– Welcome to the Huberman Lab Podcast, where we discuss scienceand science-based tools for everyday life. [energetic music] I’m Andrew Huberman, and I’m a professor ofneurobiology and ophthalmology at Stanford School of Medicine. Today, we are going totalk all about dopamine and what drives you to dothe things that you do. We’re going to talk aboutmotivation and desire and craving, but also how dopaminerelates to satisfaction and our feelings of wellbeing. And of course, anydiscussion about dopamine has to include a discussionabout the potential for dopamine induced addiction. Indeed, dopamine lies atthe 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 bodiesthat we call dopamine. I’m going to teach you whatdopamine is and what it is not. There are a lot of mythsabout the molecule dopamine.We often hear aboutso-called dopamine hits. Today, we are going todispel many common myths about dopamine, and we are going to talk abouthow dopamine actually works. We’re going to discussthe biology of dopamine, the psychology. We will discuss some neural circuits and a really excitingaspect of dopamine biology or 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 ofdopamine and in doing so, they change how much dopaminewe are capable of experiencing from what could be very satisfying events, or events that make us feel not so good because of things thatwe did or took prior. So I promise you it’s goingto be a vast discussion, but I will structure it for you, and you’ll come awaywith a deep understanding of really what drives you.You will also come awaywith a lot of tools, how to leverage dopamine sothat you can sustain energy, drive and motivation for the things that are important to youover long periods of time. Before we dive into themeat of today’s discussion, I’d like to share withyou a fascinating result that really underscores what dopamine is capable of in our brains and bodies, and underscores the factthat just through behaviors, no drugs, nothing of that sort, just through behaviors, we can achieve terrificallyhigh increases in dopamine that are very long andsustained 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 involvedis having human subjects get into water of different temperatures.So it was warm water, moderately cool waterand cold, cold water. Had them stay in thatwater for up to an hour, and they measured by way of blood draw things like cortisol,norepinephrine and dopamine. What was fascinating isthat cold water exposure led to very rapidincreases in norepinephrine and epinephrine, which is also just called adrenaline. It also led to increases in dopamine. And these increases indopamine were very significant. They kicked in around 10 or15 minutes after submersion into the cold water. And I should mention thehead wasn’t below water is just up to the neck. And the dopamine release continued to rise and rise and rise, and eventually reached250% above baseline. Now, what was interestingis after subjects got out of this cold water, that dopamine increase was sustained.And I know nowadays manypeople are interested in using cold water therapy asa way to increase metabolism and fat loss, but also to improve sense of well-being, improve cognition,improve clarity of mind. There’s something reallyspecial 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 workand for social engagement and for sport that highly alert, but calm state of mindreally is the sweet spot that I believe most ofus would like to achieve. And this cold waterexposure done correctly really can help peopleachieve that state of mind through these increases in dopamine that lasts a very long time. So I will later detail thespecifics of that study, what it entailed in terms of how long, the variations, the differentsubjects experienced, as well as how to limit theamount of stress hormone, cortisol, that’s released as a consequence of the cold water. And we will also talk aboutcompounds, supplements that people can take in order to increase their levels of dopamineshould they choose. Before we begin, I’d like to emphasize that this podcast isseparate from my teaching and research roles at Stanford.It is however, part ofmy desire and effort to bring zero cost to consumerinformation about science and science related toolsto the general public. In keeping with that theme, I’d like to thank thesponsors 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 lifetimeworking on the visual system. And I can tell you that the visual system has to go through a lot of work in order to main clarity of what you see when there are shadows, when you go into differenttypes 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 brightlight and you can see fine, but then you move into a shadow and then you have to take themoff and they don’t adjust, or they don’t adjust quickly enough. With Roka their eyeglassesand sunglasses are designed with the visual system biology in mind. So you always see thingswith perfect clarity. The glasses are also terrific because they’re very lightweight, and they won’t slip off yourface if you’re exercising, if you’re running or biking.In fact, they weredesigned for the purpose of being able to be wornwhile you’re engaging in those sorts of activitiesor simply working at your desk. I happen to wear readers at night or when I drive or when I work, and I love their sunglassescause I can wear them anywhere. And also the aesthetics oftheir sunglasses and eyeglasses are terrific. Unlike a lot of other performance glasses that frankly make peoplelook like cyborgs. The aesthetics on Roka’sare really terrific. You could wear themanywhere you’d like to go. If you’d like to try Roka glasses, you can go to www.roka.com. That’s R-O-K-A.com andenter the code Huberman to save 20% off your first order. That’s Roka, www.R-O-K-A.com. Enter the code Huberman at checkout. Today’s podcast is alsobrought to us by InsideTracker. InsideTracker is apersonalized 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 gettingregular blood work done. And now with the adventof modern DNA tests, you can also analyze your DNA to see what you ought to bedoing for your immediate and long-term health. We hear a lot thesedays about optimization, optimizing hormones,optimizing your metabolism, optimizing this, optimizing that, but unless you know themeasurements of metabolic factors, hormones and other things thatare in your blood and DNA, you don’t know what to optimize. With InsideTracker it makesall of that very easy. They can come to your house totake the blood and DNA test, or you can go to a nearby clinic.They send you the informationand you take those results. And unlike a lot of laboratoriesdoing blood work out there and DNA tests, they have a simple platform, a dashboard that walks you through your results and helps you identifywhat sorts of nutritional or behavioral or other types of practices you might want toincorporate into your life in order to positivelyimpact your immediate and long-term health. It’s a very easy system to use, and you will gain a ton of information simply by doing that test. Whether or not you end up making changes to what you’re doing or not. If you’d like to try InsideTracker, you can go towww.insidetracker.com/huberman to get 25% off any ofInsideTracker’s plans. Just use the code Huberman at checkout. Today’s episode is alsobrought to us by Headspace.Headspace is a meditation appbacked by 25 published studies and has over 600,005 star reviews. I’ve been meditating for a long time, but I confess sometimes I meditate and sometimes I’m veryinconsistent about my meditation. Ideally, I would meditateevery day for 20 or 30 minutes, but what I found over the years is that, I’ll start a meditation practice and then as life getsmore stressful or busier, which is exactly when Ineed to meditate more, I tend to meditate less often. Switching over to Headspaceas a meditation app really helped me stay consistent with my meditation practice. And that’s because they havea huge range of meditations to select from.Some are short, some are longer. And in general, I try andget 20 minutes of meditation in every day, but some days it’s just five minutes and they have some terrificjust five minute meditations. The science says that evena five minute meditation can be beneficial fordifferent aspects of our brain and body. If you want to try Headspace, you can go towww.headspace.com/specialoffer. And if you do that, you’ll get one month as a free trial with full library of meditations that you can use in any situation. This is the best deal offeredby Headspace right now. So if you’re interested, go to www.headspace.com/specialoffer to get one free one monthtrial with Headspace’s full library of meditations. 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 LearningReimagining Learning through Neuroscience. And at this event, I will be speaking, there will be other speakers as well, and I will be talkingabout neuroplasticity and its applications forteaching and for learning. I will describe what I callthe plasticity super protocol that incorporates all of whatwe know about rapid learning, efficient learning and thebest ways to teach and learn. It’s geared towardseducators of all kinds. It is zero cost. So please feel free to sign up. The event is September 30th,2021 at 3:00 p.m Eastern. You can find the registrationlink in the caption for this episode. So let’s talk about dopamine.Most people have heard of dopamine, and we hear all the timenow about dopamine hits. But actually there’s no suchthing as a dopamine hit. And actually the way thatyour body uses dopamine is to have a baseline level of dopamine. Meaning an amount ofdopamine that’s circulating in your brain and body all the time. And that turns out to beimportant for how you feel generally, whether or notyou’re in a good mood, motivated, et cetera. And you also can experiencepeaks in dopamine above baseline. Now, this has a very specific name in the neurobiology literature, so-called tonic and phasicrelease of dopamine. And I’ll explain what thatmeans in a couple of minutes. But if you remember nothingelse from this episode, please remember this, that when you experiencesomething or you crave something really desirable, really excitingto you, very pleasurable.What happens afterwardsis 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 bigpeak in dopamine after that, I’m going to feel even better because I just had this great event. Not the case. What actually happens isthat your baseline level of dopamine drops. And I will explain theprecise mechanism for that. Okay? In the neuroscience literature, we refer to this as tonic andphasic 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 peaksthat ride above that baseline. And those two things interact. And this is really important. I’m going to teach you theunderlying neurobiology, but even if you have nobackground in biology, I promise to make it all clear. I’ll explain the terms and what they mean. And I’m excited to teachyou about dopamine, because dopamine has everythingto do with how you feel right now as you’re listening to this, it has everything to dowith how you will feel an hour from now, has everything to do withyour level of motivation and your level of desire, and your willingnessto push through effort.If ever you’ve interacted with somebody who just doesn’t seem to haveany drive they’ve given up, or if you’ve interacted with somebody who seems to haveendless drive and energy, what you are looking at therein those two circumstances is without question a difference in the level of dopaminecirculating in their system. There will be other factors too, but the level of dopamineis the primary determinant of how motivated weare, how excited we are, how outward facing we areand how willing we are, to lean into life and pursue things. Dopamine is what we call a neuromodulator. Neuromodulators are differentthan neurotransmitters. Neurotransmitters areinvolved in the dialogue between neurons nerve cells. And neurotransmitters tend tomediate local communication.Just imagine two people talkingto one another at a concert, that communicationbetween them is analogous to the communication carriedout by neurotransmitters, whereas neuromodulatorsinfluence the communication of many neurons. Imagine a bunch of people dancing where it’s a coordinateddance involving 10 or 20 or hundreds of people. Neuromodulators arecoordinating that dance. In the nervous systemwhat this means is that, dopamine release changes the probability that certain neuralcircuits will be active and that other neuralcircuits will be inactive. Okay? So it modulates a bunchof things all at once, and that’s why it’s sopowerful at shifting not just our levels of energy, but also our mindset, also our feelings ofwhether or not we can, or cannot accomplish something. So how does dopaminework and what does it do? Well, first of all, it is notjust responsible for pleasure, it is responsible formotivation 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 isthat everybody be able to access increases in dopamineat different timescales. This turns out to be importantto not end up addicted to substances, but it also turns out to bevery important to sustain effort and be a happy personover long periods of time. Which I think most everybody wants. It certainly is adaptive inlife to be able to do that. Dopamine is also vitallyimportant for movement. I’ll explain the neural circuitsfor dopamine and mindset, and dopamine in movement in a moment, but in diseases like Parkinson’sor Lewy bodies dementia, which is similar toParkinson’s in many ways. There’s a depletion ordeath of dopamine neurons at a particular location in the brain which leads to shaky movements, challenges and speaking, challenges in particularin initiating movement. And because dopamine is depleted elsewhere to people with Parkinson’s and Lew’s bod, excuse me, Lewy body dementiaalso 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 somefluidity 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 dopamineimpacts mood and motivation. So what are the underlyingneural circuits? For those of you that arenot interested in biology and specific nomenclature, you can tune out now if you want, but it’s actually pretty straightforward. You have two main neuralcircuits in the brain that dopamine uses in orderto exert all its effects.The first one is a pathwaythat goes from this area in the what’s calledthe ventral tegmentum. That’s a fancy, butventral 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 inthe 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 whichdopamine influences motivation, drive and craving. It involves structures thatsome of you may have heard of before. Things like nucleus accumbensand the prefrontal cortex. This is the pathway