🫠 Psychonaut POV

Welcome to Tricycle Day. We’re the psychedelics newsletter that neuromodulates the boredom out of your brain in one read. (Results not clinically validated.) 🧐

Owen Muir is a psychiatrist who's never taken a psychedelic, a critic who genuinely wants these medicines approved, and a CMO building a company that's ready to rock either way. He also has PTSD he's deliberately choosing not to treat with psychedelics. Yet. (More on that in a minute.)

We asked Owen what gives him confidence a psychedelic medicine will be FDA approved this year, how he’s already using psychoplastogens to achieve one-day remission, and why good intentions might be the biggest liability in drug development.

One thing y’all seem to love about Tricycle Day is how we don’t pick sides.

Clinical, spiritual, regulated, decrim. It’s all good by us. We just want these medicines to be accessible to the people who’d benefit.

Psycon is the psychedelic conference and trade show with the same attitude, and they’ve got the programming to prove it.

Their event next month in Denver will have 14 tracks spanning pharmacology, business models, harm reduction, and more.

We’ll be there. Stop by our booth with Althea, say hey, and put a face to the memes.

I've never had a drink of alcohol. I've never smoked a cigarette. I have had ketamine administered to me for depression, although it's debatable whether that's a psychedelic. But I also have bipolar disorder, so I've had both mania and depression altering my consciousness endogenously. I don't need a substance to know what some unusual experiences might be like.

The most important reason, though, is that I'm highly likely to be involved as a voice in the regulatory process. I've been to the FDA three times this year already, and my concern is whether I'm giving up some of my credibility as a scientist. These compounds can alter your perspective. In a world of evangelicals and true believers, there's a role for a loyal skeptic to carry additional weight when the regulatory environment is this fraught.

I have PTSD. I've lost patients to suicide, I've lost family members, and bad stuff has happened in my life, as in so many people's lives. While my mom and I were working together on a series of reviews on psychedelic medicine for the American Journal of Therapeutics, she said, “If only this had been around when your father died.” I know these compounds have promise. But having non-dismissible voices speak up for them when questions of safety and efficacy are asked might matter more than my own healing right now. The answer thus far has been yes, it's worth waiting. I'm willing to do it the day after it's accessible for everybody.

First and foremost, it’s the team. Radial was originally founded by Elliot Cohen and John Capecelatro, co-founder and very early employee at PillPack. The original idea was to build a services solution for psychedelic medicine when it seemed right over the horizon. When MDMA-assisted therapy tanked at the FDA, they had to pivot. My wife, Carlene McMillan, who's also a co-founder at Radial, was at Osmind at the time, which has 900 clinics and helped Spravato succeed in the market by collecting real-world data and making REMS submissions easy.

The depth of the bench on our team is remarkable, and our relationships with payers are personal and go back decades. Healthcare is an iterative game; having been around matters. The track record of being decent people matters a lot, too. We've earned a lot of goodwill from the people we've worked with, and I think that's going to matter more than just ambition and money.

There's also an extremely granular operational side. You have to know what goes into having a psychiatric patient in an office all day long. There are commercial leases, hospitality considerations, marketing restrictions, and regulatory compliance. Almost all of our team has been involved in clinical trials. And since we already have neuromodulation treatments, we're a business with growing revenue. That protects us against regulatory risk on psychedelic medicines.

I'm about 70/30 that it’ll happen at the tail end of this year, but we’ll see an approval by early next year at the latest. The teams at Definium and Compass are responsible adults with serious track records. Psychedelic medicine is medicine. Clinical trials are clinical trials. Having deeply experienced leadership in drug development, not just psychedelics specifically, is what matters.

Lykos grew out of a nonprofit. It grew out of advocacy. Rick Doblin is a once-in-a-generation person with an agenda, and he’d be the first to say it wasn't to spend his life in drug development. In fairness to Lykos, you design a trial seven years in advance of it concluding, and the things relevant to regulators when they review your submission are different from when you started. But coming up with a brand new therapy manual was a bad way to commercialize a drug. Their adherence manual was basically a vibe check with no anchor points for degree of adherence. That meant the investigators couldn't even evaluate whether the therapy in the placebo group was the active treatment they thought it was.

There was also a lack of rigor around protecting individual subjects. Psychedelic exceptionalism—the idea that you don't have to follow the same rules—appeared  to be a core philosophy at MAPS, to an outsider like me. Things happened in those trials that should not have happened, perhaps because the Lykos team was insufficiently paranoid about what could go wrong. Good intentions are a great way to miss errors. We've all learned the lesson: if you are not extremely careful, things will happen in your clinical trials that prevent your drug from getting to people who need it.

Honestly, I have no idea, because it hasn't been demonstrated yet. But therapy has been around for a long time. And all therapy is integration therapy, in the sense that all therapy happens after the thing you need therapy to talk about. Therapy helps us make meaning out of our experiences when they can be challenging.

The FDA's complete response letter to Lykos said the same thing I've been saying: just use a therapy that exists. I have a bias toward mentalization-based treatment, a manualized psychodynamic psychotherapy with remarkable adherence tools. Anthony Bateman and Peter Fonagy ran a trial in antisocial personality disorder with a .7 effect size, and their rating scales could measure not just whether a therapist followed the manual, but how well. That kind of specificity is what was missing from the MDMA-AT program.

But here's the thing. There's no data yet that says therapy is meaningfully better with psychedelics than without. It has to be demonstrated. Plenty of gay men got through the HIV epidemic by going out and dancing, and many of them took MDMA and found healing. For all I know, dancing might be the best adjunctive. We already have data in neuromodulation where therapy plus an intervention was less effective than the intervention alone, because the biology inhibited the psychotherapy. One plus one doesn't always equal three; it might equal 0.5. We need more equipoise about what's likely to be the best case.

We don’t have to speculate because we're already doing it. D-cycloserine is a tuberculosis medicine, which has been approved for decades, that acts as a psychoplastogen. Researchers have published papers using it as an adjunctive to TMS for depression and OCD.

Since Radial is a company that used to be a pharmacy, we were able to source D-cycloserine despite a national shortage. We've deployed a one-day depression protocol combining D-cycloserine with TMS and treated over 50 people, as part of a trial with Ampa Health. We've also used the protocol to treat auditory hallucinations (i.e., hearing voices in your head) and achieved remission in one day. No one's ever done that before.

But the future isn't psychoplastogens versus psychedelics. Some people are going to need the trip and some won't. We don't want only one treatment for people who are suffering. We want the full range.

The question is how do you match the right patient to the right tool. That's where AI comes in. We're running clinical trials with partners, like Psyrin.ai, collecting vocal biomarkers and more, and training algorithms to see what humans alone can’t. I don't know which tool will be the best for any given person, but if we can use technology to detect signals better than humans can, we'll fumble around in the dark less. Patients want to know what's going to work for them. That's what we’re trying to build.

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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.