The New Frontiers of Mental Health - Brain Stimulation, Rapid-Acting Tools for Depression, and More
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- Опубліковано 4 лип 2024
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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: www.nature.com/articles/s4159...
[00:00] Start
[00:29] How SAINT helped Deirdre Lehman.
[06:52] Typical vs. atypical sequences of activation.
[14:11] Psychiatry 1.0, 2.0, 3.0.
[19:54] How SAINT (Stanford Accelerated Intelligent Neuromodulation Therapy) came to be.
[27:45] TMS vs. ECT.
[29:13] Rewards and risks of shortening treatment timeframe.
[36:28] Numbers treated and common side-effects.
[39:13] Patient demographics.
[42:34] Where to find current open trials.
[43:44] Observed benefits of SAINT over more conventional treatments.
[45:28] Adapting treatment when symptoms prove misleading.
[50:47] SAINT remission numbers versus those of alternative therapies.
[55:47] Delayed remission speculation.
[1:00:05] How Nolan became The Ibogaine Bachelorette.
[1:04:36] The origin of Nolan’s interest in ibogaine.
[1:05:36] Amazing results of the quickest-recruiting study Nolan has ever run.
[1:08:09] Dealing with alexithymia and self-reporting inaccuracies in research.
[1:12:31] Ibogaine research gets federal funding (approved since this conversation took place)!
[1:13:59] Isolating the ibogaine effect.
[1:14:39] The value of life review on ibogaine.
[1:19:00] How ibogaine differs from other psychedelic treatments.
[1:23:05] The challenge behind synthesizing naturally occurring compounds.
[1:24:55] Coping with ibogaine’s cardiac risks.
[1:32:56] Understanding habitual action through ibogaine, Ozempic, caffeine, and alcohol.
[1:39:17] Ibogaine for TBI.
[1:43:48] Ibogaine for alleviating opioid withdrawal symptoms.
[1:45:13] Ibogaine in Kentucky.
[1:54:51] Weighing ethics with potential outcomes in research.
[1:58:30] Can ibogaine be sourced (or synthesized) sustainably?
[2:02:26] Does 5-MeO-DMT complement ibogaine enough to justify its collection?
[2:11:04] What might Psychiatry 4.0 look like?
[2:19:35] Could we develop therapies to change hand dominance?
[2:22:34] Boosting performance.
[2:28:21] Parting thoughts.
Tim Ferriss is one of Fast Company’s “Most Innovative Business People” and an early-stage tech investor/advisor in Uber, Facebook, Twitter, Shopify, Duolingo, Alibaba, and 50+ other companies. He is also the author of five #1 New York Times and Wall Street Journal bestsellers: The 4-Hour Workweek, The 4-Hour Body, The 4-Hour Chef, Tools of Titans and Tribe of Mentors. - Навчання та стиль
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.
Brought to you by:
Nordic Naturals Ultimate Omega fish oil www.nordic.com/products/ultimate-omega/ (Use code TIM)
Eight Sleep’s Pod Cover sleeping solution for dynamic cooling and heating eightsleep.com/Tim
AG1 all-in-one nutritional supplement drinkag1.com/tim
When Nolan said 7 years (in reference to diagnosing bpd) my jaw hit the FLOOR. This episode was amazing, thank you!
00:01 Rapid-acting neurostimulation brought a dramatic improvement in Deardra's condition in just 24 hours.
02:24 Severe depression and suicidal tendencies in a bipolar patient
06:21 Brain stimulation offers effective treatment for depression.
08:31 Resting state functional connectivity MRI explained
13:00 Neuroimaging can help personalize psychiatric treatments.
15:11 Brain stimulation presents an alternative paradigm for understanding certain disorders.
19:04 Brain stimulation offers empowerment for mental health through rerouting circuitry.
21:02 Electroceuticals and reorganizing conventional TMS
24:51 Brain stimulation can modulate excitability levels in the cortex.
26:53 The original TMS trials used a low efficiency signal into the brain.
30:25 Accelerated treatment for major depressive disorder
32:16 Compressed brain stimulation protocol for rapid recovery
35:56 Accelerated TMS has shown significant clinical outcomes.