thatreally gets disrupted in addictions where inparticular drugs that influence the release of dopamine likecocaine 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 afinish line in a race, you are tapping into this so-called mesecorticolimbic pathway.This is the classic rewardpathway in all mammals. The other pathway emergesfrom an area in the brain called the substantia nigra. So-called because the cellsin that area are dark, and the substantia nigraconnects to an area of the brain called the dorsal striatum. This is not surprisingly calledthe nigrostriatal pathway. For those of you who havenever done any neuroanatomy, I’m going to teach you alittle trick right now. Everything in neuroanatomy, the first part of a word tellsyou where the neurons are. And then the second part tells you where they are connecting to. So when I say nigropstriatal pathway, it means that the neuronsare in substantial nigra and they connect to thestriatum, nigrostriatal pathway. So while it’s a lot of languagethere, some logic there.Okay? So we’ve got these two pathways. One, mainly for movement, right? This is the substantianigra 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 thatthere are two pathways. If you don’t remember thetwo pathways in detail, that’s fine. But please remember thatthere are two pathways, because that turns outto be important later. Now, the other thing tounderstand about dopamine is that, the way that dopamine isreleased in the brain and body can differ. Meaning it can be very local, or it can be more broad. Now, most of you haveprobably heard of synapses. Synapses are the littlespaces between neurons, and basically neuronsnerve cells communicate with one another by makingeach other electrically active, or by making each otherless electrically active.So here’s how this works. You can imagine one nervecell 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 meansto become electrically active is that it vomits outthese little packets, what we call vesicles. They’re little bubblesfilled with a chemical, when that chemical enters the synapse, it some of it docks orparks on the other side, in the other neuron. And by virtue ofelectrical changes in the, what we call the postsynaptic neuron, that chemical will make thatneuron more electrically active or less electrically active. Dopamine can do that likeany other neurotransmitter or neuromodulator. So it can have one neuroninfluence another neuron. But dopamine can also engage in what’s called a volume metric release. Volumetric release is like agiant vomit that gets out to 50 or a hundred or even thousands of cells. So there’s local release whatwe call synaptic release, and then there’s volumetric release.So volumetric release is likedumping all this dopamine out into the system. So dopamine is incrediblebecause it can change the way that our neural circuitswork at a local scale and at a very broad scale. And for those of you thatare only interested in tools, like how do I get more dopamine? Let me tell you thispart is really important because if you were totake a drug or supplement that increases your level of dopamine, you are influencing both thelocal release of dopamine and volumetric release. This relates back tothe baseline of dopamine and the big peak above baseline. And that turns out to be important. And I’ll just alludeto why it’s important. Many drugs and indeed many supplements that increase dopamine willactually make it harder for you to sustain dopamine release over long periods of time. And to achieve those peaksthat most of us are craving when we are in pursuit of things.Why? Because if you get bothvolume metric release, the dumping out of dopamine everywhere, and you’re getting local release, what it means is that thedifference 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 onthe height of that peak, it depends on the heightof that peak relative to the baseline.So if you increase the baselineand you increase the peak, you’re not going to achievemore and more pleasure from things. I’ll talk about how toleverage this information in a little bit, but just increasing your dopamine. Yes, it will make youexcited for all things. It will make you feel very motivated, but it will also make thatmotivation very short-lived. So there’s a better wayto increase your dopamine. There’s a better way to optimize this peak to baseline ratio. For now what we’ve talked aboutis two main neural circuits, one for movement, and one for motivationand craving with dopamine. And we’ve talked about twomain modes of communication between neurons with dopamine.One is this local synaptic release. One is more volume metric release. And in the back of your mind, you can relate this back to, again, this baseline versuspeaks above baseline. So that’s a descriptionof what we would call the spatial effects or thespatial aspects of dopamine. I said this connects to that, that connects to this. You can get local or morebroad volumetric release. What about the duration of release or the duration of action for dopamine? Well, dopamine is uniqueamong chemicals in the brain, because dopamine unlike alot of chemicals in the brain works through what are calledG protein-coupled receptors. And for those of you thatare about to pass out from the amount of detail, just hang in there with me.It’s really not complicated. There are two ways thatneurons can communicate or mainly two ways. There are third and fourth, but mostly neuronscommunicate by two modes. One, are what we callfast electrical synapses ionotropic conduction. All right? You don’t need to know what that means, but basically one neuronactivates another neuron and little holes open up in that neuron, and ions rush in. Sodium is the main ion salt by which one neuron influencesthe electrical activity of another neuron becausesodium ions contain a charge.Okay? There are other things likechloride and potassium. If you’re interested in looking this up, just look up ionic conductancesin the action potential, or I could do a post on it some time and we could go into detail. But just understand that when neurons want to influence each other, they can do it by way of thisfast 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 arecalled G protein-coupled receptors. So what happens is dopamine is released in these little vesiclesthat I’ve mentioned before, get vomited out into the synapse. Some of that dopamine will bind to the so-called postsynaptic neuron, it’ll bind to the next neuron, and then it sets off a cascade. It’s kind of like a bucketbrigade of one thing, getting handed off to the next, to the next, to the next. It’s G protein-coupled receptors. And anytime you hear about these GPCRs or G protein-coupled receptors, pay attention becausethey’re really interesting. They’re slow, but they also can havemultiple cascades of effects.They can impact even geneexpression at some level. They can change what acell actually becomes. They can change how wellor how poorly that cell will respond to the samesignal in the future. So dopamine works throughthe slower process. These G protein-coupled receptors. And so its effects tend totake a while in order to occur. This aspect of dopaminetransmission is important because it now underscores two things. One, there’s two pathwaysfor dopamine to communicate. One for movement, one for motivation and craving. There’s two spatial scalesat 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. It can actually changethe way that cells behave. One thing that’s not oftendiscussed about dopamine, but is extremely important to know is that dopamine doesn’t work on its own.Neurons that release dopamineco-release glutamate. Glutamate is a neurotransmitter and it’s a neurotransmitterthat is excitatory, meaning it stimulates neuronsto be electrically active. So now even if you don’tknow 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 the dopaminestimulates action in general, because it releases thisexcitatory neurotransmitter. It tends to make certainneurons 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 thatdopaminergic transmission or dopamine tends tostimulate sympathetic arousal. Sympathetic doesn’t haveanything to do with sympathy. It’s 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 pursuethings outside the confines of its skin. So if I were to just puta really simple message around dopamine it would be, there’s a molecule in your brain and body that when released tends tomake you look outside yourself, pursue things outside yourself, and to crave things outside yourself.The pleasure that arrivesfrom achieving things also involves dopamine, but is mainly the consequencesof other molecules. But if ever you feltlethargic and like just lazy and you had no motivation or drive, that’s a low dopamine state. If ever you felt reallyexcited, motivated, even if you’re a littlescared 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 universalcurrency in all mammals, but especially in humansfor moving us toward goals and how much dopamine is inour system at any one time compared to how muchdopamine was in our system a few minutes ago, and how much we rememberenjoying a particular experience of the past. That dictates yourso-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 aredoing 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 issomewhere in the middle, how you feel depends on whether or not you had higher dopamine a fewminutes ago or lower dopamine. This is important, your experience of life andyour level of motivation and drive depends on how muchdopamine you have relative to your recent experience. This is again, somethingthat’s just not accounted for in the simplelanguage of dopamine hits. Okay? A simple way to envision dopamine hits is every time you do something you like, you to piece of chocolate, dopamine hit. You look at your Instagram, dopamine hit.You see someone you like, dopamine hit. All these thingsdescribed as dopamine hits neglect the fact that ifyou scroll social media and you see something you really like, dopamine hit. Sure there’s an increase in dopamine, but then you get tosomething else and you go, hmm, not that interesting. However, had you arrivedat that second thing first, you might think that itwas really interesting. If you had arrived tothat second Instagram post three days later or four days later, you might find it extremely interesting. Again, how much dopamine youexperience 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 neglectedby the general language of dopamine hits. This is why when yourepeatedly engage in something that you enjoy, your threshold for enjoymentgoes up and up and up.So I want to talk about that process. And I want to explainhow that process works, because if you understand that process, and you understand some ofthese schedules and kinetics as we call them around dopamine, you will be in a terrific position to use any dopamine enhancingtools that you decide to use. You’ll be in an excellentposition to modulate and control your own dopamine release for optimal motivation and drive. I realized that was a lot of information about the biology of dopamine, sort of like trying to make you drink from the fire hose of dopamine biology.However, I realized that some people probably want even more information about the biology ofdopamine transmission. If you’re interested in that, I’ll post a link to aabsolutely stellar review that was published inNature Reviews Neuroscience called spatial and temporalscales of dopamine transmission. It is quite detailed, but they have beautiful diagrams and can walk you through all the things that I just described andget into even more detail.We’ll put a link to thatin the caption on YouTube. Right now, I want to sharewith you two anecdotes, one from my own life, and one from some fairly recent history that illustrate some of thecore biology of dopamine and how profoundly itcan shape our experience. The first one is a reallytragic situation that occurred. This was in the 80s, there was a outbreak of whatlooked like Parkinsonian symptoms in a young population. So many of you heardof Parkinson’s disease. Parkinson’s disease is a diseasein which people initially start to quake, can’tgenerate smooth movements, they’ll have issues with speech, sometimes cognition as well.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. 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 street laboratories, illicit laboratories weretrying to make a drug called MPPP, which is anopioid light compound. It’s a bit like heroin, and heroin addicts seekingheroin went out and bought what they thought was MPPP. Unfortunately, it was not MPPP. I mean, it would have beentragic if it was anyway because they were drug addicts, but what they ended up takingturned out to be a lot worse.What they ended up taking was MPTP, and MPTP can arise inthe synthesis of MPPP. So someone in a lab someplace, this was mainly in theCentral Valley in California, but elsewhere as well. Somebody created MPTP, and what ended up happeningwas 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 dopaminetransmission were disrupted. They had no motivation and drive. They couldn’t generateany movement of any kind. They were literally locked in frozen. And sadly, this is irreversible. It’s irreversible, because what MPTP does is itkills the dopaminergic neurons of the substantia nigrathat nigrostriatal pathway that’s involved in generating movement.And it kills the dopaminergic neurons of the so-calledmesocorticolimbic pathway. I was in college when thiswhole MPTP thing happened. And I remember hearing this story. At the time, I had no understanding of what it is to have veryhigh levels of dopamine or extremely depleted levels of dopamine. There was no reason why Ishould have that understanding. I mean, of course I hadexperienced different pleasures of different kinds andI’ve had lows in my life, but nothing to the extremethat I’m about to discuss. I got Giardia. And Giardia is a stomach bugthat if any of you ever had it, it is terrible. It’s terrible diarrhea. You end up very dehydrated very quickly. You drop a ton of weight andit is extremely unpleasant. I ended up going to the emergency room, and in the emergency room, I begged them for somethingto stop up my guts. And they gave it to me. They put a saline line into rehydrate me and they injected somethinginto the saline bag.And within minutes I felt more sadness, more overwhelming sense of depression, basically, lower than I’dever felt in my entire life. It was absolutely profound. I was crying endlessly withoutknowing 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 toblock dopamine receptors. It’s what’s given to peoplewho have schizophrenia. Often is given to peoplewho have schizophrenia, because schizophreniainvolves 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 somethingto get my dopamine levels “back up again.” And they did. They gave me an injectionof l-DOPA into the bag, went straight to my bloodstream. And within minutes I felt fine again.It was incredible. And it really opened upmy mind and my experience to what it is to haveabsolutely plummeted levels of dopamine. And there’s nothing moremiserable than that I’ll tell you. And these poor souls whohad this MPTP experience, unfortunately, they couldn’trecover those cells. People who have severe Parkinson’s are struggling with this as well, because in Parkinson’sand 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 totalk 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 veryprecious for movement and mood and motivation.Having experienced what it isto have very, very low levels of dopamine or in this caseto have my dopamine receptors blocked from Thorazine waseye-opening to say the least, and has given me tremendoussensitivity to the fact that dopamine is perhaps oneof the most powerful molecules that any of us has inside of us. And the one that we ought toall think very carefully about how we leverage, because while mostexperiences and most things that we do, and take and eat and cetera, won’t create enormous highsand enormous lows in dopamine. Even subtle fluctuationsin dopamine really shape our perception of lifeand what we’re capable of, and how we feel.And so we want to guard thoseand we want to understand them. So let’s lean into thatunderstanding about dopamine. And then let’s talk about some tools that we can all use to leverage dopamine in order to keep thatbaseline in the appropriate, healthy place, and still be able to accessthose peaks in dopamine. Because those, after all aresome of what makes life rich and worth living. So let’s talk about thebaseline of dopamine that we all have and the peaks in dopamine that we all can achievethrough different activities and things that we ingest. All of us have differentbaseline levels of dopamine. Some of this is sure to be genetic. Some people just simply rideat 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 moreexcited or a lot more motivated.