Control Your Brain Chemistry for Focus, Motivation & Well-Being | Huberman Lab Essentials

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Welcome to Huberman Lab Essentials where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance. I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today we are going to discuss your brain chemistry and how to control and optimize your brain chemistry for all aspects of mental health, physical health, and performance. The important thing to know is that your brain and your spinal cord and the rest of your so-called nervous system control all the organs of your body and that all the organs of your body feedback, meaning they communicate through chemicals and other means to your nervous system.

And vitally important is the fact that which neural circuits are active and which neural circuits are likely to be less active at any given moment, depends on two major categories of chemicals. It depends on hormones and it depends on so-called neuromodulators. And the four neuromodulators that we're going to talk about today that are of the utmost importance for your goals are dopamine, epinephrine, also called adrenaline, serotonin, and acetylcholine. There are many features of how neuromodulators work, but for sake of today's discussion, we only need to focus on two of those features. And those are fast acting features and longer, slower features or what we call baseline features.

Now, perhaps surprisingly, I'd like to focus on the slow actions of the neuromodulators first, because those slow actions of the neuromodulators are happening in you and in me and in everyone right now. And they set the backdrop, the context in which the various tools to manipulate dopamine, epinephrine, serotonin, or acetylcholine will work. What do I mean by the context or the backdrop or the baseline? Well, it's fair to say that most people are awake during the daytime and asleep at night. So schedules of sleep and wakefulness will vary, but in general, everybody, regardless of whether or not you're nocturnal or you're so-called diurnal, you're awake during the day, pretty much everybody follows a schedule in which from zero to nine hours after waking, that is from the time you wake up until about nine hours later, the neuromodulators dopamine and epinephrine tend to be at their highest levels that they will be at any point in the 24 hour period, in any period of the day.

So we can call this zero to nine hour period phase one of the day, just for simplicity. And I've referred to this before in a previous episode, but not in this exact context. From nine to about 16 hours is what we will call phase two. And that's when dopamine and epinephrine levels tend to subside a bit compared to the earlier phase one part of the day. And serotonin levels start to increase. And then phase three of the 24 hour cycle, which is from about, and again, about these zero approximates from about 17 hours after waking until about 24 hours after waking is phase three of the day.

We're not going to focus too much on phase three today because phase three of the 24 hour cycle, that 17 to 24 hour period is one in which you ought to be deeply asleep, whether or not you're nocturnal or diurnal. So we're mainly going to focus on what we're calling phase one and phase two. Phase one being this dopamine, epinephrine dominated phase of our day. and phase two being this more serotonergic or serotonin dominated portion of the day. And then you might say, well, what about acetylcholine? Forgot about acetylcholine. Well, we didn't forget about acetylcholine. Acetylcholine is under control more in terms of what we happen to be doing at any given moment, whether or not we're focusing or not focusing, whether or not we're learning or not learning.

And here I'm referring to acetylcholine specifically in the context of the brain and thinking, because as some of you are probably shouting out there, if you're exercise physiologist or you know anything about how the brain controls movement, acetylcholine is used at the nerve to muscle synapse. So neurons don't just control other neurons electrically. The way you're able to move in fact is because neurons are controlling the electric activity of muscles, literally the contraction of muscle fibers, and that control is exerted through the release of acetylcholine. So acetylcholine is working at muscles as well, but we're not focused on that today.

We're focused on what we can do during phase one of the day and what we can do during phase two of the day to control the specific neuromodulators, dopamine, epinephrine, serotonin, and acetylcholine toward particular end goals. So again, it's really important to understand what the backdrop of these neuromodulators is, the so-called baseline, and that they vary across the day if you're going to be able to leverage tools to optimize your brain chemistry. Before we dive into the more pointed, directed effects of specific tools on neuromodulators, I'd like to just briefly mention hormones because they are also important for understanding the background and the context and these baseline levels of neuromodulators.

