How to Stop Headaches Using Science-Based Approaches

Andrew Huberman 0:00 (soft rock music) Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today, we are discussing headaches. Headaches are something that everybody will suffer at some point in their lifetime. Now, of course, some people suffer from headaches far more often than others, and for many people, headaches can be incredibly debilitating, limiting their ability to work, to socialize, to sleep, to exercise, essentially to live life in any kind of normal way. As we'll soon discuss, there are many different kinds of headache. We have migraine headaches, tension headaches, cluster headaches. Today, we'll review all the different types of headaches and what the underlying biology of each and every one of those types of headaches is, as well as, fortunately, the many excellent treatments that exist for the different types of headache. In fact, what we'll soon discuss is that by understanding which type of headache you have and a little bit about the underlying biology of each different type of headache, it becomes quite straightforward to select the best treatment options for you to, for instance, provide relief from frequent and recurring tension headaches, cluster headaches, even sinus headaches, the sorts of headaches that are associated with sinus infections and colds where the sinuses get clogged up and you experience headache. So while today's episode focuses on all aspects and types of headaches, it will have tremendous relevance for everybody. So for those of you that experience headache every once in a while, or only when you're sick or have a sinus headache, or for those of you that suffer from debilitating migraines, today's conversation actually has a bit of optimism woven into it, meaning there are excellent treatments for each and every one of the different types of headaches. And I was quite impressed and excited to learn when researching this episode that the treatments for headache range from, of course, prescription drug treatments and over-the-counter medications of the sort of type that most of us have heard about, ibuprofen, acetaminophen, and so forth, so-called an-antiinflammatory drugs. But it turns out there are many natural treatments for headaches that, when compared to those over-the-counter drugs and even some prescription drugs, appear to be easily as effective and in many cases more effective than the typical drug treatments, many of which can carry side effects. That is, the drug treatments carry side effects, whereas the natural treatments appear to not carry side effects. Now, of course, any time we have a discussion about natural treatments, there are likely to be some eye rolls out there and people thinking, "Oh, you know, this is going to be, um, a bunch of woo science." Well, far from it. As you'll soon learn today, each and every one of the treatments for each and every one of the different kinds of headaches is grounded in solid biological understanding of why that particular treatment ought to work and does work. So for instance, you'll learn that some headache arises because of muscular pain. Other headache arises because of excessive vasodilation. The arteries and blood vessels get bigger and wider, and so there's a pressure and a swelling within the cranium that people experience as a headache. And it turns out that many of the more natural treatments out there can address either the muscular pain issue or the vasodilation issue or other issues and underlying mechanisms for headache. So again, while headaches are very intrusive, irritating, and in some cases debilitating, there is certainly light at the end of this tunnel, meaning by the end of today's episode, each and every one of you will have an array of excellent treatment options that you can choose from in order to address and provide relief from any of the different types of headache. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero-cost-to-consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's

Andrew Huberman 3:51 podcast. Our first sponsor is Thesis. Thesis makes custom nootropics, and as many of you know, I am not a fan of the word nootropics because nootropics means smart drugs. And as a neuroscientist, I can tell you there is no neural circuit in the brain for being smart. Thesis understands this and has designed different nootropics in order to bring your brain into specific states for specific types of work, so for instance, for creative work or to engage with more focus or to give you more energy for cognitive or physical work. So with Thesis, they'll design custom nootropics for you that will allow you more focus, better task switching, more creativity, and so on, and they'll be sure to include only the ingredients that you want and not the ingredients that you don't. I've been using Thesis for more than a year now and I can confidently say that their nootropics have been a total game-changer for me. I like the Clarity formula prior to long bouts of cognitive work or the Energy formula prior to physical workouts. If you'd like to try your own personalized nootropic starter kit, go online to takethesis.com/huberman. You'll take a brief three-minute quiz and Thesis will send you four different formulas to try in your first month. Again, that's takethesis.com/huberman and use the code Huberman at checkout for 10% off your first box. Today's episode is also brought to us by LMNT. LMNT is an electrolyte drink that has everything you need and nothing you don't. That means the exact ratios of electrolytes are in LMNT, and those are sodium, magnesium, and potassium, but it has no sugar. I've talked many times before on this podcast about the key role of hydration and electrolytes for nerve cell function, neuron function, as well as the function of all the cells and all the tissues and organ systems of the body. If we have sodium, magnesium, and potassium present in the proper ratios, all of those cells function properly and all our bodily systems can be optimized. If the electrolytes are not present and if hydration is low, we simply can't think as well as we would otherwise, our mood is off, hormone systems go off, our ability to get into physical action, to engage in endurance and strength and all sorts of other things is diminished. So with LMNT, you can make sure that you're staying on top of your hydration and that you're getting the proper ratios of electrolytes. If you'd like to try LMNT, you can go to DrinkLMNT, that's L-M-N-T.com/huberman, and you'll get a free LMNT sample pack with your purchase. They're all delicious. So again, if you want to try LMNT, you can go to LMNT, L-M-N-T.com/huberman. Today's episode is also brought to us by Maui Nui, which I can confidently say is the most nutrient-dense and delicious red meat available. Maui Nui spent nearly a decade building a USDA-certified wild harvesting system to help balance invasive deer populations on the island of Maui. I've talked before on this podcast, and we've had guests on this podcast that have emphasized the critical role of getting quality protein, not just for muscle repair and protein synthesis, but also for repair of all tissues, including brain tissue on a day-to-day basis. And the general rule of thumb for that is one gram of quality protein per pound of body weight per day. With Maui Nui meats, you can accomplish that very easily, and you can do that without ingesting an excess of calories, which is also critical for immediate and long-term health. I should say that Maui Nui meats are not only extremely high-quality, but they are also delicious. I particularly like their jerky, so their venison jerky. I also have had Maui Nui venison in various recipes, including ground venison, some venison steaks, and I love the taste of the venison. It's lean, but it doesn't taste overly lean or dry at all. It's incredibly delicious. So if you'd like to try Maui Nui venison, go to mauinuivenison.com/huberman to get 20% off your first order. Again, that's mauinuivenison.com/huberman to get 20% off your first order. The Huberman Lab Podcast is now partnered with Momentous Supplements. To find the supplements we discuss on the Huberman Lab Podcast, you can go to livemomentous, spelled O-U-S, livemomentous.com/huberman. And I should just mention that the library of those supplements is constantly expanding. Again, that's livemomentous.com/huberman.Let's

Andrew Huberman 7:47 talk about headaches. And as we are soon going to learn, there are different types of headaches, and different types of headaches arise from changes in different types of tissues in the head area and, indeed, in the neck area as well. Now, one of the key things to understand is that if you want relief from a headache, you need to understand which tissue is mainly involved in creating that type of headache. So for instance, many people suffer from what are called tension headaches. Now, tension headaches are a little bit of a misnomer because many people might think, "Oh, tension, I'm under a lot of tension and stress, and therefore I get tension headaches." And indeed, stress can cause tension headaches. But tension headaches are really the sort of headache that you feel around the top part of the head, not the very top, but sort of where you would put a headband, so above the eyes and around the head. It doesn't have to be experienced all the way around the head. But the main underlying reason, that is, the tissue system that mainly underlies tension headaches is the muscular system. There are a lot of muscles on the skull, believe it or not, of course on the neck, and they allow you to move your neck and head. But there are a lot of muscles that lie parallel to the skull, and oftentimes those muscles will undergo excessive amounts of constriction. Now, there are, of course, muscles in the jaw that can also lead to headache and jaw ache and things of that sort and neck aches and headaches. So what we're really j- pointing out here is that the muscles are a key player in the formation of different types of headache, tension headache in particular. But, of course, muscles and muscle tension can be involved in the other types of headaches as well. Okay? So I just want to highlight muscular issues as one particular source of the ache in headaches. The other tissue that can be prominently involved in generating the ache of a headache are the so-called meninges. Now, the meninges, in addition to being a fun word to say, are a bunch of tissues that line the outside of the brain and reside between the brain and the skull. So you might think, "Okay, between the brain and the skull, there's probably just a little bit of fluid and the brain is right up next to the skull." But it turns out that's not the case. The brain is actually