Controlling Your Dopamine For Motivation, Focus & Satisfaction

Andrew Huberman 0:00 (Instrumental 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 going to talk all about dopamine and what drives you to do the things that you do. We're going to talk about motivation and desire and craving, but also how dopamine relates to satisfaction and our feelings of well-being. And of course, any discussion about dopamine has to include a discussion about the potential for dopamine-induced addiction. Indeed, dopamine lies at the heart of addiction to all things. But today, we are mainly going to focus on how what we do and how we do it and how we conceptualize those things leads to changes in this amazing molecule in our brain and bodies that we call dopamine. I'm going to teach you what dopamine is and what it is not. There are a lot of myths about the molecule, dopamine. We often hear about so-called dopamine hits. Today, we are going to dispel many common myths about dopamine, and we are going to talk about how dopamine actually works. We're going to discuss the biology of dopamine, the psychology. We will discuss some neural circuits and a really exciting aspect of dopamine biology are so-called dopamine schedules. In other words, we are going to discuss how things like food, drugs, caffeine, pornography, even some plant-based compounds can change our baseline levels of dopamine, and in doing so, they change how much dopamine we are capable of experiencing from what could be very satisfying events or events that make us feel not so good because of things that we did or took prior. So, I promise you, it's going to be a vast discussion, but I will structure it for you, and you'll come away with a deep understanding of really what drives you. You will also come away with a lot of tools, how to leverage dopamine so that you can sustain energy, drive, and motivation for the things that are important to you over long periods of time. Before we dive into the meat of today's discussion, I'd like to share with you a fascinating result that really underscores what dopamine is capable of in our brains and bodies and underscores the fact that just through behaviors, no drugs, nothing of that sort, just through behaviors, we can achieve terrifically high increases in dopamine that are very long and sustained in ways that serve us. This is a result that was published in the European Journal of Physiology. I'll go into it in more detail later, but essentially what it involved is having human subjects get into water of different temperatures. So, it was warm water, moderately cool water, and cold, cold water. Had them stay in that water for up to an hour, and they measured, by way of blood draw, things like cortisol, norepinephrine, and dopamine. What was fascinating is that cold water exposure led to very rapid increases in norepinephrine and epinephrine, which is also just called adrenaline. It also led to increases in dopamine, and these increases in dopamine were very significant. They kicked in around 10 or 15 minutes after submersion into w- the cold water. And I should mention, the head wasn't below water. It was just up to the neck. And the dopamine release continued to r- to rise and rise and rise, and eventually reached 250% above baseline. Now, what was interesting is, after subjects got out of this cold water, that dopamine increase was sustained. And I know nowadays many people are interested in using cold water therapy as a way to increase metabolism and fat loss, but also to improve sense of well-being, improve cognition, improve clarity of mind. You know, there's something really special about this very alert but calm state of mind that seems to be the one that's optimal for pretty much everything except sleep. But for all aspects of work and for social engagement and for sport, that highly alert but calm state of mind really is the sweet spot that I believe most of us would like to achieve. And this cold water exposure, done correctly, really can help people achieve that state of mind through these increases in dopamine that last a very long time. So, I will later detail the specifics of that study, what it entailed in terms of how long the variations that different subjects experienced, as well as how to limit the amount of stress hormone, cortisol, that's released as a consequence of the cold water. And we will also talk about compounds, supplements that people can take in order to increase their levels of dopamine, should they choose. Before we begin,

Andrew Huberman 4:48 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 podcast. Our first sponsor is ROKA. ROKA makes sunglasses and eyeglasses that are of the absolute highest quality. I've spent a lifetime working on the visual system, and I can tell you that the visual system has to go through a lot of work in order to maintain clarity of what you see when there are shadows, when you go into different types of indoor lighting and so on. And a lot of glasses don't work well, because you put them on, and then you're in bright light, and you can see fine. But then you move into a shadow, and then you have to take them off, and they don't adjust, or they don't adjust quickly enough. 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Enter the code HUBERMAN at checkout.Today's podcast is also brought to us by 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'm a big believer in getting regular blood work done, and now with the advent of modern DNA tests, you can also analyze your DNA to see what you ought to be doing for your immediate and long-term health. We hear a lot these days about optimization, optimizing hormones, optimizing your metabolism, optimizing this, optimizing that. But unless you know the measurements of metabolic factors, hormones, and other things that are in your blood and DNA, you don't know what to optimize. With InsideTracker, it makes all of that very easy. They can come to your house to take the blood and DNA test, or you can go to a nearby clinic. 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I've been meditating for a long time, but I confess, sometimes I meditate, and sometimes I am very inconsistent about my meditation. Ideally, I would meditate every day for 20 or 30 minutes, but what I've found over the years is that I'll start a meditation practice, and then as life gets more stressful or busier, which is exactly when I need to meditate more, I tend to meditate less often. Switching over to Headspace as a meditation app really helped me stay consistent with my meditation practice. And that's because they have a huge range of meditations to select from. Some are short, some are longer, and in general, I try and get 20 minutes of meditation in every day. But some days it's just five minutes, and they have some terrific just five minute meditations. The science says that even a five minute meditation can be beneficial for different aspects of our brain and body. If you want to try Headspace, you can go to headspace.com/specialoffer. 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Andrew Huberman 9:10 I'd like to announce that there's an event that some of you may find very useful. This is an event put on by Logitech that I will be speaking at. It's called Rethink Education: The Biology of Learning, Reimagining Learning Through Neuroscience. And at this event I will be speaking. There will be other speakers as well. And I will be talking about neuroplasticity and its applications for teaching and for learning. I will describe what I call the plasticity super protocol that incorporates all of what we know about rapid learning, efficient learning, and the best ways to teach and learn. It's geared towards educators of all kinds. It is zero cost, so please feel free to sign up. The event is September 30th, 2021 at 3:00 PM Eastern. You can find the registration link in the caption for this episode.

Andrew Huberman 9:58 So let's talk about dopamine. Most people have heard of dopamine, and we hear all the time now about dopamine hits, but actually there's no such thing of, as a dopamine hit. And actually, the way that your body uses dopamine is to have a baseline level of dopamine, meaning an amount of dopamine that's circulating in your brain and body all the time. And that turns out to be important for how you feel generally, whether or not you're in a good mood, motivated, et cetera. And you also can experience peaks in dopamine above baseline. Now, this has a very specific name in the neurobiology literature, so-called tonic and phasic release of dopamine, and I'll explain what that means in a couple of minutes. But if you remember nothing else from this episode, please remember this, that when you experience something or you crave something really desirable, really exciting to you, very pleasurable, what happens afterwards is your baseline level of dopamine drops. Okay? So these peaks in dopamine, they influence how much dopamine will generally be circulating afterward. And you might think, "Oh, a big peak in dopamine, after that I'm going to feel even better because I just had this great event." Not the case. What actually happens is that your baseline level of dopamine drops, and I will explain the precise mechanism for that. Okay? In the neuroscience literature, we refer to this as tonic and phasic release of dopamine, tonic being the low level baseline that's always there circulating, released into your brain all the time, and then phasic, these peaks that ride above that baseline. And those two things interact, and this is really important. I'm going to teach you the underlying neurobiology, but even if you have no background in biology, I promise to make it all clear. I'll explain the terms and what they mean. And I'm excited to teach you about dopamine, because dopamine has everything to do with how you feel right now as you're listening to this, it has everything to do with how you will feel an hour from now, has everything to do with your level of motivation and your level of desire and your willingness to push through effort. If ever you've interacted with somebody who just doesn't seem to have any drive, they've given up, or if you've interacted with somebody who seems to have endless drive and energy, what you are looking a- at there in those two circumstances is without question a difference in the level of dopamine circulating in their system. There will be other factors too, but the level of dopamine is the primary determinant...... of how motivated we are, how excited we are, how outward-facing we are, and how willing we are to lean into life and pursue things. Dopamine is what we call a neuromodulator. Neuromodulators are different than neurotransmitters. Neurotransmitters are involved in the dialogue between neurons, nerve cells, and neurotransmitters tend to mediate local communication. Just imagine two people talking to one another at a concert, that communication between them is analogous to the communication carried out by neurotransmitters, whereas neuromodulators influence the communication of many neurons. Imagine a bunch of people dancing where it's a coordinated dance involving 10 or 20 or hundreds of people, neuromodulators are coordinating that dance. In the nervous system, what this means is that dopamine release changes the probability that certain neural circuits will be active and that other neural circuits will be inactive, okay? So, it modulates a bunch of things all at once, and that's why it's so powerful at shifting not just our levels of energy, but also our mindset, also our feelings of whether or not we can or cannot accomplish something. (smacks lips) So, how does dopamine work and what does it do? Well, first of all, it is not just responsible for pleasure. It is responsible for motivation and drive primarily, at the psychological level, also for craving. Those three things are sort of the same, motivation, drive, and craving. It also controls time perception. And we will get deep into how dopamine can modulate time perception and how important it is that everybody be able to access increases in dopamine at different timescales. This turns out to be important to not end up addicted to substances, but it also turns out to be very important to sustain effort and be a happy person over long periods of time, which I think most everybody wants. It certainly is adaptive in life to be able to do that. Dopamine is also vitally important for movement. I'll explain the neural circuits for dopamine and mindset and dopamine and movement in a moment, but in diseases like Parkinson's or Lewy bodies dementia, which is similar to Parkinson's in many ways, there is a depletion or death of dopamine neurons in a particular location in the brain, which leads to shaky movements, challenges in speaking, challenges in particular in initiating movement, and because dopamine is depleted elsewhere too, people with Parkinson's and Lewy's bo- and Lew- excuse me, Lewy body dementia also experience drops in motivation and affect, meaning mood. They tend to get depressed and so on. When those people are properly treated, they can, not always, but they can recover some fluidity of movement, some ability to initiate movement, and almost without question, those people feel better psychologically, not just because they can move, but also because dopamine impacts