Hormones have many different effects on the brain and body and not unlike neuromodulators, some of those effects are very fast, some of them are very slow. Today, we wanna think about hormones as they relate to these neuromodulators, the dopamine serotonin, epinephrine and acetylcholine. And in general, testosterone tends to collaborate with and increase the action of dopamine. That's not always the case, but in general, when testosterone goes up, dopamine goes up. In general, when corticosterones like cortisol and some related steroid hormones increase, epinephrine levels go up. And in general, when hormones like oxytocin or prolactin are increased, levels of serotonin go up.

And then we have poor old lonely acetylcholine off on its own, but it's not poor and lonely. It actually has incredibly potent effects on its own. So it's really that it just doesn't need much help from the hormone systems, or at least not the steroid hormone systems in order to have its tremendous effects. If you understand these four neuromodulators and you understand that while there are many tools ranging from pharmacologic to behavioral that can tap into these neuromodulator systems that can kind of press on the gas of dopamine, pull back on serotonin and so on. Well, then you can create a sort of kit, a grab bag of things that you can use in any context, or I should say that you can look to, depending on the context you're in, and create the states of body and mind that you want.

Now, once again, painting with a somewhat broad brush, but nonetheless an accurate brush, we can say that dopamine, when elevated above baseline, tends to increase states of motivation, both mental and physical motivation, drive and to some extent focus. Epinephrine and a closely related molecule called norepinephrine. And again, I want to emphasize that epinephrine is adrenaline and adrenaline is epinephrine. Norepinephrine is noradrenaline and noradrenaline is norepinephrine, but today we're going to just simply talk about epinephrine and norepinephrine. That category of neuromodulator is mainly responsible for generating our energy, our level of fuel and baseline level of forward center of mass, as I like to call it.

When epinephrine levels are high, we tend to feel agitated. We tend to feel like we want to move. We tend to feel like we can't shut down our thinking and our anticipation of what's going to happen next. And when epinephrine levels are very, very low, we actually have less physical energy. We tend to have less mental energy in terms of generating thoughts very quickly and so on and so forth. Now the neuromodulator serotonin creates a number of different states in the brain and body, but for sake of today's discussion, we're going to think about the predominant states that it creates.

And those are states of contentness, being happy, feeling fairly relaxed, feeling soothed, and to some extent, even some relief from pain or lack of pain. Serotonin is associated with a feeling of satiety, of having enough of what we already have. And acetylcholine, we can say, is mainly associated with states of focus. And we can go a step further and say that it's mainly associated with steps of focus as they relate to learning and encoding new information, so-called neuroplasticity. So let's say you want to be more motivated. You want to be more in pursuit of goals and you want to have more energy and to be more focused.

There are many ways to go about that. In fact, there's a near infinite cloud of opportunities, everything from prescription drugs to illicit drugs, which I certainly do not recommend, supplements, nutrition, you can listen to particular music, you can do all sorts of cognitive behavioral nutritional supplementation tricks, or you can just understand that what you're really after are increases in dopamine above baseline that you control. And there are ways to control them that are quite potent. And science tells us which tools are going to be the most potent and the most versatile for you. So I'm going to share those tools with you now with the caveat that each one of those tools could be its own entire podcast episode that we've done near entire episodes on each of these tools or small collections of these tools.

So I'm going to cover these in somewhat superficial manner. Let's say you want to increase dopamine for sake of increasing motivation. The first thing to do is to understand what the natural behavioral tools are for increasing dopamine and to do those as consistently as possible. Again, these are tools that you'll want to do nearly every day, if not every day. And I know I'm sounding like a broken record on this one, but here again, we come to sunlight and I should say not just the desire to, but really the need for viewing the maximum amount of sunlight that one can reasonably get given schedules and locations in the world, time of year, et cetera, in the early part of the day.

Within the first hour of waking, ideally, but certainly in the first three hours of your day, you're going to want to maximize sunlight exposure to your eyes. Never look at the sun or any other light so bright that it's painful to look at. And yes, of course, blinking is fine, but no, take sunglasses off, go outside once the sun is out and get some natural light in your eyes. So if you get sunlight exposure to your eyes and it does have to be to your eyes in the early part of the day, you increase the amount of dopamine receptor that you have which allows whatever circulating dopamine happens to be there to have a greater effect on a motivation and I should say also on mood and feelings of being in pursuit and generally in craving and pursuit of things in life.

