Food and Drug Administration (FDA) officials are laying out the agency’s “new framework” for psychedelic medicines, including steps that are taking to “make psychedelic therapies available to patients more quickly, as warranted by the nation’s mental health crisis.”
“The ongoing mental health crisis in the United States continues to worsen,” four FDA staffers wrote in a piece published in the New England Journal of Medicine (NEJM) last week. The agency “recognizes that although some people benefit from available treatment options, for others our current medications are not enough.”
“One potential avenue for the development of better treatments includes psychedelic compounds,” they said, noting that substances such as psilocybin and DMT “have been used in traditional healing and spiritual practices since long before the advent of modern psychiatry.”
While there has been a “prolonged period of quiescence” in the development of psychedelic medicines for decades, “due to research restrictions,” there has recently been a “dramatic resurgence of interest in psychedelic-based treatment for mental illness and substance use disorders” as a result of “advances in neurobiology and shifting social discourse.”
In July, FDA published guidance to help researchers studying the therapeutic benefits of psychedelics navigate the “unique challenges” of such investigations. That is part of an “evolving” approach to integrate psychedelics into existing regulatory frameworks for therapeutic drugs, the agency staffers said in the new NEJM piece.
“The guidance builds on the agency’s experience with drug development programs and incorporates relevant input from the scientific and patient community to address the distinct methodologic challenges in psychedelic clinical trial design—particularly issues around blinding, selection of control, and assessment of the durability of treatment effects.”
The publication of the NEJM piece on psychedelics comes as FDA is hosting a hearing on the issue on Monday at which agency officials will hear testimony from dozens of advocates, researchers and industry participants.
The article noted that preliminary research has indicated “favorable efficacy and safety outcomes” for psychedelics in treating “a number of psychiatric disorders.” As such, the agency has granted “breakthrough therapy” status to several substances, which allows for more intensive guidance from FDA officials as well as rolling and priority review for drug applications.
One ongoing issue in psychedelics research, the FDA officials said, is functional unblinding—when participants in trials can easily tell whether that have received a substance that is being test like psilocybin or have instead received a placebo. The agency is “open to considering comparators other than inert placebo that may help to maintain blinding,” the article said.
A recently published study found that high doses of THC from marijuana “can produce psychedelic-like states,” with the authors of that paper noting that it could potentially be useful as a comparator substances in future psychedelic research.
The new FDA article in NEJM said that the agency is “prepared to consider innovative approaches to trial design, including the choice of comparator.
“Although placebo-controlled studies raise the issue of functional unblinding and may complicate determinations of efficacy, the FDA may still expect such a study. Comparison with inactive placebo in at least one trial can help determine whether adverse events stem from the investigational drug or from other causes (such as underlying psychiatric or medical conditions). As always, close discussion with FDA staff is advisable.”
The agency officials laid out steps that they said could “compress the overall drug-development-to-approval timeline and make psychedelic therapies available to patients more quickly, as warranted by the nation’s mental health crisis.”
That includes combining rolling review and priority review with granting initial approvals “based on evidence of efficacy over a clinically meaningful duration (e.g., 12 weeks), in conjunction with a longer-term preliminary assessment of the need for and safety of treatment with additional doses (e.g., continuing blinded follow-up for 12 months),” they said, adding that issues related to optimal interval between doses and continued efficacy of treatment with additional doses “may be addressed in the post-marketing period.”
FDA, they said, may require a Risk Evaluation and Mitigation Strategy (REMS) for psychedelics, additional post-marketing studies or both.
“Given the growing demand and expanding evidence base, if psychedelics are approved, it will be imperative to establish gold-standard clinical practices for psychedelic-assisted therapy,” they wrote. “This includes rigorous training for providers, standardized dosing and monitoring protocols, and integration of FDA-approved treatments into care pathways. As such, the medical and regulatory communities must come together to ensure a framework for psychedelic treatments to be delivered safely, ethically, and effectively.”
Health and Human Services (HHS) Secretary Robert F. Kennedy Jr. said in a podcast released last week that he believes there will be an “enormous demand” for psychedelic therapies as they become legally available, and he thinks President Donald Trump is unique among his predecessors in championing the issue.
The secretary also cited an executive order that Trump signed earlier this year to streamline research and access into psychedelic medicine.
FDA and HHS in April announced steps that they say will help with “accelerating” therapeutic access to psychedelics for patients dealing with serious mental health conditions.
Last month, the Substance Abuse and Mental Health Services Administration issued a report on recent advances in psychedelic medicine, along with recommendations for state policymakers on how to prepare for formal approval of drugs like psilocybin and MDMA. It also noted how the Schedule I status of many psychedelics has hampered scientific studies on their effects for decades.
HHS and VA recently announced a partnership to collaborate on research and development of psychedelic medicines to treat people struggling with serious mental health conditions.
Previously, FDA and HHS in April announced steps that they say will help with “accelerating” therapeutic access to psychedelics for patients dealing with serious mental health conditions.
In May, a bipartisan coalition of 32 members of Congress sent a letter urging FDA to expedite ongoing reviews of psychedelic therapies.
Lawmakers recently filed a new bill that would require the Department of Defense (DOD) to evaluate how ongoing research on the therapeutic benefits of psilocybin could help members of the military.
A separate recently introduced bipartisan measure is intended to codify Trump’s psychedelics executive order into law.
An amendment adopted as part of the National Defense Authorization Act would extend a psychedelics research effort at DOD for an additional six years.
Photo elements courtesy of carlosemmaskype and Apollo.
