In July 2023, Australia became the first country to permit psychiatrists to prescribe 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin for use in psychedelic-assisted psychotherapy to treat certain mental health conditions (MDMA for post-traumatic stress disorder [PTSD] and psilocybin for treatment-resistant depression [TRD]).1 This change in regulation directly followed an action taken by the US Food and Drug Administration (FDA) that could accelerate similar changes in the US. It also came on the heels of positive published results from a clinical program evaluating MDMA as a treatment for PTSD that is close to seeking regulatory action.
In June 2023, the FDA published the draft guidance for the industry, Psychedelic Drugs: Considerations for Clinical Investigations, to provide a resource for investigations of psychedelic drugs to treat specific medical conditions (e.g., depression, PTSD, substance use disorders).2 It is the first FDA guidance document created to aid the industry in designing clinical trials for these products. In the agency’s announcement3 of the availability of the guidance, Tiffany Farchione, MD, director, the Division of Psychiatry, Center for Drug Evaluation and Research, FDA, noted that “sponsors evaluating the therapeutic potential of these drugs should consider their unique characteristics when designing clinical studies” as they are “still investigational products.” The guidance provides developers with information about clinical trial conduct, data collection, safety for trial participants, and requirements for new drug applications (NDAs).
The agency clarified in the guidance that the term “psychedelics” refers to “classic psychedelics,” which are generally understood to be drugs such as psilocybin (a hallucinogenic chemical found in specific mushrooms) and lysergic acid diethylamide (LSD) that influence the brain’s serotonin system, and “entactogens” or “empathogens” (eg, MDMA).
When conducting clinical studies for these agents, specific safety considerations include psychoactive effects (eg, mood and cognitive changes, hallucinations), which create an environment for abuse potential and require safety measures to prevent misuse throughout development. The FDA’s 2017 guidance for industry, Assessment of Abuse Potential of Drugs,4 provides information about how sponsors can assess the abuse potential of their drugs through study investigations of chemistry, pharmacology, pharmacokinetics, animal and human behaviour, abuse-related adverse events (AEs) in human studies, and abuse reports from other sources.
Investigations occurring under an investigational new drug application (IND) for products that the Drug Enforcement Administration (DEA) has classified as schedule I controlled substances under the Controlled Substances Act (CSA) must comply with applicable DEA regulatory requirements, the FDA noted. MDMA and psilocybin are both schedule I substances.
