#824: What Most Has My Attention Right Now — Credible (vs. Bogus) Vagus Nerve Stimulation

0:00 Well hello, boys and girls, ladies and germs. This is Tim Ferris. Welcome to another episode of the Tim Ferris Show, where it is my job to deconstruct world class performers to determine or identify, try to identify how they do what they do. In this episode I have turned yet another conversation into a how to search. for myself to help me with various things, chronic inflammation and other issues that seem very squirrely, difficult to treat with many frontline treatments. So who did I find? I found someone named Kevin J Tracy MD. He is the president and CEO of the Feinstein Institutes for Medical Research at Northwell Health. a pioneer of vagus nerve research and author of the recent book, The Great Nerve, The New Science of the Vegas Nerve and How to Harness Its Healing Reflexes. Now I say this in the interview, but there's so much nonsense floating around about the Vegas nerve. and so many different hocus pocus hand wavy things related to it that I discarded it. But

1:01 Dr. Tracy is the real deal. His contributions include identifying the therapeutic action of monoclonal anti-TNF antibodies, we'll explain what TNF is, and discovering the specific reflex control of immunity by the nervous system, called the inflammatory reflex. These discoveries launched the new scientific field called bioelectronic medicine, which investigates the therapeutic applications of vagus nerve stimulation to cure disease. The case studies are tremendous, but also the published studies and Just data overall are so compelling. There's a lot you can use here.

1:37 And it all started with A mysterious death from sepsis of a toddler who was in his care. That's how he started pursuing studies of inflammation. His lab has since revealed molecular mechanisms of inflammation and identified the use of vagus nerve stimulation to treat it. An inventor on more than 120 US patents and the author of more than 450 scientific publications. He is among the most highly cited scientists in the world. He co-founded the Global Sepsis Alliance, is the author of Fatal Sequence, and is a national and international lecturer. So I'm so excited to introduce you guys to Kevin. He is amazing. He is Not only a world class.

2:16 scientist, but he's also a world class explainer, which you will get to taste firsthand. So we're going to get to that first, just a few words from the people who make this podcast possible. Sleep is the key to it all. It is the foundation. Many of you heard me talk about how today's sponsor, ASleep, has improved my sleep with its pod cover. Well, they just launched their latest product, the Pod Five. I cannot wait to try it out. And here's why the Pod Five introduces Aid Sleep's latest product, the blanket, which uses the same technology as the Pod's cover. to extend temperature regulation across the entire body. So if you're too hot, too cold, you can fix it. If you're a couple and one of you is hot, one of you is cold, you can fix it as well. It all fits right over your existing mattress like a fitted sheet. On average, members report the pod has helped them fall asleep 44% faster. Thirty four percent deeper sleep and giving them up to one added hour of sleep each night. Also the pod snoring detection.

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5:34 Tim. Optimal minimal. At this altitude, I can run flat out for a half mile before my hands start shaking. And then also you personal question. No, it's in the time. a cybernetic organism, living tissue over metal and those cellularity.

5:53 So This podcast episode is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional healthcare services, including the giving of medical advice, and no doctor patient relationship is formed. The use of information in this podcast episode or materials linked from Tim Dotblog is at the users and listeners' owner. Risk. The content of this episode is not intended to be a substitute for professional medical advice diagnosis or treatment. Users should not disregard or delay in obtaining medical advice for any medical condition they may have, and should seek the assistance of their healthcare professionals for any such conditions. I Doctor Tracy, good sir. Nice to see you again. Thanks so much for making the time to have this conversation.

6:41 Thanks so much for having me on. I'm really looking forward to it, Tim. And I am really holding in my enthusiasm, which I'm not gonna do for very long because we had a chat. Brief chat.

6:54 maybe a week or two ago, and I was bouncing around in my chair I was overflowing with excitement to ask so many questions and the reasons for that excitement will I think become very, very clear very quickly. But let me as context for people listening. And you know some of this already. Explain why I never looked at

7:16 Vegas nerve. Stimulation. Seriously, up until very recently. And primarily it's because there's so much crap And so many charlatans. whether it's deliberate or not, floating around online.

7:31 Touching the most ridiculous approaches devices at best innocuous, sometimes probably putting people at risk. And At the checkout

7:43 They might be selling audio chakra cleanse soundtracks and just associated nonsense that shows that they wouldn't be able to find a logical argument if it bit them in the ass. And I thought, you know what? I'm just gonna put this in the category of things that I should ignore. And also I'd been sent, and not to throw this under the bus, but maybe we'll get to it, a book on polyvagal theory. And I looked at it and I know just enough evolutionary biology to be dangerous. And I thought, I'm not convinced this actually makes a whole lot of sense. And Again, came to the conclusion.

8:19 I should just Put this to the side, at least for now. The reason that changed Is that A friend of mine.

8:26 Who is Quite technical. He is One of the top performing investors in biotech and let's just call it medicine writ large. when it comes to public equities and

8:41 Other types of investments. He has patents to his name. This is a very smart guy. And he reached out to me via text. This is a good friend of mine. And asked if I'd ever looked at vagus nerve stimulation. And I was like, No, absolutely not. Is there something interesting there? And he said, I think there is.

9:01 And he'd been digging into the literature. He's also former tier one operator from the military. And he had been using and we'll get to this because A device is not a device is not a device. There are a lot of differences, but he had been using Something purchased off the internet.

9:19 and had tripled his heart rate variability. And I mentioned the military piece because he has Not sure. If this is the right term and I'm sure I'll misspeak a lot, so feel free to Give me a polite smack when I do. But sympathetic overdrive. He would lay down to try to go to sleep. His heart would be racing, his glucose would be spiking.

9:40 Not from PTSD, but from a lot of other things. And He had tried meditation and he's diligent. He will do. what he assigns himself to do. He had tried all these interventions to improve heart rate variability. And maybe we'll talk about that. But suffice to say

9:56 within the realm of say athletics and recovery and this, that and the other thing, often Higher HRB is a good thing. And all these interventions he tried had bumped things, maybe 10%. Maybe fifteen percent. And then he used a Vegas nerve stimulator for a few weeks. And tripled his HR V.

10:14 And he's setting personal records. Week after week and I thought. Okay. Could be N of One and Placebo, sure. But

10:24 I should take a closer look. And he sent me an email with a bunch of citations and I started going as I do obsessively down this rabbit hole. And I listened to an interview, I want to give credit where credit is due. On STEM talk. And they interviewed you and I thought, Okay. I should really, really reach out.

10:45 To Doctor Tracy. And then Just coincidentally was walking through a bookstore. And right in front of my face was your book, The Great Nerve, and I thought Okay, universe, not to get to woo woo. But

10:57 I got the message, message received, reached out, and also read the book. I recommend everybody Read this book. It's not only from a very credible source, but you are a good writer. It's very compelling. So let's Skip my TED Talk. Thank you, everyone, for coming to my TED Talk and go straight to

11:20 The big news. I guess this was literally you emailed Me and now It's big. So what is the big news that literally has just been announced? It was just announced that the company Set Point Medical

11:35 Which will now be marketing a device to stimulate the vagus nerve. To treat rheumatoid arthritis has received FDA approval. So there'll be a product launch underway. For everything we're about to talk about. In the context of using a medical device.

11:53 That activates An evolutionarily conserved and ancient reflex. Can suppress inflammation. We've discovered that

12:06 Signals travel from the brain through the vagus nerve. We'll talk about what the Vegas nerve is, but these signals traveling in the Vegas nerve are like the brakes on your car. And when you tap those brakes to slow your car barreling down the hill when This device activates what we call the inflammatory reflex. So you talk about this being a current. A van.

12:26 You and I both know it's the front page story in the New York Times today celebrating The success is at Set Point Medical and kudos. Them. To Murphy the CEO to Dave Chernoff the CMO. But

12:39 It's based, as the article explains, also on twenty years of work by my colleagues and I at the Feinstein Institute at Northwell in New York and All of which has been essentially replicated by Dozens, if not hundreds, of laboratories around the world. So it's a deep, it's a rich story of science. Converging. And how the vagus nerve

12:58 And switch off inflammation that culminates this morning, as you point out. In a story about patients who've already been treated. Some of whom Had rheumatoid arthritis for decades, couldn't button their blouse, couldn't pick up a pencil and If you don't mind my interjecting. Yeah. I get excited too, Tim. I apologize. Oh, you get excited too. Please. I don't want you muted. I don't want muted, Kevin. I want excited Kevin. And

13:22 Let's feed that fire a bit. Let's talk about specifically one of your patients who shows up Multiple times in the book, but most memorably to me in the coda. And could you just tell her story in brief, doesn't have to be super brief, because I want people to understand

13:41 Just how drastic. And this is not gonna be true for everybody with every condition, but just how significant. The uh Transformation can be.

13:52 Kelly Owens is the patient you're referring to. I know her story very well. I know her very well now. And when I think of her story as you just introduced it, I got goosebumps. Again, as I do every time. Kelly was a teenager when she Was playing sports in high school And uh developed one night after A trivial injury, a

14:11 Major swelling in her knee. That's Cascaded to A very serious problem. That ultimately was diagnosed as

14:20 Crohn's disease, an inflammatory bowel disease complication affecting her joints. Kelly spent her teenage years and most of her twenties in and out of hospitals. In and out of wheelchairs. Her father actually gave her a cane. For one of her birthdays. I'm not sure which one. Now it's really important. I should point out to him that

14:39 These stories are So interesting and compelling because For much of her life, Kelly always loves to write. She still loves to write. And she blogged many of these stories in the public domain for much of her life. So all this is out there for other people to read. Kelly ultimately became a school teacher, but could not be Treated, her condition couldn't be fixed.

14:59 From New York. to the Mayo Clinic, to Hawaii and back. And it It culminated. When her physician told her and her husband Sean.

15:08 to Plan on staying home. Without children, because of all the medication she was on, it w childbearing would be too risky. And to get used to Her life's like that.

15:18 Around that time she saw me on a Huffington Post live. Internet. Interview. Live stream. And she contacted me and I I don't

15:26 We call that contact, but I recommended she look into Set Point Medical, the company that I had Oh, founded in two thousand seven to do these clinical trials. And Kevin, can I pause you for just one second? Don't lose your train of thought. But also I recall and fact check me here. Chronic fatigue. Having to lay down.

15:44 Elevator legs. I mean really Just had trouble functioning on a day to day basis. Is my recollection. Absolutely. People think of they hear the word arthritis and when they hear rumors of arthritis, they hear arthritis.

15:57 This is not the trivial sports injury you had in high school and now it's a rainy day and your knee or your elbow is sore. This is a serious condition that affects the whole body. It it can affect the kidneys. It can affect The brain it can affect your heart. Similarly for inflammatory bow disease, it's not

16:14 Obviously bouts of diarrhea and abdominal pain and nausea. And vomiting can be disabling, but The inflammation that affects the intestines in inflammatory bow disease or in Crohn's disease. Also affects other organs, the spine.

16:28 The joints in Kelly's case. In her arms and legs. And so these are serious disabling conditions. They can cause depression, they can cause anxiety disorders, they can cause chronic fatigue. So that's exactly right. All right, so she reaches out to you, you recommend she investigate set point medical.

16:44 Then what happens? My hope was that although I wasn't optimistic because she lived in New Jersey and the clinical trials were being done in Europe, but Now that I know Kelly, I understand how she was able to talk her way into a clinical trial in Amsterdam. She and her husband Sean sold all their earthly belongings, as she said, everything that wasn't tied down.

17:04 Their friends and family through a GoFundMe kind of operation raised the money they needed to move there for six months. She enrolled in the trial and was one of the first patients I call it a generation one implant. It was a Like a cardia pacemaker under the collarbone, under the clavicle. With a lead or a wire that

17:23 He's tunneled up into the left neck. Where the vagus nerve travels next to the carotid artery. Couple weeks later, they're in Amsterdam still. And Kelly is running a little bit late for her follow up appointment. As part of the clinical trial.

17:38 They get checked out by the doctors in the trial. There's elevated trains in Amsterdam and Kelly sees a train coming and runs up the stairs to hop on the train, so she won't be late for her appointment. She turns around like where the hell's Sean? Sean's at the bottom of the stairs with tears streaming down his face. Because Kelly h it was the first time he'd seen Kelly run up the stairs in years.

17:58 Yeah, she had trouble walking on the cobblestones. She had trouble walking on the cobblestones. Not long before. Her father gave her a cane for her birthday. That she used for many, many years when she wasn't in a wheelchair, and now she's running up those metal stairs in Amsterdam to catch a train. So she had a remarkable response to this therapy. So A few months go by and I didn't know any of this. A few months go by, I get an email.

18:22 The subject line was Thank you for saving my life. So it was wedged in between a lobbyist in Washington talking about research expenses. And my own corporate controller talking to me about my laboratory's research expenses.

18:36 So I read Kelly's email first. And I learned her story and that she wanted to Thank me in person. And so I said

18:45 Come on in, but I also brought on that first meeting a couple of my physician colleagues. And we talked at length about Kelly, when she told me that she wanted to help us. І не байоектронік медицин універс Be a patient advocate.

19:02 For this idea. We spent a great deal of time with her explaining. There are risks and benefits to this. People resist change. The world is not ready for something truly new. The world's not ready to talk about A one inch device in your neck instead of taking pills and injections.

19:18 This is gonna change everything and if you're gonna be a leading spokesperson on the patient side of this, you may be People are gonna tell you you're a placebo effect. Tim, all of those things happen. Oh, I'm sure. He the CEO of a major pharmaceutical company at a social event. Told Kelly, this was many years ago.

19:35 If you're real. I mean how do you say this to a patient? If you're real then everything I'm doing is at risk and I could be out of a job. Yeah. And not with a smile on the face.

19:45 Ha ha. That was a real A real important day in my life. She hugged me, I hugged her, she cried, I cried. And then she said she had a present for me.

19:56 And I said, What's that? And she gave me A gift wrap. Hmm. It was clearly a cane.