Andrew Huberman 15:30 mood and motivation. So, what are the underlying neural circuits? For those of you that are not interested in biology and specific nomenclature, you can tune out now if you want, but it's actually pretty straightforward. You have two main neural circuits in the brain that dopamine uses in order to exert all its effects. The first one is a pathway that goes from this area in the what's called the ventral tegmentum. That's a fancy... But ventral just means bottom and tegmentum actually means floor. So, it's at the bottom of the brain, and it's the ventral part of the floor, so it's really low in the back of the brain, the ventral tegmentum, and it goes from the ventral tegmentum to what's called the ventral striatum and the prefrontal cortex. Now, that's a lot of language, but basically what we call this is the mesocorticolimbic pathway. This is the pathway by which dopamine influences motivation, drive, and craving. It involves structures that some of you may have heard of before, things like nucleus accumbens and the prefrontal cortex. This is the pathway that really gets disrupted in addictions, where in particular, drugs that influence the release of dopamine, like cocaine and methamphetamine, we'll talk about those drugs today, they tap into this pathway. But if you are pursuing a partner, a boyfriend or girlfriend, if you're pursuing a degree in school, if you're pursuing a finish line in a race, you are tapping into the so-called mesocorticolimbic pathway. This is the classic reward pathway in all mammals. The other pathway emerges from an area in the brain called the substantia nigra, so called because the cells in that area are dark, and the substantia nigra connects to an area of the brain called the dorsal striatum. This is not surprisingly called the nigrostriatal pathway. For those of you who have never done any neuroanatomy, I'm going to teach you a little trick right now. Everything in neuroanatomy, the first part of a word tells you where the neurons are, and then the second part tells you where they are connecting to. So, when I say nigrostriatal pathway, it means that the neurons are in the substantia nigra and they connect to the striatum, nigrostriatal pathway. So, while it's a lot of language, there is some logic there, okay? So, we got these two pathways, one mainly for movement, right? This is the substantia nigra to dorsal striatum, and we've got this other pathway, the so-called mesocorticolimbic pathway that's for reward, reinforcement, and motivation. I want you to remember that there are two pathways. If you don't remember the two pathways in detail, that's fine, but please remember that there are two pathways because that turns out to be important later. Now, the other thing to understand about dopamine is that the

Andrew Huberman 18:14 way that dopamine is released in the brain and body can differ, meaning it can be very local or it can be more broad. Now...Most of you have probably heard of synapses. Synapses are the little spaces between neurons, and basically neurons, nerve cells communicate with one another by making each other electrically active, or by making each other less electric-electrically active. So, here's how this works. You can imagine one nerve cell and another nerve cell with a little gap between them, a little synapse, and the way that one nerve cell causes the next nerve cell to fire, what we call fire really means to become electrically active, is that it vomits out these little packets, what we call vesicles. They are little bubbles filled with a chemical. When that chemical enters the synapse, it, some of it docks or parks on the other side in the other neuron, and by virtue of electrical changes in the, what we call the postsynaptic neuron, that chemical will make that neuron more electrically active or less electrically active. Dopamine can do that like any other neurotransmitter or neuromodulator. So, it can have one neuron influence another neuron. But dopamine can also engage in what's called a volumetric release. Volumetric release is like a giant vomit that gets out to 50 or 100 or even thousands of cells. So, there's local release, what we call synaptic release, and then there's volumetric release. So, volumetric release is like dumping all this dopamine out into the system. So, dopamine is incredible because it can change the way that our neural circuits work at a local scale and at a very broad scale. And for those of you that are only interested in tools, like how do I get more dopamine? Let me tell you. This part is really important because if you were to take a drug or supplement that increases your level of dopamine, you are influencing both the local release of dopamine and volumetric release. This relates back to the baseline of dopamine and the big peak above baseline, and that turns out to be important. And I'll just allude to why it's important. Many drugs and indeed many supplements that increase dopamine will actually make it harder for you to sustain dopamine release over long periods of time and to achieve those peaks that most of us are craving when we are in pursuit of things. Why? Because if you get both volumetric release, the dumping out of dopamine everywhere, and you're getting local release, what it means is that the difference between the peak and baseline is likely to be smaller. And this is very important, how satisfying or exciting or pleasureful a given experience is doesn't just depend on the height of that peak, it depends on the height of that peak relative to the baseline. So, if you increase the baseline and you increase the peak, you're not going to achieve more and more pleasure from things. I'll talk about how to leverage this information in a little bit. But just increasing your dopamine, yes, it will make you excited for all things, it will make you feel very motivated, but it will also make that motivation very short lived. So, there's a better way to increase your dopamine. There's a better way to optimize this peak to baseline ratio. For now what we've talked about is two main neural circuits, one for movement and one for motivation and craving with dopamine, and we've talked about two main modes of communication between neurons with dopamine. One is this local synaptic release, one is more volumetric release. And in the back of your mind you can relate this back to, again, this baseline versus peaks above baseline. So, that's a description

Andrew Huberman 22:03 of what we would call the spatial effects or the spatial aspects of dopamine. I said this connects to that, that connects to this, you can get local or more broad volumetric release. What about the duration of release or the duration of action for dopamine? Well, dopamine is unique among chemicals in the brain because dopamine, unlike a lot of chemicals in the brain, works through what are called G protein coupled receptors. And for those of you that are about to pass out from the amount of detail, just hang in there with me, it's really not complicated. There are two ways that neurons can communicate, or mainly two ways. There are a third and a fourth, but mostly neurons communicate by two modes. One are what we call fast electrical synapses, ionotropic conduction, all right? You don't need to know what that means, but basically one neuron activates another neuron and little holes open up in that neuron and ions rush in. Sodium is the main ion salt by which one neuron influences the electrical activity of another neuron because sodium ions contain a charge, okay? There are other things like chloride and potassium. If you're interested in looking this up, just look up ionic conductances in the action potential or I could do a post on it sometime and we could go into detail. But just understand that when neurons want to influence each other they can do it by way of this fast ionotropic conduction. This is a really quick way for one neuron to influence the next. Dopamine doesn't communicate that way. Dopamine is slower. It works through what are called G protein coupled receptors. So, what happens is dopamine is released in these little vesicles that I mentioned before get vomited out into the synapse. Some of that dopamine will bind to the so-called postsynaptic neuron, it will bind to the next neuron, and then it sets off a cascade. It's kind of like a bucket brigade of one thing getting handed off to the next, to the next, to the next. It's G protein coupled receptors, and any time you hear about these GPCRs or G protein coupled receptors, pay attention because they're really interesting. They're slow, but they also can have multiple cascades of effects. They can impact even gene expression at some level. They can change what a cell actually becomes. They can change how well or how poorly that cell will respond to the same signal in the future. So, dopamine works through this slower process, these G protein coupled receptors, and so its effects tend to take a while in order to occur.This aspect of dopamine transmission is important because it now underscores two things. One, there's two pathways for dopamine to communicate, one for movement, one for motivation and craving. There's two spatial scales at which dopamine can operate, synaptically or volumetrically, and dopamine can have slow effects, really slow effects, or even very long-lasting effects, and it even can control gene expression, can actually change the way that cells behave.

