Andrew Huberman explains how to control dopamine, epinephrine, serotonin, and acetylcholine for focus, energy, and well-being
A solo presentation by Andrew Huberman on the neuroscience of brain chemistry and practical tools to optimize it.
Summary
Andrew Huberman, neuroscientist and professor at Stanford School of Medicine, presents a framework for understanding and controlling the four key neuromodulators — dopamine, epinephrine, serotonin, and acetylcholine — and how they govern motivation, energy, focus, and well-being. He organizes the day into three phases based on the natural rise and fall of these chemicals, arguing that any tool used to manipulate brain chemistry will be more or less effective depending on which phase of the day it is applied. He covers behavioral, nutritional, and supplementation-based approaches for each neuromodulator, including deliberate cold exposure for dopamine, cyclic hyperventilation for epinephrine, alpha-GPC and huperzine (and, with caveats, nicotine gum) for acetylcholine, and receiving or observing gratitude for serotonin. He also highlights myo-inositol (900 mg every third night) as a personally tested serotonin-supporting supplement he reports improves sleep depth and quality — noting it had not been previously discussed on the podcast. Throughout, he emphasizes building a flexible personal toolkit rather than relying on any single intervention, and cautions those on prescription medications to consult their physicians before adding or removing anything from their protocol.
Key Takeaways
FULL TRANSCRIPT
Introduction: The Nervous System, Neuromodulators, and the Framework for Today
Andrew Huberman: 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 it for all aspects of mental health, physical health, and performance. The important thing to know is that your brain, 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 feed back — meaning they communicate through chemicals and other means — to your nervous system. Vitally important is the fact that which neural circuits are active and which are likely to be less active at any given moment depends on two major categories of chemicals: hormones and so-called neuromodulators.
The four neuromodulators we're going to talk about today — the ones of utmost importance for your goals — are dopamine, epinephrine (also called adrenaline), serotonin, and acetylcholine. There are many features of how neuromodulators work, but for today's discussion we only need to focus on two: fast-acting features and longer, slower features, or what we call baseline features.
The Three Phases of the Day and Baseline Neuromodulator Levels
Perhaps surprisingly, I'd like to focus on the slow actions of the neuromodulators first, because those slow actions 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, the backdrop, or the baseline? Well, it's fair to say that most people are awake during the daytime and asleep at night. Schedules of sleep and wakefulness will vary, but in general, everybody — regardless of whether you're nocturnal or diurnal — follows a schedule in which from zero to nine hours after waking, the neuromodulators dopamine and epinephrine tend to be at their highest levels at any point in the 24-hour period. We can call this zero-to-nine-hour period Phase 1 of the day.
From nine to about sixteen hours after waking is what we will call Phase 2. That's when dopamine and epinephrine levels tend to subside a bit compared to Phase 1, and serotonin levels start to increase. Then Phase 3 of the 24-hour cycle — from about seventeen hours after waking until about twenty-four hours after waking — 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 Phase 1 and Phase 2: Phase 1 being the dopamine- and epinephrine-dominated phase of our day, and Phase 2 being the more serotonin-dominated portion.
You might say, "What 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 learning. Here I'm referring to acetylcholine specifically in the context of the brain and thinking, because as some of you are probably aware, acetylcholine is also used at the nerve-to-muscle synapse. The way you are able to move is because neurons are controlling the electrical 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 1 and Phase 2 to control dopamine, epinephrine, serotonin, and acetylcholine toward particular end goals.
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 are going to be able to leverage tools to optimize your brain chemistry.
How Hormones Interact with Neuromodulators
Before we dive into the more pointed, directed effects of specific tools on neuromodulators, I'd like to briefly mention hormones, because they are also important for understanding the background, 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 and some are very slow.
Today we want to think about hormones as they relate to dopamine, serotonin, epinephrine, and acetylcholine. 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 acetylcholine, which doesn't need much help from the hormone systems — 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, you can create a sort of kit, a grab bag of things that you can use depending on the context you're in, and create the states of body and mind that you want.
