The US Food and Drug Administration (FDA) has issued its final guidance for drug development programmes evaluating the therapeutic potential of psychedelic drugs.
The US Food and Drug Administration (FDA) has issued its final guidance for drug development programmes evaluating the therapeutic potential of psychedelic drugs.
This is the final version following the release of the draft guidance in 2023, which received over 200 stakeholder comments. The new guidance, entitled ‘Psychedelic Drugs: Considerations for Clinical Investigations’, applies to clinical trials that will be conducted under an investigational new drug application (IND), including clinical trials conducted under a research IND that are not intended to support marketing applications.
In the guidance, the term ‘psychedelic drug’ specifically refers to 5-HT2A receptor agonists such as psilocybin and lysergic acid diethylamide (LSD), as well as entactogens or empathogens such as 3,4-methylenedioxymethamphetamine (MDMA).
The guidance includes detailed sections relating to chemistry, manufacturing and controls (CMC), nonclinical, clinical pharmacology, abuse potential assessment, and clinical disciplines. Specifically, in the extensive ‘Clinical’ section, it is reiterated that, in line with other drug types, new drug approval will be based on adequate and well-controlled investigation(s), as well as the basis for the FDA’s regulations describing the characteristics of an adequate and well-controlled investigation.
It is stated that, ‘to establish a drug’s effectiveness, it is essential to distinguish the effect of the drug from other influences, such as spontaneous change in the course of the disease, placebo effect, or biased observation’. Interestingly, the guidance is explicit in stating that an independently licensed healthcare provider with graduate-level professional training and clinical experience in psychotherapy should serve as the lead clinical trial monitor.
As anticipated with these therapies, there is a focus on safety and potential impact on daily life and activities. It is stated that, ‘Sponsors should plan to provide a quantitative and qualitative assessment of the drug effects, including effects on orientation to time and place, thought and perception, and subjective effects across time that could inform recommendations for monitoring, safety of discharge, and impact on driving. Sponsors should consider including a formal driving study in their drug development plan.’
Given this is an emerging area and there is such limited experience with study design and drug development programmes that have supported marketing approval, drug developers are strongly encouraged to engage with the FDA to discuss their specific programme.
The issue of this guidance reinforces the FDA’s commitment to developing treatments for people with severe mental health conditions such as depression, PTSD and substance use disorders.
