FDA Refuses to Approve MDMA Therapy, Seeks Further Research

The Food and Drug Administration (FDA) on Friday declined to approve MDMA-assisted therapy for post-traumatic stress disorder, dealing a major blow to the emerging field of psychedelic medicine and dashing the hopes of many Americans desperately seeking fresh treatments.

The FDA said there was not enough data to approve the drug for exploit and asked Lykos Therapeutics, the company seeking approval for the treatment, to conduct an additional clinical trial to assess whether the drug, commonly known as Ecstasy or Molly, would be safe and sound and effective.

An additional clinical trial could add years and millions of dollars to the approval process.

If approved, MDMA would become the first psychedelic compound regulated by federal health authorities. Psychedelic medicine advocates were deeply disappointed, and some said they were stunned, for assuming the promising data on the therapy would overcome the flaws in the company’s clinical trials, which were designed in collaboration with FDA scientists.

“This is an earthquake for those in the field who thought FDA approval would be a piece of cake,” said Michael Pollan, bestselling author and co-founder Center for Psychedelic Substances Science, University of California, BerkeleyHis book “How to Change Your Mind” helped spark public interest in the therapeutic potential of psychoactive compounds, which had been demonized during the country’s long war on drugs.

But the agency’s decision wasn’t entirely unexpected, after a group of independent experts convened by the FDA to review Lykos’ data met in June and did not recommend the treatment. On two main issues, the experts overwhelmingly found that the company had not proven the treatment’s effectiveness and that the drug’s benefits did not outweigh its risks.

The agency generally follows the recommendations of its external panels. Critics, however, question the panel’s competence, noting that only one of its 11 members has experience in psychedelic medicine.

Lykos said it would appeal the agency’s decision.

“The FDA’s request for another study is deeply disappointing, not only for all those who dedicated their lives to this pioneering effort, but most importantly for the millions of Americans living with PTSD, along with their loved ones, who have not seen any fresh treatment options for more than two decades,” said Amy Emerson, the company’s CEO. in the statement.

The FDA declined to discuss the decision or release the letter it sent to Lykos outlining its reasoning, citing confidentiality rules. But in a statement, an FDA spokesperson said that “the agency recognizes that there is a critical need for additional treatment options for mental health conditions such as PTSD.

“We will continue to support research and development of medicines that will drive further innovation in psychedelic treatments and other therapies to address these medical needs.”

Most psychedelic substances are Schedule I drugs, along with heroin and marijuana — illegal substances that “have no currently accepted medical exploit and a high potential for abuse,” according to the Drug Enforcement Administration.

While the FDA’s decision on Friday has sparked consternation and disappointment among researchers, patients and investors, Mr. Pollan said the decision is unlikely to halt the growing acceptance of a field of psychedelics that barely existed a decade ago. “It’s certainly not the end game. There’s enough evidence, need and energy to move psychedelic medicine forward,” he said.

Seven years ago, the FDA granted MDMA “breakthrough therapy” status, a designation that recognizes the potential benefits of a fresh drug and speeds up the review process. MDMA, or midomafetamine, is not a classic psychedelic. The drug promotes self-reflection and a sense of connection, and before it was banned in 1985, MDMA enjoyed decades of exploit among psychotherapists who valued its ability to aid patients confront deep-seated trauma.

Lykos worked closely with the FDA to design the clinical trials that were used to evaluate the safety and benefits of MDMA-assisted therapy.

The results published by the company were surprising: more than two-thirds of patients given MDMA no longer qualified for a PTSD diagnosis six months after their last treatment.

Still, Lykos’ application was admittedly unconventional, not only because of the drug’s illegal status but also because of the talk therapy component, which the company says is integral to MDMA’s therapeutic benefits. The FDA does not regulate psychotherapy, which proponents of the novel treatment say complicated Lykos’ path to approval.

In a statement Friday evening, Lykos provided guidance on the agency’s request for an additional study. The statement addressed a number of issues, including concerns that the data may have been skewed by enrolling patients who had previously tried MDMA. The company also suggested that agency officials were not convinced by data describing the durability of MDMA therapy and were unsure about the benefits of the talk therapy component of the treatment.

The prospect of a fresh treatment has been highly anticipated, especially among combat veterans, who are disproportionately affected by post-traumatic stress disorder (PTSD), suicide and substance abuse.

“We are frustrated that the FDA has delayed this despite the urgent need and clear demand from the veterans community for more effective treatments for PTSD,” said Lt. Gen. Martin R. Steele, a former commandant of the Marine Corps and co-founder of Reason for Hope, an organization that promotes psychedelic therapy for veterans with difficult-to-treat psychiatric conditions. “Delay will only lead to more unnecessary suffering and loss of life.”

It’s unclear what impact, if any, the decision will have on other “breakthrough therapy” psychedelics currently under review by the FDA, including a form of LSD used to treat generalized anxiety disorder and research investigating the exploit of psilocybin to treat major depression.

The company’s latest achievements Phase 3 clinical trial for MDMA involved more than 100 people who had suffered from PTSD for an average of 15 years. According to the company, 86 percent of participants who received MDMA in combination with psychotherapy achieved measurable reductions in symptom severity, and 71 percent improved so much that they no longer met the criteria for a PTSD diagnosis. For those who received a placebo plus talk therapy, the figure was 48 percent.

Long-term follow-up data suggested that the benefits continued for at least six months after the last dose, with 39 per cent of those given MDMA still experiencing symptom relief, compared with 11 per cent of those given placebo.

It’s been more than two decades since the FDA approved a fresh treatment for PTSD, and the existing set of drugs has circumscribed effectiveness. The two most commonly prescribed drugs, both selective serotonin reuptake inhibitors, or SSRIs, are effective in fewer than a third of patients. Even then, the drugs must be taken continuously.

In contrast, Lykos’s MDMA therapy consisted of three all-day dosing sessions.

In the lead-up to the decision, psychedelic medicine advocates have mounted a very public lobbying campaign. Earlier this week, 80 members of Congress from both political parties signed fiction to the Biden administration, urging federal regulators to approve Lykos’ application.

In recent years, thousands of Americans have traveled abroad to seek MDMA therapy, sometimes to unregulated clinics. Many have returned with Lazarus-like tales of recovery from the torment of PTSD, a condition that affects an estimated 13 million Americans.

Still, most scientists agree that more research is needed into the possible side effects of MDMA, including how the drug might affect people with heart problems — a risk the Lykos study failed to measure.

Dr. Manish Agrawal, chief executive of Sunstone Therapies, a company conducting five clinical trials on psychedelic compounds, including MDMA, said the FDA decision, while disappointing, would not significantly impact research into fresh drugs.

He added that one effect of the FDA’s decision may be to focus more research on the psychotherapeutic component of fresh treatments.

“While disappointing for the people at Lykos who have worked on this for decades, in the bigger picture it’s not a huge setback,” he said. “At the end of the day, some of the research could be refined and more nuanced, but the fact that we’re having this conversation at all, and the FDA is considering this drug and asking the tough questions, is a good thing.”

Some psychedelic medicine advocates said they don’t want to wait. Taylor West, executive director Fund for Healing in Oregon, said psychedelic medicine advocates would be better off focusing their efforts at the state level. She said Oregon and Colorado, which recently legalized psilocybin treatments, have shown there are other ways to bring psychedelic medicine to market.

“It’s clear that the path to creating access to safe and sound psychedelic-assisted therapy won’t go through Washington,” she said. “That was proven today, but the message is that states are ready to take the lead.”