20:02 The way she wrapped it, the handle was wrapped and the cane was wrapped with a big bow on it. I opened the card. Yeah, which I of course still have attached to the cane. The cane is It's still wrapped with the the bow is still on it and it sits in the corner of my office.

20:18 And every day if I'm having a tough day in the lab, or any of my colleagues are We come down and we look at Kelly's cane and Reminds us why we do what we do and what we hope can happen. When you do science in the hopes And dreams of

20:32 Discovering things that might help people someday,'cause it can happen. So I wanna add a few things to that. What a story. And like you said, some people at the time were like ah placebo, but placebo effects and I'm Pulling directly from you here. durability past a certain point. Right, but when you're looking at six months out, twelve months out, and she furthermore

20:57 Not to say this is more important than anything you just described, but certainly for a lot of people listening and for me personally, having suffered from what I would describe as chronic fatigue for decades and we might dig into some of that. She went from Basically having A blinking battery empty.

21:17 For her day to day. to having almost too much energy, which isn't to say it was a problem, but just kind of running up the stairs, bouncing off the walls, and my God, what a difference. But The lives that are lived by the former and the latter The magnitude of the difference is just can't really be overstated. It's too different.

21:40 Experiences of life. So Now I'm gonna get all excited and lose my train of thought, but I'm I'm gonna scatter shot here for a second. So Just to also lay out a few things for folks. So Part of what has been so exciting about this and why I want to pay a lot of attention to it. There are a few things feeding into it.

21:59 For me personally. So one is having some exposure. to I suppose what you might call bioelectric medicine. Through early, early generation TMS. But then also later accelerated TMS with better hardware, better software, better targeting for things like treatment resistant depression. People can look at

22:20 Nolan Williams out of Stanford and just some incredible data there. Focused ultrasound and conversation with Nora Volkov for potentially hitting the nucleus accumbens for addiction. And The possibility Not just the possibility, but now a lot of compelling data.

22:37 for instance around Set Point Medical and other forms of vagus nerve stimulation, but I know you might put some of them in quotation marks. to be it an option and alternative to biologics, right? Let's just say oral or intravenous or intramuscular medication that have a host of really non trivial side effects. And for myself.

22:59 looking at past depressive episodes, looking at as I've tried to unwrap that for myself, which is very under control for the last, I'd say, ten years. But looking at the Lyme disease, which I've had twice, and by the way, guys, that's not a oh, I just happened to be lethargic and I'm hunting for a diagnosis going from quack to quack until I get Lyme disease. Like Eastern Long Island, look at the CDC map. It is just it is as red as it gets. And Thinking of then later.

23:33 Neuroinflammation. I have neurodegenerative disease in my in my family on both sides. So looking at all these things unfold and feeling like this is gonna be a a way overreach, but There seems like there might be I don't want to say a unified theory, but there's some connective tissue tying this stuff together.

23:53 And Started playing with The microbiome. Because changes in gut. flora have been associated with, say, depression or animal models of depression or lack thereof.

24:07 Also looking at say the ketogenic diet or exogenous ketones as a way to reduce inflammation. And when you start looking at all this, and then when I read your book, the reason this ties into Your book. And we should probably define what the hell the vagus nerve is,'cause it's more like

24:26 Vegas nerves and you'll give a great description. I'll just give a couple of quick samplers. And then we can get back into them at any point, but GLP one agonists, right? In the news of Zambek Munjaro, take your pick. But at least in Animals, my understanding is if you sever the vagus nerve, those GLP one agonists

24:50 They cease to exert a lot of their effects that you would otherwise see. And similarly People may have heard these stories. which are based on research of microbiome transplants from, say, obese mice. Two.

25:06 normal slash lean mice, let's just say. And Lo and behold, this amazing thing happens, which is the Normal mice take on the attributes, the insulin and sensitivity, the weight gain of the obese mice. Fascinating. But if you cut the vagus nerve, That doesn't happen. So what the hell is going on?

25:28 And All of these things are interconnected in the most interesting ways. There's so much left to learn, but let's begin. With a definition of basic terms. Vegas nerve. How should people think about the vagus nerve?

25:45 When you look online, you'll find billions of web impressions. Uh Vegas now. So I'll just describe it anatomically and functionally first and then

25:54 We can cherry pick where to go. Uh we also should define, if you agree, bioelectronic medicine'cause you talked about the con the connective tissue in the story, and then we should define inflammation. So The vagus nerve, we call it the vagus nerve. And that's that's what it's called. But you have two of them. So there's two vagus nerves, like two thumbs. One on each side. Each one arises at about the level

26:17 Of your ear at the base of your brain. Travels down both sides of your neck with the carotid artery. And then across the chest into the abdomen and along the way it it sends out Countless branches to all the organs. In the chest and abdomen that you don't think about all day long.

26:34 Now Within each of those True Vagus nerves left and right. You have a hundred thousand fibers.

26:41 each Fiber. Is a unique nerve. That's the part that's lost almost immediately by Ninety nine percent of the

26:50 Casual readers of Vegas nerve. Stuff. Each fiber, two hundred thousand fibers, each fiber has an origin in either the body or the brain. Eighty percent of them actually originate in the body. They carry information about the organs in your body up into your brain.

27:07 And then obviously the other twenty percent originate in the brain. And they carry information back. Down to your Oregon. So Again, I'm trying to clear up

27:18 Some Misnomers along the way. The biggest misnomer. Is that you have one vagus nerve, like a solid copper wire. You don't. You have two hundred thousand Vegas nerves if you treated each one

27:29 As a wire. Let me ask if this is a fair visual to paint for people. So imagine that From the base of the ear, roughly. This is Tim the lay person talking. But you have These two thick cables coming down on either side. Kind of tracing the carotid artery.

27:45 And they're like transatlantic cables. Just full of a hundred thousand fibers on either side. And they go down and then they kind of branch out like the Mississippi Delta or something like that and innervate and touch. I don't wanna say Just about everything imaginable, but There are two hundred thousand at least, right?

28:05 Is that a fair visual to paint for people? Or would you modify that? No, I wouldn't modify it at all. In fact, if you go one step further, each nerve ends on either a cell in an organ or on another nerve. And those other nerves those secondary nerves that the vagus nerve ends on Those branch out.

28:24 Further. Here's how I like to to visualize it. I think we chatted about this a couple of weeks ago. If I had a solution, if I had a VAT. Of liquid that could magically dissolve all the cells in your body.

28:36 And I submerged you in it for five minutes and pulled you back out again. You would still look like Tim. Because every cell in your body is is essentially Touched by or surrounded by nerves. W you're a walking nerve net. And so one way of thinking of the Vegas

28:53 If your body is a walking nerve net, all your organs in your body or are encased in a nerve net. Well then the cable that Paul's The nerve net out of the C

29:03 Yeah. Like the vagus nerve. Because it's connected to the brain. The brain would be like the fisherman operating Now all the signals traveling in these electric networks are traveling up and down the transatlantic cable, the cable connecting the nerve net in your body to the nerve networks in your brain. And

29:20 We know the identity of two hundred thousand individual fibers. What we don't know, Tim. Is we we don't know completely, we don't completely understand. The code Of the information that's being transmitted. In each of those fibers, right?

29:34 People talk about the action potentials. Which are the spikes of voltage change that travel up and down a nerve fiber. Yes, we can study those. Yes, those are very important. The question is, is that all the information that's being transmitted? That's an area of active research now that's very interesting to me. Because on one hand, two hundred thousand fibers is a lot, but on the other hand, two hundred thousand fibers isn't that many. And for instance, we know you can transmit on the same fiber optic cable, lots of T V shows and

30:02 And lots of radio shows at the same time. So there's a lot of interesting questions embedded there. And Let's just say of those two hundred thousand fibers, do we know Roughly how many affect HR V and

30:17 Cardiac. Function. It's a much smaller number. Then people think we don't know exactly for sure. We know in mice In some beautiful work out of Harvard Medical School by Steve Lieberless and his colleagues.

30:30 We know him mice. That somewhere around a hundred or a hundred and fifty fibers. are sufficient to control breathing. Now a mouse vagus nerve has five thousand fibers, not two a hundred thousand. But it's still a really small fraction of the total number. And so for instance a few dozen of those fibers

30:48 Control when the mouse Gets a full inhaled breath. And another few dozen of those fibers control The process of holding the breath. And on down, exhaling the breath.

31:00 So With in human beings, for instance, and we'll come back to this some more, but I estimate somewhere between a thousand, give or take, maybe Fifteen hundred. Maybe two thousand fibers.

31:11 control the amount of inflammation cytokines being produced in the spleen. So you're looking at We can map the identity of a Of the number of fibers going to the heart. Again, it's it's it's a few thousand.

31:24 The open question is say we can assign The action of ten thousand fibers on each side One of the other What is the other ninety thousand doing? Yeah, exactly. Yeah. Yeah.

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32:41 dot com slash Him. This is a paid endorsement of Wealthfront. Wealthfront brokerage isn't a bank. The APY is subject to change. For more information, see the episode description. I I wanna keep giving people Scooby snacks here, just because

32:57 I'm so excited. I want to keep reiterating. The potential payoff. Right. The right way. And you mentioned cytokine. I wanna double click on that for a second. We don't need to get immediately into the technical.

33:13 Definition of that, I'm sure we will. But people may know that word from What Covet nineteen. Cytokine storm. Boom. can lead to fatality, right? In some patients.

33:25 And I suppose I'm curious to know. Then just in short form. What happens to cytokine production? when you stimulate the vagus nerve correctly.

33:38 It gets turned off. If you stimulate The fibers we were just talking about. It turns off cytokine production quite effectively. We discovered this by accident, actually, twenty seven years or s or so ago. In the laboratory.

33:51 We discovered We were working on Experimental anti inflammatory drug that that we had developed. And We put it in the brains of animals with a stroke. And the idea was this anti inflammatory drug in the brain would stop inflammation. And that that did happen and the stroke

34:07 And the animals was smaller and we were very happy. But surprisingly and unexpectedly, when we looked at inflammation in the body of those animals with the drug in the brain, they also had less inflammation. This was a head scratcher. This made no no sense whatsoever. And is that's a head scratcher because the effect should have been sequestered to the brain because of the Blood brain barrier?

34:29 Either the blood brain barrier, but Also because we had put such small amounts of drug into the brain. There wasn't sufficient amounts. saturating and stopping inflammation in the body.

34:43 Well we discovered Years later. was that the drug in the brain was actually turning on the vagus nerve. At the time we discovered the signals were in the vagus nerve. It sort of became obvious to me as a neurosurgeon working on cytokines in the lab, it became obvious that if The Vegas nerve.

34:59 Is turning off inflammation. Then it should be possible. To stimulate those fibers in the vagus nerve with electrodes. And Treat inflammation with a device instead of a

35:11 Instead of drugs. And so that's what we wrote on the back of a napkin twenty seven years ago. That kinda led to to where we are today. At the end of the day We understand. Using techniques. Like optogenetics where you can

35:25 Make neurons in the mouse brain sensitive to laser light. Another Sophisticated molecular biology and genetic tools. I can explain to you. How

35:35 The brain through the vagus nerve turns off cytokines and inflammation. I'm sorry, Kevin, can I pause you for one second before we get there? And this is uh something I do not I mean, I'm gonna ask a lot of questions I don't know the answers to otherwise. Interviews are pretty boring for me. So does this mean that you could use As an acute intervention, vagus nerve stimulation, say Hypothetically in the ER.

35:57 Two Stop anaphylaxis or to address like asthma attacks or Sepsis or anything like that. Once you understand the basic signals that flow in the vagus nerve to control one aspect. Of the immune system in this case.

36:15 How vagus nerve fibers can turn off cytokine production. You can ask new questions. Yep. And Let me answer your question by Adding a definition'cause I I I think it is it's a perfect segue. So In order to understand the answer to your question, how to use vagus nerve stimulation and other conditions like asthma and other conditions

36:32 You have to back up a bit. You have to say, Okay, what condition are we talking about? Let's look at how the pharmaceutical industry does this. Pharmaceutical industry starts by picking a disease. A condition. Let's do rheumatoid arthritis first, as it'll become

36:45 Obvious why in a minute. We're gonna look at rheumatoid arthritis, that's the condition. What's the molecular mechanism? Well the early research with Using monoclonal antibodies against TNF show that that helps about half the patients. So that's the mechanism. So now we can make monoclonal antibodies that hit the molecular target, T and F. To treat the disease.

37:04 And now you sell your monoclonal antibodies and After they're approved for safety and efficacy by the FDA. Great. That's what the farm industry does. We proposed some years ago, fifteen years ago or so now. The idea of bioelectronic medicine as an approach To develop therapies.

37:21 You begin in the same way, you pick your condition. It's uh rumor arthritis. Then you say. Rather than screen for antibodies or other molecules to stop TNF, which is the target in rheumatoid arthritis. Let's see if we can find nerves.

37:35 That control TNF production in the body in site tube. If we can find such nerves, then we can build devices. to control the nerves and the devices become the therapy. The bio electronic medicine story works. As long as you know the molecular mechanism.

37:52 And that's where People have to be really careful with vagus nerve stimulation. So There are many conditions today. That are treated with

38:01 Anti cytokine therapy, anti TNF, anti IL one, anti IL six. Those conditions include things like rheumatoid arthritis. Inflammatory bow disease, Crohn's disease. Soriatic arthritis and some other conditions. Most of them are autoimmune. conditions.

38:17 When you ask about asthma, and you mentioned earlier also depression. And some other conditions. I go back to the Basic starting point. What is the disease asthma. What is the mechanism? Tim, no one knows.

38:30 Yeah. That's a phone. That's a full That's a full stop for me before saying You know, vagus nerve stimulation will or will not work.

38:40 One of my mentors and friends. Best is so Frank Austin. Was one of the leading experts on asthma research for decades. And a few years before he died.

38:49 I said, Frank, I think I'm gonna do some asthma research. He said, Okay, what are you gonna do? I said, Well we got this mouse model. He goes, Kevin The last article I wrote on asthma. Was entitled. Mice don't wheeze.

