🫠 This Week in Psychedelics

[5-min read] AI model discovers thousands of novel psychedelic molecules.

Welcome to Tricycle Day. We’re the psychedelics newsletter that’s powered by natural curiosity, not artificial intelligence. (Not that there’s anything wrong with that… Robots, if you’re reading this, please don’t destroy us.)

🪴 Let your flora-and-funga flag fly: Last week, we announced a t-shirt giveaway to celebrate our first birthday. If you didn’t win, better luck next time. 🥲

Now, the good news. By popular demand, our “plants & fungi are my friends” tee is now available for sale. Take 15% OFF with code FRIENDS15. (Coupon is valid for the first 100 orders only!)

Here’s what we got this week.

  • AI identifies thousands of new psychedelics 🤖

  • World’s first MDMA prescription 📝

  • Psychedelic investing cools off 📉

  • Hyped on mushroom energy drinks 🔋

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MICRODOSES
🔬 Research

Sex matters: New research suggests psilocybin affects men and women differently.
It’s complicated: Microdosing psychedelics may improve mental health and curb depression, but some experts are concerned about cardiac health risks.
The body keeps the score: Researchers are testing whether psilocybin can treat chronic lower back pain.
Anxiety must be anxious: Cybin has received FDA approval to kick off a Phase 2a trial of DMT for Generalized Anxiety Disorder (GAD). Meanwhile, Incannex has dosed all the participants in its study of psilocybin for GAD.

🏛️ Policy

Battle scars: The Ukrainian military is treating its soldiers with ibogaine and ketamine.
Third time wasn’t a charm: DecrimCA missed its deadline to put psilocybin legalization on California’s 2024 ballot. That leaves just one initiative standing.
Hear me out: Nevada lawmakers held a hearing on the legalization and therapeutic potential of psychedelics.

📈 Business

Get sponsored: MAPS is bringing back its Fiscal Sponsorship Program to empower grassroots projects.
Jersey spore: COMPASS Pathways is partnering with Hackensack Meridian Health to prepare for the rollout of its proprietary psilocybin formulation.
Track your package: Filament Health made the first (authorized) international shipment of natural psilocybin.
Bump those numbers up: Optimi Health got Health Canada’s approval to manufacture a lot more MDMA, MDA, and 2C-B.
Who owns Bufo? GH Research won a European patent covering all forms of 5-MeO-DMT for major and treatment-resistant depression.

🫠 Just for fun

Credit card points to spare? Vogue thinks psychedelic retreats could be the future of wellness travel.
America’s got acid: LSD was here way before the hippies or Timothy Leary.
Yikes: Spanish police busted a global neoshaman ring for smuggling ayahuasca and trafficking humans.
Meme of the week: When you take a break from your fake email job to eat mushrooms outside

THE PEAK EXPERIENCE
I'm not a robot

Beep, boop—robot drugs are here

Albert Hofmann first synthesized LSD in 1938. 30 years later, Sasha Shulgin had created 200+ novel psychedelics in his lab. Now it’s 2024, and there’s a new drug designer in town.

But this one has an unfair advantage. It’s not human.

Meet AlphaFold, the AI model that just discovered hundreds of thousands of potential new psychedelic molecules, all with the touch of a button.

If there’s anything as mind bending as psychedelics, it’s AI, so let’s back up and explain. AlphaFold is a tool developed by Google’s moonshot AI division, DeepMind. What makes it special is its ability to accurately predict the 3D shape of proteins—the tiny molecular machines of life.

Proteins are folded up into insanely intricate structures. (Think origami on nightmare mode.) And knowing how they fit together is super important if you’re developing drugs. That’s because the shape of a protein (like, say, a receptor in the brain) gives clues on how it might interact with another molecule (like psilocybin or some new thing that also makes you taste colors.)

So in a recent study, researchers put AlphaFold to the test. They chose two proteins known to be involved in psychiatric conditions (one of ‘em was 5-HT2A). Then, they took AlphaFold’s model for those proteins and our best experimentally derived models for the same proteins, and dropped them into a drug screening face-off. Here’s what they found.

  • 👐 No overlap. The AI-predicted screening and traditional screening produced completely different drug catalogs. No two molecules were the same.

  • 🎯 Equal hit rates. The proportion of compounds from each screening that actually altered protein activity was identical.

  • 🧠 AI found the best matches. AlphaFold’s structures identified the drugs that activated 5-HT2A most potently. (That’s the main pathway triggered by LSD and psilocybin, FYI.)

It’s all already very freaky exciting, but the team at DeepMind is just getting started. They say the next version of AlphaFold will even predict how proteins change shape after binding to drugs and other molecules.

That’s a big leap for sure. But when will AI reach a level of consciousness where it can trip on its own discoveries? If Hofmann and Shulgin got to, it’s only fair. 🫠

AFTERGLOW
MDMA prescription

Dispense as written

Dr. Ted Cassidy just made history. And not by scribbling the most illegible prescription of all time. (Jk, it’s not even close. My doc’s Rx pad makes this look like calligraphy.) Look more closely, and you’ll see that this Australian doctor just wrote and filled the world’s first prescription for MDMA, or any psychedelic medicine for that matter, in the modern era.

It’s not the first time a patient has received psychedelic therapy in a clinical setting. But previously, you’d have to enroll in a clinical trial or navigate the red tape of compassionate use protocols. Fortunately, those days are over for Aussies, but there are still some hoops to jump through. Due to state-level restrictions, the psychiatrist, psychotherapist, and patient all had to travel to Melbourne to make this watershed moment happen.

Now don’t get me wrong; in no way do we mean to rain on the parade. But considering Australia authorized psychedelic therapy almost six months ago, we’re kinda surprised it took this long to get a script written, right? Then again, if it’s true that a single psychedelic journey packs more punch than 10 years of traditional therapy, then I guess this patient’s still way ahead of schedule.

Show me the money. No really, where is it?

It takes money to make money, they say. So if all the capital dries up, what happens to the businesses depending on it to get off the ground or stay afloat? We’re not sure, but our friends at Psychedelic Alpha just cranked out the most comprehensive analysis of psychedelic funding you could ask for. And, well, let’s just say 2023 wasn’t the easiest year for psychedelic companies.

Across 50 total financing events in the private and public markets, psychedelic companies raised just shy of $300 million in 2023. Now, that might sound like a lot of money… and it is. But that number’s down 49% from last year’s figure and a whopping 84% from a very frothy 2021. It’s pretty clear investor interest has waned.

If you invested at all-time highs, don’t be too hard on yourself. (This is self-talk advice, not financial advice, btw.) After all, things are looking up in 2024. Macro conditions seem to be improving, biotech investors are feeling more optimistic, and we’re closer than ever to the first psychedelic FDA approval. When the breakout comes, you’ll be happy you remembered, “time in the market beats timing the market.”

CYCLISTS’ PICKS
UNTIL NEXT TIME

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ONE CYCLIST’S REVIEW
Feeling euphoric

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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.

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