encased in a very thick, very durable sac or casing that's wrapped around it tight like Saran wrap. It actually has a name, which is dura, D-U-R-A. And so you can remember dura, durable. And, um, having done some surgeries, many surgeries before on brains of different types ranging from human, even though I'm not a neurosurgeon as a clinician, f- ranging from human to other types of, uh, species, what you find is that the dura is exceedingly durable. Getting through this thing really requires an, a very sharp razor blade. So the brain is actually sitting in a very fibrous-like sac that you simply could not open up with your fingertips under any conditions. It's really durable. The meninges are in that general area and also encasing the brain, and the meninges provide an additional buffer between the brain and the dura and the skull. So again, you don't want to think about the brain as just sitting right next to the skull. It's close by, but there are a bunch of other thin, fibrous tissues, many of which are very thin and fragile and others of which, such as the dura, that are very, very strong because they're very fibrous. Almost like a, uh, if you've ever felt the, for instance, the sail of a, of a sailboat. You might think, "Oh, it's just this big flapping sheet in the wind." It is anything but a sheet in the wind. (laughs) It is a very, very strong and durable material. Now, the proximity of the dura and the meninges to the brain and the fact that everything is wrapped very tightly together and the fact that there's a lot of vasculature, so that would be arteries, blood vessels, and capillaries, are all in that area on the top of the brain and throughout the brain. The fact that all of that is in very close proximity and wrapped really tight in this very durable sac is one of the reasons why when blood vessels or arteries or both become dilated, they open, there creates a pressure between the brain and those tissues. And because there isn't much distance between the tissues like the dura and the meninges and the skull, there's also pressure that allows for the brain to literally sneak up, or I sh- should say, it give the impression that your brain is expanding up against your skull. So the point here is that while muscular tension can give rise to headache, the other thing that can give rise to headache is so-called vasodilation, the expansion or the widening of the arteries, blood vessels, and capillaries. And one of the reasons why that gives rise to headache is because there's simply not a lot of space for that expansion to go. It doesn't allow anything except for the brain to push up against that very durable tissue and that very durable tissue to push up against the skull. And even though the brain itself doesn't have pain receptors, uh, that's right, the brain itself doesn't have pain receptors. That is why a neurosurgeon can take off a piece of skull and can probe around in the brain with an electrode and the person is completely unaware. And in order to get through the skull, of course, a little skin flap has to remove, be removed from the skull, and that requires a little bit of topical anesthetic. But really you don't need any anesthetic to go into the brain itself because there aren't pain receptors on the brain itself. However, the tissues surrounding the brain, such as the dura, the meninges, and the vasculature that then reaches up, believe it or not, into the skull, the vasculature (laughs) doesn't actually stop right beneath the skull. It actually, blood vessels, it get into the skull and there are actually, um, portals by which blood can move within the skull itself. Well, what that means is that since all of the tissues are very close by and very compact with respect to one another, any increase in the size of the portals that allow movement of blood there, and the fact that there are what are called nociceptors, N-O-C-I, nociceptors. These are essentially pain receptors. Because of the presence of pain receptors in the tissues around the brain, when there's an increase in the size of those vascular portals, the arteries, capillaries, and vessels, we experience that as intense pain and pressure. And fortunately, there are excellent treatments for dealing with that intense pain and pressure, but keep in mind that the intense pain and pressure, uh......that is the consequence of vasodilation, that is the widening of these different vascular portals, is very different than the type of pain that arises from muscular tension, as is the case with tension headache.

Andrew Huberman 14:06 Okay? So now we have two sources of pain, that is the ache in headache, and there are two more that we need to think about in trying to better understand the different types of headaches that we'll discuss, and in terms of trying to understand which are going to be the best treatments for the different types of headaches. And those are neural and inflammatory responses. So let's talk about the neural type first. There is a type of headache that many people unfortunately suffer from. We'll get into this in a bunch more detail in a moment. Those are called cluster headaches. Cluster headaches are c- headaches that arise not from the surface, people don't experience them as kind of a tightening of the forehead and the neck and the jaw, but rather it feels as if the headache is coming from deep within the head, and in particular from behind the orbit of one or the other eyes, and sometimes both eyes. For those of you that have ever experienced cluster headaches, they are extremely painful, even the more, or I should say the relatively more minor cluster headaches are extremely painful, and the severe ones are exceedingly painful. Cluster headaches arise from deep, or the s- we get the sensation that they are arising from deep within our head, as opposed to from the surface inward, because they are neural in origin, and there's a particular nerve pathway called the trigeminal nerve that often is the origin of these cluster headaches that people experience behind the eye. The trigeminal, as the name suggests, has three branches, tri-, okay, so there's a, a branch that essentially extends to the eye, there's also a branch that extends to the mandible, right, to the, uh, to the lip, and there's a branch that extends more or less to the, to the nasal area. And so this trigeminal nerve becomes inflamed or in other ways is hyperactivated in some cases, and that causes the deep pain below the eye because it is that first branch of the trigeminal nerve, which is the ophthalmic branch, which tends to be activated first. So people start feeling as if there's a pain behind their eye, in particular on one side. Oftentimes there's lacrimation, which is tearing up. There can be some nasal discharge. Another common symptom of this type of headache, that is the cluster headache, is that the pupils sometimes will become very small, the pupils of the eyes, and they won't dilate, even in darkness. So there are a bunch of things that are going on on one or both sides of the face that seem to arise from deep within the head, or it's almost as if it's coming from the brain outward, and that's because it's neural in origin. Okay? So we've got muscular origins of headaches, we've got meningeal origins of headaches, that is the, the stuff around the brain and as it relates to the vasculature, and we have neural origins of headaches. And, of course, there's inflammation origins of headaches. Now, inflammation is a term that gets thrown around a lot these days. People are talking about, you know, this reduces inflammation, inflammation is bad, and, and I, I suppose in some cases and when inflammation is really widespread across the brain or body it's bad, but I don't think any of us should think about inflammation per se as bad. What I mean is inflammation is just one form of signaling in the body, which of course includes the brain. Inflammation of a tissue is one way in which a set of cells, so these could be, uh, for instance, uh, cells of the immune system, and we cover this in a detailed episode all about the immune system. If you'd like to check that out, you go to hubermanlab.com, just put into our search function "immune system" and you can find that episode. By the way, all of our episodes are searchable by keyword at hubermanlab.com and it'll take you to specific episodes and timestamps for the topics you're interested in. So, for sake of this discussion about headache, inflammation is going to be the case when one particular tissue in and around the head area is releasing molecules, cytokines, which sometimes are called inflammatory cytokines, but there are also non-inflammatory or anti-inflammatory cytokines. But inflammatory molecules that are signaling to the rest of the body, "Hey, there's something going on here." There's either some intrusive object, and indeed if you were to get, you know, a BB or a splinter into a particular, uh, you know, skin area, there'd be a lot of inflammation. So it could be the introduction of a foreign physical object into an area that would cause inflammation, it can be the presence of some sort of local toxin in that area, it could be a more systemic inflammation. Nonetheless, inflammation in the neck and head area, or frankly anywhere within the sinus area, so this would include the mouth, the nose, around the eyes, because the sinuses, many of us think of sinuses as just our nose, but actually if I were to show you a skull, a human skull or any other kind of skull, you'd be very, hopefully, intrigued to learn that the skull is just not one big piece of solid bone or a, you know, a top with a jaw below it. It actually has all these small what are called fenestrations, little holes and canals that run through the skull and through the depth of the skull, like little tubes. You've got them down here on your mandible, you've got them above your lips, you have them, um, on either sides of your nose. Those are the sinuses. The sinuses allow the passage of different fluids through the skull because the skull, even though it's bone, it's not a dead tissue, right? In a, in a live person or animal, the skull is a very active living tissue. Indeed, all bone is active living tissue, and it needs to be nourished with blood, it needs to be nourished with cerebral spinal fluid in the case of the skull, it needs to be nourished with all sorts of important things. So those sinuses oftentimes can become clogged, as is in the case with sinus headache, which we'll talk about in a little bit. But more generally, any time there's inflammation of one given area of the body, so it could be a shoulder, it could be the neck, it could be the mouth, it could be the nose, or in the case of the headache, it could be any...... portion