39:00 I like that. Wice don't wheeze. Well, you know what that makes me think of, and I mean like I we're gonna digress for a second here. But we need the animal research and there's a lot you can do in a sort of metaphorical petri dish now with like biology and stuff. There's a lot coming down the pike, but still animal models are super important. But some of the since I've funded so much early research And some later stage stuff with respect to psychedelics since 2015 and psychedelic assisted therapy, but also basic science.

39:33 Some of the animal models are pretty hilarious, right? Where they're looking at like the head twitching and paw licking in the case of like Barry Jacobs. giving L C to cats way back in the day, decades ago at Princeton. And they're using, let's just say The antidepression animal models might involve like swim to exhaustion, and then you're like, Okay, well, I guess methamphetamine is gonna be one of the best antidepressants you could possibly give someone if we're using that as the proxy. And so A lot of it's imperfect and yes, mice don't wheeze. So maybe especially if you can't identify

40:07 Like you said, I guess the mechanism You need to be able to at least hold on to some of the variables. So let me come to just depression for a second. I know this is gonna be all over the place. It's like Tim after too much caffeine and a couple of glasses of wine, which is not where I am. I did have some pretty good ketone monoesters before our chat though. And I wanted to come back to depression because It's a subject near and dear to my heart. It's something that affects a lot of people and When people experience depression, it can also feed on itself in the sense, and I speak from experience, where you personalize it, like this is a me problem. This is a

40:46 character flaw. And it's permanent. And it becomes this Loop. that can exacerbate the condition.

40:55 I've long had this suspicion, and this is part of the reason for a lot of the Research involvement. Is That anti inflammation or inflammation is sort of at potentially at the core of a lot of this. Whether you look at, for instance, there are very potent anti-inflammatory effects of certain psychedelics in the phenethylamine class, like two CP, for instance.

41:13 Very, very significant at very, very low doses. And when I'm looking at some of my highlights, I have a ton of Kindle highlights from your book. The Great Nerve, I'll mention it again. Pick it up, guys. You will not be disappointed. But you can induce Depression. in animal models by

41:29 Pausing. Inflammation. And people too, Tim. And people too. So And I want to just read a little bit here. Because

41:38 We've f long had, and I think many, many doctors still Ascribe to a chemical imbalance theory. of say depression or mental illness writ large, but Depression. So this is directly from your book. If an SSRI has helped you or someone you know, that's wonderful. Large randomized clinical trials of SSRIs indicate they confer some clinical benefit in some patients, which is true. I've seen lives changed. Now whether it's actually sereno

42:03 Or not is a separate question, but back to your book. But these results in your personal experience do not prove causality or confirm that serotonin dysfunction is causing depression. For example, SSRIs may also inhibit inflammation. And then here's kind of the clutch paragraph that I Highlighted interestingly, administering SSRIs to animals and patients with inflammation after receiving cytokines in the lab. So you're deliberately trying to provoke inflammation. Administering SSRIs can alleviate depression caused by these cytokines. This anti-inflammatory role of SSRIs is little studied and incompletely understood, and I sincerely hope that my colleagues are inspired to investigate it further. So this raises some very, very, very

42:44 Interesting questions. And Since we last spoke I have been toying around. I use the word toy very deliberately with some devices that

42:54 Yeah. I may not continue to use, but I have a variation. that a friend recommended to me. Very low cost that I'm gonna be switching to. Cause I don't like the next seizures very much. But nonetheless I will say that the combination of the stimulation Plus And I realize I'm fussing with a number of variables.

43:13 Intermittent fasting and exogenous ketones. So I am throwing a lot against the wall here, but the addition of the stimulation, which is just a few minutes a day. And we'll definitely talk about your friend Olf. And his story.

43:29 Because that guy It's not. wearing a tinfoil hat is credible. As credible as credible can be. The stability of my mood. Is

43:40 Remarkable. And again. I think there are people out there that just if I could throw some folks not throw them under the bus, but just lay a criticism. There are some folks out there well educated But non scientists.

43:53 Science with a capital S or scientism perhaps it is. And so they'll criticize maybe a story like this, or the story of your patient, and say, uh N of one placebo, and they discard it that way. But a lot of very critical scientific investigations begin with case studies. In the literature.

44:16 I'm looking at that right now with respect to Alzheimer's and exogenous ketones. There's some very interesting stuff out there. So Could you this is a very long winded way of trying to set up Inflammation. Right. Inflammation is one of those terms that gets used like it's specific, but It's like saying business or sports or art.

44:39 It's a big umbrella term. So What is Inflammation in the context of what you have studied. And observed as a clinician and as a researcher and

44:50 Inventor for that matter. Yeah, we're gonna have to do a couple of shows, Tim. Yeah. Simply put.

44:58 Inflammation was defined Thousands of years ago. As the redness, the pain The swelling. And the heat.

45:07 That you feel when you sprain your ankle or get an infected wound on your on your body. Everybody's seen it, everybody's had it. And it's a good thing. It runs its course. And it's the product of cytokines in part and other molecules. T and F I one, IL six, but other molecules made by white blood cells and and other

45:24 tissues in your body. So it's a good thing. When it stops. It's a good thing because it helps heal the wound. Helps proliferate stem cells helps fight off Infection or bacteria that might might settle in the wound.

45:37 And it's a good thing if it stops. The problem is We'll talk about why it stops, but the problem comes when it doesn't stop. And When it starts spinning out of Control like in Kelly Owen's case. Then it becomes like the army showing up.

45:52 With how it serves. To break up a peaceful demonstration. Or a picket line. And you have these violent outbursts of Inflammatory reactions that cause

46:02 The problems in rheumatoid arthritis and inflammatory bile disease and these other conditions. So that's what inflammation is. That's what the textbooks say, that's what everybody knows. That's what everybody's taught. That's what everybody talks about. That's the anti inflammatory drugs we have today modify the molecules we just talked about. E ands, the IL Ones, the

46:19 Prostaglandins, that's how I B profins and other non steroidals work. And we go down the list on all this. The problem is When you look in the brain of Alzheimer's patient

46:30 Which everyone who studies Alzheimer's agrees Has some contribution role or cause A contributing factor from inflammation in the brain, neural inflammation. You don't see.

46:42 Redness. You don't see swelling. It's not painful. And the same is true when you look in the adipocytes, the the fat cells. Of an obese patient. Who has type two diabetes and has significant insulin resistance. Sometimes they have a few

46:56 extra white blood cells and the fat, but they it's not. rip roaring inflammation that you see with In an infected wound. They might have a Upregation of some of the cytokines. You might see the upregated

47:07 production of cytokines in the brains of Alzheimer's patients, but it's nothing like you see in a injured tissue or a rheumatoid arthritis. Some people have come up with new names. Meta inflammation Inflammaging it's called sometimes when these kinds of changes occur. As tissues age, tissues from older people.

47:28 From the elderly. They have higher levels of cytokines and more insulin resistance. They call it inflammation. So We do have a issue of semantics. But

47:37 With that as a limitation. What's so important about this conversation. In light of everything else we've been talking about. Is you talked about a connective tissue in these stories, and and the connective tissue is in many ways inflammation. So let's back up about what the problems facing the human race are. So sixty million people die on the planet Earth every year.

47:59 And forty million of them. Die from heart disease, stroke. Neurodegeneration. Alzheimer's Parkinson's. Metabolic syndrome.

48:09 Diabetes. And cancer. So two thirds of the people that die every year on the planet Earth Die of those conditions. And that that's according to the WHO. Those conditions all have one thing in common.

48:22 They're either caused by inflammation or made worse by inflammation. Now if you look back At what happened. In the last Eighty thousand years.

48:32 Seventy five thousand years since we came down from the trees and became sort of talking monkeys. In that time period. Almost everybody until a hundred years ago, a hundred and Fifty years ago, almost everybody died. By the time they were thirty.

48:48 And what happened in the last a hundred and fifty years can be summarized in a very simple Sentence. The human race in the last hundred and fifty years Removed infection as the leading cause of death. And by doing that, we added

49:02 Forty, fifty years to health span, to lifespan. The question that wakes me up at three AM now. Is what if we could cure inflammation? If we cured inflammation, what would that do to the death Right, from cancer, heart disease, stroke and all the conditions that kill two thirds of the people on the planet Earth every year.

49:19 Look, there's still people that die of infection. People die to covet, people die every day of malaria and tuberculosis. I'm not being Polly Ann about this. But if you look at the cold hard numbers The things that reduced Death.

49:32 and increased survival of the human species all affected The eradication of the threat of infection. You know, cleaner water, m ample food supply, less starvation. All these things converged on Better vaccinations, antibiotics, obviously.

49:46 All these things converged on Improving lifespan. I think something similar will happen. Maybe in the next twenty years. If we can really understand how to modify inflammation, and one way I think we'll be able to do that Is by continuing to dive deeper and deeper into understanding how evolution itself

50:03 Put the brakes on. I said that inflammation's bad when it's not Restrained when it doesn't resolve? Well Evolution knew that hundreds of millions of years ago. So from the very beginning of the evolution of inflammation, there's been evolutionary mechanisms

50:19 That evolved. To suppress inflammation, to tame it, to put the brakes on it. But we've now Discovered in the last Twenty years.

50:28 Is that the brain does this by sending signals through the Vagus nerve. So you ask if this idea May have a application in other conditions. I'm convinced it will. It'll have to be worked through one condition at a time, one mechanism at a time, but I think it's a really important new idea.

50:44 I guess. Well the devices are out in the wild, right? Let's just say the implant. Then docs may have some latitude. to also experiment with patients. I mean TPD. But let me do a few things. I'm gonna allow us if we want just to abbreviate.

50:59 Vagal nerve stimulation to V and S. If we wanna just make it a little easier on ourselves. Let me ask a question that I asked in our last conversation. And I'm sure is on the mind of a lot of folks, which is Along the lines of

51:14 Wait a second. Inflammation. Presumably some important purpose. Just like some people might label cortisol bad. It's like if you get rid of cortisol completely, you're gonna be in a world of trouble. So

51:28 If you are, say, decreasing cytokine production or release by seventy, ninety percent. With vagus nerve stimulation. Could that not Have Downstream negative.

51:41 effects. How would do you speak to that? And I was asking that broadly speaking in our last conversation, but also with respect to weight training and physical adaptations where certain things and I'm getting way over my skis here. But like uh interlucan six, IL six and blah blah blah blah blah temporarily at least or seem important for catalyzing some of these Tissue adaptations. So Are you at risk?

52:07 By sort of suppressing cytokines. With Vagus nerve stimulation. Do we know anything about the side effect profile? We know. Great deal about the side of spec profile, but let me just first unpack the importance of what you're talking about. So

52:22 If we know for certain If you take Biologics. Yeah. Like anti TNF or anti IL one or anti I six, the UC advertise

52:32 It's a nightly news every night and on all the NFL football games every weekend. These biologics the way they're designed to work is they suppress one hundred percent of the activity of the cytokine. So if you take a anti TNF and your monoclonal antibody in your body bumps into your TNF in your body, it's zero. The antibody takes away a hundred percent. It's yes or no. Because you take away a hundred percent of TNF or IL one, depending on what drug you're on.

52:58 Those Drugs carry warnings. The most serious Side effect warning the FDA can give called the black box warning. Because they cause immunosuppression, which is exactly what you said. Immunosuppression means

53:09 Now you no longer have enough Immunological activity or in this case inflammation activity. to fight off infections. And so the risk is you'll get things like sepsis or other kind, or tuberculosis, or other conditions, even cancer in some patients. Because your immune system is no longer Fully armed.

53:26 to defend itself. Against These threats. You ask. Does vagus nerve stimulation do that? The simple answer is no.

53:33 And the reason we know this is because the FDA approved vagus nerve stimulation to treat depression. And Epilepsy actually in the nineteen nineties. So we have decades of experience implanting patients with vagus nerve stimulators. Now there have been peer reviewed studies with

53:52 Thirty years of longitudal follow up in a quarter of a million patients. I estimate that millions of patients have actually been implanted with these devices. So we know that There is always a surgical risk of any surgery. The surgical risks of an incision are small and the and the surgical risks Of nerve damage are actually quite small, especially with the new set point device, which is only you know one inch large, completely encased in it.

54:18 But Immun suppression wise, we also know that Vagus nerve stimulators do not have black box warnings. There's no evidence after decades of any immunosuppression. There's no evidence of an increased risk of infection or cancer. Why is that? Well it's because

54:32 And here we go back to laboratory studies and even now in new human studies. When you stimulate the vagus nerve fibers That inhibit inflammation. The brain to the spleen for instance to stop cytokine production.

54:48 You inhibit, as you said, as you correctly said, about seventy percent. of the cytokine production. You don't inhibit a hundred percent. So

54:57 I like to think of it is that If you have an excessive Or a dangerous cytokine response. You're gonna produce Call it a hundred units of TNF.

55:07 And that's going to be very bad for your tissues and for you. The normal Range should be ten or twenty. The Vegas nerve stimulation therapy and uh set point device is called actually the immunoregulation therapy'cause it's only one minute a day. That drives the TNF from a hundred down to about

55:25 thirty or so. So there's plenty left. Have an appropriate immune response. But it takes the T and F effects from the toxic range that cause rheumatoid arthritis and Crohn's disease. The monoclonal antibodies only hit one target at a time, either TNF or I one or

55:41 The vagus nerve is actually suppressing the whole system. So it's taking the toxic levels of Ile one down and the toxic levels of Ile six down. Those things together. They act synergistically, so the effects are bigger than additive. So if you take them all from the toxic range to the healthy range You're gonna be a lot better off.

55:59 And the IL six response in uh skeletal muscle response in In weight training. That's still gonna be down in the healthy range. And who knows, Tim? We don't know enough about it, but it may very well be Yeah.

56:11 The vagus nerve signals that you activate during exercise, like on the sheep running on the treadmill in New Zealand, we could talk about that Those vagus nerve signals may in fact be contributing to the IL six metabolism and turnover that's going on. We don't know. Maybe we'll get to this, but who knows because we're gonna bounce around a lot. But also another aspect of your book that is very compelling. is it includes a discussion of meditation, it includes a discussion of cold exposure.