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 orfriends in the nervous system. And I’ll just name off afew of those close cousins and friends. Epinephrin also called adrenaline is the main chemical driver of energy. We can’t do anything, anything at all, unless we have some level of epinephrin in our brain and body. It’s released from the adrenal glands which right on top our kidneys.It’s released from anarea of the brainstem called locus coeruleus. And its release tends towake up neural circuits in the brain and wake up various aspects of our body’s physiologyand give us a readiness. So it should come as no surprise that dopamine andepinephrin aka adrenaline hang out together. In fact, epinephrin and adrenalineare actually manufactured from dopamine. There’s a biochemicalpathway involving dopamine which is a beautiful pathway. If ever you want to look it up, you can just look upbiochemistry of dopamine. But what you’ll find is that, l-DOPA is converted into dopamine. Dopamine is convertedto two noradrenaline. Norepinephrin, it’s also called. And noredrenaline,norepinephrin is converted into adrenaline. So not only are dopamine andepinephrin aka adrenaline close cousins, they are actually family members. Okay? They’re closely related. I’m not going to get toodeep into epinephrin today. I’m not going to talk toomuch about those pathways, but anytime I’m talking aboutdopaminergic transmission or that you have a peak in dopamine, inevitably, that meansthat you have a peak and release of epinephrin as well.What dopamine does isdopamine really colors the subjective experience of an activity to make it more pleasureful, to make it somethingthat you want more of. Epinephrin is more about energy. Epinephrin alone can befear, paralysis, trauma. Not physical paralysis,but mental paralysis, you know, frozen in fear orbeing traumatized or scared. But the addition of dopamineto that chemical cocktail, if dopamine is released in the brain, well, then that epinephrinbecomes one of excitement. Okay? I’m using a broad brush here, but essentially what youneed to know is that, dopamine and epinephrin akaadrenaline are family members. And they tend to worktogether like a little gang to make you seek out certain things. So what sorts of activities? What sorts of things increase dopamine? And how much do they increase dopamine? Well, let’s take a lookat some typical things that people do out thereor ingest out there that are known to increase dopamine. So let’s recall that you havea baseline level of dopamine and that everybody does.And even within a family, you might have family memberswho are very excitable, happy and motivated, and others who are lessexcitable, happy and motivated. But your level of dopamine has everything to do with those genetics, but also with what you’veexperienced in the previous days and the previous months and so on. When you do or ingest certain things, your levels of dopaminewill rise above baseline transiently. And depending on what you do or ingest, it will rise either more or less, and it will be very briefor a last a long time. So let’s take a look atsome 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 dopamineis increased above baseline? Now, of course, these are averages, but these are averagesthat have been measured in so-called micro dialysisstudies in animals. So actually extractingfrom particular brain areas how much dopamine is released? Or from measuring the serum, the circulating levelsof dopamine in humans.Chocolate. They didn’t look at milkversus dark chocolate. But chocolate will increaseyour baseline level of dopamine 1.5 times. Okay? So it’s a pretty substantialincrease in dopamine. It’s transient. It goes away after a fewminutes or even a few seconds. I’ll explain what determinesthe 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’sgoing to be variation there, but that’s the averageincrease in baseline dopamine caused by sex. Later, I will talk abouthow the different aspects of the so-called arousal art, the different aspects of sex, believe it or not have adifferential impact on dopamine. But for now as a generaltheme or activity, sex doubles the amountof dopamine circulating in your blood. Nicotine. In particular, nicotine that is smoked like cigarettes and so forth, increases dopamine two anda half times above baseline.So there’s a peak thatgoes 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 indopamine from nicotine is very short-lived. Cocaine will increasethe level of dopamine in the bloodstream two anda half times above baseline. And amphetamine anotherdrug that increases dopamine will increase the amount ofdopamine 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 muchsomebody subjectively enjoys that exercise. So if you’re somebody who loves running, chances are it’s going toincrease your levels of dopamine two times above your baseline, not unlike sex. People who dislike exercise will achieve less dopamine increase orno increase in dopamine from exercise. And if you like otherforms of exercise like yoga or weightlifting orswimming or what have you.Again, it’s going to vary byyour 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 actuallyhas a very specific part, which is your prefrontal cortex. The area of your forebrainthat’s involved in thinking and planning and involved in assigning a rational explanation to something, and involved in assigninga subjective experience to something, right? So for instance, the penthat I’m holding right now, it’s one of these Pilot V5s. I love these Pilot V5s. They don’t sponsor the podcast. I just happen to like them. I liked 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 becauseI have the propensity to release dopamine easily, it’s that as we startto engage with something more and more and what we say about it, and what we encourageourselves to think about it, has a profound impact on its rewarding or non rewarding properties.Now, it’s not simply the casethat 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 some form ofappreciation for something, or they think of some aspectof something that they enjoy, the amount of dopamine thatthat behavior will evoke tends to go up. So for people that hate exercise, you can think aboutsome aspect of exercise that you really enjoy. However, I will caution youagainst saying to yourself, I hate exercise or I hatestudying or I hate this person, but I love the reward Igive myself afterward. Later, we’re going to talk abouthow rewards given afterward actually make the situation worse. They won’t make you likeexercise more or study more, they actually will underminethe dopamine release that would otherwiseoccur for that activity.So certain things chemicalshave 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 and everybody that takes them. Things like exercise, studying, hard work, working through achallenge in a relationship or working throughsomething hard of any kind that is going to be subjective as to how much dopamine will be released. And we will return tothat subjective component in a little bit. But now you have a senseof how much dopamine can be evoked by different activities and by different substances. One that you might bewondering about is caffeine. I’m certainly drinking my caffeine today, and I do enjoy caffeinein limited quantities.I drink yerba mate and Idrink coffee and I love it. Does it increase dopamine? Well, a little bit. Caffeine will increasedopamine to some extent, but it is pretty modestcompared to the other things that I described. Chocolate, sex, nicotine,cocaine, amphetamine and so on. However, there’s areally interesting paper published in 2015. This is Volkow et al. You can look up it’s very easy to find.That showed that regularingestion of caffeine, whether or not it’s fromcoffee or otherwise, increases up regulation ofcertain dopamine receptors. So caffeine actually makesyou able to experience more of dopamines effects. Because as I mentioned before, dopamine is vomited out into the synapse or it’s released volumetrically, but then it has to bind someplace and trigger those Gprotein-coupled receptors. And caffeine increases the number, the density of those Gprotein-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 daysthat used to be a cigarette and a cup of coffee.Or when people drink alcohol, oftentimes they’ll smoke. And it’s well-knownthat different compounds like alcohol and nicotineor caffeine and nicotine or certain behaviors andcertain drugs can synergize to give bigger dopamine increases. And this is not terribly uncommon. There are a lot of people nowadays who for instance takepre-workout energy drinks. They’ll drink, 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 getthat big stimulation that stimulant effect for the dopamine, the norepinephrin, thatfamily of molecules that works together to make you motivated. And then they’ll also exerciseto try and get even more of a dopaminergic experienceout of that workout. Sometimes it’s also to performbetter as well, of course, but 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 themost out of experience, turns out to not be the best approach.And what you’ll find as wetalk 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 energyright after those experiences and even a couple of days later. So I’m not saying thatpeople shouldn’t take the occasional pre-workoutif that’s your thing, or drink a cup of coffeeor two before working out 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 yourcapacity to release dopamine and your level of motivationand drive and energy overall will take a serious hit. Now, I’ve been alludingto this dopamine peaks versus dopamine baseline things since the beginning of the episode. I talked about tonic andphasic release and so forth. But now let’s really drillinto what this means, and how to leverage itfor our own purposes. In order to do that, let’stake a step back and ask, why would we have adopamine system like this? Why would we have adopamine system at all? Well, we have to rememberwhat our species primary interest is? Our species like allspecies has a main interest, and that’s to make more of itself. And it’s just about sex and reproduction. It’s about forging for resources.Resources can be food, it can be water can be salt, it can be shelter, it can be social connection. Dopamine is the universalcurrency of forging and seeking, right? We call sometimes talk aboutmotivation and craving, but what we mean in theevolutionary adaptive context, what we mean is forging and seeking. Seeking water, seekingfood, seeking mates. Seeking things that make us feel good and avoiding things thatdon’t make us feel good. But in particular seeking things that will provide sustenanceand pleasure in the short-term and will extend thespecies in the long-term. Once we understand thatdopamine is a driver for us to seek things, it makes perfect sense as to why it would have a baselinelevel and it would have peaks. And that the baseline andpeaks 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 youlooked and you realized you had minimal water andyou 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 things. Okay? You need to be able to generate the energy to go seek those things. And chances are there weredangers in seeking those things. Yes, it could be saber-tooth 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 leavingyour 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 fossilrecord of the brain, but the circuits have existed. We know for tens of thousands, if not hundreds of thousands of years. And they are present in everyanimal, not just mammals, but even in little worms like C. elegans, it’s the same process. It’s mediated by dopamine. So dopamine drives you togo out and look for things. And then let’s say youfind a couple berries, and these ones are rotten, these ones are good. Maybe you hunt an animal and kill it, or you find an animalthat was recently killed and you decide to take the meat. You are going to achieve, or I should say, experiencesome sort of dopamine release. You found the reward. That’s great. But then it needs toreturn to some lower level. Why? Well, because if you just stayed there, you would never continueto forage for more. It doesn’t just increase yourbaseline 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 wentout seeking that thing. Now, this is counter-intuitive. We often think, Oh, okay, I’m going topursue the win, right? Let’s move this to modern day. 