of the head or neck. What happens is inflammation, while it's a very efficient signal, it's much like the siren on an ambulance or a, a police car, in that it sends out a very broad signal that's very clear something is wrong here and needs to be dealt with. It's not very specific. So it's very robust, but it's not very specific. So for instance, if there's a little bacterial infection or a little viral infection, the inflammation response to that site of infection tends to be far more widespread than the actual site of infection. It's a little bit different when you have a foreign object there like a splinter or some other foreign object. That tends to be a bit more localized. And the immune system is always trying to limit the, the extent of inflammation by putting in different scar tissues. Indeed, a lot of the things that we think of as kind of gross pussy, you know, pustules and boils and things like that, I know it's a gross topic, are ways in which our body tries to restrict the amount of inflammation. But the face area and the head itself are so heavily infused with blood vessels, and there's a constant profusion, as we say, of blood and cerebral spinal fluid and other things through this incredibly metabolically active tissue that we call our brain and our eyes. Those are by far the most metabolically active tissues in our entire body, even if we're running hundreds of miles in ultra-marathons, your brain is still far more metabolically demanding than all the muscles of your body combined, no matter what the conditions. Because of that, there tends to be a generalization or a spreading out of any inflammatory response, and that inflammatory response then can trigger the pain mechanisms, or what we experience as pain mechanisms, in the other three types of tissues that we talked about. So for instance, if you have a, a systemic infection or you're experiencing inflammation of any kind, and it has anything to do with or encroaches on the face or head area, that can easily and almost always spills over into activation of nerve cells, can give rise to neural-based headache, or to the meninges and can give rise to meningeal headaches, and of course, to the muscles and to muscular-type headaches. So we've got muscular origins of the ache in headache. We have meningeal origins of the ache in headache. We have neural origins of the ache in headache, and we have inflammation-based origins of the ache in headache. And that pertains to all the different types of headaches that we're going to talk about, and it's important to keep in mind that there are these different sources of the ache in headache, and that sometimes they exist alone and sometimes they exist in combination. However, and this is an important however, all pain, or I should say, all experience of pain as a perception, is going to be neural in origin. When we experience pain, when we, whether or not it's a pinprick or a cut, stub our toe, we trip and fall, or a headache, it is neural in origin. It is the nervous system and nerve cells that are going to carry that signal that we perceive as pain. So as we talk about the different sources of pain and different types of headache, we will also talk about, of course, I think what most people are interested in today's discussion, the different treatments for the different types of headache and why each of those different treatments work. But by understanding a little bit about how pain arises in the nervous system, and certainly by understanding the different types of headaches, you know, what is a tension headache? I gave you some impression that it's running around your head like a headband in many cases, versus cluster headache, which starts deep below the eye often, it feels as if it's emerging from deep in the brain, versus migraine, which we'll get into in a moment. By understanding the different types of headaches, you should be able to quickly pinpoint what type of headache you have, what types of tissues are likely involved, and therefore, what types of treatments are going to most quickly and most completely relieve that type

Andrew Huberman 23:21 of headache. Okay, so for the next three to five minutes, and I promise no more, I'm going to explain how pain arises at the level of nerve cells, and suppose this is one of those times when, if I had a highlighter pen that could go out and across the, the microphones and speakers, uh, leading to your ears, I would use it here, because what I'm about to tell you is perhaps one of the most important things to understand about your nervous system, that is your brain and you, which is that, while you have trillions of neurons, we hear that, you have trillions in, different types of neurons in your brain, and they come in different shapes and sizes and do different things, and some make dopamine, and some make serotonin, and some make glutamate and on and on. The key distinction among different types of neurons, that is, the three types of neurons that I believe everybody, scientist or no, everybody should understand exist, are some neurons, nerve cells, are what we call motor neurons, in the sense that they control the contraction of muscles, sometimes for walking, other neurons control, uh, the movements of your fingers, scientists call those digits, other ones your toes. They also control the beating of your heart, although that's a slightly different mechanism, and slightly different type of tissue than is involved in generating motor movements of your limbs. These are neurons that we call motor neurons because their goal, or their purpose I should say, they don't really know what their, their goal or purpose is, but what they do is they make sure that muscles contract so that certain things happen in your body, like your heart beats, or you move your limbs, you lift your eyelids, or your eyebrows rather, and so on and so forth. Other types of neurons are what we call sensory neurons. They communicate the same way that motor neurons do, that is, they fire what we call action potentials, which are just electrical signals. They release neurotransmitters like any other neuron, but they respond to certain events in the environment or the environment within the body, but they are not responsible for generating muscular contractions. So we call these sensory neurons. Some sensory neurons sense light touch. Other sensory neurons sense firm touch. Other sensory neurons sense pain. Other sensory neurons sense light brushing on the skin. In fact, you have sensory neurons, believe it or not, that respond specifically...... to the light brushing of a hand across your skin, any region of your body. And if that particular region of your body happens to have hair on it and you stroke the skin in the direction that the hairs lay down, we experience that as pleasurable. Whereas if you stroke in the direction opposite to the, (laughs) the way the hairs lay down, we experience that as not pleasurable. So these sensory neurons respond in some cases, for instance, within the auditory system, they respond to sound waves, in your eye they respond to photons of light, sometimes photons of light of particular wavelengths that we think of as red, green, blue and so on. Sensory neurons don't move muscles, they respond to things in the environment and they exist within us. So we have sensory neurons that sense, for instance, pressure within our head or pressure within our gut, how full or empty our gut is. Pain within our tissues like our liver or, or any kind of other internal organ. So we've got motor neurons, sensory neurons, and then the last kind of neuron is what we call modulatory neurons. These are the ones that adjust the relationship between the sensory neurons and the motor neurons to determine whether or not we do anything in response to a sensory input. That is whether or not if a sensory neuron fires, sends an electrical potential, whether or not it will generate a motor change. Let me give you a very simple example of this. So for those of you listening, uh, I'll just explain what I'm doing, and for those of you watching, you'll be able to see. I'm holding my hand out in front of me. If I were to touch the top of my hand with my fingertip, I can deliberately override, that is I can modulate the more typical reflex which is that when something touches us, if we're not aware of where it's coming from, we typically move away from that thing that touches. This is a very natural response. But we can decide we're not gonna move away, we can decide to stay still or we can decide to move toward the thing that touches us. But typically if you were to walk up to somebody and you were to touch them, they'd either turn toward you on the side that you touch them or they'd step away. It's rare that they're gonna step into you. But you could decide that you are not gonna move away or you could step into the direction of touch, and that's because you have modulatory neurons that can adjust the conversation in a very context dependent way as to whether or not the sensory neuron will cause motor neurons to contract or not. Okay? So we've got motor neurons, sensory neurons, and modulatory neurons, and you're probably thinking by now, "Why are we talking about this? I thought we were gonna talk about headache. I thought we were gonna talk about treatments for headache." But this turns out to be very important because you could imagine, and in a moment I'll explain how let's say you have tension headaches, you're somebody that has the classic symptoms of tension headache. Let me tell you what those are. These are headaches, again, that occur more or less on, on the bi- you know, kind of a headband-like fashion or they tend to start there and exist around the head. These are very common. They can arise from a number of different, um, sources. They could arise from sleep deprivation. They can arise from excessive use of caffeine intake. We'll talk about why that is. They can arise from stress. They can arise from very low level viral infections or bacterial infections. But we experience these as just, as headaches, where you've been thinking too hard or working too hard or life has been stressful. They're often also associated with jaw pain and jaw tightness and neck tightness. So tension headaches, everything you'd imagine muscular tension could cause. Well, if you want to treat tension headache, you could imagine that because all headache is neural that you'd want to go after some sort of neural mechanism to treat them. But, of course, we now know that there are three types of neurons. There are motor neurons, sensory neurons, and modulatory neurons. So we have choices. We can say, "Okay, do we want to turn off the muscles in the head, jaw, and neck that are hyper-contracted?" D- for instance, you