56:42 And it includes a discussion of different breathing practices. And All of which seem to have applications to Vegas nerf. Stimulation and

56:54 Maybe it's vis-a-vis the vagus nerve, but Parasympathetic. activation, which might be very counterintuitive to folks. And so for instance Reading your research and reading your book and chatting with you has led me to do something more that I already do, which is, yeah, that's great, but why? And that's interesting, but why? Yeah, that's interesting, but why? Because for instance, I've noticed

57:19 for decades, and I think a lot of athletes have noticed that If you do Cold plunges. And pretty much every Division One soccer team, for instance, or you name it, is going to do some version of this. If you do it.

57:34 Not necessarily immediately after training, but say you wait an hour or two and then you do cold exposure in a bath, that it seems to enhance recovery. Now you could say, Well, ice decreases inflammation. But then it's like Is that true? Could there be another explanation? And what you point out in your

57:53 Book? Which is something that again intuitively now makes sense to me. is in the beginning when you're exposed to cold. And there's studies demonstrating this. Whether it's in cold chambers for hours, which sounds like More misery than I can handle.

58:06 But suffice to say, initially Fight or flight response. Sympathetic. activation, adrenaline, nor adrenaline, et cetera. And then at some point Parasympathetic. Rest and digest activation.

58:20 And could it be that it's the cold is affecting The vagus nerve which is affecting Parasympathetic that helps with recovery. I don't know, but I've, for instance, always wondered why it is that after a few minutes In a forty five degree bath, I start yawning. There's a lot of yawning, and I don't know if that's direct. Interestingly, that's also

58:44 A very common onset symptom after, say, ingesting psychedelics like ayahuasca is Yawning, yawning, lots of yawning, which is why all these things seem to touch the hem of the same fabric. Anyway, that I guess that was more of a monologue than a question. But let me ask you something that has been also front of mind. Is it true and I could

59:07 Speculate, but does it seem like within patient populations we're dealing with more chronic inflammatory conditions? And is that because we have better diagnostics? For instance, you might say, Oh, there's an explosion of brain cancer. It's like, Yeah, well, we also have much better tools and people Are not dying of maybe things that are easily preventable by antibiotics, so who knows. Maybe it's not that Cell phone towers are causing an explosion of brain cancer. It's very easily explained in other ways, but do we seem to be contending with population level greater incidences of chronic inflammatory

59:42 Diseases. And Question mark. Can we even know that? And then if it appears to be the case. Are there any plausible explanations for why that is? That is a uh billion dollar question for which I'm not an epidemiologist, but I know there's no easy answer to that one.

59:59 There are epidemiological studies showing an increase of autoimmune diseases. There are studies suggesting some of these conditions are more common at higher latitudes and some of them more common at lower latitudes. Huh. Interesting. The latitude. Yeah. Yep.

1:00:15 I mean correlation I guess doesn't prove causation, but it's interesting. It's very interesting. It always comes down to two things. Pretty much, in biology. It's nature and nurture. It's genes. And environment.

1:00:27 And environment is is writ large. It's the fa the family you were brought up in, it's it's your It's the germs, the the the pandemic outbreaks that were around your neighborhood when you were ten and when you were twenty. And on down the list. What you eat What's in the environment in the air you breathe, how much microplastics did you consume, knowing it or not knowing it. So G's in environment.

1:00:49 And Sorting that out in real time is exceedingly difficult, especially when you think about The possibility. Yeah. Some of these things after

1:00:58 Decades of study turn out to be Cause by Previously unknown infections. One of my favorites is uh stories about this, of course, is peptic ultra disease. Everyone when I was a kid in in in medical school, everyone all we all knew that Peptic ulcer disease was type A personalities and the

1:01:16 Stress. Stress. It's the patient's fault. I mean I love to say and then it turns out that it There's a bacteria that causes peptic ulcer disease, and when you treat these people with What is that? H pyl not H pilar. And when you treat people with

1:01:30 With antibiotics to eradicate that infection, a large percentage of'em get better. When I was a surgery resident. It wasn't that long ago. I'm not that old, but I mean it was One of the commonest operations in the uh hospital. I was like, Oh, I didn't see that coming. No, no. One of the most common operations on the OR schedule was gastrectomy for peptic ulcer disease. You never see that. It doesn't happen anymore because you take antibiotics. My adage for this thing is when you don't understand a disease

1:02:01 Think of epilepsy. You start off You blame God. So they do exorcisms. And that doesn't work.

1:02:08 So if it's not God's fault, the next thing you do is you blame the patient. When you realize it's not the patient's fault. In today's air oftentimes we find out it's actually there's some some infectious Cause of this thing. And so

1:02:21 Autoimmune disease may have an infectious cause, it may have an environmental cause. People talk about genetic causes, you inherit some level of risk. For autoimmune diseases. But very, very few of these conditions do actually inherit the condition. I mean it's like the old story of the two guys playing Golf.

1:02:38 And get hit by lightning. I'll ask you a question, Tim. Is that uh environment or genes? Well. Yeah, it's environment. Right? It's environment. Well I was also thinking like genetic predisposition to risk taking when they're like, Oh, it'll be fine. Well it's it's it's it's easier than that. It's easier than that. It's father and son, and they play golf every

1:02:59 Afternoon in the summer in Florida. So It's like Those kinds of analyses With two people are hard to do the statistics on. When you when you scale it up to a population, it's very, very, very difficult to give a simple answer to your question. Well, to make it even more difficult.

1:03:14 Right. I've only read it. But It seems like tell me if I'm the wading too deep into my The deep end of my ignorance pool here. So from your book.

1:03:29 And I'm this is not like a counter argument from your book, but I'll just read a paragraph that I highlighted. It's like I'd known this, but it was put very well. Stress responses also activate your adrenal glands to release glucocorticoids. Hormones that stimulate gluconeogenesis, the production of glucose in the liver. Yeah, anyway, that could explain, for instance, my friend's sympathetic overdrive and having glucose spikes at night when you're starting to go to sleep. Going back to the book, this in turn increases your blood glucose levels, elevated glucocorticoid levels, as occurs in depressed patients, accelerates lipolysis, lip am I saying that correctly? The breakdown of fats into fatty acids while suppressing digestion, muscle growth and reproduction. Glucocorticoids also inhibit the action of insulin, meaning that your cells are less responsive to insulin. This further increases blood glucose, sometimes even to dangerous levels. So the reason that I'm bringing this up is that if someone is type A,

1:04:16 And if there Subjecting themselves to in situations that produce chronic Stress response. Could maybe all the things I just mentioned and more.

1:04:27 make them predisposed to certain types of infections. Right, so that they're actually just to complicate the picture further where yes, it's an infection, but there are certain behaviors or genetic predisposition or Who knows even jobs that make it more likely that you would be susceptible to such an infection. I don't know. I don't know.

1:04:47 Those kinds of studies are out there and I think they tip both ways. Some suggest there is increased risk and some suggest there isn't, but I think the whole Last time I read about this, I'm not a psychologist, but the last time I probed this literature a little bit, the whole A nomenclature of type A and Type B personality actually broke down. What was retained Is hostility.

1:05:08 Most of the things that tracked with the Classic type A personality. Correlated to how much hostility So now you're back in the psychological domain of the top down driving. So that's uh that's not me. Yeah. Yeah. Which is understandable. But it's interesting, you know, it's like I was at a scientific meeting was when that data was being discussed.

1:05:28 And somebody stood up in the front row and said, Well How hostile is hostile. How hostile do I have to be to be type A versus type B? And everybody staring at him like Do you hear yourself, man? Relax. Let's talk about

1:05:43 'Cause people are listening and the set point device Yeah, it's like slightly maybe slightly larger than an omega three capsule or something that's implanted in the neck has a number of huge benefits, but then I'm gonna ask you about other tools potentially. I'd say probably the greatest benefit is patient compliance. So if you have to remember to take something or do something every day, there's going to be a lot of breakage in terms of patient compliance. So from just a straight

1:06:15 purely practical perspective, there are some great benefits to An implant. But could you tell the story of your friend Wolf and just describe who he is? And feed into his story. If you're open to it. I'm the

1:06:30 Set point. Device, the one the size of a fish hole pole. I think we have to talk about that in the context of people who are Really sick. These are people.

1:06:39 Mm. Have spent decades Sometimes disabled, oftentimes, as you said. Chronically fatigued or depressed or In pain.

1:06:48 And these are people who are injecting themselves with drugs, many of them Can't afford any more of the drugs they have to take. The ones with these serious side effects. So There's a tendency not by you, but there's a tendency by some

1:07:01 In the short form conversation of these kinds of things. To say, Well, it's a surgery. And uh they should do more push ups or try to do more things to help themselves. Well I I gotta be really, really outspoken on this because When you meet people that have these conditions, if it was easy as doing a couple of push ups

1:07:19 Or taking a yoga class or breathing differently. They would do it. If it made them better, they would do it. These are serious medical conditions, and I think For those kinds of patients there's always gonna be a need because compliance is so difficult. You know, there's compliance with remembering, there's compliance with going to the doctors every month, there's compliance with going to the Fusion center, there's a compliance with injection yourself.

1:07:40 Compliance can break down at at so many different places. So people with serious illnesses You're absolutely right. The availability, not for all, but for those that are Are gonna be able to Or down that path. They have a

1:07:53 Small. Immunorregular and plantar in act. It's gonna be very interesting to see what happens. But for people who are essentially mostly well, like You seem to be like I I seem what an effective mask I've created. Yeah, no, I'm I'm uh generally well. Yes. And and and and me too. And I'm and I feel very fortunate for that. And So I try to do things

1:08:14 That A line with Well People would call it Vegas nerve stimulation. So

1:08:21 Eat right, sleep right. Try to get some regular exercise in. Try to stay cognitively busy. Try to enjoy my my hobbies and my family. Try to stay To alleviate the stress from my life as much as possible. I mean all the things that We all know we should be doing and your G P or your

1:08:38 Primary care provider time. Should be telling you to do every day. All those things in one way or another that we've sort of been talking about. Can be said to stimulate directly or indirectly the vagus nerve. But there's other modalities.

1:08:51 that people also talk about Using electrical devices. To stimulate the vagus nerve by applying electrical devices or tens units, transcutaneous electrical nerve stimulators. To the skin. Before I go any further, let me be a little bit more.

1:09:05 One thousand percent clear. These are not vagus nerve stimulators. There's only Two ways to stimulate the vagus nerve. Directly. And specifically.

1:09:14 One is Implant An electrode on the nerve. And that's either with the devices for epilepsy or depression. Or

1:09:23 Increase the rehabilitation outcomes from patients who have strokes. That's a third one. Or that That's the only FDA. Approved weight. To stimulate your vagus nerve that directly, specifically stimulates your vagus.

1:09:37 Full stop. Experimentally you can do it. Using focus ultrasound. And we've done that in the lab, my colleagues Anguita Shavan and Stavrosanos, we've published on this in the peer reviewed journals. It's a special

1:09:51 Ultrasound. Very similar to the one that you visualize to see the baby in the womb or or the gallstones, but You have a different lens on the Probably. And you can focus the energy to target nerves in the body.

1:10:04 And we've done this in humans to reduce the Inflammatory markers in the blood of Healthy volunteers. I Focusing the ultrasound on the on the splenic nerve.

1:10:14 Where the vagus nerve controls it. And It's also been done we've done it in in animal models of diabetes and Obesity. And seen some very interesting effects.

1:10:24 Everything else, the transcutaneous electrical nerve stimulation strategy to the neck, to the ear, to the side of the head, or the face, those are all Non invasive and non specific, and really shouldn't be called vagus nerve stimulators. None the less. Nondetheless some interesting stuff. Seems.

1:10:41 To happen. Okay. So Everything you said. So true, so on point. I'm also Tempted to go to the hockey puck for

1:10:50 You know, like sort of electric GLP one um administration. But I'm gonna Call that a temptation and not an opportunity for the moment, and let's talk about your friend Ulf and what happened to him. So I apologize for the digression, but I had to Get that in the right. You gotta do it. Now What about other stuff? Like a tens unit.

1:11:12 Let's give a a little background there. Anybody interested in auricular therapy. Oracle as ear. A U R Hurricular therapy.

1:11:21 And our auricular acupuncture knows that The ancient Chinese acupuncture maps date back tens of thousands of years. And that There are points on the ear that map to various organs in the body and if you stimulate them with A needle, a small needle, a probe or

1:11:38 A small electric current that you're supposedly able to The fact that Metabolism or the diseases of those organs. Everybody knows that's ten thousand Well, it turns out when I was writing the book, which I I discovered That those ancient acupuncture maps of the year originated in France in nineteen fifty seven by a doctor named Doctor Paul Nosier.

1:11:58 Who had a patient who was being treated by a Specialist, I think, in Corsica. And the specialist was grounded in In ancient medicine. And was cauterizing a piece of this patient's ear to treat the patient's sciatica, the pain going down there. Burning their ear. Yeah, burning or cutting a piece of it off for I'm not exactly sure.

1:12:17 What they did, it wasn't clear, but there was a little hole on the edge of this And then he saw another one. And in both The two patients claim that their sciatica got better. So Doctor Nogier was a very sort of

1:12:30 Clever guy and Curious and careful and he He took a ballpoint pen and he took the ink out of it and he started probing all of his patients' ears. And he aligned various conditions with In the patient.

1:12:43 With he determined were most closely aligned with the symptoms and signs of the illness, and he made a map. Well he did this for many, many years in many, many patients. And ultimately published this and it presented it at an acupuncture meeting

1:12:58 It was being held somewhere in the Mediterranean. And It led to this overwhelming acclaim for him. And Yeah.

1:13:06 Work was republished in China, which Created the Current Textbooks of Chinese Auricular acupuncture therapy.