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, nowI’m set for the entire year, I’m going to feel so much better, I’m going to feel thisaccomplishment in my body, it’s going to be so great. That’s not what happens. You might feel some of those things, but your level of dopaminehas actually dropped below baseline. Now, eventually it will ratchet back up. But two things are really important. First of all, the extent towhich it drops below baseline is proportional to how high the peak was.So if you cross thefinish line pretty happy, it won’t drop that muchbelow 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 wherethat 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 celebrationthat postpartum drop in mood and affect andmotivation is the drop in baseline dopamine. This is very important to understand, because this happens onvery rapid timescales and it can last quite a long time. It also explains thebehavior that most of us are familiar with, of engaging in somethingthat we really enjoy.Going to a restaurantthat we absolutely love, or engaging in some way with some person that we really, really enjoy. But if we continue toengage in that behavior over and over again, it kind of loses its edge. It starts to kind offeel less exciting to us. Some of us experienced thatdrop in excitement more quickly and more severely than others, but everyone experiencesthat to some extent. And this has direct rootsin these evolutionarily conserved circuits. Some of you may be hearing this and think, no, no, no, no that’snot how it works for me.I’m just riding higherand higher all the time. I love my kids, I love my job, I love school, I love wins, I don’t want losses. I agree. We all feel good whenwe are achieving things, but oftentimes we are feeling good because we are layering indifferent 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 alittle while to get back to our stable baseline.We really all have a sortof dopamine set point. And if we continue toindulge in the same behaviors or even different behaviorsthat increase our dopamine in these big peaks overand over and over again, we won’t experience the same level of joy from those behaviors orfrom anything at all. Now, that has a name. It’s called addiction. But even for people who aren’t addicted, even for people don’t an attachment to any specific substance or behavior, this drop in bay below baselineafter any peak in dopamine is substantial.And it governs whether or notwe are going to feel motivated to continue to pursue other things. Fortunately, there’s away to work with this, such that we canconstantly stay motivated, but also keep that baseline of dopamine at an appropriate, healthy level. A previous guest on theHuberman Lab Podcast was Dr. Anna Lembke. She’s head of the AddictionDual Diagnosis Clinic at Stanford. Has this amazing book, “Dopamine Nation: Finding Balancein the Age of Indulgence”. If you haven’t read the book, I highly encourage you to check it out. It’s fantastic. The other terrific book about dopamine is the “Molecule of More”, which is a similar in some regard, but isn’t so much about addiction, it’s more about other types of behaviors. Both books really focus onthese dopamine schedules and the relationship between these peaks and baselines of dopamine.In Dr. Lembke’s book, and when she was on theHuberman Lab Podcast and other podcasts, she’s talked about thispleasure pain balance that when we seek somethingthat we really like, or we indulge in it, like eating a little piece of chocolate, if we really liked chocolate, there’s 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 aswanting more of that thing. Okay? So there’s a pleasure pain balance, and I’m telling you thatthe pleasure and the pain are governed by dopamine to some extent. Well, how could that be? Right? I said before, when youengage in an activity or when you ingest somethingthat increases dopamine, the dopamine levels go up, you know, to substantial degree with all the things I listed off. Where’s the pain coming from? Well, the pain is comingfrom the lack of dopamine that follows. And you now know what thatlack of dopamine reflects.How do you know? Well, earlier we weretalking about how dopamine is released between neurons. And I mentioned two ways. One, is into the synapsewhere it can activate the postsynaptic neuron. And the other was what Icalled volumetric release where it is distributed more broadly. It’s released out over a bunch of neurons. In both cases it’sreleased from these things we call synaptic vesicles, literally little bubbles,tiny, tiny little bubbles that contain dopamine. Prrr! 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 readilyreleasable pool of dopamine. We can only deploy dopaminethat is ready to be deployed. That’s packaged in those littlevesicles and ready to go. It’s like when you order aproduct 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 ofdopamine that synthesized, and you can only release the dopamine that’s been synthesized. It’s the readily releasable pool.The pleasure pain balancedoesn’t only hinge on the readily releasablepool of dopamine, but a big part of thepleasure pain balance hinges on how much dopamine is there? And how much is ready andcapable 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 alot of dopamine around to keep your baseline going.Fortunately, most people do not experience or pursue enormous increases in dopamine leading to the severe drops in baseline. Many people do, however, and that’s what we call addiction. When somebody pursuesa 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, that readily releasable pool. The dopamine is literallynot around to be released, and so people feel pretty lousy and many people make the mistakeof then going and pursuing the dopamine evoking thedopamine releasing activity or substance again thinking mistakenly that it’s going tobring 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 depletingdopamine more and more and more. And we’ve seen this over and over again when people get addicted to something then they’re not achievingmuch pleasure at all. You can 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 playingand playing and playing, and either one of two thingshappens typically both. First of all, I always say addiction isa progressive narrowing of the things that bring you pleasure. So oftentimes what willhappen is the person only has excitement and canachieve dopamine release to the same extent doing that behavior and not other behaviors. And so they start losinginterest in school, they start losinginterest in relationships. they start losing interestin fitness and wellbeing 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 apretty serious depression and this can get very severe and people have committed suicide fromthese sorts of patterns of activity.But what about the more typical scenario? What about the scenario of somebody who is really good atworking during the week, they exercise during the week, they drink on the weekends? Well, that person isonly consuming alcohol maybe one or two nights a week, but oftentimes that sameperson will be spiking their dopamine with foodduring the middle of the week. Now, we all have to eatand 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 alot of dopamine release in the middle of the week, they’re drinking one ortwo days on the weekend, they are one of thesework, hard play hard type.So they’re swimming acouple miles in the ocean in the middle of the week as well. They’re going out dancingonce on the weekend. Sounds like a pretty balancedlife as I describe it. Well, here’s the problem. The problem is thatdopamine is not just evoked by one of these activities, dopamine is evoked byall of these activities. And dopamine is one currencyof craving motivation and desire and pleasure. There’s only one currency. So even though if youlook at the activities, you’d say, well, it’s just on the weekends so this thing is only acouple of times a week. If you looked at dopaminesimply as a function, as a chemical functionof peaks and baseline, it might make sense why this person after several years ofwork hard, play hard would say, yeah, you know I’mfeeling kind of burnt out.I’m just not feeling likeI have the same energy that I did a few years ago. And of course thereare age-related reasons why people can experience drops in energy, but oftentimes what’s happening is not some sort of depletionand cellar metabolism that’s related to aging. What’s happening is they’respiking their dopamine through so many differentactivities throughout the week, that their baseline isprogressively dropping. And in this case it can be very subtle. It can be very, very subtle. And that’s actually a verysinister function of dopamine we could say. Which is that it can oftendrop in imperceptible ways, but then at once it reachesa threshold of low dopamine, we just feel like, hmm, we can’t really getpleasure from anything anymore. What used to work doesn’t work anymore. So it starts to look a lotlike the more severe addictions or the more acute addictionsto things like cocaine and amphetamine which leadto these big increases, these big spikes in dopamine, and then these very severedrops in the baseline.Now, of course, we allshould engage in activities that we enjoy. I certainly do, everybody should. A huge part of life ispursuing activities and things that we enjoy. The key thing is tounderstand this relationship between the peaks and the baseline, and to understand how theyinfluence one another. Because once you do that, you can start to make reallygood choices in the short run and in the long run tomaintain your level of dopamine baseline. Maybe even raise thatlevel of dopamine baseline and still get those peaks andstill achieve those feelings of elevated motivation,elevated desire and craving. Because again, those peaksand having a sufficiently healthy high level of dopamine baseline are what drove theevolution of our species, and they’re really what drivethe evolution of anyone’s life progression too. So they’re a good thing. Dopamine is a good thing. Just very briefly, becauseit was also covered in the interview episodeI 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 withsome activity or some substance that led to big peaks? Just to put some colorand example on this, a few episodes ago I talked about a friend who I’ve known a long time.So it actually the child of a friend who has basically becomeaddicted to video games, he decided actually afterseeing that episode with Anna to do a 30-day complete fast from phone, from video games and fromsocial media of all kinds. He’s now at day 29 hasreally accomplished this, not incidentally, hislevels of concentration, his overall mood are up. He’s doing far far better. What he did is hard. In particular first 14days is really hard, but the way that youreplenish the releasable pool of dopamine is to notengage in these dopaminergic seeking behaviors.Because remember typicallypeople arrive at a place where they want to stopengaging in these behaviors or ingesting substances whenthat 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 ADHD. And certainly there are peopleout there who have ADHD, but what he found was thathis levels of concentration are back. He does not need to be treated for ADHD. And actually the psychiatristwondered 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 very specific, but very relevant exampleof how the dopamine system can replenish itself. Of course, if there’s a clinicalneed for ADHD treatment, by all means pursue that. But I think a lot ofADHD does go misdiagnosed because of this depletion in dopamine that occurs because ofoverindulgence in other activities in the drop in baseline.So for anyone that’s experienceda real drop in baseline who has addictive tendencies, whether or not theirbehaviors or substances, that is always goingto be the path forward. Is going to be either cold turkey or through some sort oftapering to limit interactions with the, what would otherwisebe the dopamine evoking behavior or substance. So let’s talk about the optimalway to engage in activities or to consume things that evoke dopamine. And by no means am Iencouraging 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 evoking activitiesare things like chocolate, coffee, even if it’s indirect. Sex and reproduction, provided it’s healthyconsensual context appropriate, age appropriate, speciesappropriate of course, is central to our evolutionand progression as a species. So certain things likecocaine, 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 thatevokes your dopamine.How are we supposed to engagewith these dopamine evoking activities in ways that arehealthy and beneficial for us? How do we achieve these peaks, which are so central to ourwellbeing and experience of life without dropping our baseline? And the key lies in intermittentrelease of dopamine. The real key is to notexpect or chase high levels of dopamine release every time we engage in these activities. Intermittent reward schedulesare the central schedule by which casinos keep you gambling. The central schedule bywhich elusive partners or potential partners keepyou texting and pursuing on either side of the relationship. Intermittent schedules arethe way that the internet and social media and allhighly engaging activities keep you motivated and pursuing.And we can take this backto our evolutionary adaptive scenario where you are outthere looking for water, looking for food, not every trail, not everypursuit, 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 calleddopamine 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 toengage 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 averagethe house really does win. You can transplant thatexample to any number of different pleasureful activities. If you’re not a gambler andthat doesn’t appeal to you, I have to imagine there’ssomething that appeals to you, something that you dorepeatedly because you enjoy it. And almost inevitably it’sbecause there’s an intermittent schedule. There’s a intermittentschedule 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 scheduleto export to other activities. How do you do that? Well, first of all, if youare engaged in activities school, sport, relationship, et cetera, where you experience a win, you should be very carefulabout allowing yourself to experience huge peaks in dopamine, unless you’re willing tosuffer the crash that follows and waiting a period oftime for it to come back up. What would this look likein the practical sense? Well, let’s say you are somebody who really does enjoy exercise, or let’s say you’re somebodywho kind of likes exercise, but forces yourself to do it, but you make it pleasurefulby 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 exceptthat by layering together all these things to try andachieve that dopamine