Addressing growing interest in the therapeutic potential of psychedelic drugs, the FDA has published a draft guidance noting multiple unique considerations for psychedelic drug development programs and challenges in designing trials.

The 14-page guidance steers clear of giving specific recommendations for psychedelic drug development programs, instead detailing foundational concepts that should be considered by all sponsors, including academic sponsor-investigators.

While the FDA holds psychedelics to the same regulatory and evidentiary standards as other drugs, the guidance notes, there are a number of unique hurdles in designing trials, including psychedelic effects and use of psychological/behavioral interventions.

For example, using a traditional placebo can be difficult in these trials due to the intense psychedelic effects of the investigational drugs. The “nocebo” effect — symptoms worsening when the patient realizes they did not get the active treatment — comes into play here, especially considering patients may have high expectancy of receiving the active drug in these trials. Additionally, blinding participants is difficult due to the obvious psychedelic effect the investigational drug may have.

The FDA advises sponsors to consider an inactive control “for better contextualization of any safety findings.” Additionally, alternatives to an inert placebo, such as subperceptual doses of a psychedelic drug or other psychoactive drugs that partially mimic the psychedelic experience, can be considered as well.

Sponsors should consider complementary trial designs across phases 2 and 3, the guidance advises. For instance, a trial using a low, middle and high dose without placebo could be paired with a placebo-controlled trial, with the placebo-less trial providing dose-response data without the risk of the nocebo effect. The placebo-controlled trial, while it may have risks of functional unblinding, would allow for better safety signal characterization, the FDA says.

Read the draft guidance here: https://bit.ly/3CIoh6r.