Now there's another way to increase the effect of whatever dopamine happens to be circulating in your brain and body. And this again relates to increasing the number or the efficacy of the receptors for dopamine. How do you do that? Well, it turns out that regular ingestion of caffeine at safe and appropriate levels of about 100 to 250 milligrams is going to increase the number of D2 and D3 dopamine receptors. When you drink caffeine, it's going to increase your levels of adrenaline and so-called epinephrine, which will increase your energy levels. It's going to decrease levels of something called adenosine, which builds up while you're sleepy.

It's going to make you feel less sleepy, more alert, more energetic. That's sort of obvious. But what's less obvious is that it's increasing the number and efficacy of dopamine receptors so that whatever dopamine happens to be around in your system is going to have more of a potent effect. So these are ways of modulating more or less the baseline of dopamine that you are able to produce and the ways that dopamine can have its action by way of binding to receptors more potently. Now, there are other ways to increase dopamine in a more acute or directed way, ways to spike your dopamine to enhance your state of motivation, mood, focus, and so on.

If you're somebody who has or is taking drugs for depression or mania, please be very cautious about manipulating your dopamine in any case. I don't just say that to protect us, I say that to protect you. But if we were to look at the supplement landscape and ask which supplements increase dopamine, there are a vast number of them, but the three main ones, the most effective ones that are readily available out there without a prescription are macuna prurines. This is actually the outside of a velvety bean that has been extracted and put into a supplement. Macuna prurines is actual L-dopa.

It's 99% L-dopa, which is a prescription drug that is given for Parkinson's and for other purposes where increasing dopamine is important. I don't recommend macunapurines. I'm not saying that no one should take it, but I don't take it and I don't recommend it because it tends to so potently and acutely increase dopamine that there's a pretty substantial crash afterwards. The other two supplements that can increase dopamine in a short-term way, but in a significant way, are L-tyrosine, so you can buy that as a supplemented amino acid. People vary tremendously in their sensitivity to supplementing L-tyrosine. I know people that can take two grams.

I know people that can barely take a hundred milligrams. I know people that the best dose for them is zero milligrams. So there's a lot of variation there, depending on sensitivity and their natural baseline levels of dopamine and whether or not they're doing a lot of other things to support dopamine. But nonetheless, taking L-tyrosine will lead to fairly substantial increases in dopamine within about 15 to 45 minutes. And it lasts for about 30 minutes to two hours. And then there's kind of a tapering off. Some people experience a little bit of an emotional or and or I should say energetic crash.

Some people don't. And then the other supplement that I certainly use and that I know a number of other people use is more fast-acting, but more potent, which is phenylethlamine. This relates to the so-called PEA molecule. P-P-E-A, and phenylethylamine increases dopamine and some metabolites related to dopamine in ways that really increase energy and feelings of wellbeing and motivation. And again, it's fast acting. So my particular protocol, the one I use is I'll take phenylethylamine at dosages of about 300 to 600 milligrams, along with some L-tyrosine, or I'll take it on its own with a molecule, or I should say a compound that we'll talk about a little bit later as it relates to acetylcholine alpha GPC.

But tyrosine and phenylethylamine taken alone or together will make you feel more motivated and more alert, more willing and able to lean into particular motivated behaviors, whether or not they're physical or cognitive. But leaving that aside, there are certain behavioral protocols that are unrelated to your overall goals and motivations that can increase dopamine in a very sustained way. And without question, the most potent behavioral tool for doing that is going to be deliberate cold exposure. Deliberate cold exposure has been talked about a lot here and elsewhere in terms of its ability to do things like reduce inflammation as a way to test and improve resilience because uncomfortable cold provided it's applied safely is a great way to learn to be more resilient because you're essentially staying or forcing yourself to stay in a circumstance where your system is flooded with adrenaline.