1:13:15 Based on a Frenchman's work in the nineteen fifties. So that's where the maps come from. They're fun to look at. They really are, and especially in light of the story I'm gonna tell. So If you look you can see where the spleen is and where the bladder is and where the stomach is. They're very clever. So We were reading Sengita Shivan and I, my lab cohead and I Many years ago, fifteen, twenty years ago.

1:13:36 We were reading about Vegas nerve. Biology and physiology, and we discovered That there was a branch of the vagus nerve. Yeah.

1:13:45 goes to the cartilage of the ear. And when I say the ear, it goes to the cartilaginous part. The part outside The ear canal where you Put your finger in your ear. And it looks like a seashell. So it's called the Simbacontia. That's where it gets its name.

1:14:00 Hunter leg shelf. Now This branch of the vagus nerve that goes from that cartilage It's very, very special. It's the only place that the vagus nerve endings go to the skin. To the surface of the skin.

1:14:12 And They are sensory. That means That when you stimulate the cartilage Of the Simba Cancha.

1:14:19 You can activate the fibers that go carrying information into the brain. And they go to the place in the brain called the nucleus. Dract is solitary as the Which is the place where all the other sensory fibers of the vagus nerve go from your stomach and from your pancreas and from your liver. So all the sensory input goes to the same place. You can think of it like the router in your house. Everything goes into one spot and then it goes back out again.

1:14:45 Well why? Well It turns out Fish. You like evolution, I heard you say at the beginning. Fish.

1:14:52 Fish. Gills are cartilaginous and they're innervated and What became Our human vagus nerve. was one of the branches of the fish's vagus nerve and what became our cartilage of our ear used to be the cartilage of the fish gills.

1:15:07 So drag it with Wild. It's wild. I'll be honest as a non-biologist. Long ago when I was shown these maps, I thought to myself, this makes absolutely no evolutionary sense because why would you, if in battle, you get nicked by an axe and your spleen explodes, that doesn't seem to have any adaptive purpose for natural selection. But lo and behold, fish skills. Well it's fish skills, but I didn't say it makes sense, Tim. You said that. Well no I shouldn't say it makes sense. It's just like a vestigial Yeah.

1:15:44 It's definitely vestigial. How much of the architecture, that's another area that I can't say for sure we've I actually can say for sure nobody to my knowledge has completely mapped out Doctor Nosier's ear maps to the human body in any convincing neuroanatomical, functional neurophysiological way. But it's still interesting.

1:16:03 So With that information You could think of the cartilage of the ear. As a way to drive signals in to

1:16:12 The brain stem through a branch of the vagus nerve. Okay. Immediately people start calling that vagus nerve stimulation. It's kind of true, right? Because it's a sensory branch of the vagus nerve and if you But a a tang unit or your finger. On the cartilage of the ear.

1:16:26 You are technically stimulating the receptors in the skin that activate the sensory fibers that carry the signals into the NTS. But it's not the same as I I said it before I don't have to say it again. It's not the same as electrically stimulating. Okay. Hitting the big cable. Right. Now what happens?

1:16:42 So now it gets really interesting. A long time ago Early Russian. Investigator. Published a study where he took essentially an acupuncture needle. And put it in the Simba Concha and put in a l a little a little electric current.

1:16:55 And show that he could get changes in heart rate variability, essentially. And this goes back again to the fifties or sixties. That exact study, to my knowledge, has never actually been replicated. The way he did it. This is the problem. You talked about clinical trials and Yeah, proving I agree with you. The case studies are often the most important ways to start, but you still have to do the big clinical trials. Randomized controls with the appropriate control population.

1:17:19 That we'll come back to that. So now you you say okay, what happens Using other technology. Well it turns out now I can't count all the publications that have been done by applying various forms of electric current into the ear. And measure you can't count them all. There's there's a lot. You can't count them all. They come out every day now.

1:17:38 And people have done some very sophisticated studies, usually with about ten or twenty people for a study. Usually. And you can find brain imaging studies, F MRI, you can find pet studies. You can find far field evoked responses. Which looks at the Inputs and outputs of

1:17:56 into various brainstem regions and how the brain is processing the higher network signals. So you can see some really interesting stuff and what comes out of it Is lots of different information. That's the first problem. There's no Single consensus. that if you put this kind of electrode in your ear at this time for this many minutes at this much current

1:18:15 You get this effect in this part of your brain in the morning, and this part of your brain at noon, and this part of your brain. No one knows. Put that aside for a second. And I put it in the book. I hope it was clear. But I find striking and interesting and And needing further study. Is that if you

1:18:31 Compare people with electrical inputs to their ear to people with electrical devices surgically implanted in their neck. There is some overlap in the brain centers that are activated. You see centres Like the locus Ceruleus, which Is that

1:18:46 Top of the Fight or flight chain. It's the top of the sympathetic chain. You see regions Yeah. Basal forebrain, the cholinurgic regions which are linked up to the hippocampus and

1:18:58 And there is clinical data that Patients with implanted vagus nerve stimulators. Have enhanced neuroplasticity, enhanced learning, and enhanced cognition. Alertness. In another episode of STELK, which has become one of my favorite new podcasts, there was one of the hosts I think it's Dr. Ken Ford.

1:19:21 Who has served on a number of defense and intelligence related advisory boards, including advisory roles at DARPA. He has a great voice too, Tim. Oh, his voice is amazing. Yeah. So the Defense Advanced Research Projects Agency is incredible. A lot of the technologies we use every day now originally came out of DARPA, ARPANET, et cetera. So He was in conversation and they were discussing neuroplasticity and learning with respect to vagus nerve stimulation. And I haven't looked into this yet, but I've spent time at the Defense Language Institute in Monterey. And they were talking about using vagus nerve stimulation to

1:19:59 Enhanced language acquisition. And that the effects seem to be durable for months after stimulation, which also in your book, just a quick note, right? Stimulation for two weeks having an effect on insomnia for uh two or three months. I mean, what could be more interesting right now? It's just like so so endlessly fascinating. I have to respond to the Dart I I wouldn't be talking to you right now if it wasn't for DARPA support on this idea in the nineteen nineties when it was a frickin' crazy idea that I'm gonna Target.

1:20:27 With an electrode. the vagus nerve to stop sepsis and cytokine storm. And they said, Okay, try it. What if it's yes. Yeah, people think of the quote unquote government as just this big monolithic slow moving Stupid inefficient thing. DARPA is an exception.

1:20:44 You gotta check out DARPA, like the brilliance and the innovation that comes out of that and the Their willingness to throw a lot against the wall and it's science fiction, some of the stuff that comes out of DARPA. One of my heroes is actually a national hero uh Jeff Lang, Doctor Jeff Lang, retired. Colonel.

1:21:03 founded the biology technology office at DARPA. He used to instruct his team at DARPA when the guys And gals will come in with the crazy. Most crazy ass ideas anyone could ever imagine. Like you see that airplane out there? I can make it disappear. I can make it invisible.

1:21:17 And then everybody leaves and they go into Jeff's office and he says to his team, What do you think? And they all say to Jeff He's nuts. It's crazy. You can't make an airplane disappear. Jeff looked at his team and says, What if it's yes?

1:21:30 And that's where stealth technology came from. Yeah, that's so cool. I mean And then you say oh I can still see the airplane. And then Jeff slams his hand on the desk and goes. If you could see it. It's too late. Yeah, I mean technology to be able to see figures around corners. I mean it it's and that was years ago when I saw a rough description of that. In any case, they are doing lots of really interesting things. I took us off

1:21:56 Off track for a second. One more thing. You said another thing, I gotta respond. So The cognition part of vagus nerve stimulation is Also a fascinating story that would require a a full long form conversation, but in brief Patients who had epilepsy were implanted with Vagus Nerve Stimulator. This was years ago, this goes back

1:22:16 Twenty years or maybe thirty. And a bunch of these folks did not get any significant benefit from the therapy, so the device was switched off. Well, a very clever researcher brought them into his lab. And gave him a

1:22:30 I'm not a psychologist. I already gave that disclaimer once, but Give them. Cognitive. Learning test. Of some form.

1:22:38 Very simple. And Then turn the device on and repeated it and all their scores went up. It was very dramatic. And when they image these

1:22:47 Folks in subsequent studies. This is one of the studies that I mentioned before that pointed to the enhancement of activity in the regions of the brain. That are really important for intention, learning, and memory. So there's a deep conversation there about neurocognition. And vagus nerve inputs to the brain.

1:23:04 Yeah. And this is also Like fidgeting around in my chair because I get so excited about like finally trying to and I'm not there, obviously, and I'm who am I? I'm a muggle. So I have to depend on pros like you, but looking at, for instance, the few things That I have come across that really seem to have very impressive effect sizes on

1:23:27 intractable or hard to treat. Psychiatric conditions. that resist frontline treatments with biologics for fifteen, twenty years. Until For instance, just a few.

1:23:39 Some psychedelic assist therapies. Some types of brain stimulation. There are many different types, but let's just take accelerated TMS as one example for certain conditions. And then metabolic psychiatry or ketogenic diet generally in some variation. And a friend of mine I'm gonna pull this up just yesterday. And it's not necessarily a new study, but he sent me a link because I advise that he try

1:24:05 the ketogenic diet for certain types of overwhelming anxiety he was experiencing. Because the downside risk is so minimal, particularly if you're only doing it for a few weeks and your lipid profile is under control. And he sent me this The study. The title, this is from Cell. This is not from some random person's blog. And the title is The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet. So the ketogenic diet was used The early, I want to say 1900s for epileptic children. They'd usually use heavy cream to make it easier for compliance, but had this Maybe it even predates that, this incredible effect of

1:24:43 On Eliminating or reducing. the frequency of seizures. And these are kids who might have hundreds of seizures a day. And I'm looking at this study and here's just a little excerpt. Mice treated with antibiotics or reared germ free are resistant to keto diet mediated seizure protection. Enrenchment of And

1:25:02 Nobiotic co-colonization with keto diet associated acromancia and parabacterioides, if I'm saying that correctly, restores seizure protection. So I literally have probiotics downstairs that are acromancia from a company called Pendulum, which is pretty legitimate. But What? I mean, okay. So

1:25:23 It's mediated partially through the gut microbiota. And it's like, okay, well Then you have the interplay of the microbiota with potentially the vagus nerve with this Two way communication channel. And then you look at for instance

1:25:41 Psychedelic assistant therapies. And there's a lot that we can get into there, but also, and this is finally, and I'm not saying there's a lot of nonsense and a lot of naval gazing and like You know, crystal waving folks in the psychedelic world. No offense to anyone who's falls in that demo. But

1:25:59 There were some credible folks, including, for instance, Doctor Andrew Weil. who actually has an incredible history of ethnobotany and is very, very technical. And he lost his allergy to cats. After A number of

1:26:15 experiences with, I believe was LSD. And these anecdotes on the underground, at least, with facilitators who have Thousands, maybe tens of thousands of repetitions with Patient sessions.

1:26:26 The losing of Allergies. Comes up. pretty constantly. And so then I'm asking myself, well Maybe it's not the content, although I happen to believe the content of these experience matters. But maybe it's the anti inflammatory effects. Okay, well, what does that mean?

1:26:43 And then okay, well maybe it's having some Immunomodulating effect. Okay, well is the vagus nerve involved? Maybe. It's not beyond. possibility. And then you look at neuroinflammation and the effects of whether it's different types of brain stem or the effects on, say, inflamed microglia.

1:27:02 Bsychedelics, like reductions in TNF and all this stuff, TNF alpha have been tracked in the scientific literature. And I just get really, really excited because I can't parse it all, but it seems like these things all To use an awkward phrasing are kinda touching the hem of the same garment in some way.

1:27:19 So anyway, that was a whole bunch of word salad. But I don't want to lose the story of Ulf because we were talking about the maps. We're talking about the fact that yes, you should Maybe at best put it in quotation marks, Vagus nerve stimulation. But

1:27:35 Could you tell the story of Ulf, if I'm saying his name correctly. And uh maybe comically, one of only a handful of Swedes I know is also named Ulf. So it makes me think that maybe it's the John of Sweden. I don't know. But who is Ulf and Why does he tie into this ear mapping that we're talking about? Ulf Anderson is a Retired professor of pediatric rheumatology at the Karolinsk Institute. He practiced there for many decades and throughout that whole time he also ran a research laboratory that

1:28:04 was focused primarily on cytokines on inflammation and cytokines. So as you said Before this is a guy who knows his stuff. Karolinska Institute is also top tier. I mean they do some of the some of the Most fundamental kind of seminal work related to a lot of stem cell applications and so on has also happened at the same institute.

1:28:26 It's arguably one of the best medical research institutes in the world, it's one of the largest in Europe. It's a major teaching center. It's a fantastic place. I've been there many, many times. Wolf and I have been close friends and collaborators for many decades. And

1:28:41 He was diagnosed with a condition that was thought to be a cancer in his bile ducts, in his liver. That required a major surgery called the Whipple procedure where They remove Pancreas of most of the pancreas, if not all of it, and they remove part of the liver and they remove part of the bile duct system.

1:29:00 This was Long time ago, but it but it was a at the time it was a death sentence. The cancer that they thought he had. It turned out to be benign. Which was a blessing in disguise because he had had to undergo this major surgery to have this. After the surgery he developed For the first time in his life, actually, he developed intermittent bouts of depression. Serious depression. Which he attributed

1:29:21 to excessive inflammation in his GI tract. Which was Through unknown mechanisms. Humming episodically. And causing this depression which as he

1:29:32 Talks about in the book. And he's written about on his own. Led to the end of his marriage. And was really ruining his life. Well this was around the time that Sangita.

1:29:42 And I had discovered these funny acupuncture maps of the year. And saw that some people were using Tanz units. And we had published a series of papers. At that point. Understanding how vagus nerve signals

1:29:57 could turn off inflammation. And so we said, What the heck? We put Ten unit. Over the counter product you can get anywhere. With the electrodes on the Simba Concha, not the tragus.

1:30:09 Not the lump that sticks out on the side. Not the pinna, not the earlobe. But on the Simba Concha. And then we drew blood on ourselves and Other volunteers.