release, and by getting a big peak in dopamine, you’re actually increasing thenumber of conditions required to achieve pleasure fromthat activity again. And so there is a formof this where sometimes you do all the things that you love to get the optimal workout. You listen to your favorite music, you got your favorite time of day, you have your pre-workout drink, if that’s your thing.You do all the things thatgive you that best experience of the workout for you. But there’s also a versionof this where sometimes you don’t do the dopamineenhancing activities. You don’t ingest anythingto increase your dopamine. You just do the exercise. You don’t do the exerciseand expect dopamine to arrive through some what we callexogenous source as well. You might think, well, that sounds lame. I want to continue to enjoy exercising. Ah, well, that’s exactly the point. If you want to maintainmotivation for school, exercise, relationships or pursuitsof any duration in kind, the key thing is to make surethat 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 muchdopamine you experience with each engagement in that activity. Now, some activities naturallyhave 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 A’s, sometimes we don’t getrewarded with the outcome that we would like. We don’t always have theperfect relationship outcome, but understand that yourability to experience motivation and pleasure for what comes next is dictated by how muchmotivation and pleasure and dopamine you experienced prior. The reason I can’t givea very specific protocol like delete dopamine or lowerdopamine every third time, is that that wouldn’t be intermittent. The whole basis ofintermittent reinforcement is that you don’t reallyhave 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 docertainly works for them and for activities that youwould like to continue to engage in over time, whatever those happen to be. Start paying attentionto the amount of dopamine and excitement and pleasurethat you achieve with those, and start modulatingthat somewhat at random. That might be removingsome of the dopamine releasing chemicals thatyou might take prior.Maybe you remove them every time, but then every once in awhile you introduce them,. Maybe it involves sometimesdoing things socially that you enjoy doing socially, sometimes doing the same thing, but alone. There are a lot ofdifferent ways to do this. There are a lot of differentways to approach this, but now knowing what you knowabout peaks and baselines in dopamine andunderstanding how important it is not just to achieve peaks, but to maintain thatbaseline at a healthy level, it should be straightforwardfor you to implement these intermittent schedules.For those of you that arebegging for more specificity, we can give you a tool. One would be, you can flipa coin before engaging in any of these types of activities and decide whether or notyou are going to allow other 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? It sounds like you’reundercutting your own progress, but actually you areserving your own progress both short-term andlong-term by doing that. Now, the smartphone isa very interesting tool for dopamine in light of all this. It’s extremely commonnowadays to see people texting and doing selfies andcommunicating in various ways, listening to podcasts, listening to music, doing all sorts ofthings 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 andrichness and color to life, but it isn’t just aboutour distracted nature when we’re engaging with the phone, it’s also a way of layering in dopamine. And it’s no surprisethat levels of depression and lack of motivation arereally on the increase. Everything that we’vetalked about until now sets up an explanation or interpretation of why interacting with digital technology can potentially lead to disruptions or lowering in baselinelevels 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 alittle 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 loseinterest in what I was doing. It wasn’t as pleasureful, I would feel like itjust didn’t have the same kind of oomph. And I was beginning toquestion my motivation. As I started learning moreabout this relationship between the peaks and thebass lines in dopamine. What I realized was that some time ago I probably experienceda incredible increase in the amount of dopamineduring one of my workouts, because I enjoy working outand 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 toomany of them too many times. And then it essentiallywasn’t working for me anymore. Much in the same way a drugwouldn’t work for somebody who takes it repeatedly becausetheir 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 myphone 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 justdon’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 Ithink has been misinterpreted as people can’t be alone now. People talk about, oh, you know, they can’t walk across thestreet or they can’t go anywhere, ride the bus, can’t be on the planewithout being in contact. They can’t handle just their thoughts. I don’t think that’sreally what’s going on. I think what’s happenedis that we achieved the great dopamine increase that comes from this incredible thing which I personally enjoy beingable to communicate by phone, by text and exchangepictures and send links and these kinds of things, social media.But then what happens isit 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 hardone for many people, but I do invite you totry removing multiple sources of dopamine release or what used to be multiplesources of dopamine release from activities that youwant to continue to enjoy, or that you want to enjoy more. And now you understandthe biological mechanisms that would underlie a statement like that. It takes a little bit of working with, I know it can be challengingin 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 placewhere I enjoy it that much more. I also feel as if I conquered something in terms of the circuitryrelated to dopamine. I now understand why something that I enjoyed so much hadbecome less pleasureful for me. And there’s a deep, deep satisfaction that comes from understanding, okay, there wasn’t anything wrong with me or what I was doing or anything at all. It was just there was somethingwrong with the approach I was taking, which was layering in allthese sources of dopamine and dropping my baseline.For this very same reason, I caution people againstusing 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 upregulatethese D2, D3 receptors. So it actually makes whatever dopamine is released by that activity, more accessible or morefunctional within the biochemistry and the pathways of your brain and body. However, a number of energy drinks and particular pre-workouts contain things that are precursors to dopamine, and on their own, even if youdidn’t engage in the activity would cause the release ofdopamine to a substantial degree. They do cause the release of dopamine to a substantial degree. And over time that willdeplete your dopamine. So energy drinks, pre-workout drinks, drugs of various kindsthat people take to study and pay attention.We talked about some ofthese for the ADHD episode, things like Adderall, Ritalin,armodafinil or modafinil taken repeatedly over time will reduce the level of satisfaction and joy that you get from the activities you engage in while under theinfluence of those compounds. 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 tocontinue to feel pleasureful is undercutting the process. And inevitably might not happen tomorrow, might not happen in a month, but inevitably you will havechallenges with motivation and drive related to those activities. Now, some people cankeep it right in check. They can just do the onecan have the energy drink or they only do their pre-workoutbefore really hard days, for instance. More power to you. I actually do that sometimes, frankly. But people who are tryingto get into that peak super motivated, driven, driven state, really focused every timethey engage in an activity, you are absolutelyundercutting the process and you are undermining yourability to stay motivated and focused. So just as we talked aboutintermittent reward schedules a moment ago, intermittent spiking ofdopamine if you do it at all is definitely the way to go, and chronically tryingto spike your dopamine in order to enhance yourmotivation, focus and drive will absolutely undermine yourmotivation focus and drive in the long run.Ingestion of caffeine issomewhat of an exception among the other examples of things I’ve mentioned to avoid before what would otherwise bedopamine increasing activities. Because again, caffeinecan increase the density and the efficacy ofthese dopamine receptors. It turns out that the sourceof caffeine could also matter while coffee or tea orother forms of caffeine will have this effect ofincreasing dopamine receptors.Yerba mate somethingI’ve talked about before on this podcast has someinteresting properties. First of all, it contains caffeine. It’s also high in antioxidants. It also contains something called GLP-1 which is favorable formanagement of blood sugar levels. Yerba mate turns out has also been shown to be neuroprotective specificallyfor dopaminergic neurons. Now, I should mention thisis just a couple of studies, so we don’t want to concludetoo 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 compoundswithin yerba mate can actually serve topreserve the survival of dopamine neurons in boththe movement related pathway and the motivation pathway. So perhaps you need that incentive in order to ingest your yerba mate, perhaps you don’t need any incentive. In my case, I don’t need any incentive. I already enjoy yerba mate as my principle 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 mateboth for sake of upregulating dopamine receptors and gettingmore of a dopamine increase.And of course, for thesimilar properties of caffeine if that’s what you’re seeking. And in addition to that, because your yerba mate does appear to have some sort of neuroprotective and a particular dopamineneuron protective properties. Now, that doesn’t mean thatcaffeine is always beneficial. And actually there’s oneinstance related to dopamine where caffeine can beparticularly dangerous. And this relates toMDMA so-called ecstasy. MDMA is under investigationin various clinical trials for its potential to treattrauma and depression. It’s also of course, a drugthat’s used recreationally. It’s still illegal atleast in the United States. Whether or not MDMA is neurotoxic has been very controversial.Early on it was thoughtthat 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 particularbecause one of the early papers published in science magazine claiming that MDMA was neurotoxic. That paper was retracted. It turns out that thatstudy had mistakenly used methamphetamine instead, and methamphetamine isknown to be neurotoxic. I think most of the data point to the idea that MDMA might not be neurotoxic, but in any case, caffeinehas been shown to increase the toxicity of MDMA receptors.And you might say, “Well,how could that be?” Well, now you understandwhy that could be. Caffeine increases thedensity and efficacy of these dopamine receptors,D2 and D3 receptors. MDMA is a potent drug forincreasing concentrations of dopamine as well as serotoninand other neuromodulators. And it appears that caffeineingestion by upregulating these receptors, can lead to more toxicity of MDMA. So caffeine can be a beneficialsubstance in one context, and actually can be a detrimental if not dangerous substancein another context. Two substances thatgreatly increase dopamine, namely amphetamine and cocainecan 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 proceeds in the National Academy of Sciences, a very high tier stringent journal.First author is Kolb, K-O-L-B. And the title of the paperpretty much tells the story. Amphetamine or cocaine limits the ability of later experience topromote structural plasticity in the neocortex and nucleus accumbens. Neocortex is the outer shellof the brain more or less. And the nucleus accumbens is part of that, mesolimbic dopamine pathwayfor motivation drive and reinforcement. Neuroplasticity of course, isthe brain’s ability to change in response to experience. And neuroplasticity is thebasis of learning and memory and essentially remodelingof our neural circuitry in positive ways of all kinds. And this study was reallyone of the first to show that ingesting amphetamine and cocaine because of the high peak in dopamine that it creates andthe low dopamine state, the baseline drop thatit 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 asa serious cautionary note that amphetamine and cocainenot only can cause a drop in baseline dopamine, but can actually putthe brain into a state in which it cannot learn andmodify itself to get better at least for some period of time.