It's getting harder to do psychedelic trials

Blame the 'Pollan Effect'

• Hey! Come to this online event on ‘managing risk in psychedelics and adventure sports’ featuring Jamie Wheal, Lindsay Bira and Rob Ó Cobhthaigh on December 3rd at 6pm UK time. Paid subscribers get a free ticket with the discount coupon after the paywall.

Hard times for the psychedelic renaissance right now. Many psychedelic advocates were pinning their hopes on the state ballot bill in Massachusetts (indeed, MAPS, who received funding to promote the bill, sent out an ill-considered press release the day of the election, prematurely celebrating the bill’s success). In fact, the bill failed to win a majority. Voters were apparently not enthused by the example of Oregon, which passed a similar regulated access bill in 2020, creating a legal market that is expensive, not much used, and costs the state millions.

• Check out this piece by Charles Lehmann in the Free Press on ‘why Americans said no to drugs in this election’.

With state ballots stalled, all hopes are riding on psychedelic medicines getting FDA approval. But that is proving hard as well. Compass Pathways, one of the leading psilocybin therapy companies, announced last week it was pushing back its Phase 3 results by a year and laying off 30% of its staff. CEO Kabir Nath told Psychedelic Alpha one of the problems has been meeting the FDA’s new stringent requirements and recruiting enough trial participants.

This is a challenge all psychedelic start-ups are facing at the moment. Psychedelic trials have always been bureacratically-difficult, but they have become even more so in the wake of Lykos’ failure to get FDA approval this year, over FDA concerns ranging from functional unblinding (participants know they’ve taken a psychedelic) to the high prevalence of participants who had taken psychedelics before.

One leading psychedelic researcher tells me:

The FDA is being extremely vigilant and careful, to the point where they’re making it almost impossible to actually do the research. For example, they don’t want anyone who’s used a psychedelic in the past to be included in a trial, because, if you recall, Lykos was criticized for having a sample where 40% had previously used MDMA. But the issue with that is, in the wake of Michael Pollan’s book or the rise of microdosing, it’s harder to find people who have never tried anything.  It’s very frustrating for those of us who do this work, because we only get paid if we actually enroll people, so sometimes we spin our wheels and end up wasting time.

This could be an existential issue for the field. The psychedelic renaissance was powered by a handful of academic trials, which won credibility for the field and attracted media attention from the likes of Michael Pollan. His book helped spark a boom in the underground. Now, these trials are harder and harder to do – partly because of the boom in the underground and the increasing recreational use of psychedelics.

Usually, the only way a member of the public can try an experimental new drug is by signing up for a clinical trial. That’s not the case with psychedelics – you can order them on the internet and they will arrive at your door tomorrow. That means psychedelic trials face stiff competition from the underground for recruitment – why sign up for a laborious clinical trial sometime weeks or months in the future, in which you might end up being given a placebo, when you can try to relieve your depression with some shrooms tomorrow?

In addition, FDA trials have rigid exclusion criteria around diagnoses, but in the real world, people’s mental health problems don’t always fit neatly into these diagnostic boxes. Dr Manish Agrawal, CEO of Sunstone Therapies, which runs psychedelic trials for itself and other companies, says:

Mental health conditions are rarely confined to one neatly defined diagnosis—there’s often considerable overlap, such as between trauma and depression. Yet, for research purposes, we need clear diagnostic thresholds to determine eligibility, which can make it difficult for patients who may not fit squarely into one category or whose symptoms fluctuate from day to day. Patients know when something feels wrong and may have a sincere desire to explore new treatments, but they may not align with the rigid criteria of research protocols—criteria that do not fully reflect the nuanced reality of living with mental illness. This disconnect can make recruitment a complex process, and it highlights the need for diagnostic advancements that better bridge the gap between clinical research and real-world experiences.

This, according to another psychedelic researcher, has been a challenge for Beckley PsyTech’s trial of 5-meo-DMT for treatment-resistant depression, which has struggled with recruitment:

An issue with the Beckley PsyTech trial for TRD is it has to be recurrent, which is different to having always been repressed. They also have to have non-responded to anti-depressants in the current episode. So it’s a very unique sample which, from what I’ve heard, is proving challenging to find.

I asked Beckley PsyTech about this but didn’t receive a reply yet.

David Yaden, the Roland Griffiths Professor of Psychedelic Research at Johns Hopkins University School of Medicine, says:

Recruitment is and has been one of the biggest challenges in conducting psychedelic research. The extensive screening, preparation, and safety check-ins requires a larger time commitment than many other studies. Our exclusion criteria for safety purposes also limit who can be included in the studies. Achieving a demographically representative sample is even more difficult and is probably the issue that we spend most of our time and energy on in study logistics meetings––we discuss it every single week and are constantly trying new approaches, many of which are costly and time intensive.

Is there anything that could be done to make trials easier to do? David Yaden says:

In terms of what we can do, we are developing educational materials so that people are more aware of what the process involves as I think it can seem mysterious to some, this would include discussion of the potential risks involved as well, but would focus on the basics of what a clinical trial is, why they are done, and what they involve.

The FDA could also clarify its requirements, for example only excluding people if they’ve tried psychedelics in the last year, as opposed to ever in their lifetime. Start-ups could also search further afield for trial participants, like Eastern Europe, where the Pollan effect may have been less intense.

Alternatively, some parts of US psychedelic culture seem to hope the incoming Trump government will reform the FDA, or at least introduce executive orders to make psychedelic medicines more accessible.

After the paywall, why this might not be completely fanciful thinking.

Plus other stories including: the VA is set to provide funding to a network of NGOs to make psychedelic medicines available, Fireside Project launches a coaching programme, and a new documentary lifts the lid on kundalini yoga.