As I mentioned before, dopamine tends to collaborate with epinephrine and vice versa. Many people will ask which protocols to follow. Please see the episode on the use of deliberate cold for health and performance. You'll find that at HubermanLab.com. So the use of cold water for increasing dopamine is a real tool. It's, I would say, a power tool. I want to just briefly return to the fact, however, that all of that is riding on that phase one, phase two background. meaning it's probably going to take less cold water exposure or I should say less time doing cold water exposure early in the day to get a big increase in dopamine than it would later in the day.

Because later in the day, your baseline levels of dopamine are lower and you've got more serotonin circulating. That should make sense to you now as to why that's the case. And does that mean that you should really modify your protocols dramatically? Probably not. But you might keep that in mind that if, for instance, you need to be in a highly motivated focused state in the late part of the day for whatever reason, it might take a few or more of these tools in combination in order to accomplish that. Whereas if you're somebody who feels pretty good during the day, but you're kind of lacking motivation and you want to increase dopamine levels and you don't yet need to or want to resort to prescription drugs or supplementation, well, then you might layer in a couple behavioral protocols, paying attention to, of course, the things that you might be doing that would also potentially suppress dopamine.

So again, that kit of tools is designed for you to play with if you choose, if it's safe for you to apply them, then do that. Consider doing them individually, not trying to hit all the tools all at once, right? I mean, why throw all those tools at your dopamine system at once? Better would be to have those tools in your kit and be able to deploy them depending on whether or not you're on travel, whether or not you're eating well or less well, whether or not you're sleeping well or less well. That's highly individual. And I like to think that in having those tools in hand, you'll be able to adjust them and apply them in the ways that allow you to access the dopamine increases that you're after.

So next, I'd like to talk about epinephrine, also called adrenaline. I want to point out that epinephrine is released both in the brain and the body. In fact, there's a barrier between brain and body that prevents the epinephrine that's released from your adrenal glands from crossing the blood-brain barrier. So your brain has a separate site called the locus coeruleus. This is a collection of neurons in the back of the brain that kind of sprinkler the rest of the brain with epinephrine. and essentially wakes up whatever neural circuits happen to see, or I should say, wake up any circuits where that epinephrine happens to arrive, right?

And generally increase the excitability of those networks. That's why we say epinephrine increases energy. I'm not talking about caloric energy, although that's distantly related to this, but really energy and the desire to move. For many people, increasing adrenaline or epinephrine might seem like a crazy idea. Most people will probably associate this molecule with stress and they would like to be less stressed. But there are people, including me, that want to increase our levels of epinephrine at least early in the day. I'm somebody who wakes up rather slowly. In fact, I tend to be kind of thinking about thinking about maybe being in action early in the day, but I try and push myself to get into action, which itself can increase epinephrine.

I should mention that any physical activity, any physical activity, walking, running, weightlifting, swimming, even talking for that matter, is going to increase levels of epinephrine. Locus coeruleus is a brain structure that is tightly coupled with behaviors in a bi-directional way. That is, when you are in action, you increase the amount of epinephrine released from locus coeruleus, you wake up the brain. And conversely, when locus coeruleus is active, the brain wakes up. So it's reciprocal, it goes both directions. So keep that in mind, exercise does indeed give you energy. It burns caloric energy, but it gives you neural energy by way of increasing epinephrine transmission from locus coeruleus.

So we have exercise and we have caffeine as potent tools for increasing epinephrine and thereby energy. Another potent tool that's purely behavioral, but is known to work based on excellent studies in humans is so-called cyclic hyperventilation. Some of you may be familiar with Wim Hof breathing. There's also tumo breathing, which is very similar, kundalini breathing. All of those styles of breathing involve cyclic hyperventilation, deep inhales and either passive exhales or active exhales, but repeating inhale, exhale, inhale, exhale in a very deep and repetitive way. So if you did that for 25 repetitions, 25 inhales and exhales, you would feel more alert.

