The US Food and Drug Administration (FDA) has finalised its formal guidance for clinical trials involving psychedelic drugs.
The FDA document details recommendations for trial design, participant safety, abuse potential, and data collection. In conjunction with the guidance, the FDA and Department of Health and Human Services (HHS) announced a public hearing on the therapeutic use of psychedelics, scheduled for 14 September.
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The finalised guidance focuses on a few areas, including clinical trial integrity, in which the agency places a stronger emphasis on mitigating functional unblinding and expectancy bias.
Due to the natural effects of psychedelic drugs, with the compounds able to cause profound subjective effects, patients and investigators can easily determine whether the active drug was administered. This can make psychedelic research particularly challenging.
In a previous conversation with Clinical Trials Arena, Amir Inamdar, CMO of psychedelic biopharma Cybin, said that the company’s Phase III trial is utilising a lower dose of the study drug, which should have little to no noticeable cognitive impact on patients. This approach will still allow investigators to see if there are low signals of efficacy in patients who may believe they are on a placebo.
Functional unblinding will become easier to overcome as more psychedelics reach the market because head-to-head study designs can be utilised so that a patient will not be able to determine whether they are on the study drug or comparator.
The FDA guidance also delves into the safety protocols of these candidates. The guidance establishes specific monitoring procedures, recommending that two trained monitors oversee each psychedelic administration session.
This is another trial element, however, that has been raised as a challenge due to its ability to significantly slow down studies, increase the cost due to the volume of staff required for each dosing experience, as well as increasing chair time. Some psychedelic trials can see patients needing 8-10 hours of chair time due to the potential of lengthy adverse events (AEs).
The guidance also considers the abuse potential and durability of the effects of the drugs.
Regarding abuse potential, the FDA outlined a risk-based approach to assessing abuse liability, allowing sponsors to use computational models instead of strictly requiring new animal studies in every scenario. This is tamer than the original draft guidance, which called for full assessments if the active substance has not already been well established in previous studies.
With durability, sponsors must demonstrate the long-term effect of treatment, rather than assuming symptom relief will last based on curves.
This guidance, which was first proposed in 2023, follows President Donald Trump’s executive order (EO) earlier this year to expedite clinical development of psychedelics.
The finalisation of this guidance will come as a relief to many psychedelic drug developers who will be able to better track the progression of their pipeline.
It will also be looked over by later-stage drug development companies to see if they have adhered to the FDA’s requests. Compass Pathways, which is awaiting an FDA decision on its psilocybin-based therapy COMP360, will be one of those keeping a tab on the guidance.
Earlier in July, the company announced its drug showed six-month durability in treatment-resistant depression (TRD). Compass has already submitted a New Drug Application (NDA), and an initial review with the US Food and Drug Administration (FDA) is underway, with the final submission on track to be completed in Q4 2026.
Compass anticipates the launch of COMP360 in the first half of 2027, subject to FDA approval and following Drug Enforcement Administration (DEA) rescheduling.
Dr Hans Eriksson, CMO of HMNC Brain Health, previously told Clinical Trials Arena that psychedelic medicines show great promise in the realm of psychiatry – potentially offering patients treatment durability not previously observed with traditional therapies on the market.
