The U.S. Food and Drug Administration (FDA or Agency) on June 23, 2023, released its first draft guidance concerning design and desired features of clinical trials for psychedelic drugs LSD and MDMA
There has been growing interest in studying the use of psychedelic drugs for patients with conditions such as treatment-resistant depression, substance-use disorders and post-traumatic stress disorder (PTSD). By issuing this draft guidance, the FDA is providing drug developers and researchers guidance on how to design trials to meet regulatory hurdles for approval.
In its draft guidance, the FDA, while confirming that psychedelic drugs are subject to the same regulations and same evidentiary standards for approval as other drugs, acknowledges that these drugs have "unusual characteristics" that merit special considerations when designing clinical trials. For example, psychedelic drugs can cause "intense perceptual disturbances and alterations in consciousness" that can last for several hours. Additionally, the Agency says, early research suggests that some psychedelic drugs have both rapid-onset and long-term benefits after only one or a few doses, which could make interpretation of trial data challenging.
Many psychedelic drugs are listed under Schedule I of the Controlled Substances Act because they have high abuse potential and do not have a currently accepted medical use in the United States. For those drugs, the FDA says activities associated with a clinical trial must comply with applicable Drug Enforcement Administration (DEA) regulations for research, manufacturing, importation/exportation, handling and storage requirements for Schedule I drugs. Therefore, an investigator who intends to conduct research is required to obtain a Schedule I registration from the DEA before the initiation of nonclinical and clinical studies.
The FDA is concerned about how psychedelic drugs affect the central nervous system, as well as their psychoactive effects (such as mood or cognitive changes and hallucinations). In the draft guidance, the FDA argues psychedelic drugs need to be evaluated for abuse potential during drug development. As such, data from abuse potential studies and a proposal for drug scheduling under the Controlled Substances Act is required to be included in a new drug application submission.
The draft guidance goes into further detail on other topics regarding chemistry, manufacturing and controls, nonclinical studies and clinical pharmacology and provides broad parameters of how sponsors and investigators should address key topics. No specific recommendations are included in the draft guidance.
The FDA's action takes place as Congress begins to pay more attention to psychedelic drugs. Earlier this year, Reps. Lou Correa (D-Calif.) and Jack Bergman (R-Mich.) launched the Congressional Psychedelics Advancing Therapies (PATH) Caucus. In addition, Sens. Cory Booker (D-N.J.) and Rand Paul (R-Ky.), along with Reps. Madeleine Dean (D-Pa.) and Nancy Mace (R-S.C.), introduced the Breakthrough Therapies Act, which is designed to promote drug development for Schedule I drugs.
Importantly, the FDA specifically encourages researchers and sponsors to meet with the Agency to discuss these topics in the context of specific trials early in the drug development process. The FDA is accepting comments to the draft guidance until Aug. 23, 2023.