You'd also feel more warm. Why? Because you increased epinephrine adrenaline release in the brain and body. It works the first time and it works every time to increase epinephrine and thereby energy. If you do that over and over, you're going to be very alert. You're going to have more energy. You're going to feel like you want to move around a lot more. In fact, you might even feel agitated. So people with a lot of anxiety or prone to panic attack might want to be cautious in how they train and embark on that type of breathing might want to approach it a little more carefully or avoid it altogether.

But for most people cyclic hyperventilation is simply going to get you more energized and feeling like you want to move, feeling like you can think more clearly and you will be more wide-eyed and alert because you are releasing adrenaline. And the cold water exposure protocol that I talked about earlier and that's covered in our episode on cold and in the newsletter on cold, well, that, as I mentioned earlier, potently increases dopamine, but also epinephrine. Now, we can't really say that there are foods to increase epinephrine. There are, of course, prescription drugs that will increase epinephrine. And of course, there are all sorts of so-called beta blockers that will block the receptors for epinephrine to make you feel calm for public speaking or for various heart conditions, et cetera.

That's really the domain of physicians and should really be worked out with your cardiologist, with a physician, et cetera. I think the tools of exercise and should you want very potent increases in adrenaline, high intensity exercise, as well as the tools of caffeine, cyclic hyperventilation and deliberate cold exposure really combined to give you a nice little kit, I would say a versatile kit of ways to increase epinephrine for sake of having more physical and mental energy. So next is the neuromodulator acetylcholine. And as I mentioned earlier, acetylcholine is associated with states of focus. And those states of focus can be high energy states of focus, so the ones that are accompanied by high levels of dopamine and epinephrine and where we're really excited about and really lasered in on something, or they can be the calmer, more relaxed states of focus, like reading a book or practicing music or listening very carefully to somebody in a way that's relaxed and calm.

Now, ways to increase acetylcholine in a potent way include, again, nutrition and supplementation. It is important to have baseline levels of acetylcholine be sufficiently high as well. And for that, the ideal situation is to regularly ingest foods that provide enough of the precursors for acetylcholine to be made. Eggs contain a lot of choline, beef contains choline, soybeans contain choline. So there are vegan or non-meat sources. Chicken, fish, mushrooms, kidney beans, these sorts of things contain a lot of choline. And there are other vegetables that contain choline. So depending on your dietary preferences and needs, you can select certain foods to ingest to get enough choline to synthesize enough baseline acetylcholine.

In the realm of supplementation, there's some excellent tools for increasing acetylcholine in the acute short term, meaning over the course of about 30 minutes out to about two hours or maybe even four hours. The most common of those molecules is actually nicotine. Nicotinic acetylcholine receptors are abundant throughout the body and brain. They're in various brain circuits. They are on muscle. And yes, smoking nicotine either by vaping or cigarette will activate those nicotinic receptors. But of course, smoking is a terrible thing. It will also activate things like lung cancer. So I definitely don't recommend that. It also activates addiction because of the ways that it triggers activation of the dopamine circuits.

However, some people will chew Nicorette or other nicotine type gums. Some people are very sensitive to ingested nicotine. Some people take it and feel absolutely terrible. but some people do use them as cognitive enhancers. Supplements that I have used and do use for increasing acetylcholine are things like alpha-GPC or hooperzine. Alpha-GPC is in the choline pathway such that more acetylcholine is synthesized after you ingest it. That's the general logic or framework of how it works. Whereas hooperzine is mainly in the enzymatic pathway. it tends to adjust how much acetylcholine is broken down and lead to net increases in acetylcholine. I will often take 300 milligrams of alpha GPC prior to workouts or prior to cognitive work bouts.

I tend to take it alongside caffeine and phenylethal amine. So I take that in combination either before workouts or workouts, really sharpens my focus. And again, I'm doing that three, maybe four times per week. And I'm careful to do that in the early part of the day so that it does not disrupt my sleep. So let's discuss serotonin. Serotonin, as I mentioned earlier, is associated with brain and body states of well-being, of comfort, of satiety, and therefore should come as no surprise that a lot of the prescription drug treatments for things like depression involve increasing levels of serotonin in the brain and body.

