“What’s so hard about this scientifically, and to get the scientific community fully on board with these ideas, is that we’re likely going to figure out this works before we have any idea on how it works.”
— Dr. Nolan Williams
Welcome to a very special episode of The Tim Ferriss Show, an episode that might be an example of peeking around corners and catching a glimpse of the future of mental health treatments in the next five to ten years.
My guest is Nolan Williams, MD (@NolanRyWilliams). Nolan is an associate professor within the Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine and director of the Stanford Brain Stimulation Lab. He has a broad background in clinical neuroscience and is triple board certified in general neurology, general psychiatry, and behavioral neurology and neuropsychiatry. Themes of his work include examining spaced learning theory and neurostimulation techniques, development and mechanistic understanding of rapid-acting antidepressants, and identifying objective biomarkers that predict neuromodulation responses in treatment-resistant neuropsychiatric conditions.
Nolan specializes in looking at cutting-edge treatments and new technologies that can be applied to treatment-resistant psychiatric disorders—so, treatment-resistant depression, disorders that are notoriously difficult to address, such as OCD, and many others.
Nolan’s work resulted in an FDA clearance for the world’s first noninvasive, rapid-acting neuromodulation approach for treatment-resistant depression. And I’ve tested this myself, and we get into this in the conversation. He has published papers in Brain, American Journal of Psychiatry, and Proceedings of the National Academy of Sciences. Results from his studies have gained attention in Science and NEJM Journal Watch. He has received two NARSAD Young Investigator Awards, the Gerald L. Klerman Award, and the National Institute of Mental Health Biobehavioral Research Award for Innovative New Scientists.
We also discuss things like ibogaine that are seemingly unrelated to neuromodulation, as Nolan is very well-versed in multiple disciplines and in multiple toolkits, both pharmacological and non-invasive neuromodulatory. It’s this combination, actually, this rare Venn diagram, that makes him incredibly interesting to me.
I really enjoyed this conversation. I think it is very important, highly tactical, and I hope you enjoy it as much as I did.
P.S. “Magnesium–Ibogaine Therapy in Veterans with Traumatic Brain Injuries” is now live in Nature Medicine.
The transcript of this episode can be found here. Transcripts of all episodes can be found here.
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Listen onOvercast#714: The New Frontiers of Mental Health — Dr. Nolan Williams on Brain Stimulation, Ibogaine, Rapid-Acting Tools for Depression, Enhancing Sports Performance, and More
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Want to hear another episode that explores the frontier of ibogaine therapy? Listen to my conversation with Hamilton Morris in which we discussed Alexander Shulgin’s psychedelic research at the height of the War on Drugs, concerns about psychedelic research in the for-profit sector, how ibogaine’s usefulness for treating opioid addiction was discovered, sustainable alternatives to popularly used compounds, required reading, and much more.
#511: Hamilton Morris on Iboga, 5-MeO-DMT, the Power of Ritual, New Frontiers in Psychedelics, Excellent Problems to Solve, and More
What was your favorite quote or lesson from this episode? Please let me know in the comments.
SCROLL BELOW FOR LINKS AND SHOW NOTES…
SELECTED LINKS FROM THE EPISODE
- Connect with Dr. Nolan Williams:
Brain Stimulation Lab | Twitter
- Magnesium–Ibogaine Therapy in Veterans with Traumatic Brain Injuries | Nature Medicine
- Clinical Trials (Ongoing and Upcoming Studies) | Brain Stimulation Lab
- A Life-Saving Treatment for the Severely Depressed | Magnus Medical
- Accelerated TMS: Moving Quickly into the Future of Depression Treatment | Neuropsychopharmacology
- We Do Coffee Differently | Philz Coffee
- Dr. Nolan Williams: Psychedelics and Neurostimulation for Brain Rewiring | Huberman Lab
- Anterior Cingulate Cortex | Neuroscientifically Challenged
- Dorsolateral Prefrontal Cortex (DLPFC or DL-PFC ) | Wikipedia
- Is the Dorsolateral Prefrontal Cortex Actually Several Different Brain Areas? | Journal of Neuroscience
- Targeted Neurostimulation Reverses a Spatiotemporal Biomarker of Treatment-Resistant Depression | Proceedings of the National Academy of Science
- Resting-State Functional MRI: Everything That Nonexperts Have Always Wanted to Know | American Journal of Neuroradiology
- The Psychiatry Milestones 2.0: How Did We Get from 1.0 to 2.0 and What Can Users Expect? | Academic Psychiatry
- Thorazine (Chlorpromazine) | RxList
- How Viagra Was Discovered by Accident | BBC
- Some Practical Thoughts on Suicide | Tim Ferriss
- Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) for Treatment-Resistant Depression | American Journal of Psychiatry
- Transcranial Magnetic Stimulation: A Review of Its Evolution and Current Applications | Industrial Psychiatry Journal
- What is Faraday’s Law? | Khan Academy
- Electroconvulsive Therapy: A History of Controversy, but Also of Help | The Conversation
- One Flew Over The Cuckoo’s Nest | Prime Video