Andrew Huberman 25:03 One thing that's not often discussed about dopamine, but is extremely important to know is that dopamine doesn't work on its own. Neurons that release dopamine co-release glutamate. Glutamate is a neurotransmitter and it's a neurotransmitter that is excitatory, meaning it stimulates neurons to be electrically active. So now, even if you don't know any cell biology, you should start to gain a picture that dopamine is responsible for movement, motivation, and drive. It does that through two pathways, but also that dopamine stimulates action in general because it releases this excitatory neurotransmitter. It tends to make certain neurons that are nearby or even that are far away because of volumetric release, it tends to make those more active. So dopamine is really stimulating and indeed we say that dopaminergic transmission or dopamine tends to stimulate sympathetic arousal. Sympathetic doesn't have anything to do with sympathy. It just simply means that it tends to increase our levels of alertness. It tends to bring an animal or a human into a state of more alertness, readiness, and desire to pursue things outside the confines of its skin. So if I were to just put a really simple message around dopamine, it would be, there's a molecule in your brain and body that when released tends to make you look outside yourself, pursue things outside yourself, and to crave things outside yourself. The pleasure that arrives from achieving things also involves dopamine, but is mainly the consequence of other molecules. But if ever you felt lethargic and, like, just lazy and you had no motivation or drive, that's a low dopamine state. If ever you felt really excited, motivated, even if you were a little scared to do something, maybe you did your first skydive or you're about to do your first skydive, or you're about to do some public speaking and you really don't want to screw it up, you are in a high dopamine state. Dopamine is a universal currency in all mammals, but especially in humans for moving us toward goals and how much dopamine is in our system at any one time compared to how much dopamine was in our system a few minutes ago, and how much we remember enjoying a particular experience of the past that dictates your so-called quality of life and your desire to pursue things. This is really important. Dopamine is a currency and it's the way that you track pleasure. It's the way that you track success. It's the way that you track whether or not you are doing well or doing poorly, and that is subjective. But if your dopamine is too low, you will not feel motivated. If your dopamine is really high, you will feel motivated, and if your dopamine is somewhere in the middle, how you feel depends on whether or not you had

Andrew Huberman 28:00 higher dopamine a few minutes ago or lower dopamine. This is important. Your experience of life and your level of motivation and drive depends on how much dopamine you have relative to your recent experience. This is again, something that's just not accounted for in the simple language of dopamine hits, okay? A simple way to envision dopamine hits is every time you do something you like, eat a piece of chocolate, dopamine hit, you look at your Instagram, dopamine hit, you see someone you like, dopamine hit. You know, all these things described as dopamine hits neglect the fact that if you scroll social media and you see something you really like, dopamine hit. Sure, there's an increase in dopamine, but then you get to something else and you go, "Hmm, not that interesting." However, had you arrived at that second thing first, you might think that it was really interesting. If you had arrived to that second Instagram post three days later or four days later, you might find it extremely interesting. Again, how much dopamine you experience from something depends on your baseline level of dopamine when you arrive there and your previous dopamine peaks. Okay? That's super important to understand, and it's completely neglected by the general language of dopamine hits. This is why when you repeatedly engage in something that you enjoy, your threshold for enjoyment goes up and up and up. So I want to talk about that process, and I want to explain how that process works because if you understand that process and you understand some of these schedules and kinetics as we call them around dopamine, you will be in a terrific position to use any dopamine enhancing tools that you decide to use. You'll be in an excellent position to modulate and control your own dopamine release for optimal motivation and drive. I realize that was a lot of information about the biology of dopamine, sort of like trying to make you drink from a- the fire hose of dopamine biology. However, I realize that some people probably want even more information about the biology of dopamine transmission. If you're interested in that, I'll post a link to a absolutely stellar review that was published in Nature Reviews Neuroscience called Spatial and Temporal Scales of Dopamine Transmission. It is quite detailed, but they have beautiful diagrams and can walk you through all the things that I just described and get into even more detail. We'll put a link to that in the caption on YouTube. Right now, I want to share with you two anecdotes, one from my

Andrew Huberman 30:30 own life and one from some fairly recent history that illustrate some of the core biology of dopamine and how profoundly it can shape our experience.The first one is a really tragic situation that occurred. Uh, this was in the 80s. There was a outbreak of what looked like Parkinsonian symptoms in a young population. So, many of you have heard of Parkinson's disease. Parkinson's disease is a disease in which people, uh, initially start to quake, uh, can't generate smooth movements. They'll have issues with speech, sometimes cognition as well. Uh, there are examples like Michael J. Fox, which are kind of early onset Parkinson's. Typically, it hits people a little bit later in life. There's a genetic component, um, but there is this question, and there's always been this question, whether or not certain lifestyle factors can also create Parkinson's. And some years ago, there was a situation where a laboratory, street laboratories, um, illicit laboratories, were trying to make a drug called MPPP, which is an opioid-like compound. It's a bit like heroin, uh, and heroin addicts seeking heroin went out and bought what they thought was MPPP. Unfortunately, it was not MPPP. I mean, it would've been tragic if it was anyway, because they were drug addicts, but what they ended up taking turned out to be a lot worse. What they ended up taking was MPTP, and MPTP can arise in the synthesis of MPPP. So, someone in a lab some place, this was mainly in the Central Valley in California, but elsewhere as well, somebody created MPTP, and what ended up happening was a large number of young people who were opioid addicts became completely boxed in paralyzed, couldn't speak, couldn't blink, couldn't do anything, couldn't function, couldn't move. So, both aspects of dopamine transmission were disrupted. They had no motivation and drive. They couldn't generate any movement of any kind. They were literally locked in frozen, and sadly, this is irreversible. It's irreversible because what MPTP does is it kills the dopaminergic neurons of the substantia nigra, that nigrostriatal pathway that's involved in generating movement, and it kills the dopaminergic neurons of the so-called mesocorticolimbic pathway. I was in college when this whole MPTP thing happened, and I remember hearing this story. At the time, I had no understanding of what it is to have very high levels of dopamine or extremely depleted levels of dopamine. There was no reason why I should have that understanding. I mean, of course I had experienced different pleasures of different kinds, and I've had lows in my life, but nothing to the extreme that I'm about to discuss. I got giardia, and giardia is a stomach bug that, if any of you ever had it, it is terrible. Y- it's terrible diarrhea. You end up very dehydrated very quickly. You drop a ton of weight, and it is extremely unpleasant. I ended up going to the emergency room, and in the emergency room, I begged them for something (laughs) to stop up my guts, and they gave it to me. They put a saline line in to rehydrate me, and they injected something into the saline bag, and within minutes, I felt more sadness, more overwhelming sense of depression, basically lower than I'd ever felt in my entire life. It was absolutely profound. I c- I was crying endlessly without knowing why I was crying. I was miserable, and I asked them, "What did you inject?" And they said, "We injected Thorazine." Thorazine is an antipsychotic drug. It's actually used to block dopamine receptors. It's what's given to people who have schizophrenia often. It's given to people who have schizophrenia because schizophrenia involves, among other things, elevated levels of dopamine. It was horrible. The experience of it was miserable unlike anything I'd ever experienced. And so, I actually said to them, "What did you give me?" They said, "Thorazine," and I said, "You have to give me L-DOPA. You have to give me something to get my dopamine levels back up again," and they did. They gave me an injection of L-DOPA into the bag, went straight into my bloodstream, and within minutes I felt fine again. It was incredible, and it really opened up my mind and my experience to what it is to have absolutely plummeted levels of dopamine. There's nothing more miserable than that, I'll tell you, and these poor souls who had this MPTP experience, unfortunately they couldn't recover those cells. People who have severe Parkinson's are struggling with this as well because in Parkinson's and in Lewy body dementia, the dopaminergic neurons often die. It's not just a problem with those neurons releasing enough dopamine. Later, we're going to talk about some approaches to maintaining dopaminergic neuron health and things that we can all do for that, but I will tell you, these dopamine neurons that we all have are very precious for movement and mood and motivation. Having experienced what it is to have very, very low levels of dopamine or to, in this case, to have my dopamine receptors blocked, uh, th- from Thorazine, was eye opening to say the least, and has given me, a, tremendous sensitivity to the fact that dopamine is perhaps one of the most powerful molecules that any of us has inside of us, and the one that we ought to all think very carefully about how we leverage, because while most experiences and most things that we do and take and eat and et cetera, won't create enormous highs and enormous lows in dopamine. Even subtle fluctuations in dopamine really shape our perception of life and what we're capable of and how we feel, and so we want to guard those, and we want to understand them. So, let's lean into that understanding about dopamine, and then let's talk about some tools that we can all use to leverage dopamine in order to keep that baseline in the pr- appropriate, healthy place, and still be able to access those peaks in dopamine, because those, after all, are some of what makes life rich and worth living.So,

