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Controlling Your Dopamine For Motivation, Focus & Satisfaction — Transcript

by Andrew Huberman · 22,761 words · 3,258 segments · language en · Watch on YouTube

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0:00- Welcome to the Huberman Lab Podcast,
0:02where we discuss science and science-based tools
0:04for everyday life.
0:06[energetic music]
0:09I'm Andrew Huberman,
0:10and I'm a professor of neurobiology and ophthalmology
0:13at Stanford School of Medicine.
0:15Today, we are going to talk all about dopamine
0:17and what drives you to do the things that you do.
0:21We're going to talk about motivation and desire and craving,
0:25but also how dopamine relates to satisfaction
0:29and our feelings of wellbeing.
0:31And of course, any discussion about dopamine
0:33has to include a discussion about the potential
0:36for dopamine induced addiction.
0:39Indeed, dopamine lies at the heart of addiction
0:42to all things.
0:43But today we are mainly going to focus on,
0:46how what we do and how we do it,
0:49and how we conceptualize those things
0:52leads to changes in this amazing molecule
0:55in our brain and bodies that we call dopamine.
0:58I'm going to teach you what dopamine is and what it is not.
1:01There are a lot of myths about the molecule dopamine.
1:04We often hear about so-called dopamine hits.
1:06Today, we are going to dispel many common myths
1:08about dopamine,
1:10and we are going to talk about how dopamine actually works.
1:13We're going to discuss the biology of dopamine,
1:15the psychology.
1:16We will discuss some neural circuits
1:18and a really exciting aspect of dopamine biology
1:21or so-called dopamine schedules.
1:23In other words, we are going to discuss
1:25how things like food, drugs, caffeine, pornography,
1:28even some plant-based compounds can change
1:31our baseline levels of dopamine and in doing so,
1:34they change how much dopamine we are capable of experiencing
1:38from what could be very satisfying events,
1:42or events that make us feel not so good
1:44because of things that we did or took prior.
1:47So I promise you it's going to be a vast discussion,
1:50but I will structure it for you,
1:52and you'll come away with a deep understanding
1:54of really what drives you.
1:56You will also come away with a lot of tools,
1:58how to leverage dopamine so that you can sustain energy,
2:02drive and motivation for the things
2:03that are important to you over long periods of time.
2:06Before we dive into the meat of today's discussion,
2:09I'd like to share with you a fascinating result
2:13that really underscores what dopamine
2:15is capable of in our brains and bodies,
2:17and underscores the fact that just through behaviors,
2:20no drugs, nothing of that sort,
2:22just through behaviors,
2:24we can achieve terrifically high increases in dopamine
2:28that are very long and sustained in ways that serve us.
2:32This is a result that was published
2:33in the European Journal of Physiology.
2:35I'll go into it in more detail later,
2:37but essentially what it involved is having human subjects
2:40get into water of different temperatures.
2:43So it was warm water,
2:45moderately cool water and cold, cold water.
2:49Had them stay in that water for up to an hour,
2:52and they measured by way of blood draw
2:55things like cortisol, norepinephrine and dopamine.
3:00What was fascinating is that cold water exposure
3:03led to very rapid increases in norepinephrine
3:07and epinephrine,
3:08which is also just called adrenaline.
3:10It also led to increases in dopamine.
3:13And these increases in dopamine were very significant.
3:16They kicked in around 10 or 15 minutes after submersion
3:20into the cold water.
3:21And I should mention the head wasn't below water
3:23is just up to the neck.
3:24And the dopamine release continued to rise
3:29and rise and rise,
3:30and eventually reached 250% above baseline.
3:33Now, what was interesting is after subjects got out
3:36of this cold water,
3:38that dopamine increase was sustained.
3:40And I know nowadays many people are interested
3:43in using cold water therapy as a way to increase metabolism
3:47and fat loss,
3:48but also to improve sense of well-being,
3:51improve cognition, improve clarity of mind.
3:54There's something really special about this very alert,
3:57but calm state of mind
3:59that seems to be the one that's optimal
4:01for pretty much everything except sleep,
4:04but for all aspects of work and for social engagement
4:07and for sport that highly alert,
4:10but calm state of mind really is the sweet spot
4:13that I believe most of us would like to achieve.