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 verylarge increases in dopamine, and for people with ADHD canreally improve their symptoms. But of course there’s alot of non-prescription, non-clinical use ofthose compounds as well. And it stands to reason thatthe use of those substances to increase dopaminecould very well provide the same sort of blockadeof neuroplasticity that cocaine and amphetamine do. Because when you look at theamount of dopamine increase that’s triggered by those compounds, it’s really comparable. So again, a cautionary noteagainst spiking one’s dopamine too much on a regular basis, unless there’s a validclinical need for doing that. So we’ve been focusing alot for the last few minutes on the kind of darker side of dopamine and how getting big peaks indopamine can be detrimental, but I want to acknowledge the truth, which is that dopamine feels great.Being in pursuit andmotivated and craving things feels wonderful. And I don’t want to demonize dopamine. What I’m trying to dotoday is to illustrate how dopamine works in your brain so that you can continue to engage in dopamine evoking activities. And certainly there is aplace for ingesting things that can increase dopamineprovided that they are safe for us in the short and long-term. There are activities thatwe can do that will give us healthy, sustained increases in dopamine, both the peaks when theyhappen and to maintain or even increase ourbaseline levels of dopamine. So how do we do that? What are some of these activities? Well, in recent years, there’s been a trend toward more people doing so-called cold exposure. In part, this was popularized by Wim Hof, the so-called ‘Iceman’getting into cold showers, taking ice baths, exposingoneself to cold water of various kinds can in factincrease our levels of dopamine as well as the neuromodulatornorepinephrine. This is not a new phenomenon.In the 1920s, a guy by thename of Vincent Priessnitz was one of the first peopleto popularize and formalize cold water therapies. He was an advocate of cold water exposure in order to boost the immune system and increase feelings of wellbeing. And actually this practice dates back long before Vincent’s popularized it. And Wim Hof is the morerecent iteration of this. First of all, some ofthe safety parameters. Let’s establish those first. Getting to very, very cold water. You know, 30 degree Fahrenheit or even low 40 degree Fahrenheit can put somebody into astate of cold water shock. I mean, people can die doing that. So obviously you want toapproach this with some caution, but for most people gettinginto 60 degree water or 50 degree water, or if you’re acclimatedand comfortable with it, you know, 40 degreewater or 45 degree water can have tremendously beneficial results on your neuromodulatorsystems, including dopamine. What temperature of water you can tolerate will depend on how coldwater adapted you are, and how familiar youare with the experience of getting into cold water. And when I say comfortable with, I should mention, there is never a case in which getting intocold water does not evoke a release of epinephrin.So the quickening of the breath,the widening of the eyes, the feeling as if youcan’t catch your breath and even some physical painat the level of the skin that happens almost every time, or every time that youget into cold water, even if your cold water adapted. What almost everybody knowsand understands is that, that wall, as I like torefer to it is coming.That’s always the first experience of getting into cold water. There’s no real way around that. Now, this study that I mentioned earlier, human physiological responsesto immersion into water of different temperatures, really interesting studythat was done and published in the university of, excuse me, the European Journalof Applied Physiology. I can provide a link to thatstudy in the show caption. It’s a really interesting study. They looked at peoplegetting exposed to water that was warm, moderatelycold or very cold. It was 32 degrees Celsius,20 degrees Celsius, or 14 degrees Celsius. You can just put thoseonline and do the conversion, or you can do the conversionto Fahrenheit if you like. But in any case, what theylooked at were the concentrations of things like epinephrinand dopamine and so on. And what they foundwas really interesting. First of all, upongetting into cold water, the changes in adrenalineand noradrenaline, epinephrin and norepinephrinewere immediate and fast, and these were huge increases.So that’s the getting into the cold water that everybody experiences these huge increases in adrenaline. But then what wasinteresting is they observed that dopamine levels startedto rise somewhat slowly and then continued torise and reach levels as high as 2.5 times above baseline. That’s a remarkably high increase. Remember if we go back to ourexamples of chocolate, sex, a doubling above baseline, nicotine two and a half timesabove baseline, cocaine.The increase in dopaminefrom a cold water exposure of this kind was comparableto what one sees from cocaine, except, except in this case, it wasn’t a rise and crash. It was actually asustained rise in dopamine that took a very longtime up to three hours to come back down to baseline. Which is really remarkable, and I think this explainssome of the positive, mental and physical effectsthat people report subjectively after doing cold water exposure. One question that many ofyou are probably asking is just how cold should the water be? Well, you could mimic whatwas done in this study and do 14 degrees Celsius.But for some people thatwon’t be cold enough, for some people that will be too cold. They did look at therelease of stress hormones like cortisol in additionto the release of things like epinephrin and adrenaline. And it’s interesting thatthey noted that in all cases, but especially at thatcoldest temperature, there was an increase in cortisol, but that it was transient, That eventually people’s cortisol, the stress hormone subsided a bit. There are basically twodifferent approaches to remaining in the coldwhen it’s uncomfortable. One is to try and relax yourself. Two, try and practice slow breathing, to try and dilate your gaze.I’ve talked about thisbefore in previous podcasts, you go into panoramicvision to essentially try and calm yourself so thatit’s not as stressful in the cold. Other people however, take theapproach of trying to ramp up their level of internal autonomic arousal, meaning to get really energized and kind of lean intothe friction of the cold. And they find that easier. Other people distract themselves, they recite the alphabet, or they do something, anything to try and distract themselvesfrom the discomfort. To be totally honest, it does not matter forsake of dopamine release. Because the dopamine release is triggered and then continues even afteryou get out of the cold water. Now, in this study, it waslong exposure to cold water. It was an hour. That’s a long period of time. And I do warn you againstgetting into cold water that’s so cold that it willmake your temperature drop and make you hyperthermic for an hour. That actually could bedangerous for a lot of people. You might have a hard time reheating, and hypothermia is not a good thing.They had people monitoringsubjects in these studies and paying attention totheir core body temperature. They were able to reheat them afterwards. It’s well-established nowthat getting into cold water, whether or not it’s a shower, an ice bath circulating coldwater, a stream, et cetera, that can evoke the norepinephrinerelease immediately, and the long arc of that dopamine release. Why would that be good? Up until now, I’ve basicallysaid getting increases in dopamine are detrimentalto your baseline. Well, this does appear toraise the baseline of dopamine for substantial periods of time. And most people report feelinga heightened level of calm and focus after getting out of cold water. So cold water exposure turns out to be a very potent stimulus for shifting the entire milieu, the entire environmentof our brain and body and allowing many peopleto feel much, much better for a substantial period of time after getting out of the icebath or cold water of any kind than they did before.Now, you might ask how often to do this? Some people do this every day. It can be very stimulating. So typically doing it early in the day, it’s going to be better. I don’t necessarily recommenddoing it right before sleep, but some people do it in the afternoon. And some people will indeeddo that seven days a week, other people three days a week, other people every once in a while. What I can say is once youbecome cold water adapted, once it no longer has thesame impact of novelty and feeling a bit like a, I don’t want to say ashock to your system, ’cause you don’t want togo into cold water shock, but once it is comfortable for you, then it will no longer evoke this release.There really does seem tobe something in the pathway from cold water exposure throughthe norepinephrine pathway and into the mesolimbic brainstem that causes this release in dopamine. But nonetheless, it’sa basically zero cost. I mean, you need accessto water of some sort, cold water shower, et cetera, but basically zero cost wayof triggering a long lasting increase in dopaminewithout ingesting anything, no pharmacology whatsoever. Please again, approach it witha safety and caution in mind, but it is a very potent stimulus.Again, 250% of a rise in baseline, two and a half timesrise in baseline rivals that of cocaine whichis really remarkable. Now, I’d like to talkabout the positive aspects of rewards for our behavior, and the negative aspects ofrewards for our behavior. And from that, I will suggest a protocol by which you can achievea better relationship to your activities andto your dopamine system. In fact, it will help tuneup your dopamine system for discipline, hard work and motivation.Hard work is hard. Generally, most peopledon’t like working hard. Some people do, but most people work hard inorder to achieve some end goal. End goals are terrificand rewards are terrific whether or not they aremonetary social or any kind. However, because of theway that dopamine relates to our perception of time, working hard at somethingfor sake of a reward that comes afterward, can make the hard workmuch more challenging and make us much less likelyto lean into hard work in the future. Let me give you a coupleexamples by way of data and experiments. There’s a classic experimentdone actually at Stanford many years ago in whichchildren in nursery school and kindergarten drew pictures, and they drew picturescause they like to draw. The researchers tookkids that liked to draw and they started givingthem a reward for drawing.The reward generally was a gold star or some thing that a youngchild would find rewarding. Then they stopped givingthem the gold star. And what they found is the children had a much lower tendencyto draw on their own. No reward. Now, remember this was an activity that prior to receiving a reward, the children intrinsicallyenjoyed and selected to do. No one was telling them to draw. What this relates tois so-called intrinsic versus extrinsic reinforcement. When we receive rewards, even if we give ourselvesrewards for something, we tend to associate lesspleasure with the actual activity itself that evoked the reward. Now, that might seem counterintuitive, but that’s just way that the way that these dopaminergic circuits work. And now understanding thesepeaks in baselines in dopamine which I won’t review again, this should make sense. If you get a peak indopamine from a reward, it’s going to lower your baseline and the cognitive interpretation is that you didn’t really do the activity because you enjoyed the activity. You did it for the reward. Now, this doesn’t mean allrewards of all kinds are bad, but it’s also important to understand that dopamine controlsour perception of time.When and how much dopamine we experience is the way that we carve up what we call our experience of time. When we engage in an activity, let’s say school or hard work of any kind or exercise because of the reward we are going to give ourselvesa receive at the end, the trophy, the sundae, themeal, whatever it happens to be. We actually are extending the time bin over which we are analyzingor perceiving that experience. And because the reward comes at the end, we start to dissociate the neural circuits for dopamine reward that wouldhave normally been active during the activity.And because it all arrivesat the end over time, we have the experienceof less and less pleasure from that particular activitywhile we’re doing it. Now, this is the antithesisof growth mindset. My colleague at Stanford, CarolDweck, as many of you know, has come up with thisincredible theory and principle, and actually goes beyondtheory and principle called “Growth Mindset”, which is this striving to bebetter to be in this mindset of I’m not there yet, but striving itself is the end goal. And that of course deliversyou to tremendous performance. It’s been observed overand over and over again, that people that have growth mindset, kids that have growth mindsetend up performing very well because they’re focusedon the effort itself. And all of us cancultivate growth mindset. The neural mechanism ofcultivating growth mindset involves learning to accessthe rewards from effort and doing. And that’s hard to dobecause you have to engage this prefrontal componentof the mesolimbic circuit.You have to tell yourself,okay, this effort is great, this effort is pleasureful. Even though you mightactually be in a state of physical pain from the exercise, or I can recall this from college, just feeling like I wantedto get up from my desk, but forcing myself to study, forcing myself and forcing myself. What you find over time isthat you can start to associate a dopamine release. You can evoke dopaminerelease from the friction and the challenge thatyou happen to be in. You completely eliminatethe ability to generate those circuits and therewarding process of being able to reward friction while in effort, if you are focused only on thegoal that comes at the end. Because of the way thatdopamine marks time. So if you say, oh, I’m goingto do this very hard thing, and I’m going to push andpush and push and push for that end goal that comes later.Not only do you enjoy the processof what you’re doing less, you actually make it more painful while you’re engaging in it. You make yourself less efficient at it, because if you were able toaccess dopamine while in effort, dopamine has all theseincredible properties of increasing the amountof energy in our body, and in our mind, our ability to focus by way of dopaminesconversion into epinephrin. But also you’re underminingyour ability to lean back into that activity the next time. The next time you needtwice as much coffee and three times as much loud music, and four times as much energy drink and the social connectionjust to get out the door in order to do the run or to study.So what’s more beneficialin fact can serve as a tremendous amplifier on all endeavors that you engage in. Especially hard endeavors is to A, not start layering inother sources of dopamine in order to get to the starting line, not layering in other sources of dopamine in order to be able to continue, but rather to subjectively start to attach the feeling of friction and effort to an internally generated reward system. And this is not meant to be vague, this is a system that exists in your mind, that exists in the minds of humans for hundreds of thousands of years, by which you’re notjust pursuing the things that are innately pleasureful, food, sex, warmth, waterwhen you’re thirsty. But the beauty of thismesolimbic reward pathway that I talked about earlier is that, it includes the forebrain. So you can tell yourself theeffort part is the good part. I know it’s painful, I know this doesn’t feel good, but I’m focused on this.I’m going to start to access the reward. You will find the rewards, meaning the dopaminerelease inside of effort if you repeat this over and over again. And what’s beautiful about it is that, it starts to become reflexivefor all types of effort. When we focus only on the trophy, only on the grade, only on the win as the reward, you undermine that entire process. So how do you do this? You do this in those momentsof the most intense friction.You tell yourself this is very painful and because it’s painful, it will evoke an increasein dopamine release later, meaning it will increasemy baseline in dopamine, but you also have to