37:44 Brain stimulation with opioid blockers and potential risks
41:10 Different brain stimulation methods for different types of depression
43:03 Brain stimulation trials for various mental health conditions
46:50 Deep phenotyping of Parkinson's patients' brains revealed a standard presentation of unilateral onset illness.
48:39 Customized brain-based treatment for depression subtypes
52:24 Brain stimulation methods like TMS, ketamine, and ECT offer varying levels of efficacy and risks
54:14 New frontiers in mental health treatments are promising and diverse.
57:47 Brain stimulation for memory enhancement
59:41 The old view of chemical imbalance in the brain is simplistic.
1:03:22 The development and stigma around an anti-addiction drug.
1:05:12 Researching treatment for veterans with traumatic brain injury and depression.
1:08:34 Challenges in psychedelic trials
1:10:09 Difficulty in accurately assessing improvement in mental health treatments
1:13:42 Research on therapeutic tools for mental health
1:15:31 Memories are replayed with common characteristics and a cathartic re-evaluation occurs.
1:19:18 Compartmentalization as a coping mechanism for high performers
1:21:11 Ibogaine has potential effects on a broad range of receptor systems and neurotrophic factors
1:24:33 New wave of Neuroscience tools needed to capture all effects of the drug in real time
1:26:24 Psychedelics and potential long-term cardiac effects
1:30:08 Using medication in a monitored setting reduces risks for mental health treatments.
1:31:56 Special operators experiencing a consistent reversal of disability with brain stimulation treatment
1:35:42 Caffeine intake's impact on mental health and decision-making.
1:37:30 Veterans were able to re-evaluate habitual actions and establish new patterns during the study.
1:41:11 Brain stimulation showed dramatic improvement in TBI disability at one month mark.
1:42:58 Ibogaine's unique impact on opioid withdrawal and neurotransmitter systems
1:46:38 Exploring brain stimulation as a treatment for treatment-resistant opiate use disorder.
1:48:19 Deep Brain Stimulation and Iain treatment carry risks
1:51:50 James Lind ran the first clinical trial on scurvy and citrus fruit.
1:53:35 Discussion on the complexity and funding of brain stimulation research.
1:57:30 Accelerated TMS and ketogenic diet show remarkable results for psychiatric conditions.
1:59:29 Iboga and voan gene are potential sources of healing with ethical and accessibility concerns.
2:03:02 Psychedelic substances and their commercialization
2:04:50 5-MeO seems to take the edge off depressive symptoms on gray days
2:08:20 Warning about the risks of using 5meo DMT
2:10:12 Exploring new treatment modalities for mental health
2:13:50 Brain stimulators may require battery replacements, leading to symptom reemergence.
2:15:24 Redefining illness and potential for more specific interventions in mental health
2:18:47 Brain stimulation and neuromodulation as potential solutions for mental health issues
2:20:32 Reorganizing the neural system for cross-functional attribution
2:23:57 Brain stimulation and rapid-acting tools for depression have shown promising results.
2:25:36 Brain stimulation may enhance performance in complex motor tasks
2:29:08 Brain stimulation has shown dramatic transformation and durability in mental health treatment.
Mr. Tim Ferris, thank you for sharing your own personal journey on mental health and share knowlege on the topic to people. You give value to people.
I am so grateful for this podcast and for the introduction to Nolan & TMS. I've been waiting to discover a new hero since Roland Griffiths left the building and Nolan is now in my Top Spot. Thank you Tim and thank you Nolan for continuing to search by all means necessary how to reduce the suffering of the human condition. I think TMS would make the Buddha himself blush.
Appreciate your mind, your interviews, and the out-of-the-box work you're doing. The quality of the science you are bringing to the table is amazing!
Good evening Tim and Guest
If we don't change the movie, 2024 is looking less hopeful.
Work to do! Indeed.
Interesting shared discussion.
Super leaps required, to change said movie. Me thinks!
New models for wellbeing in mental health addiction treatment and recovery, currently and desperately in need of upgrading into the 21 century not least 2024. DOABLE!
Truly grateful for your shared discussion.
💜
God bless you Tim
Excellent episode!!!
So fired up about that hubris against natual existing treatments and the snail pace of adoption!