4:15And this cold water exposure done correctly
4:18really can help people achieve that state of mind
4:21through these increases in dopamine
4:23that lasts a very long time.
4:25So I will later detail the specifics of that study,
4:28what it entailed in terms of how long,
4:31the variations, the different subjects experienced,
4:33as well as how to limit the amount of stress hormone,
4:36cortisol, that's released as a consequence
4:38of the cold water.
4:40And we will also talk about compounds, supplements
4:42that people can take in order to increase
4:44their levels of dopamine should they choose.
4:47Before we begin, I'd like to emphasize
4:49that this podcast is separate from my teaching
4:51and research roles at Stanford.
4:52It is however, part of my desire and effort
4:55to bring zero cost to consumer information about science
4:57and science related tools to the general public.
5:00In keeping with that theme,
5:01I'd like to thank the sponsors of today's podcast.
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9:48The event is September 30th, 2021 at 3:00 p.m Eastern.
9:54You can find the registration link in the caption
9:56for this episode.
9:58So let's talk about dopamine.
10:00Most people have heard of dopamine,
10:01and we hear all the time now about dopamine hits.
10:04But actually there's no such thing as a dopamine hit.
10:08And actually the way that your body uses dopamine
10:12is to have a baseline level of dopamine.
10:15Meaning an amount of dopamine that's circulating
10:17in your brain and body all the time.
10:20And that turns out to be important for how you feel
10:22generally, whether or not you're in a good mood,
10:24motivated, et cetera.
10:26And you also can experience peaks in dopamine
10:29above baseline.
10:31Now, this has a very specific name
10:33in the neurobiology literature,
10:34so-called tonic and phasic release of dopamine.
10:39And I'll explain what that means in a couple of minutes.
10:41But if you remember nothing else from this episode,
10:44please remember this,
10:46that when you experience something or you crave something
10:50really desirable, really exciting to you, very pleasurable.
10:55What happens afterwards is your baseline level
10:58of dopamine drops.
11:00Okay?
11:01So these peaks in dopamine,
11:03they influence how much dopamine
11:05will generally be circulating afterward.
11:07And you might think, oh, a big peak in dopamine after that,
11:10I'm going to feel even better
11:11because I just had this great event.
11:13Not the case.
11:14What actually happens is that your baseline level
11:17of dopamine drops.
11:18And I will explain the precise mechanism for that.
11:21Okay?
11:22In the neuroscience literature,
11:23we refer to this as tonic and phasic release of dopamine.
11:29Tonic being the low level baseline
11:32that's always there circulating,
11:34released into your brain all the time.
11:37And then phasic these peaks that ride above that baseline.
11:41And those two things interact.
11:43And this is really important.
11:45I'm going to teach you the underlying neurobiology,
11:46but even if you have no background in biology,
11:48I promise to make it all clear.
11:49I'll explain the terms and what they mean.
11:52And I'm excited to teach you about dopamine,
11:54because dopamine has everything to do with how you feel
11:57right now as you're listening to this,
11:58it has everything to do with how you will feel
12:01an hour from now,
12:02has everything to do with your level of motivation
12:04and your level of desire,
12:06and your willingness to push through effort.
12:08If ever you've interacted with somebody
12:10who just doesn't seem to have any drive they've given up,
12:14or if you've interacted with somebody
12:16who seems to have endless drive and energy,
12:18what you are looking at there in those two circumstances
12:22is without question a difference
12:25in the level of dopamine circulating in their system.
12:28There will be other factors too,
12:30but the level of dopamine is the primary determinant
12:34of how motivated we are, how excited we are,
12:37how outward facing we are and how willing we are,
12:40to lean into life and pursue things.
12:43Dopamine is what we call a neuromodulator.
12:45Neuromodulators are different than neurotransmitters.
12:48Neurotransmitters are involved in the dialogue
12:50between neurons nerve cells.
12:52And neurotransmitters tend to mediate local communication.
12:55Just imagine two people talking to one another at a concert,
12:59that communication between them is analogous
13:01to the communication carried out by neurotransmitters,
13:05whereas neuromodulators influence the communication
13:08of many neurons.
