedelics?

History suggests the odds are stacked against approval.

Research shows FDA sides with its advisory committee in most circumstances. And when the agency does deviate, it’s usually in favor of taking a more cautious approach.

“Hardly ever do they go against a negative vote,” says Dr. Aaron Kesselheim, a professor at Harvard Medical School who specializes in FDA law.

However, the FDA isn’t immune to public pressure. There are times when the agency has moved ahead in spite of its advisors, particularly when patients have mounted an aggressive advocacy campaign.

“Historically, it absolutely does make a difference,” says Kesselheim, who was caught in the middle of a contentious decision on an Alzheimer’s drug.

“The FDA doesn't operate in a vacuum. The staff read the same newspapers that you and I read,” he says.

The agency has a range of options: Lykos could be required to submit additional data, or even run a new clinical trial, which could push back the timeline considerably. Alternatively, approval could come with the requirements to do post-market research, plus tight restrictions on how the drug is administered.

“It’s so hard for me to speculate,” says Lykos’ Emerson. “But there is no stopping the work on this. We've put decades of time and resources into doing this research.”

Even those in favor of approval are hesitant to make any predictions.

“I would not hazard a guess,” says Harriet de Wit, a professor of psychiatry and behavioral neuroscience at the University of Chicago who has studied MDMA. “The FDA is faced with a very difficult decision that will set a precedent going forward. “

Arguments for approval

Still, most in the field believe that approval for MDMA is not so much a matter of if, but when.

The treatment was granted breakthrough status, and FDA staff signed off on the trial design, although it became clear during the advisory meeting that certain recommendations were not followed.

Dr. George Greer, who signed a letter with de Wit and a handful of other researchers, was surprised by the unfavorable reception in June. Still, he remains confident the drug will have its day.

“The benefits of MDMA for people with severe PTSD is virtually overwhelming,” says Greer, president of the Heffter Research Institute, a non-profit that funds psychedelic research.

Greer takes the long view, having used MDMA in therapy sessions at his San Francisco practice in the early ‘80s before the drug became a Schedule I controlled substance.

“It blocks the emotional fear response to a perceived threat,” says Greer. “It also provides the emotional energy to face those horrible trauma memories and come into a balance with them.”

The argument many U.S. veterans make in their lobbying for MDMA is that it works to heal the mental wounds of service, when other drugs like antidepressants don’t. Earlier this year, a top doctor at the Department of Veterans Affairs signaled his support for the treatment, which his agency plans to study for mental health along with other psychedelic compounds.

“The veterans have been suffering and they have not been cared for,” says Jesse Gould, a former Army ranger who heads the non-profit Heroic Hearts Project.

Gould’s group is among those advocating for MDMA’s approval, citing the alarming rate of suicide among veterans.

“These veterans do not have five years to wait for another FDA trial,” he says.

The centerpiece of the Lykos’ application are two phase 3 clinical trials, which together enrolled about 200 people. The most recent one, published last year, showed just over 70% of participants no longer met the diagnostics criteria for PTSD after three therapy sessions with MDMA, compared to about 48% who had the same therapy but took a placebo.

Neuroscientist Matthew Baggott says those results are “compelling” and the risks were already well-understood — more than 1,500 people have been given MDMA in studies not sponsored by Lykos.

“I tend to think it's more likely that it will be approved this time around,” says Baggott, who’s CEO of Tactogen, a company developing new drugs similar to MDMA.

Transformational or 'fools' gold'?

On the other side, some scientists are concerned about both the scientific rigor of Lykos’ MDMA research and serious allegations of misconduct and bias in the trials.

Lykos and investigators have steadfastly denied the latter

During June’s hearing, the FDA advisors raised a series of objections: That participants were not adequately blinded, meaning most could tell whether or not they received the drug. There were also concerns about missing data related to safety and a lack of evidence supporting the therapy protocol, to name a few.