What Each Neuromodulator Does
Painting with a broad but accurate brush: dopamine, when elevated above baseline, tends to increase states of motivation — both mental and physical — drive, and to some extent focus.
Epinephrine and a closely related molecule called norepinephrine — and I want to emphasize that epinephrine is adrenaline and adrenaline is epinephrine; norepinephrine is noradrenaline and noradrenaline is norepinephrine — that category of neuromodulator is mainly responsible for generating our energy, our level of fuel, and what I like to call baseline forward center of mass. When epinephrine levels are high, we tend to feel agitated, like we want to move, like we can't shut down our thinking and our anticipation of what's going to happen next. When epinephrine levels are very low, we have less physical energy and less mental energy in terms of generating thoughts quickly.
The neuromodulator serotonin creates a number of different states in the brain and body, but for today's discussion we're going to think about its predominant states: contentment, happiness, feeling fairly relaxed, feeling soothed, and to some extent relief from pain. Serotonin is associated with a feeling of satiety — of having enough of what we already have.
Acetylcholine is mainly associated with states of focus, and we can go a step further and say it's mainly associated with focus as it relates to learning and encoding new information — so-called neuroplasticity.
Tools for Increasing Dopamine
So let's say you want to be more motivated, more in pursuit of goals, and you want to have more energy and focus. There are many ways to go about that — everything from prescription drugs to illicit drugs, which I certainly do not recommend, to supplements, nutrition, music, and all sorts of cognitive and behavioral tricks. But what you're really after are increases in dopamine above baseline that you control, and science tells us which tools are going to be the most potent and the most versatile.
I'm going to share those tools now, with the caveat that each one could be its own entire podcast episode, and we've done near-entire episodes on each of these tools or small collections of them. So I'm going to cover these in a somewhat superficial manner.
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 — nearly every day, if not every day. Here again we come to sunlight. Not just the desire to, but really the need for viewing the maximum amount of sunlight that one can reasonably get, given schedules, locations, time of year, and so on, 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 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 — blinking is fine — but take sunglasses off, go outside once the sun is out, and get some natural light in your eyes.
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 number of dopamine receptors you have, which allows whatever circulating dopamine happens to be there to have a greater effect on motivation, mood, and feelings of being in pursuit of things in life.
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 efficacy of dopamine receptors. 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 increases your levels of adrenaline and epinephrine, which increases your energy levels. It decreases levels of adenosine, which builds up while you're sleepy, making you feel less sleepy and more alert. That's obvious. What's less obvious is that it's increasing the number and efficacy of dopamine receptors, so that whatever dopamine happens to be in your system is going to have a more potent effect.
So these are ways of modulating the baseline of dopamine that you are able to produce, and the ways that dopamine can have its action by 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, and focus. If you're somebody who is taking drugs for depression or mania, please be very cautious about manipulating your dopamine. I say that to protect you.
If we 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 readily available without a prescription — are mucuna pruriens, L-tyrosine, and phenylethylamine.
Mucuna pruriens is actually the outside of a velvety bean that has been extracted and put into a supplement. It is actual L-dopa — it's 99% L-dopa, which is a prescription drug given for Parkinson's and for other purposes where increasing dopamine is important. I don't recommend mucuna pruriens. I'm not saying 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 but significant way are L-tyrosine — you can buy that as a supplemented amino acid. People vary tremendously in their sensitivity to supplementing L-tyrosine. I know people who can take two grams. I know people who can barely take 100 milligrams. I know people for whom the best dose is zero milligrams. There's a lot of variation depending on sensitivity and natural baseline levels of dopamine and whether or not they're doing a lot of other things to support dopamine. But taking L-tyrosine will lead to fairly substantial increases in dopamine within about 15 to 45 minutes, lasting about 30 minutes to two hours, and then there's a tapering off. Some people experience a little bit of an energetic crash; some people don't.