13:09Imagine a bunch of people dancing
13:11where it's a coordinated dance involving 10 or 20
13:13or hundreds of people.
13:15Neuromodulators are coordinating that dance.
13:18In the nervous system what this means is that,
13:20dopamine release changes the probability
13:23that certain neural circuits will be active
13:26and that other neural circuits will be inactive.
13:29Okay?
13:30So it modulates a bunch of things all at once,
13:33and that's why it's so powerful at shifting
13:35not just our levels of energy,
13:36but also our mindset,
13:37also our feelings of whether or not we can,
13:41or cannot accomplish something.
13:44So how does dopamine work and what does it do?
13:46Well, first of all, it is not just responsible for pleasure,
13:50it is responsible for motivation and drive.
13:52Primarily, at the psychological level,
13:54also for craving.
13:55Those three things are sort of the same.
13:57Motivation, drive and craving.
13:59It also controls time perception,
14:01and we will get deep into how dopamine
14:03can modulate time perception,
14:05and how important it is that everybody be able
14:09to access increases in dopamine at different timescales.
14:13This turns out to be important to not end up addicted
14:16to substances,
14:16but it also turns out to be very important to sustain effort
14:20and be a happy person over long periods of time.
14:22Which I think most everybody wants.
14:24It certainly is adaptive in life to be able to do that.
14:27Dopamine is also vitally important for movement.
14:31I'll explain the neural circuits for dopamine and mindset,
14:35and dopamine in movement in a moment,
14:37but in diseases like Parkinson's or Lewy bodies dementia,
14:43which is similar to Parkinson's in many ways.
14:45There's a depletion or death of dopamine neurons
14:48at a particular location in the brain
14:50which leads to shaky movements,
14:53challenges and speaking,
14:54challenges in particular in initiating movement.
14:57And because dopamine is depleted elsewhere
15:00to people with Parkinson's and Lew's bod,
15:04excuse me, Lewy body dementia also experience drops
15:07in motivation and affect, meaning mood.
15:10They tend to get depressed and so on.
15:12When those people are properly treated,
15:15they can, not always,
15:17but they can recover some fluidity of movement,
15:20some ability to initiate movement.
15:22And almost without question,
15:24those people feel better psychologically,
15:26not just because they can move,
15:28but also because dopamine impacts mood and motivation.
15:31So what are the underlying neural circuits?
15:35For those of you that are not interested in biology
15:38and specific nomenclature,
15:39you can tune out now if you want,
15:40but it's actually pretty straightforward.
15:42You have two main neural circuits in the brain
15:45that dopamine uses in order to exert all its effects.
15:50The first one is a pathway that goes from this area
15:54in the what's called the ventral tegmentum.
15:57That's a fancy, but ventral just means bottom,
15:59and tegmentum actually means floor.
16:01So it's at the bottom of the brain,
16:02and it's the ventral part of the floor.
16:04So it's really low in the back of the brain,
16:06the ventral tegmentum.
16:07And it goes from the ventral tegmentum
16:11to what's called the ventral striatum
16:14and the prefrontal cortex.
16:15Now, that's a lot of language,
16:16but basically what we call this is the,
16:18mesocorticolimbic pathway.
16:20This is the pathway by which dopamine influences motivation,
16:25drive and craving.
16:27It involves structures that some of you may have heard
16:29of before.
16:29Things like nucleus accumbens and the prefrontal cortex.
16:32This is the pathway that really gets disrupted
16:35in addictions where in particular drugs that influence
16:40the release of dopamine like cocaine and methamphetamine.
16:42We'll talk about those drugs today.
16:44They tap into this pathway.
16:45But if you are pursuing a partner,
16:49a boyfriend or girlfriend,
16:50if you're pursuing a degree in school,
16:52if you're pursuing a finish line in a race,
16:54you are tapping into this so-called
16:56mesecorticolimbic pathway.
16:58This is the classic reward pathway in all mammals.
17:03The other pathway emerges from an area in the brain
17:06called the substantia nigra.
17:08So-called because the cells in that area are dark,
17:13and the substantia nigra connects to an area of the brain
17:17called the dorsal striatum.