tell yourself that in that moment youare doing it by choice and you’re doing it because you love it. And I know that soundslike lying to yourself, and in some ways it is lying to yourself, but it’s lying to yourselfin the context of a truth which is that you want it to feel better. You want it to feel even pleasureful. Now, this is very far and away different from thinking about thereward that comes at the end, the hot fudge sundae for afteryou cross the finish line and you can replace hot fudge sundae with whatever reward happensto be appealing to you. We revere people who are capable of doing what I’m describing. David Goggins comes to mindis a really good example.Many of you are probablyfamiliar with David Goggins, former Navy SEAL who essentially has made a post-militarycareer out of explaining and sharing his processof turning the effort into the reward. There are many other examplesof this too, of course. Throughout evolutionary history, there’s no question that we revered people who were willing to go outand forage and hunt and gather and caretake in ways that other members of our species probably found exhausting and probably would have preferredto just put their feet up or soaked them in a cool stream rather than continue to forage. The ability to accessthis pleasure from effort aspect of our dopaminergic circuitry is without question the mostpowerful aspect of dopamine and our biology of dopamine.And the beautiful thing isit’s accessible to all of us. But just to highlight thethings that can interfere with, and prevent you fromgetting dopamine release from effort itself, don’t spike dopamine priorto engaging in effort. And don’t spike dopamineafter engaging in effort, learn to spike yourdopamine from effort itself. One straightforward exampleof learning to attach dopamine to effort and strainas opposed to a process or a reward that naturallyevokes dopamine release is so-called intermittent fasting. I know this is very popular nowadays. Some people like to dointermittent fasting, some people don’t. Some people have a 12 hourfeeding window every 24 hours, some people do long fastsof two to three days even. I personally don’tmonitor a feeding window with a lot of precision. I tend to skip one meal a day, either breakfast or lunch, and then I eat the othertwo meals of the day depending on which meal I skipped. So it’s either breakfast, lunch and maybe a littlesomething in the evening, or I’ll skip breakfast and dolunch and dinner and so on.Many people are noweating this way in part, because many people findit easier to not eat at all than to eat a smallerportion of some food. And that has everything todo with the dopamine reward evoking properties of food. When we ingest food or whenwe are about to ingest food, our dopamine levels go up. And typically when we ingest food, if it evokes some dopamine release, then we tend to want even more food. Remember dopamine’s mainrole is one of motivation and seeking. And what dopamine always wantsmore of is more dopamine. More activity or thing thatevokes more dopamine release. Well, let’s just look at fasting from the perspective of dopamine schedules and dopamine releaseand peaks and baselines.Typically, when we eatwe get dopamine release, especially when we eatafter being very hungry. If you’ve ever gone camping, or you’re very, very hungry, the food tastes that much better. And that’s actually because of the way that deprivation states increase the way that dopaminergic circuits work. Our perception of dopamine is heightened when the receptors for dopamine have not seen much dopamine lately, they haven’t bound much dopamine. So when you fast, fast, fast, fast, fast, and then you finally eat, it evokes more dopamine release. So this is the big rewardthat comes at the end. Even bigger because you deprived yourself. This is true for all rewardingbehaviors and activities by the way. The longer you restrictyourself from that activity, the greater the dopamineexperience when the dopamine is finally released, because of an upregulation ofthe receptors for dopamine. but I just spent fiveminutes or more telling you that you should avoid toomuch reward at the end, and you should actuallyfocus on the dopamine that you can consciously evokefrom the deprivation strain and effort.And in fact, this is whathappens for many people that start doing fastingand take a liking to it. Many people say that their state of mind when they fast is clearer, that they actually start toenjoy the period of fasting. In fact, some people startpushing out their eating window or skipping entire daysof eating more and more in order to get deeperinto that state of mind where surely it’s not just dopamine, but dopamine is released. They will track their clock.Oh, I’ve been fasting 12hours, 16 hours, et cetera. They are starting toattach dopamine release or create dopamine releasefrom the deprivation, not from the food reward itself. And this I think makes itan interesting practice. And one that certainly hasbeen practiced by for centuries in different culturesand different religions of deliberately restricting food, not just to increasethe rewarding properties of food itself, but also to increasethe rewarding properties of deprivation. And I should emphasize that alot of the subjective aspects of the knowledge ofthe benefits of fasting serve as reinforcing dopamineamplifying aspects to fasting, meaning if somebody doesintermittent fasting and they are deep into their fast and they’re telling themselves, oh, my blood lipid profilesare probably improving.And my glucose managementis probably improving. My insulin sensitivity is going up, and I’m going to live longer. All these things that havesome basis from animal studies and some basis or not from human studies, it’s all kind of stillan emerging literature, but it does seem to bepointing in that direction that fasting can encouragethings like autophagy, the engulfment of dead cellsand things of that sort. Well, as people tellthemselves these things, they are enhancing therewarding properties of the behavior of fasting. And so this is a salient example of where knowledge ofknowledge can actually help us change these deep primitivecircuits related to dopamine. And this illustrates how the forebrain, which carries knowledgeand carries interpretation and rational thought can beused to shape the very circuits that are involved in generating reward for what would otherwisejust be kind of primitive behaviors, hardwired behaviors. And that’s the beauty ofthese dopamine circuits. That’s the beauty of dopamine.It’s not just attached to themore primitive of food, sex, heat, et cetera. It’s also attached to the things that we decide are good forus and are important for us. So telling yourselfthat exercise or fasting or studying or listening better or any kind of behavior is good for you will actually reinforce the extent to which it is good foryou at a chemical level. And a somewhat eerie exampleof what I just mentioned was a study that was published last year in the journal Neuron, Cell Press journal, excellent journal. That showed that hearing something that reinforces one’s prior beliefs actually can evoke dopamine release. So the dopamine pathway is so vulnerable to subjective interpretation that it actually makes it suchthat when we see something or hear something that validates a belief that we already have, that itself can increase dopamine release.Along the lines of howdopamine and dopamine schedules and our perception ofthings can shape the way that we experience thingsas pleasureful or not. There are beautiful studiesmainly looking at sugar appetite and our sense of pleasurefrom sweet things, but also for savory foods, et cetera. And essentially the results that come out of this are the following. If you ingest something that you like, it tastes good to you, but then you ingestsomething that’s even sweeter or even more savory. And then you go back to thefood that you ate previously.Well, you don’t like it as much, and that might seem like a duh, obviously. But that shift inperception can be blocked by blocking the shift in dopamine. And so this really speaksto these peaks and valleys in dopamine that I mentioned before and how your experience ofanything is going to depend on your prior experience of other things that evoke dopamine. Big dopamine releasemakes it more challenging to experience more big dopamine release. So dopamine is one of those things that you don’t want too highor too low for too long.It’s all about stayingin that dynamic range and that’s going to bedifferent for everybody. So for the very savory foodsthat are now everywhere, those highly savory foods or I think they call themhighly palatable foods are making more bland foods, whole foods, meaning foods that aren’t processed. It’s making those tastes lessgood at least for a while. And all it takes is a shortperiod of time, even just days, two days or so of not consumingany highly palatable foods and suddenly broccoli withjust a little bit of seasoning tastes delicious to you.All right? So again, this just speaksto the fact that dopamine is this universal currency. It establishes value based on, not just what you’reexperiencing in the moment, but what you experienced inthe days and minutes before. Now, that you understandhow your previous level of dopamine relates to yourcurrent level of dopamine, and how your current levelof dopamine will influence your future level of dopamine, it should become obviouswhy things like pornography, not just the accessibility of pornography, but the intensity ofpornography can negatively shape real world romantic andsexual interactions.This is a serious concern. The discussion is happening now. The underlying neurobiological mechanisms you now understand. And this isn’t to pass judgment on whether or not people like ordon’t like pornography, that’s an ethical discussion, and it’s a moral discussionthat has to be decided for each individual byvirtue of age, et cetera. But again, any activity that evokes a lot of dopamine releasewill make it harder to achieve the same level andcertainly the greater level of dopamine through asubsequent interaction. So yes, indeed many peopleare addicted to pornography and yes, indeed many peoplewho regularly indulge in pornography experienced challenges in real-world romantic interactions. You now understand the mechanisms behind what I’m telling you. Now, there are circumstancesin which increasing levels of dopamine is desirable and advantageous and clinically helpful. Good example of this wouldbe the drug Welbutrin also called bupropionwhich increases dopamine and norepinephrine. Wellbutrin bupropion was developed as an alternative treatment for depression because some people whotake the so-called SSRI, selective serotonin reuptake inhibitors which as the name suggestsincreased serotonin suffer from serotoninrelated side effects.Things like decreasedappetite, decreased libido, or sometimes increasedappetite or other side effects that they don’t want. And Wellbutrin seems to avoidthe sexual side effects. It can blunt at appetiteand these sorts of things because of the increase innorepinephrine and dopamine increases levels ofmotivation and craving, but also can create astate of elevated alertness that can sometimes get inthe way of healthy eating and things of that sort.So one has to work with theirclinician as psychiatrist. It is a prescription drug in order to find the dosage of Welbutrinthat’s correct for them. In addition, thingslike Welbutrin bupropion can increase anxiety becauseof the way that dopamine and norepinephrine are stimulating and tend to place peopleinto heightened levels of alertness. Nonetheless, many peoplehave gained terrific relief from depression from Wellbutrin bupropion, and many of those samepeople had serious trouble with some of the SSRI.So it does seem to be a very useful drug in certain contexts, both for depression and forthe treatment of smoking for people desiring to quit smoking. And of course there area lot of people out there who are seeking to increasetheir baseline levels of dopamine withouttaking any prescription pharmaceutical compounds. And nowadays there exist alot of supplements to do that. The two most common ones that are directly within the dopaminepathway are Macuna Pruriens which is actually a velvetybean whose contents are l-DOPA. Believe it or not, thecontent of this being is the precursor to dopamine. So Macuna Pruriens issold over the counter at least in the United States. And it literally is theprecursor to dopamine. Meaning if you take it, you will experience verylarge increases in dopamine. Those increases are transientand very, very intense.And in fact, if you look atthe constellation of effects of Macuna Pruriens, what you find is thatthey’re pretty striking and they look a lot likeif not identical to l-DOPA. The most obvious ofthose is in the context of Parkinson’s disease. There are at least fivestudies that have shown that Macuna Prurienscan reduce the symptoms of Parkinson’s disease, much in the same waythat l-DOPA can reduce the symptoms of Parkinson’s disease. And that shouldn’t come as any surprise given what I just told youthat is essentially l-DOPA. It also can reduce a particularhormone called prolactin. Dopamine and prolactintend to be in somewhat push pull fashion. When dopamine is up, prolactin is down and vice versa. Prolactin is involved inmilk letdown in women. It’s involved in settingthe refractory period for sex after ejaculation in males. The reason mating canoccur and then not occur after a ejaculation is becauseof an increase in prolactin.Macuna Pruriens is oftenused a blunt prolactin, and they’re actually acouple of studies showing that it can indeed do that. Macuna Pruriens has anumber of other effects that lie in the sex andreproduction pathway that are worth noting. Sperm concentration, sperm quality is actually greatlyincreased by Macuna Pruriens. These are kind of curiouseffects until you understand a little bit more aboutthe biology of dopamine which I’ll mention in a moment, but there are several studies, four in fact that describehow Macuna Pruriens can increase sperm count, sperm quality, and sperm motility. So for those of you seekingto conceive children, Macuna Pruriens mightbe an interesting choice if you’re interested in exploring non-prescription compounds. However, I should mention that any time you consume a substancethat increases dopamine by mimicking dopamine oracting as a direct precursor to dopamine, there’s almost inevitablya crash or a reduction in the baseline in dopaminethat we referred to previously.So many people who take Macuna Pruriens feel really elevated, reallymotivated, really alert, all the sorts of thingsthat one would expect from a dopaminergic