The medical field does not mind denying a treatment until they deem it is evidence based. Their allegiance is to their egoic self inage, paycheck, and career with secondary regard and insufficient consideration of the desperation of those waiting years and decades for relief (or checking out), strangely enough, doesn't seem to bother them.
This was such an interesting podcast! So many possibilities explored for future treatment options in psychiatry. Seems like the future is bright.
Thanks for covering this! Tms helped my depression a lot! I did need boosters after a while but I’m using a home device now.
man I love you guys
Hi Tim! Happy 2024 🥳
Interesting. This aligns with many studies and lived experiences with chronic pain such as fibromyalgia, hypermobility, migraines and being depressed but not identifying to depression as a disorder.
Also can alleviate symptoms for treatment resistance or when side effects outweigh the success of a medication.
Incredibly inspiring. I think psychiatry will have a golden period in a few decades.
Hi, awesome content, as always. 😊 I have 2 questions: 1- Has there been any trials for TMS efficiency (such as presented in the episode) for Parkinson’s disease?
2- Seeing the importance of the healing effects of TMS, are there any studies investigating the impact of environmental magnetic influence on development of diseases and disorders? As a cause I mean?
Thanks
Hi Tim, amazing and incredibly valuable talk. Thanks really. For the fasting study idea please (in case you haven't alrready) look into TrueNorth Health Center and Hippocrates Health Institute. The True North center does have a medical team for monitoring fasting (I think they do 21 days or 40 days at most, don't remember exactly) and have actually done a study in regards to high blood pressure if I'm not mistaken.
Therapeutic fasting, together with juice fasting and herbal "fasting" (herbal infusions, tisanes, etc coupled with water fasting) as well as strong nutraceuticals and supplements (some informal studies I think with using high dose vitamin c for addiction and depression) , as well as some form of meditation, are in my opinion the cheapest most effective most accesible choices outside of the tools mentioned in this video. Keep up the good work. Regards
Thank you! I learnt a lot!
PS. why didnt you write a guest name in the title?
🎯 Key Takeaways for quick navigation:
00:52 🧠 *Dr. Nolan Williams shares a story about Deirdre Lehman, a woman with bipolar disorder, who experienced a rapid and dramatic improvement in her severe depression through a neurostimulation approach.*
04:59 ⚡ *Dr. Nolan Williams discusses accelerated TMS (Transcranial Magnetic Stimulation), a rapid-acting neurostimulation approach that can bring individuals out of severe depressive states quickly.*
10:55 🧊 *The sequencing of brain activation, specifically the timing of blood flow between different brain regions, is discussed as a potential biomarker for treatment responsiveness.*
13:48 🧠 *The concept of psychiatry 3.0 is introduced, emphasizing a shift from chemical imbalance theories to understanding psychiatric disorders as circuit problems. This paradigm shift offers more targeted and empowering treatment options.*
21:10 🧠 *Dr. Nolan Williams discusses SAINT (Stanford Accelerated Intelligent Neuromodulation Therapy) and reorganizing conventional TMS in time and space.*
22:09 ⚡️ *TMS (Transcranial Magnetic Stimulation) explained as a method to selectively turn on cortical neurons by inducing current in the brain tissue.*
26:13 🤔 *Dr. Nolan Williams explains the hypothesis of using excitatory stimulation to address hypoactivity in the prefrontal cortex associated with depression.*
30:25 🔄 *Accelerated TMS protocol details: 600 pulses of intermittent theta burst stimulation (ITBS) once a day, five days a week, for six weeks, compressed into a single day.*
31:22 🌟 *The term "remitters"refers to people who completely lose all depressive symptoms to a level within the normal range.*
36:03 🚨 *Headache is a common side effect, but no TMS-related seizures have been observed; the focus is on the intensity rather than the frequency or density of stimulation.*
38:21 💤 *Side effects include fatigue, similar to the feeling of having crammed for exams, but not the fatigue associated with depression.*
39:44 📉 *Patient population in the SAINT trial had an average of nine years of depression, five medication failures, and a lifetime load of depression of about 25 years.*