17:18This is not surprisingly called the nigrostriatal pathway.
17:22For those of you who have never done any neuroanatomy,
17:24I'm going to teach you a little trick right now.
17:26Everything in neuroanatomy,
17:27the first part of a word tells you where the neurons are.
17:32And then the second part tells you
17:33where they are connecting to.
17:34So when I say nigropstriatal pathway,
17:37it means that the neurons are in substantial nigra
17:39and they connect to the striatum, nigrostriatal pathway.
17:42So while it's a lot of language there, some logic there.
17:45Okay?
17:46So we've got these two pathways.
17:47One, mainly for movement, right?
17:49This is the substantia nigra to dorsal striatum.
17:53And we've got this other pathway,
17:55the so-called mesocorticolimbic pathway,
17:57that's for reward, reinforcement and motivation.
18:00I want you to remember that there are two pathways.
18:03If you don't remember the two pathways in detail,
18:05that's fine.
18:06But please remember that there are two pathways,
18:08because that turns out to be important later.
18:10Now, the other thing to understand about dopamine is that,
18:13the way that dopamine is released in the brain and body
18:17can differ.
18:19Meaning it can be very local,
18:22or it can be more broad.
18:24Now, most of you have probably heard of synapses.
18:27Synapses are the little spaces between neurons,
18:30and basically neurons nerve cells communicate
18:32with one another by making each other electrically active,
18:36or by making each other less electrically active.
18:39So here's how this works.
18:40You can imagine one nerve cell and another nerve cell
18:43with a little gap between them,
18:44a little synapse.
18:45And the way that one nerve cell causes
18:48the next nerve cell to fire.
18:49What we call fire really means to become electrically active
18:52is that it vomits out these little packets,
18:55what we call vesicles.
18:56They're little bubbles filled with a chemical,
18:58when that chemical enters the synapse,
19:01it some of it docks or parks on the other side,
19:04in the other neuron.
19:06And by virtue of electrical changes in the,
19:10what we call the postsynaptic neuron,
19:12that chemical will make that neuron more electrically active
19:15or less electrically active.
19:17Dopamine can do that like any other neurotransmitter
19:20or neuromodulator.
19:22So it can have one neuron influence another neuron.
19:25But dopamine can also engage
19:28in what's called a volume metric release.
19:30Volumetric release is like a giant vomit that gets out to 50
19:35or a hundred or even thousands of cells.
19:37So there's local release what we call synaptic release,
19:40and then there's volumetric release.
19:42So volumetric release is like dumping all this dopamine out
19:44into the system.
19:46So dopamine is incredible because it can change the way
19:50that our neural circuits work at a local scale
19:52and at a very broad scale.
19:54And for those of you that are only interested in tools,
19:57like how do I get more dopamine?
19:59Let me tell you this part is really important
20:01because if you were to take a drug or supplement
20:05that increases your level of dopamine,
20:07you are influencing both the local release of dopamine
20:11and volumetric release.
20:13This relates back to the baseline of dopamine
20:16and the big peak above baseline.
20:18And that turns out to be important.
20:20And I'll just allude to why it's important.
20:23Many drugs and indeed many supplements
20:26that increase dopamine will actually make it harder
20:31for you to sustain dopamine release
20:33over long periods of time.
20:34And to achieve those peaks that most of us are craving
20:38when we are in pursuit of things.
20:39Why?
20:40Because if you get both volume metric release,
20:43the dumping out of dopamine everywhere,
20:45and you're getting local release,
20:47what it means is that the difference between the peak
20:49and baseline is likely to be smaller.
20:52And this is very important,
20:55how satisfying or exciting or pleasureful
20:58a given experience is,
21:00doesn't just depend on the height of that peak,
21:03it depends on the height of that peak relative
21:06to the baseline.
21:08So if you increase the baseline and you increase the peak,
21:12you're not going to achieve more and more pleasure
21:14from things.
21:15I'll talk about how to leverage this information
21:18in a little bit,
21:20but just increasing your dopamine.
21:22Yes, it will make you excited for all things.
21:25It will make you feel very motivated,
21:27but it will also make that motivation very short-lived.
21:31So there's a better way to increase your dopamine.