Andrew Huberman 36:58 let's talk about the baseline of dopamine that we all have and the peaks in dopamine that we all can achieve through different activities and things that we ingest. (smacks lips) All of us have different baseline levels of dopamine. Some of this is sure to be genetic. Some people just simply ride at a level a little bit higher, they're a little bit more excited, they're a little bit more motivated, or maybe they're a lot more excited or a lot more motivated. (smacks lips) Some people are a little mellower. Some people are a little less excitable, and some of that has to do with the fact that dopamine doesn't act alone. Dopamine has close cousins or friends in the nervous system, and I'll just name off a few of those close cousins and friends. Epinephrine, also called adrenaline, is the main chemical driver of energy. We can't do anything, anything at all unless we have some level of epinephrine in our brain and body. It's released from the adrenal glands, which ride atop our kidneys. It's released from an area of the brain stem called locus coeruleus, and its release tends to wake up neural circuits in the brain and wake up various aspects of our body's physiology and give us a readiness. So, it should come as no surprise that dopamine and epinephrine, AKA adrenaline, hang out together. In fact, epinephrine and adrenaline are actually manufactured from dopamine. There's a biochemical pathway involving dopamine, which is a beautiful pathway. If ever, uh, you want to look it up, you could just look up biochemistry of dopamine. What you'll find is that L-DOPA is converted into dopamine. Dopamine is converted into noradrenaline, norepinephrine, it's also called, and noradrenaline, norepinephrine is converted into adrenaline. So, not only are dopamine and epinephrine, AKA adrenaline, close cousins, they are actually family members, okay? They're closely related. I'm not going to get too deep into epinephrine today, I'm not going to talk too much about those pathways, but anytime I'm talking about dopaminergic transmission or that you have a peak in dopamine, inevitably that means that you have a peak in release of epinephrine as well. What dopamine does is dopamine really colors the subjective experience of an activity to make it more pleasureful, to make it something that you want more of. Epinephrine is more about energy. Epinephrine alone can be fear, paralysis, trauma, not physical paralysis, but mental paralysis, you know? Frozen in fear or being traumatized or scared, but the addition of dopamine to that chemical cocktail, if dopamine is rel- released in the brain, well then that epinephrine becomes one of excitement, okay? I'm using br- a broad brush here, but essentially what you need to know is that dopamine and epinephrine, AKA adre- adrenaline, are family members and they tend to work together like a little gang to make you seek out certain things.

Andrew Huberman 40:06 So, what sorts of activities, what sorts of things increase dopamine and how much do they increase dopamine? Well, let's take a look at some typical things that people do out there or ingest out there that are known to increase dopamine. So let's recall that you have a baseline level of dopamine and that everybody does, and even within a family you might have family members who are very excitable, happy, and motivated and others who are less excitable, happy, and motivated, but your level of dopamine has everything to do with those genetics, but also with what you've experienced in the previous days and the previous months and so on. When you do or ingest certain things, your levels of dopamine will rise above baseline transiently, and depending on what you do or ingest, it will rise either more or less and it will be very brief or it'll last a long time. So, let's take a look at some of the typical things that people take and do and eat. Some are good for us, some are not good for us, and let's ask how much dopamine is increased above baseline. Now, of course, these are averages, but these are averages that have been measured in so-called microdialysis studies in animals, so actually extracting from particular brain areas how much dopamine is released or from measuring the serum, the, the circulating levels of dopamine in humans. Chocolate, they didn't look at milk versus dark chocolate, but chocolate will increase your baseline level of dopamine 1.5 times, okay? So it's a pretty substantial increase in dopamine. It's transient, it goes away after a few minutes or even a few seconds. I'll explain what determines the duration in a minute, but 1.5 times for chocolate. Sex, both the pursuit of sex and the act of sex increases dopamine two times, so it's a doubling above baseline. Now, of course, there's going to be variation there, but that's the average increase in baseline dopamine caused by sex. Later, I will talk about how the different aspects of the so-called arousal arc, the different aspects of sex, believe it or not, have a differential impact on dopamine, but for now as a general theme (laughs) or activity, sex doubles the amount of dopamine circulating in your blood. Nicotine, in particular nicotine that is smoked like cigarettes and so forth, increases dopamine two and a half times above baseline. So there's a peak that goes up above baseline two and a half times higher. It is very short-lived.Anyone who's ever been a chain smoker or observed a chain smoker understands that the increase in dopamine from nicotine is very short lived. Cocaine will increase the level of dopamine in the bloodstream two and a half times above baseline. And amphetamine, another drug that increases dopamine, will increase the amount of dopamine in the bloodstream 10 times above baseline, a tremendous increase in dopamine. Exercise. Now exercise will have a different impact on the levels of dopamine depending on how much somebody subjectively enjoys that exercise. So if you're somebody who loves running, chances are it's going to increase your levels of dopamine two times above your baseline, not unlike sex. People who dislike exercise will achieve less dopamine increase or no increase in dopamine from exercise. And if you like other forms of exercise like yoga or weightlifting or swimming or what have you, again, it's going to vary by your subjective experience of whether or not you enjoy that activity. This is important and it brings us back to something that we talked about earlier. Remember that mesocorticolimbic pathway? Well, the cortical part is important. The cortical part actually has a very specific part, which is your prefrontal cortex, the area of your forebrain that's involved in thinking and planning and involved in assigning a rational explanation to something and involved in assigning a subjective experience to something. All right. So for instance, the pen that I'm holding right now is one of these Pilot V5s. I love these Pilot V5s. They don't sponsor the podcast. I just happen to like them. I like the way that they write, how they feel. If I spent enough time thinking about it or talking about it, I could probably get a dopamine increase just talking about this Pilot V5. And that's not because I have the propensity to release dopamine easily. It's that as we start to engage with something more and more, and what we say about it and what we encourage ourself to think about it has a profound impact on its rewarding or non-rewarding properties. Now it's not simply the case that you can lie to yourself and you can tell yourself, "I love something," and when you don't really love it, and it will increase dopamine. But what's been found over and over again is that if people journal about something or they practice, uh, some form of appreciation for something, or they think of some aspect of something that they enjoy, the amount of dopamine that that behavior will evoke tends to go up. So for people that hate exercise, you can think about some aspect of exercise that you really enjoy. However, I will caution you against saying to yourself, "I hate exercise," or, "I hate studying," or, "I hate this person, but I love the reward I give myself afterward." Later, we're going to talk about how rewards given af- afterward actually make the situation worse. They won't make you like exercise more or studying more. They actually will undermine the dopamine release that would otherwise occur for that activity. So certain things, chemicals have a universal effect. They make everybody's dopamine go up. So some people like chocolate, some people don't, of course. But in general, it make, has, causes this increase in dopamine. But sex, nicotine, cocaine, amphetamine, those things cause increases in dopamine in everybody that takes them. Things like exercise, studying, hard work, working through a challenge in a relationship, or working through something hard of any kind, that is going to be subjective as to how much dopamine will be released. And we will return to that subjective component in a little bit.