The other supplement that I use and that I know a number of other people use is more fast-acting but more potent: phenylethylamine. This relates to the so-called PEA molecule. Phenylethylamine increases dopamine and some metabolites related to dopamine in ways that really increase energy, feelings of well-being, and motivation. It's fast-acting. My particular protocol is to take phenylethylamine at dosages of about 300 to 600 milligrams along with some L-tyrosine, or to take it on its own alongside a compound we'll talk about a little bit later as it relates to acetylcholine — alpha-GPC. L-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 physical or cognitive.
Leaving supplementation aside, there are certain behavioral protocols that are unrelated to your overall goals and motivations but that can increase dopamine in a very sustained way. Without question, the most potent behavioral tool for doing that is deliberate cold exposure. Deliberate cold exposure has been talked about a lot in terms of its ability to reduce inflammation, and 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 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.
The use of cold water for increasing dopamine is a real tool — I would say a power tool. I want to briefly return to the fact that all of that is riding on that Phase 1 and Phase 2 background. It's probably going to take 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 now as to why that's the case.
Does that mean you should dramatically modify your protocols? Probably not. But you might keep in mind that if 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 more of these tools in combination to accomplish that. Whereas if you're somebody who feels pretty good during the day but is lacking motivation and doesn't yet want to resort to prescription drugs or supplementation, you might layer in a couple of behavioral protocols — paying attention, of course, to the things you might be doing that could also suppress dopamine.
That kit of tools is designed for you to play with. Consider doing them individually rather than throwing all those tools at your dopamine system at once. Better to have those tools in your kit and be able to deploy them depending on whether you're traveling, whether you're eating well or less well, whether you're sleeping well or less well. That's highly individual.
Tools for Increasing Epinephrine
Next, I'd like to talk about epinephrine, also called adrenaline. Epinephrine is released both in the brain and the body. There's a barrier between brain and body that prevents the epinephrine released from your adrenal glands from crossing the blood-brain barrier. So your brain has a separate site called the locus coeruleus — a collection of neurons in the back of the brain that essentially sprinkles the rest of the brain with epinephrine and wakes up whatever neural circuits happen to receive it, generally increasing 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, but really energy and the desire to move.
For many people, increasing adrenaline or epinephrine might seem like a crazy idea. Most people probably associate this molecule with stress and would like to be less stressed. But there are people — including me — who want to increase our levels of epinephrine, at least early in the day. I'm somebody who wakes up rather slowly. I tend to be thinking about thinking about maybe being in action early in the day. But I try to push myself to get into action, which itself can increase epinephrine.
Any physical activity — walking, running, weightlifting, swimming, even talking — is going to increase levels of epinephrine. The locus coeruleus is a brain structure that is tightly coupled with behaviors in a bidirectional way. When you are in action, you increase the amount of epinephrine released from the locus coeruleus, which wakes up the brain. And conversely, when the locus coeruleus is active, the brain wakes up. So it goes both directions. Exercise does indeed give you energy — it burns caloric energy, but it gives you neural energy by way of increasing epinephrine transmission from the locus coeruleus.
So we have exercise and 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 tummo breathing, which is very similar, and Kundalini breathing. All of those styles involve cyclic hyperventilation — deep inhales and either passive or active exhales, repeating inhale, exhale, inhale, exhale in a very deep and repetitive way. If you did that for 25 repetitions — 25 inhales and exhales — you would feel more alert. You'd also feel warmer. Why? Because you've increased epinephrine and 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, have more energy, and 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 who are prone to panic attacks might want to be cautious about how they approach that type of breathing — 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, thinking more clearly, and more wide-eyed and alert because you are releasing adrenaline.
The cold water exposure protocol I talked about earlier also potently increases epinephrine in addition to dopamine.
We can't really say that there are foods to increase epinephrine. There are of course prescription drugs that will increase epinephrine, and there are so-called beta blockers that will block the receptors for epinephrine to make you feel calm for public speaking or for various heart conditions — but that's really the domain of physicians and should be worked out with your cardiologist or a physician.
The tools of exercise — and for very potent increases in adrenaline, high-intensity exercise — as well as caffeine, cyclic hyperventilation, and deliberate cold exposure combine to give you a versatile kit of ways to increase epinephrine for the sake of having more physical and mental energy.
