AI and ultra-large docking in drug discovery

Bryan L. Roth is a drug receptor scientist who solved the crystal structure of LSD inside a serotonin receptor and took $26.9 million from DARPA to build a non-hallucinogenic psychedelic — a compound that hits the same receptor as psilocybin, produces antidepressant effects in mice, and doesn't cause a trip.

Expect to learn how his mother's schizophrenia launched a 40-year career in pharmacology, why Salvia divinorum has zero serotonin activity and works entirely through the kappa opioid receptor, why serotonin and opioid receptors converge in the claustrum, why DARPA funded non-hallucinogenic alternatives for soldiers, how his lab screens a trillion compounds that don't physically exist, why only 100 of 26,000 protein targets have ever been drugged, and much more…

Timestamps:

00:00 Bryan L. Roth — The Man Who Builds Non-Hallucinogenic Psychedelics

02:41 Falling Into Receptor Science by Accident

04:58 When Only 5 People on Earth Studied Psychedelic Receptors

06:07 Why "Psychedelic" Was Banned From Research Grants

07:28 The 2016 Papers That Changed Everything

08:26 The Scientist Friend Who Got "Cured" by Psilocybin

10:41 The Vietnam Vet With a Gun in His Mouth — Ibogaine's Power

12:50 What Is Ibogaine and Why Can It Kill You?

18:06 Why the Kappa Opioid System Breaks Reality

19:07 The Hidden History of Psychotomimetic Opioids

22:16 Why Opioid Researchers Deny Kappa Causes Hallucinations

23:18 The Claustrum: Where Serotonin and Opioid Receptors Meet

24:14 Multiple Entry Points Into Reality-Altering Brain Systems

28:35 Why Psychedelic Experiences Feel So Meaningful

29:58 DMT: "More Real Than Reality" — And Nobody Knows Why

31:28 Salvia: Becoming Plaid on a Wall

33:48 Trump's $50M Psychedelic Order Won't Buy One Clinical Trial

35:33 No Other Psychedelic Touches the Kappa Receptor

38:10 The Real Reason He Built a Non-Hallucinogenic Psychedelic

41:33 DARPA: More Psychiatric Casualties Than Physical in the Military

44:48 Biased Agonism: Stripping the Trip From the Therapy

47:19 How GPCRs Work and Why Drug Design Is Still Trial and Error

49:50 People Who Will Never Touch a Psychedelic But Do Cocaine Weekly

52:27 "I Don't Discuss That" — Whether He's Taken Psychedelics

52:47 Screening a Trillion Drugs That Don't Exist

55:02 The Real Bottleneck: 26,000 Targets, Only 100 Drugged...

Email for sponsorship enquiries: evan@thegiantsshoulder.com ❤️ Subscribe to our main channel - https://www.youtube.com/@thegiantsshoulder?sub_confirmation=1💚 Follow on Spotify - https://open.spotify.com/show/5m3Gta5MtIYdk59pb2GJ7M?si=Ka2rAQv7TyqiC9wvGwERpA💜 Follow on Apple Podcasts - https://podcasts.apple.com/ie/podcast/the-giants-shoulder/id1752486249Download my FREE EBook 26 Neuroscience Books for 2026 HERE: https://thegiantsshoulder.com/