41:12 🎯 *Dorsal lateral cingulate stimulation may benefit those with impaired attention in depression.*
42:34 🧠 *Brain imaging used to categorize individuals neurologically for targeted stimulation.*
43:04 🧪 *Ongoing trials at Stanford Brain Stimulation Lab for various mental health conditions.*
44:02 📊 *SAINT (Accelerated TMS) showed 79% remission in severe depression, 90% in original pilot study.*
45:24 🌐 *TMS reveals potential subpopulations with different neuroanatomy in depression.*
48:34 🔄 *Future of psychiatry involves personalized treatment based on specific brain physiology (biotypes).*
53:43 💊 *Conventional TMS efficacy decreases in higher treatment resistance levels.*
57:29 🧠 *Delayed remission in older adults undergoing Accelerated TMS may be related to reduced brain plasticity.*
01:00:11 🧠 *Dr. Nolan Williams discusses potential treatments for rapid-acting, durable antidepressant effects, mentioning a forthcoming paper on ibogaine's use for military traumatic brain injury.*
01:02:31 🤔 *Dr. Nolan Williams, known for TMS, expresses openness to unconventional treatments and discusses his involvement in an ibogaine trial, highlighting challenges with the Institutional Review Board (IRB).*
01:03:54 ⚠️ *Dr. Nolan Williams addresses concerns and stigma around ibogaine, citing a death risk and the difficulty of studying the drug. He also recalls his exposure to ibogaine through a book by Daniel Pinchbeck.*
01:05:20 🔄 *The discussion shifts to the ibogaine trial for military veterans with traumatic brain injury (TBI), revealing surprising positive outcomes and improvements in patients' conditions.*
01:07:40 📊 *Dr. Nolan Williams reflects on the unexpected success of the ibogaine trial, emphasizing consistent positive outcomes and the plan to publish the results in Nature Medicine.*
01:10:32 💡 *Tim Ferriss and Dr. Nolan Williams discuss the delayed recognition of treatment effects by patients, comparing it to the narrative catching up with a hardware upgrade.*
01:13:08 🇺🇸 *Dr. Nolan Williams mentions the trial focused on military veterans, particularly Army Rangers and Navy SEALs, and the potential political support for ibogaine research in the veteran community.*
01:14:55 🌈 *Describing the ibogaine experience, Dr. Nolan Williams notes a stereotyped life review or slideshow phenomenon, where individuals become observers of emotionally salient memories, providing a unique introspective opportunity.*
01:18:37 🔄 *Dr. Nolan Williams emphasizes the potential importance of ibogaine as a tool for resolving childhood trauma and providing a cathartic reevaluation of problematic memories.*
01:19:05 🧠 *Special operations vets' ability to compartmentalize trauma contributes to high performance in high-stress environments.*
01:20:32 🍄 *Ibogaine's mechanisms differ from classic psychedelics like psilocybin, affecting various receptors and promoting neurotrophic factors.*
01:22:23 🐭 *Ibogaine's effect on alcohol self-administration in mice and potential link to GDNF in dopamine system.*
01:24:48 🎶 *Ibogaine's complex and unique multi-receptor symphony effect makes it challenging to reproduce synthetically.*
01:30:22 🛌 *Monitoring in a cardiac bed and pre-treatment with IV magnesium can mitigate ibogaine's cardiac risks.*
01:34:03 ☕ *Ibogaine trial participants reported spontaneously quitting caffeine, indicating a systemic change in habitual actions.*
01:38:39 🍔 *Ibogaine's potential contrast with Ozempic-Ozempic reduces cravings, while ibogaine introduces a level of choice in habitual actions.*
01:39:34 🧠 *Tim Ferriss discusses the concept of "reopening critical windows" in mental health and the importance of*
01:59:36 🌿 *Dr. Nolan Williams discusses the ethical concerns related to global demand for ibogaine and iboga, leading to high prices and potential extinction of natural supplies.*
02:00:34 🌍 *Dr. Nolan Williams explains an alternative to iboga extraction using the Voacanga africana tree in Ghana, providing voacangine as a similar alkaloid to ibogaine but without the ethical concerns.*
02:01:57 🔬 *Dr. Nolan Williams discusses the challenges of full chemical synthesis of ibogaine and the potential for biosynthesis or alternative methods to avoid dependence on trees, making the process more scalable and environmentally friendly.*