That said, anytime you talk about prescription drugs for serotonin, we also want to acknowledge that there are often side effects associated with increasing serotonin, In particular, if serotonin levels go too high, that is, if the dosages of those treatments go too high, people will, for instance, feel reduced appetite, reduced libido, increased lethargy, et cetera. And there's a so-called serotonergic syndrome. That said, there are behavioral tools, nutritional tools, and supplementation tools that can tap into the serotonin system, not to the same degree in potency, but nonetheless, in ways that can still impact our feelings of wellbeing in positive ways. What sorts of things?

Well, for instance, physical contact, things like holding hands, believe it or not, hugs, cuddling, et cetera, can increase serotonin transmission and they make people feel good. This shouldn't really come as a surprise. There's also gratitude, and we did an entire episode about gratitude. There's a lot of misunderstanding about gratitude. Turns out, first of all, that receiving, not giving gratitude, is what has the most potent effects on increasing serotonin and activity of the brain circuits that involves serotonin and that lead to increases in feelings of wellbeing. So it's interesting, receiving much more than giving gratitude is what activates those serotonergic pathways.

The other thing about gratitude that's somewhat counterintuitive is that observing others giving and receiving gratitude is immensely powerful for evoking serotonin and the activity of serotonergic circuits in you, the observer. So receiving and observing gratitude turns out to be the most potent way to increase serotonin in the brain and body. Now, what about nutritional approaches to increasing serotonin? Well, just as we have tyrosine as an amino acid precursor upstream of dopamine synthesis, we have the amino acid tryptophan, which is upstream of serotonin synthesis. And one simply has to go online and put in tryptophan containing foods. And you will discover that there are a lot of foods that are enriched in tryptophan that can lead to net increases in the amount of serotonin available in the brain and body.

Now, one molecule that I've found to be particularly interesting and useful, and this is one that I haven't talked about yet on this podcast, is inositol, in particular myoinositol. Myoinositol can have the effect of increasing serotonin and other neurochemicals, but primarily, at least in terms of the neuromodulators discussed today, serotonin. I've been taking 900 milligrams of myoinositol every third night or so as a test of its ability to improve sleep. And I have to say the depth and quality of sleep that I've been obtaining on myoinositol is pretty remarkable. And of course I should mention that no supplement, either added or withdrawn from your protocol should ever be used as a direct replacement for prescription drug treatments that your physician has given you.

You should always talk to your physician anytime you remove or add something to your drug protocol or prescription protocol, of course. And again, this is a general theme of all four of these neuromodulators, dopamine, epinephrine, acetylcholine, and serotonin. You want to make sure that you have sufficient baseline levels of those things through things like diet, regular behaviors, and then you have the opportunity to use supplementation. And if it's appropriate for you, prescription drugs and certain behavioral protocols to try and get these potent increases, these acute increases in whichever the neuromodulators you happen to want to leverage for your particular goals.

So that brings us to the end of at least this exploration of the neuromodulators, dopamine, epinephrine, acetylcholine, and serotonin. Whether or not you're using nutritional tools or supplementation or prescription drugs or any other sort of protocol to try and create a desired effect of focus or energy, motivation, relaxation, you're playing with the same neurochemical ingredients. So what I'm hoping is that rather than decide that any one tool is the most useful or that any one neurochemical is most useful for that matter, that the information that I've provided today allows you a kit of versatile tools that allows you to figure out what levels of dopamine and augmentation of dopamine are appropriate and necessary for you.

what levels of acetylcholine and tools for manipulating acetylcholine are going to be most useful for you and so on and so forth. So I'd like to thank you once again for joining me today in our discussion about these incredibly powerful molecules we call neuromodulators and the things we can do and take in order to control them so that we can enhance our mental health, physical health and performance. And last but certainly not least, thank you for your interest in science.