Andrew Huberman 46:46 But now you have a sense of how much dopamine can be evoked by different activities and by different substances. One that you might be wondering about is caffeine. I'm certainly drinking my caffeine today and I do enjoy caffeine in, uh, limited qua- quantities. I drink yerba mate and I drink coffee, and I love it. Does it increase dopamine? Well, a little bit. Caffeine will increase dopamine to some extent, but it is pretty modest compared to the other things that I described, chocolate, sex, nicotine, cocaine, amphetamine, and so on. However, there's a really interesting paper published in 2015. This is Volkow et al. You can look it up, it's very easy to find. It showed that regular ingestion of caffeine, whether or not it's from coffee or otherwise, increases upregulation of certain dopamine receptors. So caffeine actually makes you able to experience more of dopamine's effects. Because as I mentioned before, dopamine is vomited out into the synapse or it's released volumetrically, but then it has to bind some place and trigger those G protein coupled receptors. And caffeine increases the number, the density of those G protein coupled receptors. Now sitting back and thinking about that, you might think, "Oh yeah, you know, sometimes I'll notice people," at least in the old days, that it used to be a cigarette and a cup of coffee, or when people drink alcohol, oftentimes they'll smoke. And it's well-known that different compounds like alcohol and nicotine or caffeine and nicotine or certain behaviors and certain drugs can synergize to give bigger dopamine increases. And this is not terribly uncommon. There are a lot of people nowadays who, for instance, take pre-workout energy drinks. They'll drink a, I won't name names, but they'll drink a canned energy drink or they'll drink a pre-workout and they'll try and get that big stimulation, that ha- stimulant effect for the dopamine, the norepinephrine, that family of molecules that works together to make you motivated. And then they'll also exercise to try and get even more of a dopaminergic experience out of that workout. Sometimes it's also to perform better as well, of course.As we'll talk about in a few minutes, that aspect, or that approach rather, of trying to just get your dopamine as high as you possibly can in order to get the most out of an experience, turns out to not be the best approach. And what you'll find as we talk about dopamine schedules is that layering together multiple things, substances and activities, that lead to big increases in dopamine actually can create pretty severe issues with motivation and energy right after those experiences, and even a couple of days later. So, I'm not saying that people shouldn't take the occasional pre-workout, if that's your thing, or drink a cup of coffee or two before working out f- now and again. Some people really enjoy that. I certainly do that every once in a while. But if you do it too often, what you'll find is that your capacity to release dopamine, and your level of motivation and drive and energy overall, will take a serious hit. Now, I've been alluding

Andrew Huberman 49:54 to this dopamine peaks versus dopamine baseline thing since the beginning of the episode. Talked about tonic and phasic release and so forth. But now let's really drill into what this means and how to leverage it for our own purposes. In order to do that, let's take a step back and ask, why would we have a dopamine system like this? Why would we have a dopamine system at all? Well, we have to remember what our species' primary interest is. Our species, like all species, has a main interest, and that's to make more of itself. It's not just about sex and reproduction. It's about foraging for resources. Resources can be food, it can be water, it can be salt, can be shelter, can be social connection. Dopamine is the universal currency of foraging and seeking. All right? We call, sometimes talk about motivation and craving, but what we mean in the evolutionary adaptive context, what we mean is foraging and seeking. Seeking water, seeking food, seeking mates, seeking things that make us feel good and avoiding things that don't make us feel good. But in particular, seeking things that will provide sustenance and pleasure in the short term and will extend the species in the long term. Once we understand that dopamine is a driver for us to seek things, it makes perfect sense as to why it would have a baseline level and it would have peaks, and that the baseline and peaks would be related in some sort of direct way. Here's what I mean by that. Let's say that you were not alive now, but you were alive 10,000 years ago. And you woke up and you looked and you realized you had minimal water and you had minimal food left. Maybe you have a child, maybe you have a partner, maybe you're in an entire village, but you realize that you need s- you need things. Okay? You need to be able to generate the energy to go seek those things. And chances are, there were dangers in seeking those things. Yes, it could be saber-toothed tigers and things of that sort. But there are other dangers too. There's the danger of a cut to your skin that could lead to infection. There's the danger of storms. There's the danger of cold. There's the danger of leaving your loved ones behind. So, you go out and forage, right? You could be hunting, you could be gathering, or you could be doing both. The going out and foraging process was, we are certain, driven by dopamine. I mean, there's no fossil record of the brain, but these circuits have existed, we know, for tens of thousands, if not hundreds of thousands of years. And they are present in every animal. Not just mammals, but even in little worms like C. elegans. The same process is mediated by dopamine. So, dopamine drives you to go out and look for things. And then let's say you find a couple berries. These ones are rotten. These ones are good. Maybe you hunt an animal and kill it, or you find an animal that was recently killed and you decide to take the meat. You are going to achieve, or I should say, experience some sort of dopamine release. You found the reward. That's great. But then it needs to return to some lower level. Why? Well, because if you just stayed there, you would never continue to forage for more. It doesn't just increase your baseline and then stay there. It goes back down. And what's very important to understand is that it doesn't just go back down to the level it was before. It goes down to a level below what it was before you went out seeking that thing. Now, this is counterintuitive. We often think, "Oh, okay, I'm going to pursue the win." Right? Let's m- let's move this to modern day. "I'm going to, I'm going to run this marathon. I'm going to train for this marathon." Then you run the marathon and you finish, you cross the finish line. You feel great. And you would think, "Okay, now I'm set for the entire year. I'm going to feel so much better. I'm going to feel this accomplishment in my body. It's going to be so great." But that's not what happens. You might feel some of those things, but your level of dopamine has actually dropped below baseline. Now, eventually it will ratchet back up. But two things are really important. First of all, the extent to which it drops below baseline is proportional to how high the peak was. So, if you cross the finish line pretty happy, it won't drop that much below baseline afterward. If you cross the finish line ecstatic, well, a day or two later, you're going to feel quite a bit lower than you would otherwise. You might not be depressed because it depends on where that baseline was to begin with. But the so-called postpartum depression that people experience after giving birth, or after some big win, a graduation or any kind of celebration, that postpartum drop in mood and affect and motivation is the drop in baseline dopamine. This is very important to understand because this happens on very rapid timescales, and it can last quite a long time. It also explains the behavior that most of us are familiar with of engaging in something that we really enjoy, going to a restaurant that we absolutely love, or engaging in some way with some person that we really, really enjoy. But if we continue to engage in that behavior over and over again, it kind of loses its edge. It starts to kind of...... feel less exciting to us. Some of us experience that drop in excitement more quickly and more severely than others, but everyone experiences that to some extent. And this has direct roots in these evolutionarily conserved circuits. Some of you may be hearing this and think, "No, no, no. That's not how it works for me. I'm just riding higher and higher all the time. I love my kids. I love my job. I love school. I love wins. I, I don't want losses." I agree. We all feel good when we are achieving things, but oftentimes we are feeling good because we are layering in different aspects of life, consuming things and doing things that increase our dopamine. We're getting those peaks. But afterward, the drop in baseline occurs, and it always takes a little while to get back to our stable baseline. We really all have a sort of dopamine set point, and if we continue to indulge in the same behaviors, or even different behaviors that increase our dopamine in these big peaks over and over and over again, we won't experience the same level of joy from those behaviors or from anything at all. Now, that has a name. It's called addiction. But even for people who aren't addicted, even for people who don't have an attachment to any specific substance or behavior, this drop in ba- below baseline after any peak in dopamine is substantial, and it governs whether or not we are going to feel motivated to continue to pursue other things. Fortunately, there's a way to work with this, such that we can constantly stay motivated, but also keep that baseline of dopamine at an appropriate, healthy level.