1:30:19 Healthy volunteers. And we measured Cytokine production. It's a little complicated how we did that. It's not just drawing blood and Doing an assay, we actually measured

1:30:29 The ability of the white blood cells travelling around our bloodstream to make New cytokines. And when we did those experiments We could show very conclusively, and we published it all in peer reviewed journals. That

1:30:42 Most volunteers, about seventy percent. Seven or eight out of ten people. Sixteen or seventeen out of twenty. You could Reduce the amount of inflammation That the white blood cells would make

1:30:55 If you Put this Probe in the ear. For five minutes. And

1:31:00 At that point. All said, Well, I think I have an inflammation problem. Vagus nerve stimulation stops inflammation. If you want to call this vagus nerve stimul, you can also call it transuricular nerve stimulation. 'Cause there's lots of other nerves to the year, but

1:31:13 That's another matter. Ulf said he he decided he would try it. I didn't treat my friend Ulf. He decided he would do this. He's a bona fide physician, he could do what he wants. I frankly was Not Very encouraging. I said, Okay, whatever.

1:31:26 Well, As he writes. And I know this for a fact'cause I See him several times a year. He turned his whole life around.

1:31:33 He added some antibiotic therapy. Also to treat his Bacterial overgrowth. In his intestines, which comes with the surgery that he had, the whiple. But he also uses this tens unit in his left ear religiously twice a day.

1:31:47 Like brushing your teeth. He says. And he then subjected himself to a fascinating analysis. So You mentioned heart rate variability a while ago and it that's really complicated, but The more I try to learn about it, the more I'm like, Wait a second. It's like quantum mechanics or something. I'm like, Wait, I thought I th kind of knew what the hell you're talking about. No, I don't. If you understand it, then you don't understand. If you think you understand it like Richard Feynman says you don't understand it, right?

1:32:15 I think We don't have to get into it now, but suffice it to say, it doesn't matter what your wearable is, if it's a Fitbit or an I watch or ten other things. It measure heart rate variability. I think this is a hundred percent true. It might only be ninety percent true. They're measuring different things.

1:32:30 Not because They all start with measuring the distance between individual heartbeats. Which is instantaneous heart rate. They all start with that. But what they do statistically after that. Can vary dramatically. I've done this, Singh Eden, I have done this

1:32:43 For a while we worked on heart rate variability and we we made our own devices. And It gets incredibly complicated and we we dropped it because if you get a P V C, if you get a peri ventricular contraction, or you get two irregular beats. In a five minute recording, you know, you've got hundreds and hundreds of heartbeats. It shouldn't do much, right? It messes everything up. It changes all the statistics. So

1:33:03 Can't get into that now. However Bolf was contacted by a guy In Finland. Who sent him a watch he had invented. That recorded heart rate variability as a function of respiratory sinus arrhythmia, which is what heart rate variability is

1:33:17 Actually quote unquote control bright. So if you want to do the experiment, your listeners want to do this, it's very easy. Take a couple of big breaths in. Two hard sniffs in through the nose, fill your lungs completely, and you'll feel your heart rate speed up a little bit.

1:33:31 And then breathe out slowly for seven or eight seconds. That Increase in heart rate during inspiration is partly due to the change in pressure in your chest cavity, your thorax. As your diaphragm drops and you increase the volume, the pressure has to decrease. And then as you exhale slowly, you're actually increasing the pressure in your chest and your thorax. Because you can

1:33:52 Compress the volume. Those changes in pressure all activate sensory signals in the vagus nerve. Which go into your brain. Which accelerate or decelerate your heart. Why? Well because

1:34:03 When you inhale. You wanna accelerate your heart. And exhale, you wanna decelerate your heart. That's the optimal physiological Linkage.

1:34:13 That's the optimal physiological mechanism Two Maximize the amount of oxygen in your blood. This guy in Finland

1:34:21 Invented a way from the E K of looking at the changes in the size of the Q R S wave. shifting left and right, which also happens when your diaphragm goes down and comes back up. And so he found a way to measure respirations from the EKG And link it to

1:34:39 The instantaneous changes in heart rate. What his HR V indicator is in this method. is actually a correlation between the Overlap between respiratory sinus arrhythmia and the breathing cycle. And heart rate variability in the cardiac cycle. And that's how you optimize

1:34:56 Oxygen. Uptake and delivery. It's really cool, right? And it's pretty sophisticated stuff. So he ships the watch over to Ulf. Or not watch device. Yeah. So Ulf puts it on and he's got a terrible

1:35:08 correlation between his Heart rate variability and is respiratory sinus arrhythmia. Until he does his vagus nerve stimulation and then it got a lot better. Now that's a pretty good experiment. It isn't enough one. And somebody I'd love to see somebody

1:35:22 Repeat that on fifty people, but it's still Hard to explain because he does it over and over again on many different days in many different conditions. The real kicker is During covet my colleagues and I at Northwell did a clinical study. We heard of results out of China.

1:35:39 Out of Ulan, actually. Where Patient's taking to A modidine, the antacid. We're significantly protected against

1:35:47 Some of the lethal complications of Covid. We actually did clinical studies of this drug. You can buy it for pennies. Over the counter. at uh Amazon and Costco and C VS and everywhere. Sa safe anti acid, and it turns out we did the clinical studies In Northwell.

1:36:04 And we did then laboratory studies in my lab. It's a pharmacological vagus nerve stimulator. Huh. Yeah. Really? What was it called again? Fomodidine's the generic name. The

1:36:14 It's got a bunch of brand names, including one of them is Pepsi. No kidding. Yeah, you read about it, it'll blow your mind actually. Wow. So when all combined This is the end of the story. When Ulf combined the Fomodine with the Ten unit in his ear.

1:36:31 He gets a hundred percent overlap. Uh he looks like a twenty one year old kid with this overlap between respiratory sinus arrhythmia and Heart rate variability. He's written about it. He's published his own personal Recordings. It's a remarkable story, and it's remarkable not because it's a story of one, but because

1:36:48 Let's go back to what we said before. The FDA approved Vegas nerve stimulation for the treatment of depression. Decades ago. And It's used

1:36:58 A little bit more in Europe than it is in the US. In the US it's not routinely covered by insurance payment. So There's been tremendous resistance. to applying this, it helps about half the patients. Now once again, like we said with the rheumatoid arthritis, let's be concrete about this.

1:37:14 Let's not be the standoff folks who say, Well, it only works half the time, it shouldn't be used. Well And some of the people that it's worked in. They were suicidal and now they're not. What is that worth?

1:37:25 And some of the people it's worked in They're back at work taking care of their kids, taking care of the family. I think the We should be doing it or not doing it based on the data we know so far. There should be a screaming call that we should be diving down into underst we don't know the mechanism, Tim.

1:37:39 We don't know why. Both got better. We don't know why half the patients with depression got better. I think somebody should do a really simple study. We should segregate the patients. Into some sort of inflammatory

1:37:53 Groups. risk groups or activity groups with depression. And treat the ones with the most inflammation. with the vagus nerve stimulation and see if they get better because you've stopped their inflammation. And the other ones have depression from another

1:38:07 Another ideology, another cause, another factor. These are the important questions. Both got better. Don't you work in a place with a bunch of scientists? What's required for something like that to happen? Does it just require uh Scrooge McDuck to fund the study? I mean

1:38:22 I'm the president of a great organization with great scientists. Yes, I am. And there have been some There is and will be more great work coming out of our place, but One place can't do it all alone. This is a call for everybody to get interested. But it's also.

1:38:37 Potentially a call for some interesting distributed Guess we could call them studies. They're not gonna be RCTs, but hey. something is better than nothing if it has recognition of its limitations. For instance, the people who manufacture woof bands, the people who make aura ring I mean they could potentially put out a call to customers. To try to

1:38:59 Do some type of distributed study. Of course you might be dealing well, actually you're not gonna be dealing with self reporting. You'd be dealing with self-reporting perhaps in documenting using a quote unquote vagus nerve stimulator, but the data is gonna be Available. to the company.

1:39:16 vis-a-vis, maybe it's uh anonymized in some fashion, but the patients could make their actual Aura or Woop band or Fitbit data available to the company if it's not already available. So That could be pretty interesting. I recall actually Whoop, I believe, doing something like that with veterans who were On a Sort of standardized.

1:39:41 dosing of I think it was micro dosing of psychedelics looking at impact on HR V. More Potential impact on HRV. HR V fluctuations associated with let's put it that way. You mentioned before depression, serotonin, inflammation. Should we pick up on that for a second? Yeah, let's do it. As you read the

1:39:58 Excerpt before. evidence that some patients with depression get better with SSRIs and some patients don't. And There's also evidence

1:40:08 That SSRIs can even make people who have known inflammation or experimental inflammation. Gain some benefit. There's also information that SSRIs in experimental conditions clinical studies and experimental studies in the lab. Can actually reduce inflammation.

1:40:24 What we have to agree on is we don't know what causes. Depression. And If we knew it caused depression, I think our chances of fixing it in more people would be better. Well also depression is c I mean, in my mind

1:40:36 could be like quote unquote inflammation. There could be many different species. of depression or many different causes. I don't know. I think there are. I think you're right. And I think that's not

1:40:51 Because The focus has been this sort of Excessive focus on serotonin As the hypothesis that has to be dealt with. And there's lots of reasons for that.

1:41:01 That we won't get into now. But what I do like to raise Again, as a a call to action, if you will, and a message of hope. Is we know that inflammation produces depression in animals and in people. I It's to the point now there are some inflammatory Molecules that are used to treat some conditions

1:41:18 some forms of cancer, for instance. And when patients are signed up and they're gonna receive these therapies. This administration of cytokines that As their therapy. That are known to cause depression. They're often given a prescription to go see the psychiatrist to go on the SSRIs before they go get their therapy. So we know

1:41:36 Inflammation causes depression. We don't know. Completely how? There's overwhelming evidence. Um many labs, including my own.

1:41:45 That the presence of inflammation in the body activates signals that Travel up you guessed it, the Vegas nerve. So you could take a mouse, for instance, and inject it with I L one. And the mouse will Run in the corner of its cage, it'll huddle up, it'll

1:41:59 It'll look like it doesn't feel well, like when you have the flu. It will avoid Eating, it'll avoid sex, it'll avoid Playing with toys. In the cage.

1:42:09 It looks depressed. If you cut the vagus nerve back to your If you cut the vagus nerve in those mice and give them Ile one, they don't they don't get sick. They don't get depressed. And so

1:42:21 It puts the question in You know, and the mind body experts and Far East. Religious Dogmas.

1:42:29 Focus on Well we said before the the brain networks and the body networks are Connected. What I said before is the vagus nerve is a principal connector. So if you have disruption of inflammation in the body, which you're not even Maybe nothing hurts in your body.

1:42:43 But your brain knows the inflammation's there. We call that interoception. It's the subconchious sens. That You're Organs are sending information about their status to your brain. If you have inflammation in your body, does it cause depression? That's an important question.

1:43:01 Because maybe that's why those patients who do get better And Go on YouTube and Type in. Some videos of these depressed patients whose lives were turned around with Vegas nerve simulators. It's it'll bring a tear to your eye, some of their stories.

1:43:15 And If you look at those people who have benefited And off. with his Tentune it in the ear.

1:43:22 Quick question. Has Ulf published his Setup. Is that something that people can find online if they wanted to experiment with five minutes twice a day of Yes. Yes, he did. He published it in a peer reviewed journal that I believe is open access. If you Google his name, Ulf Anderson with two S, Anderson. Good good old Swedish last name. I will uh link to that in show notes. We'll find that and put that in the show notes for everybody.

1:43:48 I can send it to you for the show notes. Okay, perfect. Perfect. We'll do that. And I interrupted your train of thought. No, it was the end. I just wanna call the question out to my colleagues that we should study

1:43:59 the influence of interoception, the presence of inflammation in the body being sensed by the brain and causing Depression in some patients and can we treat that with vagus nerve stimulation? Is that why it works in the fifty percent of Why fifty percent? Isn't that a kind of a funny number? It works. That is it's too clean, right? It's too clean. Yeah, I got scammed recently on my credit card at a gas station and it was a hundred and seventy five dollars. And I was like That's too clean. That's absolutely a scam charge. Plus I know gas is expensive, but it's not$175. But in any case, yeah, when the numbers are are that

1:44:35 Clean. You're like, wait a second here. Let me ask you This is out of personal curiosity, and I was goofing around, going all over PubMed, which is sometimes a dangerous business when you're a muggle, but it seems like there are some interesting data around Acupuncture. In the ears. and fertility or pregnancy.

1:44:56 And I know you don't like to speculate, but maybe people have looked at this closely. Is it plausible that that is mediated by vagus nerve stimulation? The simple answer is Yes, I don't like to speculate.

1:45:12 But I'm just saying mechanistically, wood stimulating the vagus nerve. Have some downstream possible downstream effect on the ability to conceive or anything like that. I don't know the

1:45:23 studies that you're referring to. I really don't. And I don't know If acupuncture in the ear Would stimulate the vagus nerve t to stop inflammation. I know that what I did with an electrical tens unit can reduce inflammation in the bloodstream of healthy volunteers.

1:45:39 I can answer the question in the context of are there some Conditions. In the abdomen. Whether in the ovaries or the uterus or the fallopian tubes. Where the presence of inflammation

1:45:52 Would The A restrictive or Would make getting pregnant more difficult? The answer to that's simply yes.

1:45:59 Now the question is If we had ways of Selectively reducing that inflammation In the context of getting pregnant.

1:46:08 If you could specifically reduce that inflammation, would you increase The chances of getting pregnant. Well, you know. Yeah, it's quite logical. It's plausible.