- Could I Lose My Job If I Admitted Myself to a Hospital (Having a Mental Crisis)? | Quora
- FDA Clears SAINT Rapid-Acting Brain Stimulation Approach for Those Suffering From Resistant Major Depression | Brain & Behavior Research Foundation
- Does TMS Therapy Cause Headaches? | Principium Psychiatry
- TMS for Migraine: Benefits, Effectiveness, Precautions, and More | Healthline
- Endogenous Opioids Mediate Left Dorsolateral Prefrontal Cortex rTMS-Induced Analgesia | Pubmed
- Personalized (N-of-1) Trials: A Primer | JAMA Pediatrics
- NSAIDs (Nonsteroidal Anti-Inflammatory Drugs) | Cleveland Clinic
- Montgomery-Asberg Depression Rating Scale (MADRS) | MDCalc
- Anhedonia | Cleveland Clinic
- What Is Idiopathic Parkinson’s Disease? | Verywell Health
- Parkinson’s vs. Parkinsonism | Davis Phinney Foundation
- Parkinson’s UK Brain Bank | Parkinson’s UK
- Deep Phenotyping: The Details of Disease | Nature
- Substantia Nigra (SN) | Cleveland Clinic
- Sequenced Treatment Alternatives to Relieve Depression (STAR*D) | Wikipedia
- Lexapro (Escitalopram) | Cleveland Clinic
- Celexa (Citalopram) | Cleveland Clinic
- Effexor (Venlafaxine) | Cleveland Clinic
- Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression | NEJM
- A Trip into the Future | American Physiological Society
- Inside Ibogaine: A Promising and Perilous Drug for Addiction | Time
- Fighting for Those Who Fought for Us | VETS
- Former GOP Texas Governor Promotes Psychedelics Research for Veterans at Event with Leading Experts | Marijuana Moment
- Human Subjects Institutional Review Board | Research Compliance Office, Stanford
- The Bachelorette | ABC
- Torsades de Pointes | Cleveland Clinic
- Howard Lotsof Dies at 66; Saw Drug Cure in a Plant | The New York Times
- Breaking Open the Head: A Psychedelic Journey into the Heart of Contemporary Shamanism by Daniel Pinchbeck | Amazon
- What is an Open-Label Clinical Trial? | News-Medical.Net
- Alexithymia Causes, Symptoms, and Treatments | Healthline
- Biden Signs Defense Spending Bill Funding Psychedelic Research | Forbes
- Dr. Deborah Mash: Ibogaine Can Make You Review Your Life | The New Health Club with Anne Philippi
- Listen: Neil Gaiman Reads ‘A Christmas Carol’ | The New York Public Library
- Minority Report | Prime Video
- Comparing Iboga to other Psychedelics and Entheogens | Root Healing
- Glial Cell Line-Derived Neurotrophic Factor (GDNF) | Wikipedia
- Brain-Derived Neurotrophic Factor (BDNF) | Wikipedia
- 5-HT2A Receptor | Wikipedia
- Controversial Drug Shown to Act On Brain Protein to Cut Alcohol Use | UC San Francisco
- The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation | Molecules
- Noribogaine | Wikipedia
- From Bwiti to Ibogaine and Back: A Transnational History of Tabernanthe iboga | Chacruna
- Treatment | Ibogaine Safety Guidelines
- Woman Dies While Being Treated for Drug Addiction | NZ Herald
- Tikosyn (Dofetilide) | Cleveland Clinic
- Walmart’s Food Sales Are Rapidly Dropping — Is Ozempic to Blame? | Eat This, Not That
- Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity | The Tim Ferriss Show #667
- Concussion/Traumatic Brain Injury (TBI) | CDC Injury Center
- Why Ibogaine for TBI? | VETS
- Five Myths about Using Suboxone to Treat Opiate Addiction | Harvard Health
- What is Naltrexone? | SAMHSA
- Kentucky Eyes Ibogaine, a Psychedelic, to Treat Opioid Addiction | The Economist
- Can Brain Ultrasound Treat Addiction? Study at WVU, UVA May Hold Answers | WV News
- Deep Brain Stimulation for Severe Opioid Addiction | NIH HEAL Initiative
- Finding the Cure for Scurvy | Naval History Magazine
- Chris Palmer, MD, of Harvard Medical School — Optimizing Brain Energy for Mental Health, The Incredible Potential of Metabolic Psychiatry, Extraordinary Case Studies, and Harnessing Mitochondria for Anxiety, Depression, OCD, PTSD, and More | The Tim Ferriss Show #633
- I Feel Love: MDMA for Autism and Social Anxiety by Rachel Nuwer | Tim Ferriss
- The Psychoactive Drug Ibogaine Could Save Lives — And Everyone Wants to Cash In | National Geographic
- An Urgent Plea to Users of Psychedelics: Let’s Consider a More Ethical Menu of Plants and Compounds | Tim Ferriss
- Voacanga: An Alternative, Sustainable Source of Ibogaine Treatment | Psychedelic Times
- Voacangine | Wikipedia
- Hamilton Morris on Iboga, 5-MeO-DMT, the Power of Ritual, New Frontiers in Psychedelics, Excellent Problems to Solve, and More | The Tim Ferriss Show #511
- Bufo Alvarius: The Psychedelic Toad of the Sonoran Desert by Ken Nelson, Expanded and Updated Edition by Hamilton Morris | Department of Information
- Open-Label Study of Consecutive Ibogaine and 5-Meo-Dmt Assisted-Therapy for Trauma-Exposed Male Special Operations Forces Veterans: Prospective Data from a Clinical Program in Mexico | The American Journal of Drug and Alcohol Abuse
- U-M Study Investigating If Magic Mushrooms Can Help Fibromyalgia | WXYZ
- Dr. Nora Volkow — Director of the National Institute on Drug Abuse (NIDA) | The Tim Ferriss Show #673
- Scientists Use High-Tech Brain Stimulation to Make People More Hypnotizable | Stanford Medicine
- Clinical Translation of Ultrasonic Ketamine Uncaging for Non-Opioid Therapy of Chronic Pain | NIH RePORTER
- Snow Crash by Neal Stephenson | Amazon
- Corpus Callosotomy Surgery | Children’s Hospital of Philadelphia
- Aaron Rodgers Pushes for Acceptance of Psychedelics | ESPN
SHOW NOTES
- [07:49] How SAINT helped Deirdre Lehman.
