The Food and Drug Administration (FDA) has released first-of-its-kind draft guidance on the “unique” considerations that researchers should take into account when studying psychedelics, which the agency says show “initial promise” as potential therapies.
Two days after bipartisan congressional lawmakers filed a bill to direct the issuance of such guidance, FDA published a 14-page draft document that appears to be responsive, providing scientists with a framework to carry out research that could lead to the development of psychedelic medicines.
A notice about the move is set to be published in the Federal Register on Monday. At that point, a 60-day public comment period will open for interested parties to submit feedback on how final guidance should be shaped.
This is the first FDA draft guidance that presents considerations to industry for designing clinical trials of psychedelic drugs.
— U.S. FDA (@US_FDA) June 23, 2023
“Psychedelic drugs show initial promise as potential treatments for mood, anxiety and substance use disorders. However, these are still investigational products,” Tiffany Farchione, director of the Division of Psychiatry in the FDA’s Center for Drug Evaluation and Research, said in a press release on Friday. “Sponsors evaluating the therapeutic potential of these drugs should consider their unique characteristics when designing clinical studies.”
“By publishing this draft guidance, the FDA hopes to outline the challenges inherent in designing psychedelic drug development programs and provide information on how to address these challenges,” she said. “The goal is to help researchers design studies that will yield interpretable results that will be capable of supporting future drug applications.”
Interest in psychedelics has grown exponentially over recent years as cities and states across the country have moved to promote research, remove criminal penalties and regulate access to substances such as psilocybin and MDMA—both of which have already been designated by FDA as “breakthrough therapies.”
The agency’s draft guidance “describes basic considerations throughout the drug development process including trial conduct, data collection, subject safety and new drug application requirements,” it said.
One factor that FDA said was important to note is the fact that many psychedelics produce psychoactive effects that could give them higher abuse potential. Also, entheogenic plants and fungi like psilocybin are Schedule I drugs under the Controlled Substances Act (CSA), requiring researchers to go through a more complex registration process with the Drug Enforcement Administration (DEA) in order to obtain them for study purposes.
“The evidentiary standard for establishing effectiveness of psychedelic drugs is the same as for all other drugs. However, there are unique factors investigators may need to consider when designing their clinical trials if those trials are to be considered adequate and well-controlled,” FDA said. “The draft guidance also addresses the role of psychotherapy in psychedelic drug development, considerations for safety monitoring and the importance of characterizing dose-response and the durability of any treatment effect.”
With respect to psychedelics in psychotherapy, that’s also the focus of a bill filed by Reps. Dan Crenshaw (R-TX), Mariannette Miller-Meeks (R-IA) and Ro Khanna (D-CA) on Wednesday.
The legislation calls on the secretary of the U.S. Department of Health and Human Services (HHS), acting through the FDA commissioner, to “issue for public comment draft guidance on considerations for conducting clinical trials for psychedelic assisted therapy, including how those seeking an investigational use exemption for such clinical trials should request interactive support by the Food and Drug Administration.”
If enacted, it would have required FDA to produce that draft guidance within 180 days. But the agency was evidently prepared to release it much sooner. The bill would also mandate FDA to finalize its guidance 180 days after the draft document’s publication, so lawmakers may still be interested in advancing the measure with that provision.
On the same day that the legislation was introduced, Crenshaw discussed it at a House Energy & Commerce Committee hearing, where he talked about psychedelics as one possible “solution” to the country’s substance misuse issues.
The congressman said that he was working on “getting clinical trial guidance for psychedelic therapies from the FDA,” adding that “this therapy will be earth-shattering. It already has been already changed dozens of lives.”
“We’re not talking about 1960s LSD trips. This therapy is supervised by a medical practitioner [and] often occurs with repeat treatments in a controlled setting,” he said. “And when it comes to the efficacy of this therapy, the proof is in the data, in the testimonies—but we need the FDA to issue clinical trial guidance for psychedelic assisted therapy so that the the industry can actually invest in this.”
“Right now, it’s difficult for researchers to pursue these trials without any direction at all from FDA,” Crenshaw said. “Without that direction, it’s even more difficult for us to conduct the research to tap into this breakthrough treatment option.”
