Veterans and Lawmakers Lobby for Approval of MDMA Therapy

More than a half century after federal regulators banned most psychedelic compounds, the Food and Drug Administration is nearing a decision on a novel treatment for post-traumatic stress disorder that pairs talk therapy with MDMA, the club drug commonly known as Ecstasy or Molly.

The decision, which is expected in the coming days, has generated a groundswell of lobbying by veterans groups, researchers and members of Congress from both parties. Eighty lawmakers signed letters to the Biden administration this week, urging the F.D.A. to approve the application by the drug company Lykos Therapeutics.

The campaign was prompted in part by an expert panel’s unanimous rejection in June of Lykos’s application, because of what participants said were flaws in the company’s clinical trials and insufficient data.

“We have a mental health crisis and a suicide epidemic, with thousands of military veterans taking their own lives every year,” said Representative Jack Bergman, Republican of Michigan and a former Marine Corps general who helped organize the letter’s 60 backers in the House. “I would just ask the F.D.A. to consider the negative ramifications of them not taking action, which means more veterans will die needlessly.”

The lobbying campaign, unusual for a prospective new drug, underscores the high stakes and intense emotions surrounding psychedelic medicine, a field that has been growing in recent years as the country’s top universities race one another to establish psychedelic research institutes.

The passions — and the millions of dollars in private investment flooding the field — have been buoyed by a growing body of data suggesting that compounds like LSD, psilocybin mushrooms and MDMA can have significant therapeutic effects on hard-to-treat mental health conditions like depression, anxiety and obsessive compulsive disorder. The federally prohibited substances are listed as Schedule I drugs that have “no currently accepted medical use and a high potential for abuse.”

According to the most recent study cited in the Lykos application, more than 86 percent of participants who took MDMA experienced a measurable reduction in the severity of their PTSD symptoms, and 71 percent improved enough that they no longer met the criteria for a diagnosis. Of those who took the placebo, 69 percent improved and nearly 48 percent no longer qualified for a PTSD diagnosis, according to the company’s data.

Perhaps most striking was that the benefits of MDMA therapy endured six months after the final, three-dose regimen, the study found.

“I’d argue that these benefits are better than any psychiatric medication that has been discovered in the history of psychiatry,” said Dr. David Rabin, a neuroscientist and psychiatrist who conducts clinical trials on psychedelic compounds and is not affiliated with Lykos.

But the path toward approval has been bumpy, with advisers to the F.D.A. noting several shortcomings in Lykos’s application and in gaps in the data the company had submitted. The panel, which voted 10 to 1 against the application, cited a number of concerns, including Lykos’s failure to collect detailed data on MDMA’s potential for abuse, its possible cardiac risks and what panelists said were the challenges of standardizing the treatment’s psychotherapy component.

Although not considered a traditional psychedelic, MDMA, or midomafetamine, is a synthetic compound that fosters self-awareness, feelings of empathy and social connectedness.

Should it win F.D.A. approval, federal health authorities and the Justice Department would have to follow certain steps to reclassify the drug to a lower level than the current Schedule I ban, much like the process now underway with cannabis.

The Drug Enforcement Administration could also set production quotas for the drug’s ingredients, as it does with the stimulant medications used to treat ADHD.

The F.D.A. had worked closely with Lykos to develop the clinical trials that evaluated the therapy’s risks and benefits. But the fact that the F.D.A. does not regulate talk therapy has compounded the headwinds facing the company’s application.

Days before the panel vote in June, an independent analysis by the Institute for Clinical and Economic Review, a nonprofit that reviews drugs and their costs, found there was insufficient evidence to determine the overall benefit of MDMA therapy.

Although the advisory panel’s decision is not binding, the agency often follows the recommendations of its experts.

Amy Emerson, the chief executive of Lykos, said the company was confident its application would ultimately secure approval. “We feel the data is really strong, and that none of the concerns that have been raised represent the totality of that patient pool, and they do not negate the overall safety and efficacy findings,” she said.

In rejecting the application, many of the panel’s members said they were concerned about
“functional unblinding,” a problem that affects many studies involving psychoactive compounds because participants may be able to identify whether they have received the drug or the placebo. To reduce the odds of bias skewing the results, those who took part in Lykos’s so-called double-blinded studies were not told whether they had received MDMA or a placebo. But the intensity of the MDMA experience allowed a vast majority to correctly guess which one they had been given.

Dr. Stephen Ross, the associate director of the New York University Langone Health Center for Psychedelic Medicine, said researchers in the field have long struggled to find ways to dampen the effects of functional unblinding. “No one yet has found the holy grail of a placebo that effectively obscures that someone got a drug that creates an unusual experience and does not have therapeutic effects,” he said.

Dr. Maryann Elizabeth Amirshahi, a toxicologist and addiction specialist in Washington, D.C., who served on the F.D.A. advisory panel, said she worried that patients who had a positive experience with MDMA-assisted therapy would seek out illicit forms of the drug, increasing the risk of adverse events. “The last thing you want to do is withhold a promising treatment, but there are just so many unanswered questions in Lykos’ data,” she said in an interview.

Advocates of psychedelic medicine and many experts in the field have been highly critical of the panel’s vote, saying that 10 of the panel’s 11 members had no experience in the field of psychedelics.

“We were shocked because we know the science is there, and after 25 years without new treatments for PTSD, we desperately need this to be approved,” said Marcus Capone, a former Navy SEAL whose organization, Veterans Exploring Treatment Solutions, helps veterans obtain psychedelic therapy at clinics outside the United States.

The F.D.A. could issue a more limited approval requiring Lykos to closely monitor its MDMA-therapy program and report any adverse effects to the agency. It could also require the company to undertake additional studies, a decision that would most likely add years to the approval process. The agency could simply postpone a final decision and ask Lykos to provide additional data. Such a determination, known as a Complete Response Letter, is likely to be confidential.

Postponing approval could cast a chill over the entire field.

“We need the big biotech funds to be investing in psychedelics, and a no vote would validate why many of them have been sitting on the sidelines until now,” said Dustin Robinson, the managing principal of Iter Investments, which focuses on psychedelic companies.

The F.D.A. does not comment on impending decisions, but experts say the political sensitivities surrounding MDMA are especially daunting given the high-profile support from veterans groups. The agency is also undoubtedly mindful of regulatory failures, including criticisms of its own shortcomings, that helped fueled the nation’s opioid crisis.

What no one disputes is the urgent need for new treatments for PTSD. Heroic Hearts Project, an organization that helps veterans obtain psychedelic treatment at clinics outside the United States, has more than 1,000 veterans on a waiting list.

Juliana Mercer, a board member with the organization and a Marine Corps veteran, said she and other supporters worried that the unconventional nature of psychedelic therapies was dampening the application’s prospects at the F.D.A.

“We just want to make sure that the stigma associated with MDMA doesn’t influence their decision,” she said. “It would be a shame for stigma to keep a lifesaving treatment from millions of people.”