- [13:59] Typical vs. atypical sequences of activation.
- [21:00] Psychiatry 1.0, 2.0, 3.0.
- [26:41] How SAINT (Stanford Accelerated Intelligent Neuromodulation Therapy) came to be.
- [34:00] TMS vs. ECT.
- [35:26] Rewards and risks of shortening treatment timeframe.
- [43:43] Numbers treated and common side-effects.
- [46:32] Patient demographics.
- [49:51] Where to find current open trials.
- [51:01] Observed benefits of SAINT over more conventional treatments.
- [52:45] Adapting treatment when symptoms prove misleading.
- [58:03] SAINT remission numbers versus those of alternative therapies.
- [1:02:50] Delayed remission speculation.
- [1:07:06] How Nolan became The Ibogaine Bachelorette.
- [1:11:37] The origin of Nolan’s interest in ibogaine.
- [1:12:40] Amazing results of the quickest-recruiting study Nolan has ever run.
- [1:15:19] Dealing with alexithymia and self-reporting inaccuracies in research.
- [1:19:41] Ibogaine research gets federal funding (approved since this conversation took place)!
- [1:21:09] Isolating the ibogaine effect.
- [1:21:49] The value of life review on ibogaine.
- [1:25:56] How ibogaine differs from other psychedelic treatments.
- [1:30:05] The challenge behind synthesizing naturally occurring compounds.
- [1:31:54] Coping with ibogaine’s cardiac risks.
- [1:39:37] Understanding habitual action through ibogaine, Ozempic, caffeine, and alcohol.
- [1:45:43] Ibogaine for TBI.
- [1:50:08] Ibogaine for alleviating opioid withdrawal symptoms.
- [1:51:34] Ibogaine in Kentucky.
- [2:00:59] Weighing ethics with potential outcomes in research.
- [2:04:31] Can ibogaine be sourced (or synthesized) sustainably?
- [2:08:24] Does 5-MeO-DMT complement ibogaine enough to justify its collection?
- [2:16:48] What might Psychiatry 4.0 look like?
- [2:25:12] Could we develop therapies to change hand dominance?
- [2:28:08] Boosting performance.
- [2:34:01] Parting thoughts.
UPDATE FROM BRYAN HUBBARD:
Since Dr. Williams’ interview, a new Attorney General has assumed office in Kentucky. In a letter dated December 26th, 2023, Bryan Hubbard resigned from the Kentucky Opioid Abatement Advisory Commission due to the new Attorney General’s opposition to the use of its funds for ibogaine research.
MORE DR. NOLAN WILLIAMS QUOTES FROM THE INTERVIEW
“You’re actually sending a memory signal into the brain. The stimulation pattern you’re sending into the brain, this kind of Morse code, is really a ‘Turn on, stay on, remember to stay on’ memory signal that’s going into the brain. You’re just basically taking the hippocampus, the part of the brain that’s involved in memory and that signaling that comes out of there, and you’re playing that back through the prefrontal cortex in a way to try to tell the prefrontal cortex to ‘Turn on, stay on, and remember to stay on.’”
— Dr. Nolan Williams
“I’m a pragmatist … for me, the patient’s the most important thing. I have this view of psychiatry that it’s going to look like in-patient cardiology in 20 years where we’re going to use drugs, we’re going to use devices, we’re going to be able to figure out what the best thing is for that patient.”
— Dr. Nolan Williams
“If we gave one of the big pharma companies a hundred billion dollars and said, “Don’t just re-synthesize ibogaine, but make a drug that works like ibogaine,” … I think they’d have a hard time doing it because we don’t have the neuroscience to understand what’s going on there.”
— Dr. Nolan Williams
“What’s so hard about this scientifically, and to get the scientific community fully on board with these ideas, is that we’re likely going to figure out this works before we have any idea on how it works.”
— Dr. Nolan Williams
“If people think it’s really weird, it’s a positive signal that I need to do it.”
— Dr. Nolan Williams
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