Andrew Huberman 56:46 A previous guest on the Huberman Lab Podcast was Dr. Anna Lembke. She's head of the Addiction Dual Diagnosis Clinic at Stanford, has this amazing book, Dopamine Nation: Finding Balance in the Age of Indulgence. If you haven't read the book, I highly encourage you, uh, to check it out. It's fantastic. The other terrific book about dopamine is The Molecule of More, which is, uh, similar in some regard, but isn't so much about addiction. It's more about other types of behaviors. Both books really focus on these dopamine schedules and the relationship between these peaks and baselines of dopamine. In Dr. Lembke's book, and when she was on the Huberman Lab Podcast and other podcasts, she's talked about this pleasure-pain balance, that when we seek something that we really like, or we indulge in it, like eating a little piece of chocolate, if we really like chocolate. There is some pleasure, but then there's a little bit of pain that exceeds the amount of pleasure. And it's subtle, and we experience it as wanting more of that thing. Okay, so there's a pleasure-pain balance, and I'm telling you that the pleasure and the pain are governed by dopamine to some extent. Well, how could that be, right? I've said before when you engage in an activity or when you ingest something that increases dopamine, the dopamine levels go up, you know, to a substantial degree with all the things I listed off. Where's the pain coming from? Well, the pain is coming from the lack of dopamine that follows, and you now know what that lack of dopamine reflects. How do you know? Well, earlier we were talking about how dopamine is released between neurons, and I mentioned two ways. One is into the synapse, where it can activate the postsynaptic neuron, and the other was what I called volumetric release, where it is distributed more broadly. It's released out over a bunch of neurons. In both cases, it's released from these things we call synaptic vesicles, literally little bubbles, tiny, tiny little bubbles that contain dopamine. They get vomited out into the area or into the synapse. Well, those vesicles get depleted. For the synaptic physiologists out there, we call this the readily releasable pool of dopamine. We can only deploy dopamine that is ready to be deployed, that's packaged in those little vesicles and ready to go. It's like when you order a product and they say, "Out of stock until two months from now." Well, it's not ready to be released. Same thing with dopamine. There's a pool of dopamine that's synthesized, and you can only release the dopamine that's been synthesized. It's the readily releasable pool. The pleasure-pain balance doesn't only hinge on the readily releasable pool of dopamine, but a big part of the pleasure-pain balance hinges on how much dopamine is there and how much is ready and capable of being released into the system. So, now we've given some meat to this thing that we call the pleasure-pain balance, and now it should make perfect sense why if you take something or do something that leads to huge increases in dopamine, afterward your baseline should drop, because there isn't a lot of dopamine

Andrew Huberman 1:00:00 around to keep your baseline going. Fortunately, most people do not experience or pursue enormous increases in dopamine leading to these severe drops in baseline. Many people do, however, and that's what we call addiction. When somebody pursues a drug or an activity that leads to huge increases in dopamine, and now you understand that afterward the baseline of dopamine drops because of depletion of dopamine, the readily releasable pool. The dopamine is literally not around to be released, and so people feel pretty lousy. And many people make the mistake of then going and pursuing the dopamine-evoking, the dopamine-releasing activity or substance again, thinking mistakenly that it's going to bring up their baseline, it's going to give them that peak again. Not only does it not give them a peak, their baseline gets lower and lower because they're depleting dopamine more and more and more. And we've seen this over and over again. When people get addicted to something, then they're not achieving much pleasure at all.You even see this with video games. People will play a video game. They love it. It's super exciting to them, and then they'll keep playing and playing and playing, and either one of two things happens, typically both. First of all, I always say addiction is a progressive narrowing of the things that bring you pleasure. So oftentimes what will happen is the person only has excitement and can achieve dopamine release to the same extent doing that behavior and not other behaviors, and so they start losing interest in school. They start losing interest in relationships. They start losing interest in fitness and well-being, and depletes their life, and eventually what typically happens is they will stop getting dopamine release from that activity as well, and then they drop into a pretty serious depression, and this can get very severe and people have committed suicide from these sorts of patterns of activity. But what about the more typical scenario? What about the scenario of somebody who is really good at working during the week, they exercise during the week, they drink on the weekends? Well, that person is only consuming alcohol maybe one or two nights a week, but oftentimes that same person will be spiking their dopamine with food during the middle of the week. Now, we all have to eat, and it's nice to eat foods that we enjoy. I certainly do that. I love food, in fact. But let's say they're eating foods that really evoke a lot of dopamine release in the middle of the week. They're drinking one or two days on the weekend. They are one of these work hard/play hard types, so they're swimming a couple miles in the ocean in the middle of the week as well. Uh, they're going out dancing once on the weekend. Sounds like a pretty, pretty balanced life as I describe it. Well, here's the problem. The problem is that dopamine is not just evoked by one of these activities. Dopamine is evoked by all of these activities, and dopamine is one currency of craving, motivation, and desire and pleasure. There's only one currency. So, even though if you look at the activities, you'd say, "Well, it's just on the weekends," or, "This thing is only a couple times a week." If you looked at dopamine simply as a function, as a chemical function of peaks and baseline, it might make sense why this person after several years of work hard/play hard would say, "Yeah, you know, I'm feeling kind of burnt out. I'm just not feeling like I have the same energy that I did a few years ago." And of course there are age-related reasons why people can experience drops in energy. But oftentimes what's happening is not some sort of depletion in cellular metabolism that's related to aging. What's happening is they're spiking their dopamine through so many different activities throughout the week that their baseline is progressively dropping, and in this case it can be very subtle. It can be very, very subtle, and that's actually a very sinister function of dopamine, we c- we could say, which is that it can often drop in imperceptible ways, but then it, once it reaches a threshold of low dopamine, we just feel like, hmm, we can't really get pleasure from anything anymore. What used to work doesn't work anymore. So, it starts to look a lot like the more severe addictions or the more acute addictions to things like cocaine and amphetamine which lead to these big increases, these big spikes in dopamine, and then these very severe drops in the baseline. Now, of course, we all should engage in activities that we enjoy. I certainly do. Everybody should. A huge part of life is pursuing activities and, and things that we enjoy. The key thing is to understand this relationship between the peaks and the baseline, and to understand how they influence one another, because once you do that, you can start to make really good choices in the short run and in the long run to maintain your level of dopamine baseline, maybe even raise that level of dopamine baseline, and still get those peaks and still achieve those feelings of elevated motivation, elevated desire, and craving, because again, those peaks and having a su- a sufficiently healthy high level of dopamine baseline are what drove the evolution of our species and they're really what drive the evolution of anyone's life progression, too. So, they're a good thing. Dopamine is a good thing. Just very briefly, because it was also covered in the interview episode I did with Anna Lembke about addiction, some of you might be asking, "What should I do if I experience a drop in my baseline level of dopamine because of engagement with some activity or some substance that led to big peaks?" Uh, just to put some color and example on this, uh, a few episodes ago I talked about a, a friend who I've known a long time, this is actually the child of a friend, who has basically become addicted to video games. He decided, actually after seeing that episode with Anna, to do a 30-day complete fast from phone, from video games, and from social media of all kinds. He's now at day 29. He's really accomplished this. Not incidentally, his levels of concentration, his overall mood are up. He's doing far, far better. What he did is hard, in particular the first 14 days is really hard, but the way that you replenish the releasable pool of dopamine is to not engage in these dopaminergic seeking behaviors, because remember, typically people arrive at a place where they want to stop engaging in these behaviors or ingesting substances when that dopamine is depleted, when they're not getting the same lift. In his case, he was feeling depressed. He thought he had ADHD. They were starting to treat it as, as ADHD, and certainly there are people out there who have ADHD, but what he found was that his levels of concentration are back. He does not need to be treated for ADHD, and actually the psychiatrist wondered if he did prior to this video game/social media fast. He's feeling good. He's exercising again. I'm not making this up. This is really a, a very specific but very relevant example of how the dopamine system can replenish itself.Of course, if there's a clinical need for ADHD treatment, by all means pursue that. But I think a lot of ADHD does go misdiagnosed because of this depletion in dopamine that occurs because of overindulgence in other activities and the drop in baseline. So for anyone that's experienced a real drop in baseline, who has addictive tendencies, whether or not they're behaviors or substances, that is always going to be the path forward, is going to be either cold turkey or through some sort of tapering to limit interactions with the, what would otherwise be the dopamine-evoking behavior or substance. So let's talk about the optimal way to engage