Tools for Increasing Acetylcholine
Next is the neuromodulator acetylcholine. As I mentioned earlier, acetylcholine is associated with states of focus. Those states can be high-energy states of focus — the ones accompanied by high levels of dopamine and epinephrine, where we're really excited and really lasered in on something — or they can be the calmer, more relaxed states of focus, like reading a book, practicing music, or listening very carefully to somebody in a way that's relaxed and calm.
Ways to increase acetylcholine in a potent way include nutrition and supplementation. It is important to have baseline levels of acetylcholine be sufficiently high, 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. There are also other vegetables that contain choline. Depending on your dietary preferences and needs, you can select certain foods to get enough choline to synthesize sufficient baseline acetylcholine.
In the realm of supplementation, there are some excellent tools for increasing acetylcholine acutely — over the course of about 30 minutes out to about two to four hours. The most common of those molecules is actually nicotine. Nicotinic acetylcholine receptors are abundant throughout the body and brain — in various brain circuits and on muscle. 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. I definitely don't recommend it. It also activates addiction because of the ways it triggers the dopamine circuits. However, some people will chew nicotine gum or other nicotine-type gums as cognitive enhancers. Some people are very sensitive to ingested nicotine and feel absolutely terrible from it, but some people do use it in that way.
Supplements that I have used and do use for increasing acetylcholine are alpha-GPC and huperzine. Alpha-GPC is in the choline pathway such that more acetylcholine is synthesized after you ingest it — that's the general framework of how it works. Whereas huperzine is mainly in the enzymatic pathway; it tends to adjust how much acetylcholine is broken down and leads 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 phenylethylamine — either before workouts or cognitive sessions. It really sharpens my focus. 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.
Tools for Increasing Serotonin
So let's discuss serotonin. Serotonin, as I mentioned earlier, is associated with brain and body states of well-being, comfort, and satiety. Therefore, it 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, meaning if the dosages of those treatments go too high. People will, for instance, feel reduced appetite, reduced libido, increased lethargy, and so on. There is 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 of potency, but nonetheless in ways that can still impact our feelings of well-being in positive ways.
What sorts of things? Physical contact — things like holding hands, hugs, cuddling — can increase serotonin transmission and make people feel good. This shouldn't really come as a surprise.
There's also gratitude, and we did an entire episode about it. There's a lot of misunderstanding about gratitude. It turns out, first of all, that receiving — not giving — gratitude is what has the most potent effects on increasing serotonin and the activity of the brain circuits that involve serotonin and lead to increases in feelings of well-being. Receiving much more than giving gratitude is what activates those serotonin 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.
What about nutritional approaches to increasing serotonin? Just as we have L-tyrosine as an amino acid precursor upstream of dopamine synthesis, we have the amino acid tryptophan, which is upstream of serotonin synthesis. One simply has to go online and search for tryptophan-containing foods to discover that there are a lot of foods enriched in tryptophan that can lead to net increases in the amount of serotonin available in the brain and body.
One molecule that I've found to be particularly interesting and useful — and this is one I haven't talked about yet on this podcast — is inositol, in particular myo-inositol. Myo-inositol 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 myo-inositol every third night or so as a test of its ability to improve sleep, and the depth and quality of sleep I've been obtaining on myo-inositol is pretty remarkable.
Of course, 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 or prescription protocol.
Putting It All Together
That brings us to the end of this exploration of the neuromodulators dopamine, epinephrine, acetylcholine, and serotonin. Whether or not you're using nutritional tools, supplementation, prescription drugs, or any other sort of protocol to try and create a desired effect of focus, energy, motivation, or relaxation, you are playing with the same neurochemical ingredients.
What I'm hoping is that rather than deciding that any one tool is the most useful — or that any one neurochemical is most useful, for that matter — the information I've provided today allows you a kit of versatile tools that lets you figure out what levels of dopamine augmentation 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.
Thank you 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.