Veterans, lawmakers lobby for MDMA therapy approval

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

The decision, expected in the coming days, has sparked a wave of lobbying from veterans groups, researchers and members of Congress from both parties. Eighty lawmakers have signed fiction this week to the Biden administration, urging the FDA to approve the pharmaceutical company’s application Lycos Therapy.

The campaign was sparked in part after a gigantic majority of experts rejected Lykos’ application in June, saying the company’s clinical trials were flawed and the data were insufficient.

“We have a mental health crisis and a suicide epidemic, with thousands of veterans taking their own lives every year,” said Rep. Jack Bergman, a Michigan Republican and former Marine general who helped organize 60 supporters of the letter in the House. “I would ask the FDA to consider the negative consequences of their inaction, which means more veterans will die needlessly.”

The lobbying campaign, unusual for a modern drug, underscores the high stakes and mighty emotions surrounding psychedelic medicine, a field that has been booming in recent years, with the country’s top universities racing to establish research institutes dedicated to psychedelic substances.

Passions—and millions of dollars of private investment pouring into the field—have been fueled by mounting data suggesting that compounds like LSD, psilocybin mushrooms, and MDMA could have significant therapeutic effects on hard-to-treat mental health conditions like depression, anxiety, and obsessive-compulsive disorder. Federally banned substances are listed as Schedule I drugs that have “no currently accepted medical apply and a high potential for abuse.”

According to the majority last examination quoted in the Lykos application, over 86 percent of participants who took MDMA experienced measurable reductions in the severity of their PTSD symptoms, and 71 percent improved enough that they no longer met criteria for the diagnosis. Of those who took a placebo, 69 percent improved, and nearly 48 percent no longer qualified for a PTSD diagnosis, according to the company.

What was most striking, the study found, was that the benefits of MDMA therapy persisted six months after the final three-dose cycle.

“I would say these benefits are better than any psychiatric drug ever discovered in the history of psychiatry,” said Dr. David Rabin, a neurobiologist and psychiatrist who conducts clinical trials of psychedelic compounds and is not affiliated with Lykos.

But the road to approval was bumpy, with FDA advisers noting several shortcomings in Lykos’s application and gaps in the data the company presented. The panel, which voted 10 to 1 against the application, cited a range of concerns, including Lykos’ failure to collect detailed data on MDMA’s abuse potential, possible heart risks and what panelists described as challenges with standardizing the psychotherapy component of the treatment.

While MDMA (midomafetamine) is not considered a classic psychedelic drug, it is a synthetic compound that enhances self-awareness, feelings of empathy, and social bonds.

If the drug wins FDA approval, federal health regulators and the Department of Justice would have to take certain steps to reclassify it below the current Schedule I prohibition, similar to what is currently done with marijuana.

The Drug Enforcement Administration (DEA) could also set manufacturing limits for drug ingredients, as it does for stimulant drugs used to treat ADHD.

The FDA worked closely with Lykos to design clinical trials that assessed the risks and benefits of the therapy. But the fact that the FDA does not regulate talk therapy has compounded the headwinds the company’s application faces.

A few days before the committee vote in June, independent analysis by the Clinical and Economic Review Institute, a nonprofit organization that analyzes medications and their costs, concluded that there is insufficient evidence to establish an overall benefit of MDMA therapy.

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

Amy Emerson, Lykos’ chief executive, said the company is confident its application will ultimately win approval. “We think the data are really mighty and that none of the concerns raised apply to this group of patients in general, and they don’t negate the overall findings of safety and efficacy,” she said.

Many committee members in rejecting the motion said they were concerned about “functional unblinding,” a problem that plagues many studies involving psychoactive compounds because participants may be able to tell whether they were receiving the drug or a placebo.

To reduce the likelihood of bias skewing the results, subjects in the double-blind Lykos studies were not told whether they had received MDMA or a placebo. However, the intensity of the MDMA experience allowed the expansive majority to correctly guess which drug they had been given.

Dr. Stephen Ross, associate director of Fresh York University Langone Health Center for Psychedelic Medicine, said researchers in the field have long struggled to find ways to mitigate the effects of functional unblinding. “Nobody has yet found the holy grail of placebos that effectively hides the fact that someone has received a drug that creates an unusual experience and has no therapeutic effects,” he said.

Dr. Maryann Elizabeth Amirshahi, a Washington, D.C., toxicologist and addiction specialist who served on the FDA advisory panel, said she worries that patients who have had positive experiences with MDMA-assisted therapy will seek out illegal forms of the drug, increasing their risk of side effects. “The last thing you want to do is stop a promising treatment, but there are so many unresolved questions in the Lykos data,” she said in an interview.

Psychedelic medicine advocates and many experts in the field were highly critical of the panel’s vote, saying 10 of the 11 panel members had no experience with psychedelic substances.

“We were shocked because we know there’s scientific evidence for this, and after 25 years with no modern treatments for PTSD, we desperately need validation,” said Marcus Capone, a former Navy SEAL whose organization, Veterans Exploring Treatment Solutions, helps veterans get psychedelic therapy in clinics outside the United States.

The FDA could issue a more restricted 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 conduct additional studies, which would likely add several years to the approval process. The agency could simply delay a final decision and ask Lykos to provide additional data. Such a determination, known as a Complete Response Letter, would likely be confidential.

Delaying approval could send shockwaves through the entire industry.

“We need huge biotech funds to invest in psychedelics, and a ‘no’ vote would validate why many of them have been sitting on the sidelines,” said Dustin Robinson, managing director Iter Investmentswhich focuses on companies dealing with psychedelic substances.

The FDA does not comment on impending decisions, but experts say the political sensitivity surrounding MDMA is particularly overwhelming, given the high level of support from veterans groups. The agency is also undoubtedly aware of regulatory failures, including criticism of its own shortcomings, that have contributed to the nation’s opioid crisis.

No one questions the urgent need to develop modern treatments for PTSD. Heroic Hearts Projectan organization that helps veterans get psychedelic treatment at clinics outside the United States, has more than 1,000 veterans on a waiting list.

Juliana Mercer, a board member of the organization and a Marine Corps veteran, said she and other advocates are concerned that the unconventional nature of psychedelic therapies weakens the prospects of the application at the FDA.

“We just want to make sure that the stigma associated with MDMA doesn’t influence their decision,” she said. “It would be a shame if the stigma deprived millions of people of access to life-saving treatment.”