More bad news for psychedelics manufacturers: FDA expands investigation after rejection

There is more bad news for the company behind an experimental MDMA therapy for post-traumatic stress disorder that the US Food and Drug Administration flatly rejected earlier this month.

According to a report in the Wall Street Journal, the FDA is now expanding its investigation into clinical trials of experimental psychedelic therapy – even though the agency has already rejected them. Agency investigators reportedly interviewed four more people last week, asking whether side effects were underestimated in the trials.

People involved in the study have previously alleged, among other things, that side effects such as suicidal thoughts were not documented and that study participants were discouraged from reporting them in order to increase the chances of FDA approval. Overall, the MDMA trials were heavily criticized during FDA review. Outside experts and advisers to the agency pointed to allegations of sexual misconduct at one study site, as well as flaws in the study design, multiple sources of bias and claims that the company behind the therapy, Lykos, promoted a cult-like belief in psychedelics.

According to the Journal, the recent interviews were conducted by the FDA's Office of Regulatory Affairs, which oversees inspections, and a subdivision of that office called the Biomedical Research Monitoring Program, which is designed to ensure the quality and integrity of data submitted to the FDA. When the agency rejected MDMA, it advised Lykos to conduct a new trial.

While the FDA's rejection and expanded investigation are bad enough for Lykos, the company announced this month that it was laying off 75 percent of its workforce and restructuring its leadership team. These actions are in response to the FDA's rejections, the company said. In addition, a scientific journal has retracted three of the company's MDMA studies, citing “protocol violations amounting to unethical conduct” in the studies, echoing allegations made during the FDA's review.

Disturbing roots

The allegations and criticisms against Lykos are based on its roots in drug advocacy. Lykos is a commercial offshoot of the psychedelic nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS). For decades, MAPS has worked to legalize psychedelics and researched their use as a potential treatment, particularly for mental illnesses such as PTSD, anxiety disorders and substance abuse. MAPS was founded by Rick Doblin, a longtime psychedelic activist and advocate who openly believes that the use of psychedelics will lead to world peace. Doblin left his post on Lykos' board as part of the leadership restructuring this month.

“After over 38 years of work, I am deeply saddened by the FDA's decision on this much-needed therapy, but I am encouraged that Lykos continues to conduct clinical research that answers FDA's questions,” Doblin said in a statement. “I can speak more freely as a public advocate by stepping down from Lykos' board. The delays at the FDA make it more important than ever that I work at MAPS to develop global legal access to MDMA and other psychedelics for the benefit of the public through MAPS' multidisciplinary research, education and drug policy reform.”

Lykos did not immediately respond to Ars' request for comment on the FDA's investigation. In a response to the Journal, a company spokesperson said, “Lykos is committed to working with the FDA and answering any questions it raises.” The spokesperson also noted that the company plans to meet with the FDA about the denial, which it is appealing.

But those involved in the process and outsiders are making severe criticism of the company, which is unlikely to be overcome.

“The prospect of a therapy cult taking a suggestibility-enhancing drug through clinical trials raises unique risks that have never been publicly discussed,” Neşe Devenot, a lecturer in the Johns Hopkins University writing program who focuses on the issue of drugs in society, said in public comments before the FDA's rejection. “The trials should be scrutinized as closely as if Scientology or NXIVM had submitted a new drug application to the FDA.”

Those public comments appeared in a scathing report from the Institute for Clinical and Economic Review, which concluded there was insufficient evidence to support MDMA-based therapy. According to the Journal's report, Devenot was among the people recently interviewed by FDA investigators.

Lykos' story was a blow to the psychedelic community in general and to many patients, especially veterans, who reported a positive effect of taking MDMA in treating PTSD, a disease that desperately needs effective treatment.

Given Lykos' difficulties, the company has hired David Hough as chief medical advisor to oversee clinical and regulatory work. Hough is a former vice president at Johnson & Johnson, where he notably helped develop Spravato (esketamine), a ketamine-related drug approved in 2019 to treat treatment-resistant depression.