Andrew Huberman 1:07:50 in activities, or to consume things that evoke dopamine. And by no means am I encouraging people to take drugs of abuse. I would not do that. I am not doing that. But some of the things on these lists of dopamine a- evoking activities are things like chocolate, coffee, even if it's indirect, um, sex and reproduction provided it's healthy, consensual, context appropriate, age appropriate, species appropriate, of course, is central to our evolution and progression as a species. So certain things like cocaine, amphetamine, I will put in the classification of bad. I'm willing to do that. And other things are part of life, food, exercise, if that evokes your dopamine. How are we supposed to engage with these dopamine-evoking activities in ways that are healthy and beneficial for us? How do we achieve these peaks which are so central to our well-being and experience of life without dropping our baseline? And the key lies in intermittent release of dopamine. The real key is to not expect or chase high levels of dopamine release every time we engage in these activities. Intermittent reward schedules are the central schedule by which casinos keep you gambling, the central schedule by which elusive partners or potential partners keep you texting and pursuing on either side of the relationship. Intermittent schedules are the way that the internet and social media and all highly engaging activities keep you motivated and pursuing. And we can take this back to our evolutionary adaptive scenario where you are out there looking for water, looking for food. Not every trail, not every pursuit, not every hunch about where the animals will be, where the food will be, where the berries will be, not every single one of those played out. There's something called dopamine reward prediction error. When we expect something to happen, we are highly motivated to pursue it. If it happens, great. We get the reward. The reward comes in various chemical forms, including dopamine. And we are more likely to engage in that behavior again. This is the basis of casino gambling. This is how they keep you going back again and again and again, even though on average the house really does win. You can transplant that example to any number of different pleasureful activities. If you're not a gambler and that doesn't appeal to you, I have to imagine there's something that appeals to you, something that you do repeatedly because you enjoy it. And almost inevitably it's because there's an intermittent schedule. There's a intermittent schedule by which dopamine sometimes arrives, sometimes a little bit, sometimes a lot, sometimes a medium amount. Okay? That intermittent reinforcement schedule is actually the best schedule to export to other activities. How do you do that? Well, first of all, if you are engaged in activities, school, sport, relationship, et cetera, where you experience a win, you should be very careful about allowing yourself to experience huge peaks in dopamine, unless you're willing to suffer the, the crash that follows, and waiting a period of time for it to come back up. What would this look like in the practical sense? Well, let's say you are somebody who really does enjoy exercise. Or let's say you're somebody who kind of likes exercise but forces yourself to do it, but you make it pleasureful by giving yourself your favorite cup of coffee first, or maybe taking a pre-workout drink, or taking an energy drink, or listening to your favorite music, and then you're in the gym and you're listening to your music. That all sounds great, right? Well, it is great except that by layering together all these things to try and achieve that dopamine release, and by getting a big peak in dopamine, you're actually increasing the number of conditions required to achieve pleasure from that activity again. And so there is a form of this where sometimes you do all the things that you love to get the optimal workout. You listen to your favorite music. You go at your favorite time of day. You have your pre-workout drink if that's your thing. You do all the things that give you that best experience of the workout for you. But there's also a version of this where sometimes you don't do the dopamine-enhancing activities, you don't ingest anything to increase your dopamine. You just do the exercise. You don't do the exercise and expect dopamine to arrive through some what we call exogenous source as well. You might think, "Well, that sounds lame. I want to continue to enjoy exercising." Ah, but that's exactly the point. If you want to maintain motivation for school, exercise, relationships, or pursuits of any duration and kind, the key thing is to make sure that the peak in dopamine, if it's very high, doesn't occur too often. And if something does occur very often, that you vary how much dopamine you experience with each engagement in that activity. Now some activities naturally have this intermittent property woven into them. Right? We sometimes have classes that we like and other classes we don't like. We don't always get straight As. Sometimes we don't get rewarded with the outcome that we would like. We don't always have the perfect relationship outcome. But understand that your ability to experience motivation and pleasure for what comes next is dictated by how much motivation and pleasure and dopamine you experienced prior.The reason I can't give a very specific protocol like delete dopamine or lower dopamine every third time is that, that wouldn't be intermittent. The whole basis of intermittent reinforcement is that you don't really have a specific schedule of when dopamine is going to be high and when dopamine is going to be low and when dopamine is going to be medium. That's a predictable schedule, not a random intermittent schedule. So do like the casinos do, certainly works for them, and four activities that you would like to continue to engage in over time, whatever those happen to be, start paying attention to the amount of dopamine and excitement and pleasure that you achieve with those and start modulating that somewhat at random. That might be removing some of the dopamine releasing chemicals that you might take prior. Maybe you remove them every time, but then every once in a while you introduce them. Maybe it involves sometimes doing things socially that you enjoy doing socially, sometimes doing the same thing but alone. There are a lot of different ways to do this. There are a lot of different ways to approach this, but now knowing what you know about peaks and baselines and dopamine and understanding how important it is not just to achieve peaks, but to maintain that baseline at a healthy level, it should be straightforward for you to implement these intermittent schedules. For those of you that are begging for more specificity, we can give you a tool. One would be, you can flip a coin before engaging in any of these types of activities and decide whether or not you are going to allow other s- dopamine supportive elements to go, for instance, into the gym with you. Are you going to listen to music or not? If you enjoy listening to music, well then flip a coin and if it comes up heads, bring the music in. If it comes up tails, don't. Okay. Sounds like you're undercutting your own progress, but actually you are serving your own progress both short term and long term by doing that. Now the smartphone is a very interesting tool

Andrew Huberman 1:15:29 for dopamine in light of all this. It's extremely common nowadays to see people texting and doing selfies and communicating in various ways, listening to podcasts, listening to music, doing all sorts of things while they engage in other activities, or going to dinner and texting other people or making plans, sharing information. That's all wonderful. It gives depth and richness and color to life. But it isn't just about our distracted nature when we're engaging with the phone, it's also a way of layering in dopamine and it's no surprise that levels of depression and lack of motivation are really on the increase. Everything that we've talked about until now sets up an explanation or an interpretation of why interacting with digital technology can potentially lead to disruptions or lowering in baseline levels of dopamine. I can use a personal example for this. I happen to really enjoy working out. I've always really enjoyed it, but in recent years I noticed that if I was bringing my phone to my workouts, then not only was I a little bit more distracted and not focusing on what I was doing as much as I could have or should have, but also I started to lose interest in what I was doing. It wasn't as pleasureful. I would feel like it just didn't have the same kind of oomph. And I was beginning to question my motivation. As I started learning more about this relationship between the peaks and the baselines in dopamine, what I realized was that some time ago, I probably experienced a incredible increase in the amount of dopamine during one of my workouts because I enjoy working out and I enjoy listening to music. I also enjoy listening to podcasts. I also enjoy communicating with people. Those are all wonderful pursuits, but I had layered in too many of them too many times, and then it essentially wasn't working for me anymore. Much in the same way a drug wouldn't work for somebody who takes it repeatedly because their baseline of dopamine is dropping. So at least for this calendar year, I've made a rule for myself, which is I don't allow my phone into my workouts at all. No music, at least not from the phone. It can be in the room. I might listen to a podcast in the room, but I don't listen to anything or engage in anything on my phone, no texting whatsoever. And most of the time I just don't even bring it with me for that period of time. It's only a short period of time. I'm not training that often. This is something that I think has been misinterpreted as people can't be alone now. People talk about, oh, you know, they can't walk across the street or they can't go anywhere, ride the bus, can't be on the plane without being in contact. They can't handle just their thoughts. I don't think that's really what's going on. I think what's happened is that we achieved the great dopamine increase that comes from this incredible thing, which I personally enjoy being able to communicate by phone, by text and exchange pictures and send links and these kinds of things, social media. But then what happens is it doesn't have that same fulfilling aspect to it, and it tends to remove the excitement and the pleasure of the very activities that we are engaged in. So I know this is a hard one for many people, but I do invite you to try removing multiple sources of dopamine release or what used to be multiple sources of dopamine release from activities that you want to continue to enjoy or that you want to enjoy more. And now you understand the biological mechanisms that would underlie a statement like that. It takes a little bit of working with. I know it can be challenging in the first week or so of not engaging with the phone during any kind of workout, that actually was really tough. But now I'm back to a place where I enjoy it that much more. I also feel as if I conquered something in terms of the circuitry related to dopamine. I now understand why something that I enjoyed so much had become less pleasureful for me, and there's a deep, deep satisfaction that comes from understanding, okay, there wasn't anything wrong with me or the, what I was doing or-Anything at all. It was just a, there was something wrong with the approach I was taking, which was layering in all these sources of dopamine and dropping my baseline.