The draft FDA guidance released on Friday notes that many psychedelics that are being developed with the intent of having them administered “while the subject is experiencing the acute effects of the drug or in a subsequent session.”
“This additional variable both complicates the assessment of effectiveness and presents a challenge for any future product labeling,” FDA said.
The agency advised, for example, that the “therapist monitoring the session can usually deduce the treatment assignment by observing the subject’s behavior,” so “it is preferable that the in-session monitor is not involved in post-session psychotherapy because their knowledge of the treatment could bias the delivery of subsequent therapy.”
FDA emphasized that after the guidance is finalized it will simply represent the agency’s “current thinking…on this topic.”
“It does not establish any rights for any person and is not binding on FDA or the public,” it told researchers. “You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.”
The move is timely, as lawmakers and health officials have shown serious interest in quickly expanding research into psychedelics as studies have revealed their potential in the treatment of conditions such as severe depression, post-traumatic stress disorder and addiction.
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Marijuana Moment asked HHS Secretary Xavier Becerra last week about the department’s current thinking around psychedelics policy, and he said he needed to “defer” to the expertise of the National Institute on Drug Abuse (NIDA), which also falls under his agency, “because I want to make sure that I touch base with what they’ve been doing on that.”
This month, NIDA called for research into the impact of evolving laws around psychedelics, including the effects of allowing regulated access to substances like psilocybin.
NIDA separately announced in May that it is soliciting proposals for a series of research initiatives meant to explore how psychedelics could be used to treat drug addiction, with plans to provide $1.5 million in funding to support relevant studies.
At a Senate committee hearing in May, NIDA Director Nora Volkow told members that there’s emerging evidence that psychedelics carry “significant potential” as therapeutic treatments for certain mental health conditions, and it’s a topic of “great interest” for researchers.
Meanwhile, congressional lawmakers have also pushed for psychedelics reform.
For example, one House committee approved a spending bill on Wednesday that included a GOP-led amendment to require a study into the therapeutic potential of psychedelics for active duty military members under the U.S. Department of Defense (DOD).
Last year, Sens. Brian Schatz (D-HI) and Cory Booker (D-NJ) pushed top federal officials to provide an update on research into the therapeutic potential of psychedelics, arguing that ongoing federal prohibition has stymied studies.
NIDA responded to the inquiry by saying that federal prohibition makes it more difficult to study the benefits of psychedelics, requiring researchers to jump through additional regulatory hoops. Volkow previously said that she personally hesitates to study Schedule I drugs because of those complications.
The director told Marijuana Moment in 2021 that researchers need to prioritize psychedelics research, as more people are likely to use them as they’re exposed to studies showing the therapeutic potential of the substances.
Bipartisan congressional lawmakers also introduced a bill last month that would create a $75 million federal grant program to support research into the therapeutic potential of psychedelics for certain health conditions among active duty military service members. Crenshaw is also the lead sponsor of that measure.
At a press briefing outside of the U.S. Capitol last week, several GOP lawmakers and military veterans discussed that legislation, and Rep. Morgan Luttrell (R-TX), a military veteran, says undergoing psychedelic-assisted treatment with ibogaine and 5-MeO-DMT “changed my life” and was “one of the greatest things that ever happened to me.”
In March, bipartisan and bicameral congressional lawmakers filed an updated version of a bill to streamline the federal rescheduling of “breakthrough therapies” like psilocybin and MDMA in order to promote research and drug development.
Booker, along with Sen. Rand Paul (R-KY) and Rep. Nancy Mace (R-SC) also led a separate bill last year that was designed to clarify that federal “Right to Try” (RTT) laws give seriously ill patients access to Schedule I drugs, including marijuana and psychedelics like psilocybin and MDMA. It was not enacted by the end of the session, however.
The introduction of the bipartisan psychedelics bill this session roughly coincided with the re-launch of a congressional caucus focused on promoting research into the therapeutic potential of entheogenic substances.
Read the text of the FDA psychedelics research guidance bill below:
Photo courtesy of Wikimedia/Workman.