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Halloran’s View on FDA’s Draft Guidance on Psychedelic Drugs

The U.S. Food and Drug Administration (FDA) recently issued a draft guidance for industry on “Psychedelic Drugs: Considerations for Clinical Investigations.” As FDA notes, this guidance is intended to support ethical conduct of trials, uphold trial integrity, and ensure reliability of trial results.

This guidance raises the following questions for Halloran:

Why is This Guidance Needed?

Interest in psychedelic drugs for unmet medical need has increased substantially in recent years. FDA understands sponsors in this space face unique challenges and have thus outlined their recommendations to address these challenges. Challenges include the impact of the psychedelic experience (e.g., mood or cognitive changes and hallucinations), the rapid onset and long-lasting effects of psychedelics, and the therapy component integral to many psychedelic drug trials.

What Does this Guidance Have in Common with Other Drug Development-Related Guidances?

Much of this guidance is aligned with existing guidances issued for clinical investigations of therapeutics. For instance:

What Elements of This Guidance are Unique to Psychedelics?

Evaluation of the Psychedelic Drug as a 5-HT2B Receptor Agonist

Consensus opinion in the psychedelic research community is that these drugs exert their effect at the 5-HT2A (serotonin) receptor; however, these drugs also commonly bind to the 5-HT2B receptor – a receptor linked to heart valvulopathy in humans. Sponsors should thus conduct studies to determine whether the psychedelic drug under development is a 5-HT2B receptor agonist. If the drug is a 5-HT2B receptor agonist, the sponsor should conduct a microscopic evaluation of heart tissue in animal models in repeat-dose toxicology studies. The outcome of this evaluation should be considered when defining clinical study inclusion and exclusion criteria to protect potential participants at risk of heart valve disease.

Requirement for an Abuse Potential Assessment

An assessment of the abuse potential of a drug product under development is typically conducted as a component of its safety evaluation. Products that are assessed for abuse potential include new molecular entities active in the central nervous system, and those containing drugs scheduled under the Controlled Substances Act.

Additional considerations:

Study Drug Control

Trial Monitors

FDA advises on qualifications for trial monitors. This, we believe, is likely to prove the most contentious section of the draft guidance. FDA states the lead monitor “should be a healthcare provider with graduate-level professional training and clinical experience in psychotherapy” (e.g., psychiatrist, Master of Social Work, psychiatric nurse practitioner). The agency also states the assistant monitor should have a bachelor’s degree and at least one year of clinical experience in a licensed mental healthcare setting.

What Do We Think FDA Should Reconsider Before Finalizing this Guidance?

Our major concern with this guidance – assistant monitor qualifications – hinges on the use of the word “should.” FDA’s guidance explicitly states that “should” denotes a suggestion or recommendation, not a requirement; however, in our experience “should” often means “must.” On the other hand, we are encouraged FDA acknowledges the study of psychedelic drugs as an “emerging area” in drug development and has drafted its guidance based on current clinical knowledge. Considering there is little experience to inform specific recommendations in trials of psychedelics, FDA urges sponsors to engage with them early to seek advice on their drug development program. We infer there is room for negotiation, though how far this flexibility extends is yet to be tested.

At Halloran, we continue to develop expertise to support interdisciplinary teams in the nascent field of psychedelic therapeutics.

To learn how Halloran can partner with you to achieve your goals in the development of psychedelic drugs, please contact us today.