want to take a muscle relaxer or relaxant or would you want to try and change the sensory input itself? Maybe don't change the way the muscles are behaving, but shut off the sensory part of it, your ability to sense it. There are certainly ways you can do that. Or would you want to adjust the modulatory neurons? Would you want to make it such that you have the headache but you don't perceive the headache? That is you cut off communication between the sensor and the motor so that the muscles relax. Turns out there are treatments and approaches for each and every one of those. Each and every one of those has, uh, different advantages and disadvantages, but as you can quickly see, we are going to have different types of headaches and different approaches to treating headache, but if you keep in the back of your mind that you have neurons that contract muscles to create movement or tension of muscles, remember you can turn off those neurons and allow those muscles to relax, you have sensory neurons that sense input and actually sense the pain, and you have modulatory neurons which can allow you to adjust the relationship between the sensory neurons and the motor neurons. And of course some of you are probably screaming at me by now saying, "Wait, why would you ever want to deal with the motor neurons or, or the modulatory neurons? Wouldn't you want to just go straight to the source and just cut off the pain?" Uh, well, the problem there is that many pain killers have other issues as well. In particular, they can be sedative. Many of them can be habit forming or even addictive, and for many people, not all but many people, they don't want to take drugs whether or not they're over-the-counter or prescription drugs or even more natural supplement-based type treatments, and they would rather use, for instance, a behavioral approach in which they can modulate, they can deliberately turn off the communication between sensory neurons and motor neurons. It turns out those approaches exist as well. Okay,

Andrew Huberman 31:05 so at this point I promise you that I'm not going to give you any more of a biology lesson in terms of, uh, pain sensing and headaches as a more, uh, conceptual phenomenon. Instead what I'd like to do next is talk about the different types of headaches, and I think this is something that's very important and not often discussed except for those people out there that unfortunately suffer repeatedly from certain kinds of headaches like migraine or cluster or tension headache. But I think for most people out there who experience headache, and again that is everybody at some point experiences headache, rather than just think of headache as one thing, understanding the major types of headache and how they differ from and are similar to one another will really help you identify what the best source of treatments for those are. So I'd like to talk about what the different types of headache are now.The first type of headache we're going to discuss is the tension-type headache. Again, tension-type headaches tend to start off, not always, but tend to start off as more or less a halo or a headband around the forehead and the area above the eyes, often also include the jaw, the neck muscles, and can extend even into the upper back. Again, this can be caused by some low level of infection, but more often than not, tension-type headaches are going to come on because of some chronic psychological stress, usually combined with lack of sleep, usually combined with lifestyle issues, and of course, without getting into a long discussion about it, any time you have lack of sleep, you're going to have excessive stress. Any time you have excessive stress, you're going to have to make sure you're offsetting that by getting proper sleep. Most people don't when they're under excessive stress. By the way, we have excellent tools, they are grounded in excellent science, available to you at zero cost if you are experiencing chronic stress or even short-term stress, we have a master stress, uh, episode of the Huberman Lab Podcast. Again, just go to hubermanlab.com and all that's timestamped for you. Tension-type headaches begin in a more or less a headband pattern, but can really extend to other tissues as well, not so often in the face, but really the head and, and often will start to climb up toward the top of the head. They are not always in this halo pattern. Sometimes they can be localized to one area, such as the, you know, back of the head or the front of the head or one side of the head more than others, and that's often the case because of tension within muscles of the neck that tend to bias the ache towards one side of the head.

Andrew Huberman 33:25 I'd like to take a quick break and acknowledge one of our sponsors, Athletic Greens. Athletic Greens, now called AG1, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking Athletic Greens since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking Athletic Greens and the reason I still take Athletic Greens once or usually twice a day is that it gets me the probiotics that I need for gut health. Our gut is very important. It's populated by gut microbiota that communicate with the brain, the immune system, and basically all the biological systems of our body to strongly impact our immediate and long-term health, and those probiotics in Athletic Greens are optimal and vital for microbiotic health. In addition, Athletic Greens contains a number of adaptogens, vitamins, and minerals that make sure that all of my foundational nutritional needs are met, and it tastes great. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman and they'll give you five free travel packs that make it really easy to mix up Athletic Greens while you're on the road, in the car, on the plane, et cetera,

Andrew Huberman 34:29 and they'll give you a year's supply of vitamin D3K2. Again, that's athleticgreens.com/huberman to get the five free travel packs and the year's supply of vitamin D3K2. The other type of headache that unfortunately is very common is migraine headaches. Migraine headaches are defined generally as disorders of recurring attacks of headaches. So people who get migraines often get them in a recurring fashion. Some people get them very often, other people get them less often, but migraines are very debilitating. The numbers, that is the prevalence of migraine, is still pretty debated. One thing that we know for sure is that females suffer from migraine headaches at a rate at least threefold higher than do males. And surprisingly, this does not seem to have any direct hormonal origin, because we're also going to talk about hormonal headaches, that is headaches that relate to a dip in estrogen and progesterone, a particular phase of the menstrual cycle, that is the ovulatory cycle. So there's a bit of a mystery here, and the mystery is, why is it that migraine headaches occur at such greater frequency in females, even independently of the menstrual cycle? So when you control for changes in hormones, that still appears to be the case. And overall, migraines are very common. Now, the numbers on migraine and just how common migraine is are extremely wide. This was a little bit frustrating for me in researching this episode. You will find, for instance, that 17% of women suffer from migraines. You will also hear that 6% of males suffer from migraines. You will also hear that 43, 43% of females suffer from migraine, that is recurring headaches that qualify as migraine headaches, and that 17% of men suffer from migraine headaches on a recurring basis, which is, again, the definition of a migraine headache, or one of the key definitions. So all we can say for sure is that many, many millions of people, maybe even billions of people suffer from migraine headaches. It's kind of a staggering, uh, thing to contemplate, but we know it's extremely common and we know that it's more prevalent in females. In any of the studies that you will find in terms of they compare the overall prevalence of headache, it's going to be higher, substantially higher in females than males, does not seem to be related to the ovulatory menstrual cycle. There are some interesting facts related to that, that I'll just, you know, touch on for a moment. Pregnancy, for whatever reason, seems to be protective against migraine headaches. That is, women who suffer from recurring migraines before they get pregnant, when they get pregnant, and often after they give birth, they experience fewer migraine headaches. So there may be something hormonal, it may be something else. What do we know for sure? We know that headache, that is the ache in headache, is neural. So whether or not the origins are hormonal or whether or not the origins are inflammation or gut microbiome or some other feature of the body-brain axis, at this point, all we know is that neural pain or the experience of pain at the neural level is the final common pathway and it's more prevalent in females. So as I mentioned, migraines tend to be recurring, so some people get them once a week, some people get them once a month, some people get them far more frequently, that they can be extremely debilitating. Oftentimes, people who experience migraine, because it is a recurring phenomenon, will know when a migraine is coming on. They'll say, "My migraine is coming on." They kind of sense it coming.... there's this notion of aura, and we'll talk about aura in a b- in a little bit. Some people think of aura just as visual aura, or the sense of kind of a haloing of light, or the sense that there's something outside the body. The actual definition of aura is that it's the experience that something is about to happen. It's this kind of feeling of anticipation. It's not deja vu. Deja vu is different, and very interesting in its own right, but different. It's this feeling that something's about to happen. And the fact that aura is such a prominent feature of migraine headaches, or at least that people feel that the headache is coming on long before they feel the actual ache of the headache and the other debilitating symptoms, suggests that migraine has something of deep neural origin, that it arises from deep within the nervous system, spinal cord and brain, and that it's not something like a tension headache that is going from outside in. You know, the constriction of the muscles in the jaw and head. So migraine headaches are very different than tension headaches, even in terms of how they come on or their onset. The other feature of migraine headaches that I think is important to note is that dilation of the vessels ... Remember the vasodilation, so the widening of those pipes that we call arteries, vessels, and capillaries, is a very prominent feature of migraine. And