番茄社区

As research interest in the therapeutic potential of psychedelics has grown -- with academic centers popping up across the country, and compounds already -- the FDA recently caught up, issuing a on managing clinical trials of these drugs.

The was released on June 23, as one of the largest U.S. was under way. It outlined the agency's views on best practices in clinical trial design for psychedelic drugs -- including psilocybin, lysergic acid diethylamide (LSD), and methylenedioxymethamphetamine (MDMA) -- in the treatment of medical conditions including psychiatric or substance use disorders.

In an email to 番茄社区, an FDA spokesperson called psychedelics "a very active and challenging area of drug development."

"As an emerging area of drug development, there is limited experience as to the configuration of programs that may support approval of a psychedelic drug," the spokesperson wrote. "The guidance presents foundational constructs that all sponsors, including academic sponsor-investigators, studying the therapeutic potential of psychedelic drugs should consider."

At least one pharmaceutical company with clinical trials under way said it had anticipated the FDA guidance based on prior communication with the agency. Compass Pathways, which is already conducting on psilocybin, said in an emailed statement to 番茄社区 that it was "pleased to see this guidance from the FDA, which is aligned to what we already understand of the agency's thinking -- especially the need for rigor and high standards for trial execution and evidence. We see no need for changes to our trial designs as a result of the draft guidance."

Academic researchers studying psychedelic therapy similarly praised the FDA for providing needed guidance on this rapidly growing field of clinical research -- though some took issue with certain recommendations.

Paul Hutson, PharmD, MS, director of at the University of Wisconsin in Madison, told 番茄社区 that one of the more controversial aspects of the guidance will be the "expectations for facilitator credentialing that you see near the end of the guidance."

FDA recommended that subjects of psychedelic clinical trials should be observed by two monitors for the full duration of the treatment, which can last up to 12 hours. One of the observers should be a "healthcare provider with graduate-level professional training and clinical experience in psychotherapy, licensed to practice independently, serving as the lead monitor."

The guidance listed several acceptable professional credentials for this role, including a clinical or counseling psychologist (PhD/PsyD), a psychiatrist or other physician (MD/DO), a master of social work (MSW), or a psychiatric nurse practitioner.

The second monitor should have a bachelor's degree and "at least 1 year of clinical experience in a licensed mental healthcare setting." The agency also recommended that an on-call physician be able to reach the treatment location within 15 minutes, if the lead is not a physician.

Hutson noted that this recommendation could potentially derail research efforts by failing to define proper credentials and overburdening research teams attempting to run clinical trials. He said the FDA also was not clear about its expectations for the optimal format for psychotherapy with psychedelic treatments.

"They haven't really explained why we need two people and why they need the credentials that they have stipulated," Hutson said. "Frankly, one of the things that we're most concerned about is not that these drugs will be approved by the FDA -- I think at some point they will -- but that we won't have the capacity of adequately trained therapists that can provide those dosing sessions."

Sandeep Nayak, MD, a psychiatrist and an assistant professor at the , told 番茄社区 that he also found the credential and monitoring recommendation to be too broad and needlessly cumbersome.

"I think that's completely appropriate for psychedelic trials for psychiatric indications," Nayak said. "However, that's not the only use case of psychedelics. ... So I think it kind of takes what is very appropriate for psychiatric research, but sort of overextends the model for every possible research case of psychedelics."

Nayak noted that several trials have been conducted on psychologically healthy people who don't require extensive psychotherapy for treatment because they have a neurological problem; for example, a trial of psilocybin for cluster headaches. He said this requirement could hinder future research in these areas of psychedelic treatment.

Nayak also expressed concern about the recommendation for how follow-up should be conducted, especially when it comes to psychological support sessions with a trusted person during and after the treatment sessions.

Current standards are to have one person be available for support through the trial, but the guidance statement emphasized that follow-up should be conducted by a professional not involved in the treatment session. This recommendation, he said, could lead to emotional and psychological issues for participants in these trials.

However, Nayak noted that most of the guidance offered positive expectations and outlines for the future of psychedelic research. One example, he said, was the agency's acknowledgement that psychedelic clinical trials should not require placebo control to show efficacy. Overall, Nayak said the agency is moving the conversation in the right direction.

"Twenty years ago, if you wanted to run a psychedelic study, you're kind of on your own," Nayak said. "And I think as they've just gotten more and more studies, they've begun to get more and more consistent in what they're asking for, so I think it reflects that the FDA is taking seriously this area of research."

All of the experts and representatives who spoke with 番茄社区 said they plan to submit comments during the 60-day comment period in hopes of altering the guidance statement to address these issues.

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