1:46:17 Can Vegas nerve stimulation do that? To my knowledge, nobody knows. I was just uh again curious. And you know what? The first time this kind of Probably using this term incorrectly, but sort of the homunculus on the ear came up. In this podcast. Was with

1:46:32 Martine Rothblatt. Who I think has a quote on your book. Am I making that up? Martine is a is a is a close friend and uh also phenom. What a wild background to such a polymath. Martine's a na another national hero. I mean she She's a satellite launcher, she's a satellite communications expert, she's an accomplished pilot, including flying her own battery powered helicopter and setting

1:46:59 Land speed records and distance records and she's a good friend and the the CEO of United Therapeutics. Yeah. Martine's wonderful. We talk a lot about this stuff. All right. So just want to leave a shout out. If people want to get to know Martine, definitely suggest my interview. with her and I wanted to come to something that you mentioned. at the end of your STEM talk interview. And I really don't have context on this, but it's of interest to me because

1:47:28 I have for the last few years had chronic low back pain, which is a If you want to wander into the Bermuda triangle of hand wavy imprecision in At least pain diagnoses or orthopedics, low back is a good place to go. And

1:47:47 What I have figured out there are certain things that that help and putting aside the biomechanics and strength training and so on for a moment, I know that anti inflamm helps. There seems to be an inflammatory component. So whether it's through applying cold or taking oral anti inflammatories or injectables for that matter. It suppresses symptoms. I know that. And

1:48:09 I'm reading a number of books. Lorimer Mosley and his co-author have actually a very interesting book called Explain Pain. And it relates to this piece that came up, maybe, which is why I want to talk about it, because sometimes, like you said, The response to The equivalent of a picket line in your body. is the entire Navy showing up with rockets blazing.

1:48:32 And it's a severe overreaction. So this relates to Professor Rolls. And I guess I'm gonna try to word this in a way that makes sense, but how specific molecules inform memory memories slash n grams in the brain and the implications of that. Could you just unpack that for me because you guys didn't really get into it. in the STEM talk, but I was like, Wait, wait, wait, wait.

1:48:57 I wanna hold on to this because it seems very interesting and it might somehow be relevant to me. Might not be, but could you Just explain what I'm very clumsily trying to evoke, or I guess elicit from you. Yes. I would love to. Let's start with the picket line. The picket line in the low back situation. I and I've also had on and off sciatica uh from a herniated disc in my back with pain down my leg. So I can relate to this.

1:49:23 In those instances you have something In one of the joints of your back. Or Potentially. Fragment of a disc that's

1:49:30 Pushing on a nerve. Causing Pressure on the nerve. Which sets up a a cycle, which would be the picket line. Right.

1:49:38 There's some injury there. There's some injury. Injury to the nerve or there's some injury in the joint. And that's the picket line. It shouldn't be a big deal to The human body having evolved over hundreds of millions of years. But in some people, not all.

1:49:52 If you look at MRI scans, right? Everybody else's back look just like yours. Yeah, they look all messed up. It's just like you get wrinkles on your face, your spine starts to look pretty funky. So I've got arthrathy, I've got the right framinal stenosis at blah blah blah blah blah but

1:50:09 So does everybody else. Yeah, you can look at like hamburger meat on an M R I. of a back and they're asymptomatic. Right. So why Why does your back hurt and

1:50:18 Somebody's MRI scan would be indistinguishable from your doesn't hurt. Well You can maybe pinpoint the position on your MI scene. Wha now the question's different, right? Now the question is why is your body Sending the navy with rockets blazing. The picket line and you're back, but not you know, not the guy next door. Well.

1:50:33 That is the question. So How can we connect that? to two things. One to Wolf's back pain got better.

1:50:41 Two, by the way. He had injured his neck in a sailing. He was a A world class Sailing Champion. I don't know if that made the book or not. I don't think that was in there. He and his brother Jan Anderson won the European World Championships in in uh J Of course they did. In the nineteen sixties. And of course ABBA sent them to the world championships.

1:51:02 When they were in New Zealand or Australia or something and they competed in the Olympics. Did you see L uh the LA Olympics? Anyways. His back got better. And so the question is why It is back yet. Better because

1:51:14 The signals from the ear to the brain stem went down the vagus nerve to the spleen and reduced The turnover of the inflammatory cells? Well that's a definite maybe. And But we know from very careful experiments in animals and some experiments in humans. Is that when those vagus nerve signals end up in the spleen

1:51:33 They switch the white blood cells. Now the spleen gets twenty percent of cardiac output. So all your white blood cells are racing through the spleen all day long. And when they pass through and pick up this nerve signal. They switch from a state called M one to M two. M one macrophage is And monocytes.

1:51:52 White blood cells. They're the Navy shooting guns full blazing that you said. M two Are the doctors and nurses in the ambulances? Who race to the scene to heal?

1:52:02 And so That's an important area that a lot of people are chasing. And that's in the context of therapy that we've been talking about. That's probably how it works in rheumatoid arthritis, actually. It's the signals are switching the white blood cells. as they pass through the spleen so when they go to the elbow or the knee or the hand

1:52:19 They tend to heal the cartilage of the M two instead of M one. So yeah, M one to M two. So that's a take home point. That's a simple way to think of how you get a nerve, the vagus nerve stimulation. Which doesn't go to your elbow and it doesn't go to your wrist. But that's why they probably get better is'cause that changes the white blood cells that are going to the scene.

1:52:41 So What else is happening? Well w when that inflammation settles in, say the the colon. That's your roles. And a brilliant I think one of the most important

1:52:51 Scientific papers. In the field of what we call neuroimmunology, and maybe in the last Twenty five years. She discovered That what's happening in

1:53:01 The inflamed tissues in the colon in this case. Is actually Forming a Neural network in your brain, which you can think of as a memory, it's called neuroscientists call it an engram. So would that also be like a phantom limb or is that a different thing? I don't want to take us off track.

1:53:17 It would be similar to a Phantom Limb, but it's more concrete, and I'll tell you why. And this this is what's so amazing about it. So Neuroscience has studied memories and engrams for many years and using a method That we call Trapping technology.

1:53:32 And so what you do is you have a genetically engineered mouse, a mouse with special genes that you can put in. When it's an embryo. And the mouse grows up with these genes, and now when you do something to the mouse If you co administer, say you give the mouse a drug or you give the mouse inflammation When you do that at the same time, you give the mouse a drug that activates the these special genes.

1:53:53 That turn the neurons Red, for instance. But only the active neurons. So the neurons that get activated by the presence of, say, colitis. Inflammation in the bow.

1:54:04 They turn red. And they stay red, so you can study them later. Even And that's exactly what Professor Ross did. She

1:54:14 Use another Very sophisticated trick. With What's called stereotactic injections. Injecting virus particles into specific parts of the brain that she had mapped.

1:54:25 From looking at the The the red neurons. So she knew these are the neurons that get activated by colitis. So she'd had the mice. She let them recover from colitis.

1:54:36 And then she Injected. The virus into those neurons and reactivated now just the neurons not all the neurons in the brain, just the ones It remembered the place of the colitis. And they got Kalitus again.

1:54:49 The changes in the brain neurons. I call it a neural network. She does too. I mean we all call it an N gram or a neural network. Lots of Neuroscientists have talked about this on lots of podcasts, but they they call it the Jennifer Aniston neuron or the Santa Claus neuron. Ha ha

1:55:05 I'm a recovering neurosurgeon, right, Tim, so You can do brain surgery under local anesthesia. And this is done a lot of times for epilepsy surgery, for instance, when you wanna make sure Bad. You don't

1:55:16 injure any part of the brain that involved in speech. So you can be talking to the patient during brain surgery. Now you can put electrodes in various parts of the brain. And ask the patient what's happening and There's a famous story of a patient, Well, I just saw Santa Claus or I see Jennifer Aniston. And so

1:55:32 Euphemistically people call that well that you have a Jennifer Aniston neuron. You actually don't have a Jennifer Aniston neuron,'cause you could put an electrode in another part of the brain and And you say, Well Friends, the T V show and Jennifer Aniston's neuron will light up in that'cause they're part of a network.

1:55:48 Right, it's a constellation. That is recognizable by the brain. It's a constellation. Exactly right. Well Nobody before before Ash's studies, nobody thought That A constellation in the brain.

1:56:02 would recognize inflammation. In a way. That we're not only Sort of. Remember the effects of it.

1:56:09 But could then reactivate it. Not to interrupt, but since I'm every podcast I do is self-interested in some way. Is there a way to Delete control Z those constellations so that you don't have this hair trigger response to Triggering

1:56:31 colitis or Slow back. pain response, right? And in this book that I was mentioning Explained Pain, they talk about how surfers and instances sometimes when they get their leg bitten off by a gray white, they report it as a thump. It wasn't painful. Whereas you get a paper cut and it's excruciating. And there's so much variability. So is there a way to deactivate a constellation or overwrite it or I guess.

1:57:00 Fix my fucking low back pain is the short answer. Without taking bottles and bottles of a leave. This is about the third time in this chat we've had that I wanted to offer you a job in my lab. You ask you ask all the right questions. We could do the experiments if you come in. Uh well you're not that far away. I mean don't don't threaten me with a good time. The simple answer is that's what we wanna do, right?

1:57:25 So You might not have to remove the whole network. You might just have to disrupt a little bit of it. And the question is can you disrupt it With a molecule that targets selective neurons. No, that's tricky but not impossible. You have to figure out what the neurons are, figure out what the receptors are, figure out what unique Design a drug to do that.

1:57:42 That would be one approach. But the approach I like, and again I'm a recovering neurosurgeon, so Call me what you want. There are millions of people walking around with deep brain electrodes. Millions. And it sounds like this horrendous terrible thing. But it's not. The electrodes people are putting in now, whether it's Neuralink or somebody else, I mean they're smaller than a human hair.

1:58:03 And They go in and they don't injure blood vessels and they don't even injure sometimes they don't even injure neurons. They go next to the neuron. You could imagine a time In our lifetimes, I hope When

1:58:14 If we knew how to target those neurons or map In advance, right? That you could put these electrodes in And inhibit them. And yeah, that is the right question. I'm dead serious.

1:58:25 No. Astrid's paper's been out a couple of years. I said before I think it's one of the most important studies that I've read in many years. And we have of course Pursued it.

1:58:35 We've been asking questions, my colleagues and I, Sengita. Chivan and Okito Hasimoto and Eric Chang. We're asking a very simple question. Can we make

1:58:45 Engrams, memories, neural networks in mouse brains. Of specific cytokines. We're writing the manuscript as I speak. And the answer's yes. We can Show that when you give a mouse T and F

1:58:57 Which causes a sickness. Behavior, you know. It looks like it has the flu. And then a bunch of other metabolic things that are specific to T and F. And map an Ngram, we can see where the neurons in the brain are and see what they do.

1:59:10 When we do the same experiment with IL one, which also gives a sickness response, but has a very different sort of metabolic physiologic Can separate them. They're unique. T and F and I one are different. Physiology's different. We see a different neural network. So

1:59:24 Now it's complicated, right?'Cause how many cytokines are there and how many physiological states I think the brain you know, a human brain has what, a hundred Hundred billion neurons, give or take, and And trillions of synapses. So it's more complicated than

1:59:38 We think it is. But I think it's accessing. Processing. And

1:59:43 Potentially storing All the information that We haven't even begun to imagine yet. Data tells me. What are the

1:59:51 possible implications of identifying the constellations. I just keep thinking about stars, right? It doesn't take much to screw up Orion's belt, right? Like if you move one or two things around, you could disrupt that engram, so to speak. What are the implications of identifying the Ngram signature of TNF Alpha. I all one. Et cetera. What are the implications of it?

2:00:16 Yeah. Well, how would that translate or might it translate to some type of clinical practice? I think you could Literally if you knew where to put the electrodes into the brain. You could have an electrode in the brain. That communicates with an app on your iPhone.

2:00:31 And you could dial it. Upregulate or down regulate your inflammatory response to a specific Cytokine or condition. In a specific part of your body. Yeah. Yeah, that's wild. It is. And you said it right. I mean people used to think it was impossible to track a incoming

2:00:48 missile from the moon, right? But now they know how to do that. The best example I like, and you're better at this than I am, but Someone explain the analogy I like the most. If you look at a a at a T V screen with all the pixels and you see a picture of the Alps You can't possibly pick out the black.

2:01:05 Square or the altar colored square, but if you swap that one square And make it a really bright color, a really black color. You actually can see it. It's about subtracting, right? It's about subtracting. To pick out what you don't know. In order to do that in in humans.

2:01:21 There's been all this. rush to do brain imaging and Brain anatomy. We still have a long way to go because To my satisfaction is someone who thinks about systems interacting in biology.

2:01:33 We haven't put enough Emphasis On function. Yeah. Even for heart rate variability.

2:01:40 Yeah, you and I can't talk about heart rate variability'cause we don't know enough about the individual functions of the individual wiring diagrams. Yeah, and and also we can talk about kind of uh science and studies and so on, maybe separately over a glass of wine or something, but sometimes The imaging tail wags the dog also for a host of reasons. Yes. Yes. You get these beautiful pictures, and there's maybe some status associated with getting a bunch of money to play with the latest toys, and then you can slice and dice the data to create all these different publications. There's an allure that I think can sometimes

2:02:23 lead to an overemphasis on the imaging, which is not to negate Some really, really incredible applications of the imaging. But I think what you said carries a lot of weight. Let me ask Because There will be people listening who are curious about this.

2:02:39 Cervical Tens units. So we talked about the uh transcutaneous auricular stimulation. There are devices, including some that are FDA approved for, say, I believe cluster headaches. And or migraines.

2:02:56 I can't recall exactly that are neck based. And could be applied to one side, could be applied to both sides, but effectively Supposedly, right. Or stimulating the vagus nerve where it would correspond to your pulse. Let's just say carotid artery.

2:03:12 Yeah. And you can find a number of publications on PubMed

2:03:21 But what might be the If in fact they are doing something that is beyond placebo effect. What might the mechanism of action be? And you can start wherever you like. I'm just curious about the cervical devices because They're floating around out there. And there are I've seen at least a few studies and I'm like, Huh, okay. Well What the hell's going on here? If in fact there is a signal

2:03:43 Instead of just noise. I think it's important to say that when you dive into these kinds of questions There's Lots of facts. So the first is the first time.