fortunately, that allows for very particular types of treatment and ways of dealing with the s- pain specific to migraine headaches. The other feature that's common in migraine headaches is so-called photophobia. Many of you are probably familiar with photophobia if you've ever been sleep-deprived. Simply, if you're sleep-deprived and you go outside in the morning, the light is going to seem very, very bright, much brighter than were you to have had a really good night sleep. And that's because during sleep, there are all sorts of reset mechanisms in the brain. There's the washing out of metabolic debris and things in the brain, the so-called glymphatic washout that's essential. There's also an adjustment of the neural tissue of the eyes, which, as many of you have heard me say before, are actually two pieces of brain that have been extruded from the cranial vault. So your eyes, yes, indeed, are two pieces of brain, the only two pieces of brain outside the cranial vault. And within your eyes, you have neurons and mechanisms that adjust the, the sort of sensitivity of your eyes to light and of your brain to light. And when you are sleep-deprived or when you have a low-level viral infection or a cold or a flu of any kind, you tend to experience light as brighter than it actually is when you're rested or you're in the healthy state. So photophobia is something that's very, very common in migraine, and often the photophobia is a prominent feature of the experience that a migraine is coming on. People will start saying, "Oh, you know, it's just too bright in here." And normally they'd be able to tolerate that level of sunlight or of indoor, uh, lighting with no problem. So there are two aspects of migraine that I think are particularly important to understand for sake of, of the treatment, and that's the dilation of vessels. So we ... If we want to treat migraine, we're gonna have to think about things that can constrict blood vessels in the brain area, but we also need to think about photophobia. Not photophobia just as a symptom of migraine, but that maybe by adjusting our sensitivity to light, we can actually short-circuit some of the onset and subsequent pathology of the migraine. That is, if we can prevent photophobia, partially or completely, can actually offset a lot of the ache of the migraine that would otherwise occur. So that's an exciting avenue, uh, for addressing, uh, migraine headaches. We'll get into photophobia and how to deal with that. We'll also talk about aura a little bit more, uh, in a few minutes. But for the time being, we've talked about tension headaches, we now talked about migraine headaches. Again, keep in mind, knowing what kind of headache you have is essential. It's, I would say, indispensable for selecting the best treatment. Many people out there will simply get a headache and decide, "Oh, I'm gonna pop a couple of aspirin." Okay. What does aspirin do? A- aspirin's an anti-inflammatory. It also has pronounced effects on the vasodilation and vasoconstriction system. It actually allows more blood to flow through those arteries, vessels, and capillaries. A lot of people actually use baby aspirin or small amounts of aspirin as a way to offset cardiovascular disease. That's another discussion. But what do we know? We know that in migraine, there's a hyperdilation of the blood vessels, a hyperdilation of the very little portals that exist in the brain and around the brain and that are going to cause the pain. They're gonna activate those sensory neurons, those nociceptors that will then give us the experience of extreme headache in migraine. So taking an aspirin or something like it for migraine, in some cases, the worst possible choice. Again, so knowing what kind of headache you are experiencing is going to be essential here. The other thing that you'll sometimes hear is that drinking a cup of coffee or getting caffeine through tea is a great way to deal with headache. Why would that be? Well, it turns out that coffee can cause either vasoconstriction or vasodilation depending on when you take it. And we'll get into the use of caffeine as a treatment for headache, because indeed it can be a very potent treatment for headache. But you absolutely need to know what kind of headache you are experiencing because in some cases, drinking caffeine, whether it's in tea or coffee, can absolutely alleviate the pain of a headache, especially if you catch that onset of a migraine or a tension-type headache early on. But in some cases, it can make it far, far worse. Again (laughs) , knowing which type of headache you're experiencing and how the different treatments work is key. Okay, so we

Andrew Huberman 43:10 have tension-type headaches, migraine-type headaches. I think you're starting to get the picture. They have different underlying biologies. The next type of headache is cluster headaches. Cluster headaches are the ones I mentioned earlier that arise from deep within the head. They feel as if they're c- coming from the inside out, and they tend to be on one side or the other, what scientists and clinicians call unilateral. It tends to originate behind the eye and sometimes the nose region, sometimes in the mouth region as well. It feels kind of patchy, but as if it's coming from the inside out. And again, that's because of that trigeminal nerve. For those of you, um, listening and not watching this on YouTube, I've got three fingers as if I'm putting up three fingers and I'm ... I've got one pointed toward my eye, one pointed towards my nose region, and one, uh, towards my upper lip.The trigeminal nerve is an easy one to remember and it will completely explain, um, cluster headaches and what to do about cluster headaches in a moment. If you remember that the herpes 1 virus, and not herpes 2, not genital herpes, but herpes 1 virus is the one that gives cold sores on the mouth. Herpes 1 virus, by the way, is exceedingly common, up to 90% of people, many children in fact have these. Again, this is not a sexually transmitted herpes, although it can be, of course, transmitted through kissing and sexual contact, but that's not the only origin of it, okay? It can be passed by skin contact and mucosal contact. Um, so mucosal-mucosal, so that would be kissing, mucosal lining, or even skin to mucosal lining, so that's why it's so common. And the reason why cold sores develop on the mouth for people that have herpes 1 is because the virus actually lives on the trigeminal nerve. And yes, it is true that sometimes the virus will, uh, inflame the nerve and the inflammation will occur at the level of the eye, so people do unfortunately sometimes get herpes of the eye. It actually can be quite dangerous. If you have an infection of the eye, a herpes infection of the eye, you should see an ophthalmologist. Or the nose region, they can experience pain in the mucosal tissue of the nose. More often than not, the most inflammation is occurring on the, the branch that innervates the lip or the region close to the lip, and that's why a cold sore develops there, an immune response there signaling that there's inflammation due to the herpes, uh, virus, which lives on that neuron for a very long time. Neurons don't turn over in, uh, in the lifespan, so it can live on there for the extent of, of the person's life. However, most people hopefully treat their HSV-1, but if they don't, uh, the, the sort of, um, frequency and the severity of infections tends to taper off with time. We'll have an entire discussion about viruses and herpes in particular in a future episode. But the thing to keep in mind here is that this very nerve is the one that gets inflamed in these cluster-type headaches. Now, cluster-type headaches are associated with a bunch of very uncomfortable symptoms. Again, they tend to be unilateral, they tend to d- begin very deep, and they tend to be excruciatingly painful, excruciatingly painful. They can last anywhere from 30 minutes to three hours. Some people experience these in sleep. In fact, this is one of the cases where men experience a headache more than females. Men experience cluster-type headaches that have a sudden onset during sleep at five times the frequency than do females. The origins of that aren't exactly clear. They do seem to have something to do with the biological clock mechanisms, the so-called circadian mechanisms. So if you are a, a man or woman for that matter and you're waking up in the middle of the night with a unilateral headache and it seems like it's deep within your, um, within your head or it's starting there and it's on one side and localized to the eye and maybe these other regions the trigeminal is involved in, you may be suffering from a cluster-type headache and you should talk to your physician. The other symptom that's quite common in cluster-type headache is a droopy eyelid, which should make sense because the trigeminal innervates the eye region and there are other nerves that control the eyelid, but they're in that general region and they can be impacted. The other thing is something called meiosis, which is that you can't dilate the pupil. I mentioned this before. So that your pupils might get really, really small and they won't dilate. And the other thing is lacrimation, tearing, and then nasal discharge, all because of a neural inflammation problem. Why do I tell you with such detail about cluster headaches? Well, if you are somebody that's experiencing the kind of pain that is consistent with cluster headache, taking a standard anti-inflammatory or (laughs) doing something that is going to adjust the vil- the, excuse me, the dilation or constriction of blood vessels may have an indirect impact on cluster headache, but is unlikely to relieve cluster headache either acutely, meaning right away, or in preventing cluster headaches. You have to deal with this as a neural issue, and we'll talk about some of the main causes of inflammation and activation of these cluster-type headaches at the level of the trigeminal nerve in a little bit, because fortunately there are some excellent treatments. The

