FDA Paves Way For Psychedelic Studies: New Guidelines

In June 2023, the Food and Drug Administration (FDA) published a draft guidance to “highlight fundamental considerations to researchers investigating the use of psychedelic drugs for potential treatment of medical conditions, including psychiatric or substance use disorders”.

This is the first draft guidance from the FDA with recommendations for designing clinical trials which involve using “classic” psychedelics (5-HT2 agonists, such as psilocybin and MDMA).

 

About the FDA and Draft Guidances

The FDA is responsible for ensuring that human and animal drugs, as well as medical devices, marketed for sale and use in the United States are 1) safe, and 2) effective. The FDA is also tasked with ensuring our food and cosmetics, are safe for Americans to use and consume. (You can learn more about what the FDA does in this article.)

A guidance document describes how the FDA interprets a regulatory issue, and any policy the FDA will pursue relevant to said issue. In other words, they report where the FDA currently stands on a topic.

There are some key facts about FDA draft guidances to point out:

• FDA draft guidances carry no legal weight

• FDA draft guidances do not create or confer any rights for anyone or to anyone

• Neither the FDA nor the public are bound to anything contained within an FDA draft guidance

• Draft guidances may be “withdrawn”, meaning the FDA has changed stances or no longer endorses what is within the guidance; withdrawn guidances are still available to access on the FDA’s website for transparency purposes (scientists shouldn’t be afraid to admit when they’re wrong, it’s how we learn and grow).

Think this sounds interesting? The FDA seeks input from interested parties and stakeholders when developing these documents. (Learn more about opportunities here.)

Our takeaway points for an FDA draft guidance:

1. They offer insight into the FDA’s current thoughts on a subject

2. They’re not legally binding

3. The FDA encourages outside participation in the process (democracy is neat!).

 

What’s Inside the New Guidance?

The FDA acknowledges the growing interest in psychedelics and their therapeutic potential:

‘Psychedelic drugs show initial promise as potential treatments for mood, anxiety and substance use disorders. However, these are still investigational products. Sponsors evaluating the therapeutic potential of these drugs should consider their unique characteristics when designing clinical studies,’

said Tiffany Farchione, M.D., director of the Division of Psychiatry in the FDA’s Center for Drug Evaluation and Research.

‘By publishing this draft guidance, the FDA hopes to outline the challenges inherent in designing psychedelic drug development programs and provide information on how to address these challenges. The goal is to help researchers design studies that will yield interpretable results that will be capable of supporting future drug applications.’

What “unique characteristics” must be considered when designing clinical trials involving psychedelics?

Take a minute and brainstorm. What comes to mind? (If this newsletter has done its job, you can come up with at least one!)

Psychedelics cause intense alterations in consciousness and changes to our perception that typically last several hours. I can safely say that most blood pressure, diabetes, and cholesterol medications don’t have that effect. When designing clinical trials to evaluate whether a medication is effective at lowering blood pressure, there’s a much lower chance that a participant has an experience described as “finding God” or “becoming nothing in time and space” necessitating monitoring from a therapist and some light unpacking after – not to mention ensuring the person is in a safe environment away from dangers like traffic or balconies.

To account for this, some research involving psychedelics incorporate some sort of behavioral or psychological intervention. This is a plan for what the research team will do in the event that a person participating in the study has a “bad trip” or other unpleasant side effects unique to psychedelics due to how they work.

Psychedelics have unique characteristics beyond trippy side effects.

There’s some evidence to suggest that psychedelics have both quick-acting and long-term effects on mental health, including the ability to cause long-term effects after only one or a few doses. This is quite different from an antidepressant capsule that must be taken every day – and the clinical study design must account for this.

If a person takes psilocybin once, and then three months later has substantial improvements in depressive symptoms, that’s great news! But, how do we know whether it was psilocybin or another factor that caused the effect? What if the patient took other actions during those three months, such as leaving a job or relationship that caused distress, which can impact symptoms?

The FDA aims to address these issues by offering guidance on how researchers can design clinical trials to properly evaluate the medical use of psychedelics. The goal is to help drive down costs and barriers to conducting research by addressing common issues and problems that have arised in studies to date, and to ensure that the research produces useful, impactful data.

 

We won’t go into every detail, but some fun tidbits from the guidance include:

• A brief mention of chemistry, manufacturing, and controls – researchers must follow strict guidance since psychedelics are still classified as Schedule I substances (I’m going to cry when the day comes that I can stop typing that)

• A statement that it “may be reasonable” to initiate research in the absence of “typical animal toxicology testing” when information about exposure in humans is available from previous studies and no serious safety concerns were found. Another step that helps save money when conducting testing, as it eliminates duplicate work.

• Encouraging researchers to investigate the interaction between the psychedelic drug and the serotonin (5-HT) receptor subtypes – in other words, keep exploring how classic psychedelics interact with serotonin and the serotonin receptor, so we can continue learning how these drugs interact with our body chemistry. Exploring how drugs interact with a receptor, and receptor subtypes, often leads to new theories about how a drug works or other conditions that drug may be useful in treating.

• Encouraging researchers to explore the “dose-response relationship”, as it is poorly understood for most (all?) psychedelics. The “dose-response relationship” is exactly what it sounds like – what response is produced by a dose, and what does this relationship look like along a continuum of doses? This work helps us narrow down ranges for drug doses that produce therapeutic effects, versus “too high” doses that produce side effects or “too low” doses that don’t have a positive effect.

 

Why Does This Matter?

This is a massive development for the credibility and legitimacy regarding medicinal use of psychedelics, and the momentum of the legalization movement.

The FDA oversees all drug development in the United States. Cancer drugs, heart disease drugs, HIV drugs – all are within the realm of the FDA. Publishing this guidance not only shows the FDA takes the therapeutic potential of psychedelics seriously – in my opinion, it’s a sign the FDA is encouraging this research. Which is exactly what they should be doing.

Acting as a flexible governing body that helps private research happen in a cost-effective AND safe manner, encouraging innovation while also ensuring the lessons learned from past tragedies in drug development are remembered.

Think of this issuance as the FDA saying, “We want to help the people conducting psychedelic research in the U.S.” The agency responsible for whether or not a prescription drug gets approved and marketed for use has acknowledged the therapeutic potential for psychedelics and is encouraging research.

We’ve come a long way from reefer madness.

 

Conclusion

By issuing this guidance on psychedelic drug trials, the FDA acknowledges the therapeutic potential for these agents, and actively encourages research into their use. This is a massive turning point for the perception of psychedelics, further solidifying their place among legitimate medicinal agents. While the recommendations are nonbinding and carry no legal weight, they should help firms save time and money when designing and conducting psychedelic drug studies.