🫠 Psychonaut POV

Welcome to Tricycle Day. We're the psychedelics newsletter that was born to be wild. Somehow we ended up A/B testing subject lines. 👹

Adie Rae spent twenty years in the weeds of, well, weed. And she saw what happened when cannabis rolled out without anyone bothering to track what it did to patients. So now she co-directs the first federally funded registry of legal psilocybin services.

We asked Adie who's showing up to Oregon's psilocybin services, what surprised her about psilocybin’s impact on pain, and why true informed consent is still out of reach.

As you’re about to read, clinical trials only tell you so much. The “real world” of psychedelics is a different animal.

We couldn't agree more. So on Friday, we spent 75 mins discussing exactly that. What happens when regular people do legal psilocybin therapy?

Henry, founder of Tricycle Day, sat down with Althea CEO Niko Skievaski to dig into the patterns across thousands of real-world sessions and answer questions about safety, outcomes, antidepressants, trauma, and more.

The full replay is up now. (It’s free.)

Watch it, and then go find the experience that’s right for you.

I spent my undergraduate, graduate, and postdoctoral years studying cannabis using electron microscopes, looking at synaptic plasticity, neurophysiology, and neuropharmacology. My main goal was to understand how cannabis and cannabinoids could reduce the harms of opioids, so it was always funded by the National Institute on Drug Abuse. I ended up spending two decades trying to develop evidence for the therapeutic potential of a Schedule I substance. Sound familiar?

All of that expertise mapped really well onto the regulated psilocybin market. When Measure 109 was first being drafted as a ballot initiative, the people putting it together approached me for support to ensure it aligned with the literature. So from the earliest days of Oregon’s psilocybin program, I had a front-row seat to what it was going to do.

Knowing what we got wrong with the rollout of medical cannabis laws and how much higher the stakes might be with psilocybin, I was well-positioned to help develop a team that would fill the gap between policy and science. My colleagues Chris Stauffer and Todd Korthuis were serving on the Oregon Psilocybin Advisory Board at the time, so they knew exactly what the regulations would look like in practice. Together with Jason Luoma, we formed a Open Psychedelics Evaluation Nexus (OPEN) to track what happens to people after they receive services, a gap OHA didn't have the resources to fill itself.

The whole point of a clinical trial is to control everything. You set the dose, the preparation, the number of people in the room, and the integration hours. The exclusion criteria are lengthy too, which means people with complex health conditions and those on a lot of medications end up ineligible. The result is a participant pool that's mostly white, educated, and male. The big question is whether those results generalize to a regulated state environment where the population is far more diverse.

In a registry, nothing is controlled. We're watching what's happening in the real world, with a much more diverse population. We’re tracking everything from depression, anxiety, and PTSD to spirituality, sense of life satisfaction, and physical pain. And unlike the aggregate data OHA is required to collect by statute, a registry captures the patient-level story. An average dose reported over the past quarter tells you nothing about this person with this facilitator getting this dose and having these outcomes. That granularity is exactly what a registry is for. 

We know what it looks like when that patient-level data doesn't exist. California rolled out compassionate use of cannabis in 1996, but the federal government didn't fund a registry to track patient outcomes until 2023. In that window, we gave people access without ever following up on what was working and what wasn't. One consequence was cannabinoid hyperemesis, where people treating their nausea with cannabis were actually making themselves sicker with THC. Proper monitoring could have caught that from day one. When it comes to psilocybin and its potential longer-term consequences, we can't afford to get this wrong.

These services are expensive, so we predicted that people who can afford to pay a few thousand dollars out of pocket would be the ones engaging, and lo and behold, that’s the case. They're high-net-worth individuals, who also tend to be white and educated, so the current picture of who's accessing services in Oregon isn't a diverse one. But there is no way to improve access for lower-income individuals or minority communities if we don't first understand the extent of the problem. We need this data to motivate people outside our research group to do something about it. 

The most realistic route to equitable access is insurance coverage, and the model for that already exists. Psilocybin services are where acupuncture was fifteen or twenty years ago. The benefits are real, but access is almost entirely out-of-pocket. What it took for acupuncture to get covered was rigorous studies with compelling statistics in real-world populations. That's what we're building. 

On the clinical side, the pain data has been the most surprising. I assumed going in that pain relief would be a byproduct of depression relief, since at a neuronal level the brain doesn't really differentiate between the two. They share the same brain areas and neurotransmitters. But roughly 10% of our cohort had moderate to severe pain at baseline, and at follow-up they no longer did. That improvement showed up in people with depression and people without it, so psilocybin appears to be acting on pain directly, independent of what it's doing to mood. That tells me how much more work there is to do in this field.

This podcast is speaking our language. In the latest episode, an Oregon psilocybin therapy provider shares results from a real-world outcomes study, and announces a fully funded pain study now recruiting (travel stipend included).

At the time we were writing these grants, the only part of the NIH that had any interest at all in psychedelics was the National Institute on Drug Abuse. So we started with substance use because that's where the funding was. Since then, other parts of the NIH have perked their ears up. More recently, we've submitted a grant to the National Institute on Mental Health, which is more aligned with what people typically associate with psilocybin's benefits.

But it’s not just about funding. My colleague Todd Korthuis is an addiction medicine doctor who has spent his career directly helping patients recover from substance use disorders, so the focus is genuinely his too. And there’s a real scientific community building around this question. Matthew Johnson has extremely compelling data on psilocybin's impact on smoking cessation. 

What all substance use disorders have in common is that the brain is essentially stuck in a mode of needing something external to fulfill its well-being. Addiction is a disease of disconnection, a void, a rut in the mind. Considering psilocybin's ability to act as a neuroplastogen and rewire habitual circuits, addiction is a scientifically sound place to focus. The clinical trial data is promising, NIDA is funding it, and the neurobiological rationale is strong.

The biggest one is what factors could lead to better informed consent. Rosalind Watts has this analogy where consenting to a psychedelic service is like getting in a boat with your facilitator and rowing out to the middle of the ocean. They drop you down on a line and stay in the boat the whole time. They can't tell you what you'll find, only that eventually you'll come back up and return to shore. That's the best we currently have. We should be able to tell someone the likelihood of an extreme event, the likelihood they'll need a new medication afterward, and the likelihood they'll never experience anxiety symptoms again.

The other thing I care deeply about is how we measure outcomes without doing an injustice to the experience itself. We use all the best clinically validated measures: the PHQ-9 for depression, the GAD-7 for anxiety, the PCL-5 for PTSD, DSM-5 criteria for substance use. But you know what we're doing when we over-rely on these quantifiable metrics? We're shoving a person's ineffable experience into a set of boxes.

That's why all of our studies include a mixed-methods approach. We capture all the boxes that need to be checked, and we also ask them, their spouses, and their family members, how are you actually doing? That narrative picture is just as valuable as the clinically validated measures. What makes this field so cool is that while no one can observe your rebirth experience, no one can tell you that you didn't have one. Psychedelics break open the dogma of science to accept that subjective reality is reality.

Check out OPEN’s ongoing projects and publications, or make a gift to support its research.

That’s all for today, Cyclists! Whenever you’re ready, here’s how we can help.

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DISCLAIMER: This newsletter is for educational and informational purposes only and is not intended as a substitute for professional medical advice. The use, possession, and distribution of psychedelic drugs are illegal in most countries and may result in criminal prosecution.