Andrew Huberman 47:47 next type of headache that is quite common are hormonal headaches. Now, the phrase hormonal headache should already cue you to the fact that it's far too general a term, because there's (laughs) so many different hormones, testosterone, estrogen, thyroid hormone, growth hormone, and on and on and on, and they all have many different functions in the brain and body. Every single hormone, and in particular the so-called steroid hormones, steroids, again, not just limited to, uh, things that people take for sports. In fact, the steroid hormones refers to estrogen, testosterone of the sort that we all make, that men and women make naturally. And those steroid hormones can impact gene expression, they can... Are, of course, what turns on the growth of the, of the breast tissue, of the testicular tissue, of, um, hair growth, and, and on and on. And that's all because of gene expression. If you're really gonna change the identity and function of a cell long-term, right? You're gonna literally change the breast tissue or change the penile tissue or change the ovarian tissue in some sort of consistent way across the lifespan, you can bet that there are changes in gene expression. And those changes in gene expression occur because these steroid hormones have this incredible ability, sort of like the X-Men of hormones, to pass through the outer membrane of a cell, which we call the extracellular membrane, and into the so-called nuclear membrane. They can go into the area where genes are made and turn on and off different genes. However, they m- multitask in their life. That is, these steroid hormones, like estrogen in particular and testosterone in particular, can also bind to the surface of cells and impact all sorts of things at the level of the cells that have nothing to do with changes in gene expression. And that second mechanism of binding to the surface of cells is one of the ways in which estrogen can control different aspects of headache. Now, that doesn't necessarily mean the estrogen gives you headaches. In fact, it's just the opposite. It turns out that low estrogen and another hormone, low progesterone, combine to give rise to headache because of the ways that low estrogen and low progesterone impact vasodilation and vasoconstriction and the inflammatory response. We'll talk about how to deal with hormone-based headaches-... in particular, hormone-based headaches that occur because of low estrogen and progesterone in a moment. But the key thing to know is something that we covered in the fertility episode. I did a very long, very detailed episode on fertility, so I'm not going to go into this in significant detail now. You can refer to that episode, uh, for probably more detail than you ever wanted, but also a lot of tools as it relates to fertility in both males and females. But right now, I'm just going to give you a course overview of that in about 60 to 120 seconds so that you'll understand when hormonal headaches are most likely to take place. Keep in mind that hormonal headaches are most likely to take place when estrogen and progesterone are lowest. So if you understand that during the follicular stage of the ovulatory/menstrual cycle, okay, so menstrual cycle is about 28 days on average, not in everyone, but it's about 28 days on average, in the first half of that, estrogen starts creeping up, up, up, up, up, up, up, up, up, up. And as we learn in endocrinology, estrogen primes progesterone, so estrogen will then peak and then start to fall low, low, low, low, low, low, low, pretty quickly, right about the time that the egg ovulates. An egg is released and will essentially be ready for fertilization. If the egg is fertilized, a whole bunch of other things happen as it relates to pregnancy. If not, what ends up happening is that during the luteal phase, which is the second half of the menstrual cycle, there's been a buildup of the lining of the uterus because of an increase in progesterone. So estrogen goes up during the follicular phase, then it goes down, and then progesterone goes up, up, up, up, up, which is important for generating that thick lining of the uterus to allow the fertilized egg, if it's fertilized, to implant. And if it's not fertilized, all of it gets released from the body in this bleeding process that we call menstruation. If menstruation occurs, and day one of the menstrual cycle is considered the first day in which bleeding occurs, well then what that means is that estrogen is already low, because remember, estrogen was low at the start of the follicular phase and went up, up, up, up, up, up. Then it comes down right at the time ovulation, and progesterone goes up, up, up, up, up during the luteal phase. In fact, it's more than a thousand-fold increase in progesterone, but if there's no fertilization of the egg, progesterone starts coming down, down, down, down, down. What does that mean? That means that on the first to about the fourth or fifth day of the menstrual cycle, first being the first day of bleeding, till about the fourth or fifth day of the menstrual cycle, both estrogen and progesterone are very, very low. And it is at that time, at the very beginning of the menstrual cycle, so about the first week of the menstrual cycle, that many women are very prone to hormonal headaches. Hormonal headaches, not because estrogen's high, that's a common misconception, rather because estrogen and progesterone are both low. And now that you understand the contour or the under- underlying reasons for hormonal headache, you can start to ask, "Well, what happens when estrogen is low?" Well, estrogen has strong impact on the vasodilation/vasoconstriction system, as does progesterone. We'll talk about that a little bit later. But now that you know what hormonal headache is, at least this one particular type of hormonal headache, which is very, very common given the number of women that are menstruating and the fact that low estrogen, low progesterone is the cause of the hormonal headache, and the fact that, of course, there are women who are no longer menstruating, so they're either in perimenopause and menstruation is becoming more infrequent or they're in menopause and it has ceased entirely. Well, now you understand what the origin of the hormonal headache is, and so all we need to know is what do estrogen and progesterone normally do in order to prevent headache? And thereby, you'll know exactly how to offset, that is prevent or treat, hormonal headache in that first week of the menstrual period. The last

Andrew Huberman 53:38 type of headache that I'd like to discuss is headache associated with head hits, that is traumatic brain injury. Although I definitely want to underscore the fact that even people who do not have traumatic brain injury can experience headaches as the consequence of hitting their head. So the line between traumatic brain injury and lower-level brain injury is one that still seeks definition. In fact, this is one of the major goals of the clinical field as it relates to concussion. You know, it's also what comes up a lot during the discussion about football. You know, these days you'll see players hit really hard and depending on whether or not they're laying there for five seconds, 30 seconds, or three minutes, you know, the crowd and the, uh, people watching on television and everywhere else are all speculating as to whether or not the person should be allowed to play. And to be quite direct, there really is no way to assess the extent of brain damage after the consequence of hitting one's head or having one's head hit because first of all, almost all of the best ways to detect traumatic brain injury, except the most severe ones, tend to require a lot of very large equipment like MRI and functional MRI and CT scans, none of which are available on the side of the field or in the locker room. But also because many, many, if not most of the effects of traumatic brain injury are going to occur not in the immediate minutes or even hours after the injury, but several hours, days, or even weeks after that injury. This is a discussion that we should hold off for a longer full episode on traumatic brain injury, keeping in mind, of course, that football is this very salient example of traumatic brain injury and concussion, as is boxing, as is even soccer with heading of the ball. Believe it or not, repeated low-level impact to the forehead and other parts of the head, um, can give rise to, over time, traumatic brain injury without the need for any kind of full-blown concussion or being, quote-unquote, "knocked out." But sports-related concussion actually occupies just a tiny fraction of the majority of traumatic brain injury and concussion. Most traumatic brain injury and concussion and low-level brain injury that can accumulate over time to become traumatic for sake of daily living, that is lowered cognition, disruption in mood, sleep, et cetera, is actually the consequence of things other than sports. So for instance, bicycle accidents, playground accidents, construction accidents, and this is often forgotten. For some reason, all the sports, and in particular football, tend to grab all the attention as it relates to concussion. Keep in mind that while, uh, for certain people is a-... path to a, a living. For most people, traumatic brain injury is going to occur in a car accident, construction work, or other types of work for which people generally don't have many options in terms of the type of work that they're doing, so they are prone to concussions and head injuries t- simply by virtue of their work without any, you know, millions of dollars contracts or the opportunity to necessarily, some cases they do, but necessarily to do other things. And certainly car accidents or bike, bicycle accidents are not, uh, voluntary events. So the point being traumatic brain injury and headache-related ch- traumatic brain injury extends far beyond the realm of sports, and in fact, if you were to look at the numbers, what you find is that more than 90% of traumatic brain injury, so people coming into the hospital or clinic, or people, um, claiming that they've got consistent headaches, uh, they're not sleeping well, their mood is off, they're feeling more irritable after having hit their head even once, is not the consequence of sports. It's going to be the consequence of accidents, uh, either on, uh, at the workplace or, uh, in terms of a bicycle or other sorts of transportation-based accident like a car accident. With that in mind, any kind of head hit, certainly if it involves a concussion or traumatic brain injury, often leads to headaches, either infrequent but severe headaches or chronic low-level headaches or a feeling that there's kind of a stuffiness or a fullness to the head. There can be a lot of different origins to that. A common origin is going to b- actual swelling of the, not necessarily the brain tissue directly, but if you recall our discussion about the meninges, which include the dura and the other tissues that surround the brain, there are actually three layers that we call the, the meninges, the dura just being one of them, and there's a very little space between those, the brain, the meninges that surround it, and the skull, and it's called the subarachnoid space, very cool, right? Arachnoid like spider. Well, if there's even a slight bit of swelling in the brain or even distant brain tissue, so for instance, even if the- there's