The US Food and Drug Administration (FDA) has issued its first comprehensive guidance on how psychedelic drugs should best be studied in clinical trials, signalling a shift toward recognizing the potential of these therapeutics. The report also outlines what's needed to see promising compounds approved.
In the new report, Psychedelic Drugs: Considerations for Clinical Investigations – Guidance for Industry, issued this week, the FDA outlines what researchers will need to provide in order to administer therapeutics such as psilocybin, LSD and MDMA in trial stages, and what will be expected when seeking regulatory approval.
The report doesn’t go as far as changing laws or approving any specific drugs, obviously, but it does address some unique challenges that these potential therapeutics face in clinical investigation.
Psychedelics are challenging to test due to "functional unblinding”. Essentially, because these drugs produce obvious psychological side effects, participants and therapists – for the most part – know who has received the active drug rather than a placebo. That runs the risk of influencing expectations and potentially exaggerating reported benefits.
While the agency doesn’t propose to solve this issue, it outlines to researchers that future trials must be designed to minimize this bias or convincingly demonstrate that positive results are real despite of the inherent influence.
And even though the FDA acknowledges that interest in psychedelic medicine has increased rapidly and that these drugs may have therapeutic potential for conditions like major depressive disorder (MDD), post-traumatic stress disorder (PTSD) and substance use issues, it nonetheless remains cautious.
The agency pushes back against the assumption that one or two psychedelic sessions can provide lasting relief from chronic psychiatric illnesses. Instead, it recommends that researchers study patients for at least 12 weeks before seeking regulatory approval and ideally continue monitoring them for around a year.
Essentially, this timeline is recommended in order to determine whether drug benefits persist, if symptoms return or if repeat doses are necessary.
The FDA also addressed the role of psychotherapy in psychedelic trials. Most clinical clinical trials combine drug administration with extensive psychological support before, throughout and after treatment. Because of this, the agency believes it may not be clear how any benefits demonstrated are the result of just the psychedelic, independent of therapy.
As such, the body highlights the importance of study design that can separate these effects.
In terms of safety, the FDA recommends continuous observation by two trained monitors during trial periods, with robust documentation of every psychological effect that participants displayed.
It also outlines requirements for emergency medical backup, long-term monitoring for potential heart valve problems due to the activation of certain serotonin receptors.
The FDA also emphasizes that expected psychedelic experiences – like hallucinations, altered thinking and euphoria – should still be recorded as adverse events to better understand both the safety and abuse potential of the drugs.
In related writings, the agency also highlights its concerns about misuse of psychedelics. Many, like LSD and MDMA remain Schedule I substances.
The FDA says researchers will need to conduct formal assessments of abuse potential and consider how approved medicines could be protected from non-medical use or accidental exposure. As such, the agency notes that any approved drugs might need further safety and risk management studies – though it’s unclear as to what these would entail.
While the report has a “cautious optimism” tone, it nonetheless shows that psychedelics are moving out of the experimental research space and into mainstream drug development. As such, it provides researchers and pharmaceutical companies with what the FDA requires in order to approve novel compounds for the US market.
Companies that design trials according to the report’s recommendations are more likely to generate evidence the FDA considers credible. In this sense, the new guidelines are likely to shape the future of psychedelic clinical trials in the US.
Source: US Food and Drug Administration
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