drugwhich Macuna Pruriens is. And then they feel a lowor a reduction in drive and excitement and enthusiasmafter the drug wears off. Just like they would with other dopamine increasing compound. For that reason, many people have turned to the use of L-tyrosine. L-tyrosine is an aminoacid precursor to l-DOPA.So it lies further up thedopamine synthesis pathway. And nowadays it’s verycommon because all L-tyrosine is sold over the counterin the United States that people will take L-tyrosine as a way to get more energized alert and focused. Indeed, there are data thatL-tyrosine will accomplish that. L-tyrosine is typicallytaken in capsule form or powder form anywhere from 500 to 750 to a 1000 milligrams. It is a potent stimulusfor increasing dopamine. And the timescale for increasing dopamine is about 30 to 45 minutes after ingestion. Dopamine levels start to peak. The classic study that really nailed down the fact that tyrosine has this effect was published way back in 1983, Journal of ClinicalEndocrinology and Metabolism that directly comparedL-tyrosine supplementation with tryptophan ingestion onplasma dopamine and serotonin. Tryptophan being a precursor to serotonin. And indeed what they found isthat ingestion of L-tyrosine can increase the amount ofdopamine circulating in the blood and in the brain too, of course.The L-tyrosine ingestion induced dopamine increases within 45 minutesand they were short-lasting after about 30 minutesthe effect had dissipated, meaning the levels of dopaminehad dropped down to baseline. And even though they didn’t look at levels of baseline dopamine past that time point, the expectation basedon everything we know about dopamine biology isthat it would then drop below baseline due to the depletion of the readily reservablepool of dopamine vesicles that we talked about wayback at the beginning of this episode. The nice thing about this studyis it does show specificity of effect because ingestion of tryptophan did not increase dopamineinstead it increased serotonin.So there’s reallyspecificity of these pathways that rule out any placebo type effects. I’m not suggesting that anybody, everybody increase their dopaminelevels by way of tyrosine or Macuna Pruriens. For those of you thatare seeking to increase your dopamine levelswithout prescription drugs, those are the most direct route to that. Of course, if you have a pre-existing dopaminergic condition, so schizophrenia or psychosis of any kind, bipolar, anxiety, things like Macuna Pruriens and L-tyrosine will not be good for you. And if you don’t, you shouldjust understand and expect that it’s going to lead toan increase in dopamine. You’ll certainly feel an elevated state for some of you that might be agitating, for some of you that mightbe really pleasureful, and then you will feel a crash afterwards. How deep is that crash willreally depend on your biology and where your dopamine baseline began. So I personally am nota fan of using things like Macuna Pruriens at all for myself for the reasons I mentioned earlier, just too intense and too much of a crash.I do use L-tyrosine from time to time for enhancing focus and motivation, but I want to emphasize from time to time. So I might use it once a week,occasionally twice a week, but I’ve never been one totake L-tyrosine regularly in order to focus or train ordo any kind of mental work. I just don’t want to relyon any exogenous substance in order to get my dopaminecircuits activated. And I don’t want to experiencethe drop in dopamine that inevitably occurs someperiod of time afterwards. I should also mentionthings that can reduce your levels of baseline dopamine. One that is rarely discussed is melatonin. I have talked before on thispodcast about melatonin, why I am not a fan of using melatonin in order to enhance sleep.It can help one get to sleep, but not stay asleep. Dr. Matt Walker sleep expert from University of California, Berkeley. I think I don’t want toput words in his mouth, but in our discussion aboutmelatonin on this podcast when Matt was a guest in hisbook and on other podcasts, Matt has generally statedthat the use of melatonin except for treatment of jet lag is generally not a good idea. And I agree. I think that melatonin isnot often thought about as impacting the dopamine pathway, but there’s at least onestudy published in 2001 first author is Nishiyamajust as it sounds. It’s spelled just as it sounds. Acute effects of melatonin administration on cardiovascular autonomicregulation in healthy men. So the study wasn’tspecifically about dopamine, but they looked at norepinephrineand dopamine levels, and they found a statisticallysignificant decrease in dopamine 60 minutes aftermelatonin administration. I’ve talked before abouthow viewing bright lights between the hours of10:00 p.m and 4:00 a.m has been shown in studiesby Dr.Samer Hattar, David Bersin, excellentcircadian scientists to reduce levels ofdopamine for several days after that light exposure. So dim the lights at night, if you can avoid exogenous melatonin, meaning if you don’thave to take melatonin and you can find a better alternative that would be a good idea if you want to maintainhealthy levels of dopamine. Now, there is one compoundthat you are all familiar with, and you’ve probably actuallytaken without realizing it, that increases dopamine. And that’s something calledPEA for phenethylamine, technically beta phenethylamine. And PEA is found in various foods. Chocolate just happens tobe one in enriched in PEA and can increase synapticlevels of dopamine. I personally take PEA from time to time as a focus and work aidin order to do intense bouts of work. Again, I don’t do that too often. This might be once a weekor once every two weeks. I might use it for training, but typically I don’t, it’s usually for mental work. And I will take 500 milligrams of PEA and I’ll take 300 milligrams of Alpha-GPC. That’s something that I personally do.That’s what’s right for me, it’s within my marginsof safety for my health. Again, you have to checkwith your doctor and decide what’s right for you. It leads to a sharp but verytransient increase in dopamine that lasts about 30 to 45 minutes. And at least in my systemI’ve found to be much more regulated and kind of eventhan something like L-tyrosine and certainly much more regulated and even and lower dopamine release than something like Macuna Pruriens.One of the lesser talked aboutcompounds that’s out there, but that’s gaining popularityfor increasing dopamine and as a so-called nootropic is something called huperzine A. Huperzine A is a compoundsold over the counter at least in the United States that can increaseacetylcholine transmission, a different neuromodulator entirely. But what’s interesting isthat huperzine A somehow by way of interactionsbetween the cholinergic system and the dopaminergic systemleads to increases in dopamine in the medial prefrontalcortex and hippocampus. Hippocampus, of course,being an area of the brain associated with learning and memory. And prefrontal cortex being associated with the mesolimbic pathway,decision-making focus, et cetera. And so I think the reasonwhy we’re seeing an increase in popularity of companiesincluding huperzine A and nootropic compounds isboth for the cholinergic stimulating properties, but also for stimulating dopamine release.I personally have never tried huperzine A. You can go to www.examine.comor put huperzine A into PubMed if you’d like to search around and see some of the science behind it. Again, I’m not recommendinganyone take these things. In fact, I recommend againstanyone just diving in, and starting to consume thingswithout gaining knowledge about how they function, whether or not they’re right for you. But nonetheless, I thinkin the years to come, we are going to see alot more of L-tyrosine, PEA phenethylamine andhuperzine as a way of tapping into the dopaminergicand cholinergic circuits certainly along with things like Alpha-GPC as non-prescription, short-lived somewhat milder alternatives to things that really spike dopamine, things like Adderall, Ritalin,modafinil, armodafinil and similar.And I can’t help but sharewith you one more result. It’s not related to pharmacology. It’s related to behaviorsand social interactions. And that’s the very interesting and I would say important finding that was made a few years agoby my colleague, Rob Malenka, who’s in our departmentof psychiatry at Stanford, showing that oxytocinand social connection is actually directly stimulatingthe dopamine pathway. I think for many years, all of us including mewould hear and thought that oxytocin was inthe serotonergic pathway that it was about pair bonding, and it was about someof these neuromodulators that were more associatedwith things related to feeling good with what wehave in the present moment. That’s typically what wethink of when we think of the opioid system orthe serotonergic system. The dopamine system is reallyabout seeking and reward, but in a paper published in2017 in the journal Science, excellent journal. The papers titled gaining ofsocial reward by oxytocin, excuse me, in the ventral tegmental area. You now know what theventral tegmental area, it’s that area of the mesolimbic pathway.What this paperessentially showed is that, oxytocin social connectionand pair bonding itself triggers dopamine release. And as everyone read thisresult, we all realized, ah, this makes total sensethat for the evolution of our species, indeed for any specieswhere social connections are important, it’s also important to goseek social connections. And so, while it’s fun tothink about pharmacology and underlying neurocircuitryand cold water baths and all these different thingsrelated to dopamine schedules and reward mechanisms andattaching reward to effort and all the various thingsthat we’ve talked about today in terms of science andtools and protocols, I’d be remiss if I didn’t includedescription of this result and just emphasize thatsocial connections, close social connections in particular that evoke oxytocin release. So those are romantic type, those are parent-child type, those are friendship related, and those can even be justfriends at a distance related, right? It doesn’t actually require skin contact to get oxytocin release, but oxytocin release iscentral to stimulating the dopamine pathways.So the take home messagethere is quite simple, engage in pursue quality,healthy social interactions. I know I’ve covered alot of material today. I’ve really tried hard to focus on things that lie directly withinthe dopamine pathway and circuitries, as well as things that directly stimulate those pathways and circuitries. What I haven’t talkedabout are all the things that indirectly servethe dopamine pathways. And out there on the internet and indeed in the scientific literature, you will find for instance, that things like Maca rootcan increase dopamine. Things like the gut microbiomecan influence dopamine. And indeed they can, but they do that throughindirect mechanisms. By creating a environment, a milieu in which dopamineand dopamine circuits can flourish.Maca is a good example of that. It will reduce cortisol andthrough some indirect pathways related to cortisol can increase dopamine. But it’s not a directincrease in dopamine. And so as a consequence,it’s rather subtle compared to the variouscompounds and behaviors that I talked about today. Indeed cold water exposureleads to huge increases in dopamine as we talked about before, and very sustained ones at that. I realize in giving you a lotof information about science and mechanism all the wayfrom psychological biological to circuitry and synaptic transmission, volumetric transmission and so forth, that it might seem overwhelming. The most important thing is to understand, or that these dopamine pathways really are under your control. And the locus of controlresides in the fact that your previous levels of dopamine are influencing your levelsof dopamine right now. And your current levels of dopamine and where you take them next, will influence your dopaminelevels in the next days and weeks to come.So I hope both with the mechanismsthat you now have in hand plus some of the tools to tapinto the dopaminergic system, both behavioral,pharmacologic prescription, and non-prescription, et cetera, that you’ll feel thatyou have more control over your dopamine system. And certainly that youhave a better understanding of your dopamine systemso that you can modulate and adjust your levelsof dopamine in the ways that serve you best. If you’re learning from andor enjoying this podcast, please subscribe to our YouTube channel. That’s a terrific way to support us. In addition, please leaveus a comment or a suggestion for a guest you’d like us to interview or a topic you’d like us to cover. In addition, please subscribeto us on Apple and Spotify.And on Apple, you have the opportunity to leave us up to a five-star review and to leave us a comment there as well. Please also check outthe sponsors mentioned at the beginning of today’s podcast. That’s a terrific way to support us. In addition, if you’d liketo support the Huberman Lab and research at Stanford onstress, stress mitigation and human performance, you can do that by going to, www.hubermanlab.stanford.edu/giving. And there you can make atax deductible donation to the research in my laboratory. In addition, we have a Patreon. It’s www.patreon.com/andrewhuberman. And there you can supportthe podcast at any level that you like. Today and on previous podcast episodes we talked a bit about supplements. Supplements certainly aren’t necessary, but many people find them beneficial for things like adjustingtheir levels of dopamine or for other purposes.If you’re going to use supplements, it’s very important thatthe supplements you use be of very high quality, and that the quantity of ingredients that are on the label match what’s actually in those bottles. For that reason, we’vepartnered with Thorne. T-H-O-R-N-E because Thornehas the highest levels of stringency with respect to quality and how much of each supplementthey put in the products that they sell. If you’d like to see thesupplements that I take, you can go to Thorne, www.T-H-O-R-N-E.com/u/huberman. And there, you can see what I take. You can get 20% off anyof those supplements.And if you navigate into the Thorne site through that portal, then you can get 20% offany of the supplements that Thorne makes. If you’re not alreadyfollowing us on Instagram at Huberman Lab, please do so. There I teach neurosciencetools and information. Oftentimes, it’s tools and information that I don’t cover on the podcast. We’re also on Twitter,also at Huberman Lab. And last but certainly not least, thank you for your interest in science. [energetic music].