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“This is just shoddy research,” says Dr. Jeffrey Lieberman, a professor of psychiatry at Columbia University Medical Center who has written critically about the hype surrounding psychedelics.

Lieberman says he’s “bullish” about the therapeutic potential of psychedelics, but views the current enthusiasm as largely “speculative” because of weaknesses in the underlying data – including Lykos’ studies.

“We're sort of at a Promethean moment where we have the potential to discover something that could be transformational. On the other hand, it could be fool's gold,” he says, “I just don't want us to squander the opportunity.”

However, many involved with psychedelic research were dismayed by the committee’s hang-up on issues like inadequate blinding of participants.

“I think that was overblown,” says Dr. Amy McGuire, director of the Center for Medical Ethics and Health Policy at Baylor College of Medicine.

She says it’s hard to tell how much the committee’s opposition was rooted in an “overly conservative” approach because of MDMA’s status as an illicit drug rather than legitimate concerns about lack of clinical benefit.

“I would just advocate for data-driven decision making that doesn’t exceptionalize psychedelics in ways that aren't justified,” she says.

Controversy clouds the application

The wildcard in the FDA’s decision may be the ethical controversy over how Lykos’ ran its trials.

There is a well-documented instance of therapists having inappropriate physical contact with a patient, Meaghan Buisson, while she was under the influence of MDMA during the phase 2 trials. Sarah McNamee, a participant in the phase 3 trial, has described her own experience of “worsening symptoms” of suicidality and being inappropriately influenced by her therapist.

These issues and others were raised in a report from an institute that evaluates clinical research and in a petition to the FDA, calling for a public hearing because of allegations that bias influenced the results and some patients experienced adverse events that were not reported.

During the June advisory meeting, FDA staff alluded to an ongoing investigation, but a spokesperson told NPR the agency cannot comment on the details.

“I think any approval would require a full investigation of how Lykos conducted its trials,” says Neşe Devenot, who has helped lead opposition to the drug’s approval along with several others affiliated with the non-profit Psymposia, which describes itself as a watchdog for the psychedelic industry.

Since the hearing, online disputes have played out between the factions in favor of and against approval, with both questioning their underlying motives. For her part, Devenot says trial participants who’ve contacted her are afraid to come forward publicly because of the possible backlash.

The concerns and doubts about MDMA reflect issues with the history of the drugmaker and this trial, not necessarily the broader psychedelic industry, says Tactogen’s Baggott.

Lykos was incubated by a non-profit advocacy group, the Multidisciplinary Association for Psychedelic Studies, or MAPS, which started clinical research on MDMA two decades ago.

“You had this disorganized, activist organization that had this quixotic quest to make an illicit drug into a medicine, and slowly, over time, they became more professional,” he says.

The form of therapy used in MDMA sessions, which was developed by MAPS, has faced criticism that it can lead to abuses of power when patients are under the influence and vulnerable to suggestion.

“We cannot just use this sense of urgency to push forward a harmful model, which would ultimately backfire,” says Devenot, a senior lecturer in writing at Johns Hopkins, who studies psychedelics.

Even though MDMA goes hand-in-hand with psychotherapy, the agency doesn’t actually regulate that component, so ultimately “there's no way to require that therapeutic approach be used” when treating patients, says Baggott.

McGuire, the Baylor College bioethicist, notes people are already seeking out the drug in the context of underground psychedelic retreats. Her research has tallied nearly 300 of them, many of which are advertising in the U.S., raising all kinds of safety issues.

“To me a harm reduction approach might be to have an approved medication that people can get administered under medical supervision,” she says.

By Baggott’s estimation, MDMA is unlikely to be a “blockbuster drug.” More than anything, he says, approval would be a big deal culturally and trigger investment in future psychedelics.

Rogers Masson, who benefitted from the treatment, wants to see MDMA approved, but he’s mindful of not overselling the drug.

“It's just another tool. It’s not a magic pill,” he says, “There's still a lot of self-work that has to go into it.”