🫠 Psychonaut POV

Welcome to Tricycle Day. We're the psychedelics newsletter that’s too big to fail. If our open rates drop, we fully expect a taxpayer-funded bailout re-engagement campaign. 🫴

Doug Drysdale won’t do a victory lap, so we’ll brag for him. In three years, the guy took Cybin from a half-baked plan to sell mushrooms on Amazon to a breakthrough therapy designation in Phase 3 trials. Then he handed the keys over and started advising the next batch of companies trying to figure it out.

We asked Doug how he knew it was time to move on, why a non-hallucinogenic LSD derivative is worth his time, and what big pharma's recent acquisition spree tells us about where the sector is headed.

This experience is designed for athletes carrying psychological weight that outlasts physical recovery, whether that's lingering fear after injury, emotional blocks limiting performance, or an identity shift after stepping back from sport. The facilitator is a Certified Rolfer with over 16 years of experience working with athletes' bodies and takes a non-directive, somatic approach to psilocybin facilitation.

I've been involved in CNS and mental health a few times in my career, across different products and companies. What pulled me into psychedelics specifically was a couple of things. First, when I saw the data from the early psilocybin trials out of Johns Hopkins and Imperial College, I couldn't really believe it. I was honestly quite skeptical.

But the more I dug in, the more excited I got. Having worked with SSRIs at previous companies, I saw their limitations. These early psychedelic trials were showing something entirely different. These weren't drugs that masked symptoms. These were treatments that could actually change the course of disease.

Part of what pushed me to leap in was also personal. My aunt became very depressed after her husband died, turned to alcohol, and ultimately took her own life. My mom died at 41 from smoking; she'd been doing it since she was 12. There's a pattern of depression and addiction in my family, and beyond that, in friends and colleagues too. When you've watched people struggle like that, and you've watched medicine come up short, being part of something that could actually change that trajectory, not just manage it, is pretty exciting.

Companies have to make changes as they grow. When I joined Cybin, the business plan included selling functional mushrooms on Amazon. We quickly pivoted from that to full-on drug development, through preclinical work, Phase 1, Phase 2, and into Phase 3. Each stage requires a different skill set and a different scale.

When I left, the company was well funded and on a solid runway. The next goal was commercialization, and that requires a different kind of operator. I love the early part. My strength is building teams and bringing groups of strangers together into high-functioning units all focused on the same problem.

When I look back on those three years, the standout lesson isn't specific to psychedelics. It’s that culture is everything. We started Cybin during COVID, fully remote from day one, hiring people wherever they were. As we scaled and tackled increasingly complex work, none of it would have been possible without a strong, cohesive culture.

Pretty much everyone who joined had some personal reason for doing so, which makes a real difference. People weren't just clocking in; they were driving themselves. The team ultimately became highly selective about who else they let in, because they understood how much power that culture had.

People think drug development is glacially slow, but behind the scenes everyone is running like crazy, doing fifty things at once to produce one visible outcome. That takes massive coordination, urgency, and speed. We couldn't have executed the way we did without our culture.

After I left Cybin, about twenty or thirty companies reached out wanting me to look at their assets. It was a lot of early-stage neuroplastogen work. Some of it had potential, and some of it was going to be very hard to back up. With BetterLife, I'm helping as a corporate advisor, trying to find the best path forward for a specific asset that I think is genuinely promising.

It's a derivative of BOL-148, also known as 2-bromo-LSD, a compound that's been around since the 1950s. What BetterLife has worked out is that BOL-148 is a racemic mix of four stereoisomers. They’ve discovered that one of those stereoisomers is active at the receptors of interest, while the others aren't. That's enabled them to patent a compound that otherwise would have been unprotectable.

They've also figured out a way to synthesize it without using LSD as a precursor, which means no controlled substances are involved at any stage of development or production. That's a massive deal. The DEA licensing hurdles for Schedule I work, from security cameras and secure storage to unannounced DEA inspections, add enormous time and cost to any clinical program.

The asset is non-hallucinogenic, and it doesn't induce tolerance the way something like MDMA or classical psychedelics do. This compound could be dosed daily. That makes it ideal for chronic, at-home use in neurodegenerative diseases.

At the moment, our focus is cluster headache. In 2010, a small pilot study of about 10 patients found that, after just a few doses, headache frequency dropped significantly. That's human data on efficacy, which is already ahead of a lot of what's out there. I look forward to seeing where neuroplastogens go beyond psychiatry, whether that’s Parkinson's, TBI, or the applications we haven't gotten to yet.

It's changed a lot. In 2020 and early 2021, we saw a real hype cycle. Capital flooded in and companies formed fast. It was a bit of a gold rush. Funds were piling into multiple companies before anyone really understood what they were investing in.

Then by the second half of 2021, things shifted. After the initial rush of excitement, everyone took a breath and realized they weren’t going to see results from any of these investments for years. The short-term return expectations evaporated. On top of that, biotech in general has been in a downturn the last three or four years with fewer IPOs, less funding, and too many companies chasing the same targets.

But things are genuinely looking up now. We've seen a significant increase in biotech financing and IPOs since late last year, and we now have multiple billion-dollar-plus market cap psychedelics companies at a stage where they're largely unstoppable, barring a catastrophic trial result. I'm thinking of AtaiBeckley, Compass Pathways, GH Research, MindMed (now Definium), and Cybin (now Helus). I suspect Lykos (now Resilient) will come back in some form, too. The flimsiness of the early sector is gone.

On the acquisition side, the hesitation I kept hearing from big pharma was never about the science. They were easily convinced by the data. It was always the commercial practicalities. How do you sell this? How do you handle the PR and the stigma? How do you run supervised clinic networks and manage a controlled supply chain?

That hesitation is clearly gone. Otsuka's move on Transcend didn't surprise me. They've been among the most aggressive in chasing psychiatric assets, and they'd already done the commercial work. AbbVie going out and adding a psychedelic compound on top of a portfolio that already included a neuroplastogen tells you the same thing.

Until neuroplastogens came along, we thought we'd already hit the limit. The assumption was that you couldn't actually change the brain. You could manage symptoms, but the underlying structure was fixed. Pretty much all pharmaceuticals, SSRIs included, worked on that premise.

What psychedelics have opened up is a different thought process. Maybe we can actually change the brain in a way that's durable, or even permanent. We're already seeing stem cell approaches to Parkinson's disease, where a patient's own skin cells are being used to generate brain cells that are a genetic match.

There's also a broader shift happening toward a consumer health model. Look at what Lilly is doing with GLP-1s. They're moving their attention from tackling the metabolism of obesity to tackling the neurology of it, intervening at the brain level rather than the gut level. That's the same frame psychedelics introduced to psychiatry.

The next decade in mental health and neurology is going to be extraordinary, but it won’t be easy to get there. Founders in early-stage companies have a tough journey ahead. Probably 50 or 60, maybe more, companies that started in this space no longer exist. Persistence is everything. My advice is to stick at it, and find the people who can help you, because they're always out there.

Check out his free resources for biopharma and life sciences leaders at Katogen, or follow him on X.

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.