whiplash, so there's swelling of the tissue, muscular tissue and neural tissue in the neck area, that can constrict the flow of things like cerebral spinal fluid, blood flow, and indeed mucus and other, other things that are essential. We all hear mucus and we think illness, but mucus is a vital, vital (laughs) um, uh, substance within the body for a lot of important reasons in health as well as in sickness. Well, if there's less of that liquid and other fluids and mucus being delivered to that space, well then it can clog up. So sort of the plumbing is clogged up or that it's caught at the level of the site of hit or injury because there's some local swelling and inflammation there. So there are many different mechanisms that can underlie headache associated with head hits or traumatic brain injury. Now fortunately, there's some recent data pointing to some what I would call non-obvious treatments for headache in traumatic brain injury. Keeping in mind that anytime we're talking about injury or disease or health for that matter, mental health or physical health, we have to highlight a fact that's going to come up again and again in every single episode of this podcast, and I think it's not, um, being overly redundant to do so, which is that regular sufficient amounts of deep sleep each night are going to be important for all aspects of mental health, physical health and performance and have been shown over and over again to reduce the frequency of headache and to reduce the time to repair after traumatic brain injury and can improve cognition and on and on and on. So sleep is essential for all the normal things that encourage healthy activity of the different tissues that are involved in brain and body to occur. So sleep deprivation, of course, is going to limit those. But I do want to point out that sleep, sunlight, and I've talked about this almost ad nauseum on this podcast, but regular circadian cycles, getting sunlight in your eyes early in the day and in the evening as well and as much as possible throughout the day without burning your skin and limiting your exposure to artificial lights at night and on and on, all of which is covered in the Light for Health episode of the Huberman Lab Podcast, the Master Your Sleep episode of the Huberman Lab Podcast, and in the Perfect Your Sleep episode of the Huberman Lab Podcast. You can find all that at hubermanlab.com. Getting light and avoiding light at the proper times of the 24-hour cycle is also going to favor all the pathways ranging from gut-brain access to the inflammatory, anti-inflammatory pathways, neural pathways, et cetera, that of course if you do that, you're going to improve and offset any kind of detriment caused by traumatic brain injury. Is it treating traumatic brain injury directly? No. But is not getting sufficient sleep, not getting sunlight at the right times of day and getting too much artificial light at night going to make any impact of traumatic brain injury including headache far worse? Yes. There are certainly a ton of data to support that statement as well. And then of course nutrition and exercise are also important. So we can list out sleep, sun, proper nutrition, exercise, and I would p- uh, proper social connection, whatever that means to you. Healthy social connections include romantic, friendship, familial, and relationship to self. Those five things, sleep, exercise, sun, nutrition, and social connection, are all critical for maintaining baselines of health and raising your baselines of health. And I mention that, I kind of segment this out now because I think that anytime we're about to start discussing pointed treatments, that is things that you can take or do to reduce headache or things that you can take or do to improve anything within mental health, physical health and performance, we have to remember that the foundation of mental health, physical health and performance is only set at its highest level by tending to those other things and that nothing really surpasses any of those things. Or put differently, there's no replacement for any of those things in the form of a f- pill, a powder, even a behavioral practice. There are things you can do to offset getting less than ideal sleep, there are things that you can use like bright artificial lights during the day to try and partially offset lack of sunlight, but really there is no exercise pill. There is no sunlight, uh, device, although some bright lights are very bright, there's n- no replacement for actual sunlight. There's no replacement for actual sleep. There's no replacement for actual nutrition. And I do feel it's an important conversation to have as we head into the next segment, which is what

Andrew Huberman 1:02:08 can you take or do to reduce headache? And in order to address this, we're going to start first with the headaches associated with head hits and traumatic brain injury-... because turns out there's a surprising and very useful approach to doing that. But this same approach also can help offset and treat headache in other conditions as well, meaning not just for headaches caused by traumatic brain injury, but also headaches caused by sudden-onset tension headache or migraine headache, or even perhaps, again, perhaps, cluster-type headaches. So the first substance that I'd like to highlight that has been shown to significantly reduce the intensity and/or frequency of headaches is creatine. Now, creatine, as many of you know, is something that people supplement and take. Most often, creatine is discussed in the context of muscle performance, not just for people who weight lift, but for people who do endurance exercise. And it's often been said that 5 to 10 grams per day of creatine monohydrate, depending on how much you weigh, 5 to 10 grams per day of creatine monohydrate can increase creatine phosphate stores in muscles, can bring more water into muscles, can make you stronger, get increased power output, and that is all true. That is all completely true. We discussed this in the Huberman Lab Podcast with Dr. Andy Galpin when he was a guest on the, uh, Huberman Lab Podcast or standard series, and we discuss this extensively in an upcoming episode from Dr. Andy Galpin in his special six-part guest series where he is a guest on the Huberman Lab Podcast, but where really he's the one doing the majority of the teaching. That series covers everything from strength, hypertrophy, endurance, and there's an episode on supplementation where we go deep into the discussion about creatine. Now, in that discussion, and again now, we highlight the fact that creatine, while most often discussed online and in the media as a supplement for sports performance for the reasons I just mentioned, actually has far more data behind it, that is, laboratory studies exploring the role of creatine in the clinical setting. So I'd like to highlight a paper from that literature now that will make very clear as to why creatine is interesting and, in fact, very effective for treating headache, in particular headache caused by head hits or traumatic brain injury. The title of the paper is Prevention of Traumatic Headache, Dizziness, and Fatigue With Creatine Administration. Now, keep in mind this is a pilot study. It was performed in humans, so when you hear the words pre-clinical, that is if you hear, "There was a pre-clinical study on blank," that means almost always that the study was performed on animal models, mice, rats, primates, et cetera. A clinical trial is something that's carried out on humans, and a pilot study means that the study was carried out on humans but on a fairly small cohort, a very s- fairly small group, uh, or s- limited number of subjects. Nonetheless, if the data are robust, as it is in this case of this paper, I think it's worth paying attention to. So in this study, what they looked at was creatine administration. So what they did is they had people ingest a certain amount of creatine, I'll tell you in a moment, in fluids, so it could be taken in water or milk with or without food, doesn't really matter what time of day. They had people take creatine. Why would they have people take creatine after traumatic brain injury and in particular for people that are suffering from headache, dizziness, fatigue, et cetera? The reason is that neurons, nerve cells, rely very heavily on the regulation of calcium in order to generate those action potentials to communicate with one another. So it doesn't matter if it's a motor neuron, a sensory neuron, or a modulatory neuron, they all generate action potentials or something similar to it, and calcium is important for that process. Calcium becomes dysregulated after traumatic brain injury in a number of different ways, in particular in ways that impact the energy production systems of cells that are related to ATP, adenosine triphosphate, for those, uh, aficionados out there that want to look it up. You can simply look up calcium, ATP, and neurons, and you can learn about that cycle. Creatine can be stored in muscles, as we talked about before, but creatine, and in particular the phosphorylated form of creatine, which is the readily available fuel source form of creatine, can also be stored in brain tissue and is actually quite prominently stored in the forebrain, the area or the real estate of, of your brain just behind the forehead which is involved in planning and action and understanding context. So it's very important for cognition. It's important for personality too. It's important for a number of different aspects of life that have to do with making plans, being able to focus very intensely on your work, et cetera, or on anything for that matter, all functions that become heavily disrupted in people who have traumatic brain injury and concussion. Creatine's ability to communicate with the calcium and the ATP system was the motivation behind this study. That is, the authors hypothesized on the basis of pre-clinical data in animals that by increasing creatine stores within the brain, not just in the muscle, but in particular within the brain, that the availability of creatine would allow for better cognitive function in general. Now, they didn't look at cognition specifically in this paper, but they did look at the other aspects, that is, the, the bad stuff associated with TBI, and they had people supplement with creatine at a level that is much higher than the typical level that people supplement with creatine simply for sports performance. So as I mentioned before, most people, if they supplement with creatine for sports performance, they take creatine monohydrate, typically 5 grams per day, sometimes 10 grams per day if they're about 100 kilograms or, or greater in body weight. 