02:04:43 🐸 *Tim Ferriss and Dr. Nolan Williams discuss the challenges and ethical considerations related to 5-MeO-DMT, particularly its use in addressing the "gray day" following ibogaine administration and its potential benefits in therapy.*
02:06:34 🧠 *Dr. Nolan Williams acknowledges the difficulty of studying the specific effects of 5-MeO-DMT, highlighting the challenge of distinguishing its impact from the profound improvements seen with ibogaine alone.*
02:09:50 🌐 *Dr. Nolan Williams speculates on the future of psychiatry, suggesting that advancements may lead to more targeted interventions, potentially manipulating specific content within the brain to address mental illnesses.*
02:18:32 🧠 *Brain stimulation can temporarily shut down fear responses or the salience of the environment without using a whole-body anesthetic, potentially applicable in emergencies.*
02:19:00 🌐 *Speculation on using drugs or deep brain stimulation to shut down psychotic symptoms temporarily, offering a potential solution in the ER.*
02:19:53 🤔 *Sci-fi discussion: Could handedness or hand dominance be changed? Dr. Williams suggests it might be hard but feasible during childhood or through neuro-rehabilitation.*
02:20:50 💡 *Evidence of reorganizing the neural system in cases of stroke or corpus callosotomy in children, raising questions about making the brain more plastic for better neuro-rehabilitation.*
02:21:20 🤯 *Exploring the idea of bringing the brain to a more juvenile state with psychedelics, potentially enhancing neuro-rehabilitation outcomes.*
02:22:40 🤔 *Tim Ferriss discusses anecdotal reports of increased visual acuity or color contrast with accelerated TMS, drawing parallels to psychedelic experiences and their potential use in enhancing perceptual faculties for athletes.*
02:24:37 🏃♂️ *Athletes reporting improved performance after remission from symptoms, sparking interest in potential neurostimulation applications for performance enhancement in sports.*
02:25:30 🤝 *Dr. Williams shares experiences of patients achieving mindful moments post-treatment, speculating on the potential of neurostimulation for enhancing performance and offering philanthropic gifts for athlete performance trials.*
02:27:54 🛌 *Discussion on the potential future of neurostimulation, suggesting a more comprehensive approach for treating various functions and conditions beyond depression and isolation.*
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Great episode! But I’m wondering why an oura ring on each hand?
I'd love to try TMS to treat my depression. Where do I sign up?
Keto for schizophrenia? That's new... Thank you for this interview.
In light of this network paradigm (psychiatry 3.0) what does this do with types of disorders that are based in trauma? Not knowing wether or not that actually would help or not, it feels iffy and off to treat these trauma-based disorders based on the electroceutical restructuring of one's brain dynamics. Any thoughts?
So I have treatment resistant ptsd. I know there are some clinics that do psilocybin, etc. But I'm not really up for spending $2-3k for one or two sessions with mushrooms. I'm not partial to any particular drug or chemical. I don't want to go the illegal route. So do you or your guest have any suggestions on where a person can reasonably get access to some of these psychedelics? Also, with the targeted tms, when do you think that will be readily available to patients? - Thanks very much
Perhaps on Meet Up. I’ve noticed ‘churches’ may ceremonies
Also I heard you can find a repeatable source and zoom with your therapist.
For your diagnosis you may want to think outside of the box. And do so in a safe manner.
Great suggestion, thank you. @@janetstauffer9138
Grow them yourself
Some places have low cost sliding scale psychedelic assisted therapy for ketamine. I am one of this patients in California who has ptsd, was desperate and now healing. Where are you located? Ca by any chance?
@@Saavycupcake I'm in Connecticut. For some reason I thought ketamine was more for depression.
What is the device they are talking about?
Transcranial magnetic stimulation
@@trismegistus3461 thank you 💚!
45:28
TMS did squat for me - after $11,000 out of pocket. Worst decision ever.
79% passed through the remission point. Clever way to exaggerate but I don't fall for it. Nice try.
what do you mean
@@Danny-qt5vt passed through (but how many regressed back)?
Where’s the caption and time stamps bro??
Takes a bit bro!!
The entitlement of that comment is mind-blowing.
🧠🪄