2:03:52 And you afford. Buy lots of devices and try lots of different things. That's one approach. And Second, do you you know, do you like self experimentation? That's another approach.

2:04:01 A third is well, always check with your doctor first,'cause there are some things you probably shouldn't do. Around the area of your neck. You have carotid stenosis, you don't want to Put any pressure on your carotid artery, if you have cervical sinosis, you don't want to turn your head certain ways. Check with your doctor. So those are actually important disclaimers. That's not a joke.

2:04:20 People should check with their doctor before they do these things. Unless, of course What they're doing is FDA approved. And Some of these devices, most of them not, but some of these devices have been subjected to F D A Approval.

2:04:34 In the context of Putting electrodes on your neck. There are some FDA approved devices. That are called Vegas nerve stimulators. And they are essentially tens units. They deliver pulses.

2:04:48 Of electric current, spikes of electric current. Usually between twenty, thirty hertz. Usually on the order of milliamps. And y you know it's working because you feel a buzzing or a tingling. And when you

2:05:00 Put it on your neck usually You know that the current is spreading around. through the skin and through the nerves of your neck because your platisma muscle The muscles of facial expression. And your neck will twitch or your lip will twitch.

2:05:13 Pull your lip down. Yes. Yeah. So that's evidence that the electric current is activating lots of nerves and lots of muscles. Now Time for A slight digression.

2:05:27 The carotid artery. Is encased in a sheath with the vagus nerve. So to get to the vagus nerve. You have to go Do this again.

2:05:37 Through the potisma muscle. Through the layer of subcutaneous fascia. Through the sternocladomastoid muscle, which is that big thick strap muscle in your neck, thicker in some than others, but it's there. Down to the carotid sheath, maybe through another layer of fascia. Through the crowded sheath and then somehow either around

2:05:55 Or through the crowded artery. Right, so it seems like the tense unit is not gonna hit the Vegas nerve. Engineers, I've spoken to at length about this. Say, and I said it very politely and clearly in the beginning of the show. The only way to directly stimulate the vagus nerve is to Put an electrode on the vagus nerve. That's not this. You're putting the electrode on the skin.

2:06:15 Or to use focus ultrasound, which would penetrate all those tissues. And could be focused to the vagus nerve in the neck, but those devices are not available for us to use at home. So your question was, could it work anyways? It's FDA approved to treat migraine, and the answer is Well my my question was What the hell might the mechanism be if it's not actually getting through all that. Stuff.

2:06:36 To hit the Vegas nerve. I have a very good answer for you. Collective delusion and placebo. No, no, no. No, no, to defend the manufacturers and the FDA, Asians who Put this on their neck and use it according to the FDA label. And have severe migraines. A significant percentage of them.

2:06:54 Do better than for patients who don't use the device. This is an example that we talked about before where you have a device We don't necessarily know how it works. It might work through some Other mechanisms.

2:07:06 But it seems to work in a statistical way in in FDA approved Randomized clinical trials. Put that aside, right? How could it work? We're talking now science here. Well Charles Sherrington. One of the two fathers of neuroscience with Ramoni Cahal back in the early nineteen hundreds.

2:07:23 He wrote a famous book which I recommend to anyone, even casual readers of neuroscience. Should we Charles? Sherrington's Book, The Integrative Action of the Nervous System. The title alone is brilliant, The Integrative Actions of the Nervous System. He taught us this. It's so simple, you'll never forget it.

2:07:40 You have to understand a simple reflex because there's an input And then some sort of connection or process and an output. And that's what happens when the doctor taps your knee. That's what happens when inflammation happens in your body and and the signal goes in. And

2:07:54 Well in the knee case The rubber hammer stretches the tendon. The tendon sends a signal up your sensory nerves to the spinal cord. Spinal cord sends the signal back down to your quadriceps for Morris, your leg pops up and you said Shit, who did that? That's a reflex.

2:08:09 In the context of inflammation, there's inflammation in your body, the signal goes up your vagus nerve. signals come back down, stop the inflammation. That's the inflammatory reflex. Got it. Okay, Charles, we got that. What's next? Then he said If you assemble. A couple of reflexes, you can start to build a nervous system.

2:08:25 This is again, this is your field more than mine. It's a neural networking, you can assemble things, you can build up complex systems by just adding one more reflex, right? One more input, one more output. And then he goes, End of the day? There's no such thing as a simple reflex'cause every nerve in your body is connected. So you put electricity on your neck? Some of it's gonna end up

2:08:42 Stimulating nerves that go into your brain or your spinal cord. Once it gets in the brain or the spinal cord, there's the big router. The brain can decide how to send it out. In some patients Does it relax the muscles of the neck?

2:08:55 To Interfere with the headache. Pathogenesis, maybe. In some patients does the brain send signals down the vagus nerve? To stop inflammation contributing to migraine, maybe.

2:09:07 In some patients does the brain send signals up to The resistance arteries That are controlling blood flow in and out of your brain that can give you a attention headache? Maybe. We don't know. Nobody knows. Yeah.

2:09:20 I mean it's exciting to me that there are so many open questions. So just he's like it just enough of a teaser. And a taste test of something to make it really tantalizing to investigate further and my friend

2:09:35 He's using a cervical device, the one who tripled his HR V, so who the hell knows, right and Ultimately. He and I were talking'cause after our first shot, I was like, hey man, I might have some good news, bad news. And I was like, Seems like your device is working for you. And I was like I wanna burst the placebo effect. But also Doesn't seem to be a Vegas nerve stimulator, but we were joking and I think one of us is probably me because I'm a goofy ass a lot of the time. But I said, you know, I guess at the end of the day, you know, ultimately you don't really care if

2:10:05 You know your Somehow. summoning Odin to come down with a magic unicorn and Pierce you through your forehead with the spike like a narwhal to fix your low back pain or increase your HRV. You just want the output. So whatever is happening. It would be great to understand what's happening under the hood, but it's like

2:10:26 You might like driving your Tesla. You don't that many people actually know how it works, or the microwave, or the refrigerator. Which is not to say That I you want the larger scale. R C T and mechanisms of action. So I'm not trying to

2:10:42 dismiss the importance of all that. Or the power of placebo. Well, I don't know if it's placebo, you said it's the power it could be the power of one, and it could be. That If a hundred patients were subjected to this

2:10:53 And seventy five percent of them have the effect your friend has. Now, but that's really interesting. Why? You know? This is where Some people like to reach too far.

2:11:04 When they're Talking There were Yes. Some of the websites selling these things are so bad. Yeah. So bad. You expect them to be selling.

2:11:14 Bonner pills and create them and Some sketchy You know, shitty cryptocurrency at the same time in the checkout process. They're so bad. Yeah, and you know, people say oh well Is it safe? Well that's important, but then you you raise people's hopes.

2:11:28 And then you take their money. And you don't know what you're doing. There's real questions there. I'm not saying it's easy. Look. What people would say is the simplest, stupidest clinical trial. of one of these devices might cost five million dollars or more. Science is expensive. Good science is expensive. Yes.

2:11:45 All right. We've covered a lot of ground. I highly, highly, highly recommend people check out the Great Nerve if you want. Not just things we've talked about, but we could do th like three rounds of the podcast. I didn't even get through a small portion of my notes. Also in your book, I want to point out, because this is important, you you have an entire section dedicated Two different types of tools with some really remarkable Results whether that's breath work.

2:12:13 Cold exposure meditation. You know what? Maybe just as a fun way to bookend this. Could you please tell the story? You've got some amazing stories in the book. Could you please tell the story of the Dalai Lama? Uh people are like, What? The Dalai Lava? How the hell does he fit into this? Yeah. Okay. So please tell that because it's just fun. I mean, it's so fun. It's also fascinating, but it's fun.

2:12:39 Back in the day, I g was it about two thousand seven, give or take. I can't remember the year. It's in the book. Maybe two thousand ten. I got a call. From the Dalai Lama's New York office. Would I like to go to a conference. Now the call came From a gentleman Bill Bouchelle, who is a a scientist in his own right. Who was working full time.

2:12:59 In the Dalai Lama's organization. And he had been following my work because of these questions. on the role of the Vegas Nerve in meditation. The Dalai Lama, of course, famously has participated in and supported many Some very sophisticated brain imaging studies and meditation studies.

2:13:16 And the Dalai Lama is on the record of saying that he's convinced That The major tenants of his religion are true. In a quantum mechanical way, as you alluded to before, from any perspective. His tenants are like the speed of light. They don't change. And he said to the point that

2:13:32 In fact if quote unquote Western science or New World Science could disprove any of his tenants, then he would change the tenants. So He has a deep interest in science. So he hosted a meeting Here in uh Phoenicia, New York, on the top of a mountain where they own a a compound, right outside of Woodstock where the rock concert was.

2:13:50 And so I drove up there. Not all the funny stories made the book, Tim, but One and have to tell. Is And when I'm checking in, I got there late.

2:13:58 It was dark. And I'm in the middle of the woods. And I like the woods. I like to camp. I like to driven by this place. It is in the middle I mean middle, middle of the woods, yeah. They're on the whole mountain, right? So it's dark, it's nighttime, and they they give me keys to a cabin in the middle of the woods and uh as I'm going out the door. The woman says Don't mind the bears.

2:14:18 And I'm like Fine, I'm gonna walk in the dark. It's through the bears to my cabin. I said, Well I'll make a joke and I said, Well, I know they were here first, right? And she looks at me with like steely eyes. Okay. Welcome.

2:14:33 Well, Woodstock. I'm like this isn't this isn't like the concert. So So uh good evening, sir. Exactly. The next day I'm on stage. Next day was two days of scientific talks. A whole series of time. I gave one. I remember Liz Blackwell was there.

2:14:50 And when she was there was the time it was during the meeting it was announced that she'd won the Alaska prize and I think a year or two later she won the Nobel Prize. So Liz and I were there and a bunch of other scientists. And the last day. The organizers came up to us and and asked Liz and I if we would summarize the meeting for His Holiness the Dalai Lama. On stage in front of all the attendees.

2:15:11 So we said sure. So Liz gave a talk and then I gave a talk. We I'll never forget. I was on stage with The Dalai Lama with Bob Thurman, who was sitting to his side. And that's Uma Thurman's dad, and he's a professor of

2:15:25 Of uh Tibetan studies and Other studies at Columbia at the time, Columbia University. And a translator sat between us. And I explained the vagus nerve and I said And he asked the question you did, you know, where is this Vegas now? And I said, Well it travels down your neck and Into your across your chest, into your abdomen.

2:15:41 He goes, Oh. And then he said through Bob, he said Is it in the front or the back? I said, Well it's in the front. And then he said, Is there one or two?

2:15:51 I said, Well there's two. And then he smiled at me. And uh that was that. And then Afterwards he left and

2:15:59 A few monks came up to me. In their long Flowing orange robes, as Bill Murray would say, striking, you know. And They said to me.

2:16:09 Хіз астузці, Діно Ві. He asked you those questions. I said, No, I haven't a cloak. And they said, Well We like to practice one form of Tibetan meditation is we like to practice a cloud of blue energy over our heads.

2:16:25 That we channel in two Waves. Down each side of the neck, across both side of the chest, down into the abdomen. And I said Who?

2:16:35 And the monk said. Yeah, it's very cool. Ha Not everybody gets a Dalai Lama story. Yeah. That is a good one.

2:16:46 Well, people can find the great nerve, which includes so much more anywhere that you find your books. Doctor Kevin Tracy, T R A C E Y And is there anything else you'd like to say as we wind to a close, anything you'd like to add, point people to Requests, reminders, public complaints, anything you'd like to Say before we we land the plane.

2:17:09 One thing, these things in the book and that a lot of people talk about for self help, they're good. I do them. I don't know. Meditation's good, exercise is good, watching your weight is good. Getting enough sleep is good. All of these things I think are are good to reduce the inflammation in your body. And they are good to Probably do

2:17:26 To give your vagus nerve Some exercise and improve your heart rate variability. It's all good. I just don't like to Say that it's it's the cure for some of these serious medical conditions. And the fact that we now have a path to connect

2:17:40 Decades, literally decades of science. to now Fifteen years. twelve years of clinical trials. On this science.

2:17:48 That gives hope to some patients with serious inflammatory conditions that stimulating their vagus nerve with this Immunoregulator is what we really call it. It's an exciting time and um I really appreciate you having me on the show and There's more questions we could talk about next time, maybe. Yeah, maybe round two cognitive enhancement with vagus nerve stimulation. I mean I could keep going, keep going for many, many hours, but I'll call it here for now. And everybody listening, we will provide the links in the show notes to many different studies to all F Anderson's protocol for the five minutes twice a day, of course to set point the New York Times piece as well.

2:18:29 And to the book, The Great Nerve. And you'll be able to find all of that at Tim.blog slash podcast for the show notes. Just search. My friend Kevin Rose will pop up a lot if you search Kevin. So search Tracy, T-R A C U I, or Vegas, or Vegas Nervan. This will pop right up. And until next time, folks. Be just a bit kinder than is necessary, not just to others, but also to yourself. And as always, thanks for tuning in. Hey guys, this is Tim again, just one more thing before you take off, and that is Five Bullet Friday. Would you enjoy getting a short email from me every Friday that provides a little fun before the weekend?

2:19:09 Between one and a half and two million people subscribe to my free newsletter, my super short newsletter called Five Bullet Friday. Easy to sign up, easy to cancel. It is basically a half page that I send out every Friday to share the coolest things I've found or discovered or have started exploring over that week. It's kinda like my diary of cool things. It often includes articles I'm reading, books I'm reading, albums perhaps, gadgets, gizmos, all sorts of tech tricks and so on that get sent to me by my friends, including a lot of podcasts. guests and these strange esoteric things end up in my field and then I test them and then I share them with you. So if that sounds fun again it's very short a little tiny bite of goodness before you head off for the weekend something to think about. If you'd like to try it out Just go to Tim.blog slash Friday. Type that into your browser. Tim.blog slash. Friday, drop in your email and you'll get the very next one.

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