100 kilograms is 200, approximately 220 pounds. So the dosage that was used for s- supplementing creatine in this study to address the potential impact of creatine on headache, dizziness, and fatigue was quite a bit higher than the dosages used simply for muscle performance. In this study, they had people take a dose of 0.4 grams of creatine monohydrate per kilogram of body weight. So for somebody that weighs 100 kilograms or 220 pounds, that would be 40 grams of creatine per day. If someone weighs half that much, they would take w-... 20 grams of creatine per day. And they did that over a period of six months. And we know that when you take creatine over and over, day-to-day, that there's a buildup of creatine stores both in the muscles and within the brain tissue. Now, what they found as a consequence of this creatine administration was really striking and I think quite exciting. They found a very significant decrease in the frequency of headache in people that were supplementing with creatine as opposed to the controls. Now, keep in mind that this is a pilot study, but the effects are very dramatic. They found a very statistically significant decrease in the frequency of headache in people that were taking creatine. In fact, if you look at the controls and you see that they're basically getting headache at a frequency of 90% or more after TBI, the reduction in headache frequency is down to about 10 or 12% in the people taking creatine. So that's quite, quite a dramatic effect. And if you look at the other measures they took, keep in mind again, this is a pilot study, so a limited number of subjects, but again, the results are very impressive. What they found is that the number of people experiencing dizziness was significantly reduced in people supplementing with creatine, as was the number of people experiencing fatigue, kind of acute fatigue and chronic fatigue. Again, not chronic fatigue syndrome per se, but chronic fatigue, which was in this study defined as a general sense of bodily weakness and even mental weakness. Mental weakness is a little bit hard to quantify, but, um, they were very careful to distinguish between cognitive and mental fatigue versus physical and somatic fatigue. Um, they acknowledged that both of those occur in TBI or post-TBI. The headache is quite frequent. Basically, the takeaway of this study is that for people experiencing headache, dizziness, and fatigue due to TBI and perhaps, and I want to underline perhaps because it hasn't really been explored yet, but perhaps headache, dizziness, and fatigue due to other conditions, symptoms or causes of headache, creatine monohydrate supplementation might be, again, might be an excellent candidate for people to try. Why do we say that? Well, first of all, creatine monohydrate is relatively inexpensive. It's considered safe at the dosages used in this study and, uh, certainly for sports performance as well. And there are very few other compounds that have been shown to have as significant an impact on headache over the long term as has creatine monohydrate in these studies of people with TBI. It's also important to highlight the fact that many, many people suffer from TBI, as I mentioned earlier, and as now, there are very few treatments for TBI. You tend to get the basic advice coming back, and I, again, I think it's excellent advice, you know, get proper amounts of sleep, get exercise, but don't get another traumatic brain injury. That's obvious, but you'd be surprised how many people go right back to work because they have to and, you know, we have to be sympathetic to the fact that many people just can't stop working or go on disability, so many people have to go back to work. That could be sport or it could be other kind of work where they are then subject to perhaps getting more TBI, maybe they're getting less rest as a consequence, and stress. Obviously stress is a, uh, confounding issue for TBI. But sleep, exercise, sun, nutrition, all of those things, proper social connection, are what people are encouraged to do when they have TBI, but there have been very few compounds, in particular very few over-the-counter compounds, that are known to be safe that have shown efficacy in dealing with TBI. So I think that while this is a po- uh, pilot study and, uh, we can consider it preliminary, I think, um, it's important enough and the effects were dramatic enough that people with headache, and in particular people with TBI, ought to consider supplementing with creatine in order to deal with their headaches. And of course, I eagerly await other studies exploring the role of this high dosage of creatine, or I should say relatively high dosage of creatine monohydrate, for offsetting headache. Meanwhile, I think there are a number of people out there suffering from headache, um, who might consider using creatine monohydrate in an exploratory fashion and seeing whether or not it helps offset their headaches. Keep in mind, of course, any time you're going to add or remove anything, uh, supplement or otherwise, from your, uh, from your treatment, your nutrition, et cetera, I do suggest that you consult with your physician, in particular if you have chronic headaches. I don't say that to protect me. I say that, of course, to protect you.

Andrew Huberman 1:12:22 I'd like to take a brief break and thank our sponsor, InsideTracker. InsideTracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. I've long been a believer in getting regular blood work done for the simple reason that many of the factors that impact your immediate and long-term health can only be analyzed from a quality blood test. The problem with a lot of blood and DNA tests out there, however, is that you get data back about metabolic factors, lipids and hormones and so forth, but you don't know what to do with those data. InsideTracker solves that problem and makes it very easy for you to understand what sorts of nutritional, behavioral, maybe even supplementation-based interventions you might want to take on in order to adjust the numbers of those metabolic factors, hormones, lipids, and other things that impact your immediate and long-term health to bring those numbers into the ranges that are appropriate and indeed optimal for you. InsideTracker's ultimate plan also now includes a measure of apolipoprotein B. Apolipoprotein B, sometimes also called apoB, has emerged in recent years as among the most important measures to evaluate your overall levels of cardiovascular health and health overall, and that's because apolipoprotein B levels are predictive of cardiovascular function, disease, and things that cardiovascular function and disease can impinge on, including brain health and longevity. If you'd like to try InsideTracker, you can visit insidetracker.com/huberman and get 20% off any of InsideTracker's plans. That's insidetracker.com/huberman

Andrew Huberman 1:13:55 to get 20% off. What I'd like to discuss next, I find extremely exciting. Why? Well, what I'm about to describe is a compound, or I should say a set of compounds, that are available over the counter that have been shown to be very effective in reducing the frequency and intensity of headaches, and not just one kind of headache, but multiple types of headaches. So, what I'll describe has been shown to have significant effects in reducing the intensity or frequency of tension-type headaches, migraine-type headaches, as well as hormone-type headaches that are related to the menstrual cycles that I described earlier. Now, there are a lot of data centered around this general topic, but I'm gonna focus on three main papers.... what I haven't told you yet, of course, is what is the compound that I'm referring to? What is this over-the-counter compound? Well, it turns out this over-the-counter compound is not just available over the counter, it's also available in food. So it turns out that nutrition can have a very strong impact on the frequency and intensity of headache, although supplementation with this particular compound can accomplish the same thing as well. What I'm referring to here are omega-3 fatty acids. Many of you are probably familiar with omega-3 fatty acids. These are (smacks lips) fatty acids that come in the form of so-called EPA and DHA, and omega-3 fatty acids are commonly distinguished from the so-called omega-6 fatty acids. Omega-6 fatty acids come in a bunch of different foods, and they, of course, can be supplemented as well. Omega-3 fatty acids come in a bunch of different foods and can be supplemented as well. Common forms of omega-3 fatty acids, or I should say common sources of omega-3 fatty acids in foods include fatty ocean fish, including salmon, salmon skins, sardines, anchovies, things of that sort. Common sources in supplement form are so-called fish oil capsules or liquid fish oil. Again, omega-3 fatty acids and almost always when we're talking about omega-3 fatty acids, we're talking about a combination of EPA and DHA, but really, it is the quantity of EPA omega-3 fatty acids that seems to be the most impactful for the sorts of health metrics that we're going to talk about in a few minutes. (smacks lips) Now, with respect to omega-6 fatty acids, the most typical food sources of omega-6 fatty acids are seed oils. I know nowadays seed oils have become quite controversial. I've given my stance on this in a, a prior podcast, but I'll just repeat it for those of you that haven't heard it. I am not of the belief that all seed oils are bad, that they're all inflammatory, that they are killing us or making us sick, uh, that they are the major cause of metabolic dysfunction, et cetera. However, I think it is very clear, and I learned this from Dr. Layne Norton when he was a guest on this podcast and taught us all about nutrition, um, in great depth, I, I highly recommend that episode if you're interested in nutrition, that people are consuming a lot more oil generally, and a lot of those oils that people are consuming more of nowadays include a lot of the so-called omega-6 fatty acids, and a lot of those oils are seed oils. The particular omega-6 fatty acid that's going to be relevant for today's discussion is linoleic acid, and that is common in a lot of seed oils. So again, I'm not going to tell you that seed oils are bad, however, it does seem to be the case that many people are consuming far too many seed oils, and in doing so, are consuming far too many calories, and perhaps are consuming too much of the omega-6 fatty acids relative to the omega-3 fatty acids. Now, with that said, I think there is general agreement among nutritionists and health professionals that we could all stand to get more omega-3 fatty acids, perhaps for cardiovascular health, although that's a little bit debated, but certainly for immune system function, for mood, and for