Andrew Huberman 1:19:45 For this very same reason, I caution people against using stimulants every time they study, or every time they work out, or every time that they do anything that they would like to continue to enjoy and be motivated at. There's one exception, which is caffeine, because as I mentioned before, if you like caffeine, that actually could be a good thing for your dopamine system, because it does upregulate these D2, D3 receptors. So it actually makes whatever dopamine is released by that activity more accessible or more functional within the biochemistry and the pathways of your brain and body. However, a number of energy drinks, and in particular, pre-workouts, contain things that are precursors to dopamine, and on their own, even if you didn't engage in the activity, would cause the release of dopamine to a substantial degree. They do cause the release of dopamine to a substantial degree, and over time that will deplete your dopamine. So energy drinks, pre-workout drinks, drugs of various kinds that people take to study and pay attention. We talked about some of these for the ADHD episode, things like Adderall, Ritalin, armodafinil, modafinil, taken repeatedly over time will reduce the level of satisfaction and joy that you get from the activities you engage in while under the influence of those compounds. Um, I'm not trying to demonize those compounds for their clinical use. What I'm saying is taking stimulants and then engaging in activities that you would like to continue to feel pleasureful is undercutting the process. And inevitably, it might not happen tomorrow, might not happen in a month, but inevitably you will have challenges with motivation and drive related to those activities. Now, some people can keep it right in check. They can just do the one can of the energy drink, or they only do their pre-workout before really hard days, for instance. More power to you. I actually do that sometimes, frankly. But people who are trying to get into that peak, super motivated, driven, driven state, really focused every time they engage in an activity, you are absolutely undercutting the process, and you are undermining your ability to stay motivated and focused. So just as we talked about intermittent reward schedules a moment ago, intermittent spiking of dopamine, if you do it at all, is definitely the way to go. And chronically trying to spike your dopamine in order to enhance your motivation, focus, and drive will absolutely undermine your motivation, focus, and drive in the long run.

Andrew Huberman 1:22:20 Ingestion of caffeine is somewhat of an exception among the other examples of things I've mentioned to avoid before what would otherwise be dopamine increasing activities because, again, caffeine can increase the density and the efficacy of these dopamine receptors. It turns out that the source of caffeine could also matter. While coffee or tea or other forms of caffeine will have this effect of increasing dopamine receptors, yerba mate, something I've talked about before on this podcast, has some interesting properties. First of all, it contains caffeine. It's also high in antioxidants. It also contains something called GLP-1, which is favorable for management of blood sugar levels. Yerba mate, it turns out, has also been shown to be neuroprotective, specifically for dopaminergic neurons. Now, I should mention, this is just a couple of studies, so we don't want to conclude too much from these studies. More needs to be done. But they showed that in a model of damage to dopamine neurons, ingestion of yerba mate and some of the compounds within yerba mate can actually serve to preserve the survival of dopamine neurons in both the movement related pathway and the motivation pathway. So perhaps you need that incentive t- in order to ingest yerba mate tea. Perhaps, uh, you don't need any incentive. In my case, I don't need any incentive. I already enjoy yerba mate as my principal source of caffeine, although I do drink coffee as well. But if one were going to consume caffeine, you might consider consuming that caffeine in the form of yerba mate, both for sake of upregulating dopamine receptors and getting more of a dopamine increase and of course, for the stimulant properties of caffeine, if that's what you're seeking. And in addition to that, because yerba mate does appear to have some sort of neuroprotective, and in particular dopamine neuron

Andrew Huberman 1:24:20 protective properties. Now, that doesn't mean the caffeine is always beneficial, and actually there's one instance related to dopamine where caffeine can be particularly dangerous, and this relates to MDMA, so-called ecstasy. MDMA is under investigation in various clinical trials for its potential to treat trauma and depression. It's also, of course, a drug that's used recreationally. It's still illegal, at least in the United States. Whether or not MDMA is neurotoxic has been very controversial early on. It was thought that it is neurotoxic, that it can destroy serotonergic neurons. There were other papers that came out which argued that's not the case, and that's in particular because one of the early papers published in Science Magazine claiming that MDMA was neurotoxic, that paper was retracted. It turns out that that study had mistakenly used methamphetamine instead, and methamphetamine is known to be neurotoxic. I think most of the data point to the idea that MDMA might not be neurotoxic, but in any case, caffeine has been shown to increase the toxicity of MDMA receptors. And you might say, "Well, how could that be?" Well, now you understand why that could be. Caffeine increases the density and efficacy of these dopamine receptors, the D2 and D3 receptors. MDMA is a potent...... drug for increasing concentrations of dopamine as well as serotonin and other neuromodulators. And it appears that caffeine ingestion by up regulating these receptors can lead to more toxicity of MDMA. So, caffeine can be a beneficial substance in one context and actually can be a detrimental, if not dangerous substance in another context. Two substances that greatly increase dopamine, namely

Andrew Huberman 1:26:15 amphetamine and cocaine, can cause long term problems with the dopaminergic pathways. And this is largely based on a study that was published some years ago, 2003, but still holds a lot of merit. This is a paper published in Proceedings of the National Academy of Sciences, a very high tier stringent journal. First author is Kolb, K-O-L-B, and the title of the paper pretty much tells the story, "Ampetamine or cocaine limits the ability of later experience to promote structural plasticity in the neocortex and nucleus accumbens." Neocortex is the outer shell of the brain, uh, more or less, and the nucleus accumbens is part of that mesolimbic, uh, dopamine pathway for motivation, drive, and reinforcement. Neuroplasticity, of course, is the brain's ability to change in response to experience, and neuroplasticity is the basis of learning and memory, and essentially remodeling of our neural circuitry in positive ways of all kinds. And this study was really one of the first to show that ingesting amphetamine and cocaine, because of the high peak in dopamine that it creates and the low dopamine state, the baseline drop that it creates afterwards limits plasticity and learning subsequent to taking amphetamine and cocaine. It was, at least in this study, shown to be a long lasting effect, I doubt it's a permanent effect, but this should serve as a serious cautionary note that amphetamine and cocaine not only can cause a drop in baseline dopamine, but can actually put the brain into a state in which it cannot learn and modify itself to get better, at least for some period of time.

Andrew Huberman 1:27:57 In a previous episode on ADHD, I talked about the widespread use of drugs like Adderall, Ritalin, Modafinil, and Armodafinil, all of which lead to very large increases in dopamine and for people with ADHD can really improve their symptoms. But of course there's a lot of non-prescription, non-clinical use of those compounds as well, and it stands to reason that the use of those substances to increase dopamine could very well provide the same sort of blockade of neuroplasticity that cocaine and amphetamine do. Because when you look at the amount of dopamine increase that's triggered by those compounds, it's really comparable. So, again, a cautionary note against spiking one's dopamine too much on a regular basis, unless there's a valid clinical need for doing that.

Andrew Huberman 1:28:45 So we've been focusing a lot for the last few minutes on the kind of darker side of dopamine and how getting big peaks in dopamine can be detrimental, but I want to acknowledge the truth, which is that dopamine feels great. Being in pursuit and motivated and craving things feels wonderful, and I don't want to demonize dopamine. What I'm trying to do today is illustrate