21:34There's a better way to optimize
21:36this peak to baseline ratio.
21:38For now what we've talked about is two main neural circuits,
21:41one for movement,
21:42and one for motivation and craving with dopamine.
21:45And we've talked about two main modes of communication
21:47between neurons with dopamine.
21:50One is this local synaptic release.
21:53One is more volume metric release.
21:56And in the back of your mind,
21:57you can relate this back to,
21:58again, this baseline versus peaks above baseline.
22:02So that's a description of what we would call
22:04the spatial effects or the spatial aspects of dopamine.
22:08I said this connects to that,
22:10that connects to this.
22:11You can get local or more broad volumetric release.
22:13What about the duration of release
22:16or the duration of action for dopamine?
22:19Well, dopamine is unique among chemicals in the brain,
22:23because dopamine unlike a lot of chemicals in the brain
22:26works through what are called G protein-coupled receptors.
22:29And for those of you that are about to pass out
22:31from the amount of detail,
22:32just hang in there with me.
22:33It's really not complicated.
22:35There are two ways that neurons can communicate
22:38or mainly two ways.
22:39There are third and fourth,
22:40but mostly neurons communicate by two modes.
22:45One, are what we call fast electrical synapses
22:49ionotropic conduction.
22:50All right?
22:51You don't need to know what that means,
22:52but basically one neuron activates another neuron
22:56and little holes open up in that neuron,
22:58and ions rush in.
23:00Sodium is the main ion salt
23:03by which one neuron influences the electrical activity
23:06of another neuron because sodium ions contain a charge.
23:10Okay?
23:11There are other things like chloride and potassium.
23:12If you're interested in looking this up,
23:13just look up ionic conductances in the action potential,
23:17or I could do a post on it some time
23:18and we could go into detail.
23:20But just understand that when neurons
23:22want to influence each other,
23:23they can do it by way of this fast ionotropic conduction.
23:26This is a really quick way for one neuron
23:29to influence the next.
23:31Dopamine doesn't communicate that way.
23:34Dopamine is slower.
23:35It works through what are called G protein-coupled
23:37receptors.
23:38So what happens is dopamine is released
23:40in these little vesicles that I've mentioned before,
23:42get vomited out into the synapse.
23:45Some of that dopamine will bind
23:47to the so-called postsynaptic neuron,
23:49it'll bind to the next neuron,
23:50and then it sets off a cascade.
23:53It's kind of like a bucket brigade of one thing,
23:55getting handed off to the next,
23:56to the next, to the next.
23:58It's G protein-coupled receptors.
24:00And anytime you hear about these GPCRs
24:02or G protein-coupled receptors,
24:04pay attention because they're really interesting.
24:06They're slow,
24:07but they also can have multiple cascades of effects.
24:11They can impact even gene expression at some level.
24:14They can change what a cell actually becomes.
24:17They can change how well or how poorly that cell
24:20will respond to the same signal in the future.
24:24So dopamine works through the slower process.
24:26These G protein-coupled receptors.
24:28And so its effects tend to take a while in order to occur.
24:34This aspect of dopamine transmission is important
24:37because it now underscores two things.
24:39One, there's two pathways for dopamine to communicate.
24:42One for movement,
24:43one for motivation and craving.
24:44There's two spatial scales at which dopamine can operate
24:49synaptically or volumetrically.
24:51And dopamine can have slow effects,
24:55really slow effects,
24:56or even very long lasting effects.
24:58And it even can control gene expression.
25:00It can actually change the way that cells behave.
25:03One thing that's not often discussed about dopamine,
25:05but is extremely important to know
25:07is that dopamine doesn't work on its own.
25:11Neurons that release dopamine co-release glutamate.
25:15Glutamate is a neurotransmitter
25:18and it's a neurotransmitter that is excitatory,
25:21meaning it stimulates neurons to be electrically active.
25:24So now even if you don't know any cell biology,
25:28you should start to gain a picture
25:29that dopamine is responsible for movement,
25:32motivation and drive.
25:34It does that through two pathways,
25:35but also the dopamine stimulates action in general,
25:39because it releases this excitatory neurotransmitter.
25:42It tends to make certain neurons that are nearby
25:45or even that are far away,
25:47because of volumetric release,
25:48it tends to make those more active.
25:50So dopamine is really stimulating.
25:52And indeed we say that dopaminergic transmission
25:56or dopamine tends to stimulate sympathetic arousal.
26:00Sympathetic doesn't have anything to do with sympathy.
26:02It's just simply means that it tends
26:05to increase our levels of alertness.
26:07It tends to bring an animal or a human
26:09into a state of more alertness, readiness
26:13and desire to pursue things outside the confines
26:16of its skin.
26:17So if I were to just put a really simple message
26:21around dopamine it would be,
26:22there's a molecule in your brain and body
26:24that when released tends to make you look outside yourself,
26:30pursue things outside yourself,
26:32and to crave things outside yourself.
26:36The pleasure that arrives from achieving things
26:39also involves dopamine,
26:40but is mainly the consequences of other molecules.
26:43But if ever you felt lethargic and like just lazy
26:46and you had no motivation or drive,
26:48that's a low dopamine state.
26:50If ever you felt really excited, motivated,
26:52even if you're a little scared to do something.
26:55Maybe you did your first skydive,
26:57or you're about to do your first skydive,
26:59or you're about to do some public speaking
27:00and you really don't want to screw it up,
27:02you are in a high dopamine state.
27:05Dopamine is a universal currency in all mammals,
27:08but especially in humans for moving us toward goals
27:13and how much dopamine is in our system at any one time
27:17compared to how much dopamine was in our system
27:20a few minutes ago,
27:22and how much we remember enjoying a particular experience
27:25of the past.
27:27That dictates your so-called quality of life
27:30and your desire to pursue things.
27:33This is really important.
27:34Dopamine is a currency,
27:36and it's the way that you track pleasure.
27:38It's the way that you track success.
27:40It's the way that you track
27:42whether or not you are doing well or doing poorly.
27:44And that is subjective,
27:47but if your dopamine is too low,
27:50you will not feel motivated.
27:52If your dopamine is really high,
27:54you will feel motivated.
27:55And if your dopamine is somewhere in the middle,
27:57how you feel depends on whether or not
27:59you had higher dopamine a few minutes ago or lower dopamine.
28:04This is important,
28:05your experience of life and your level of motivation
28:08and drive depends on how much dopamine you have relative
28:14to your recent experience.
28:17This is again, something that's just not accounted
28:20for in the simple language of dopamine hits.
28:23Okay?
28:24A simple way to envision dopamine hits
28:26is every time you do something you like,
28:28you to piece of chocolate,
28:29dopamine hit.
28:30You look at your Instagram,
28:30dopamine hit.
28:31You see someone you like,
28:32dopamine hit.
28:34All these things described as dopamine hits
28:37neglect the fact that if you scroll social media
28:40and you see something you really like,
28:42dopamine hit.
28:43Sure there's an increase in dopamine,
28:45but then you get to something else and you go,
28:48hmm, not that interesting.
28:49However, had you arrived at that second thing first,
28:53you might think that it was really interesting.
28:56If you had arrived to that second Instagram post
28:59three days later or four days later,
29:01you might find it extremely interesting.
29:03Again, how much dopamine you experience from something
29:07depends on your baseline level of dopamine
29:09when you arrive there,
29:10and your previous dopamine peaks.
29:14Okay?
29:15That's super important to understand,
29:16and it's completely neglected by the general language
29:19of dopamine hits.
29:20This is why when you repeatedly engage in something
29:23that you enjoy,
29:25your threshold for enjoyment goes up and up and up.
29:29So I want to talk about that process.
29:30And I want to explain how that process works,
29:32because if you understand that process,
29:34and you understand some of these schedules and kinetics
29:37as we call them around dopamine,
29:38you will be in a terrific position
29:40to use any dopamine enhancing tools that you decide to use.
29:44You'll be in an excellent position to modulate
29:46and control your own dopamine release
29:48for optimal motivation and drive.
29:51I realized that was a lot of information
29:53about the biology of dopamine,
29:55sort of like trying to make you drink
29:56from the fire hose of dopamine biology.
29:59However, I realized that some people
30:00probably want even more information
30:02about the biology of dopamine transmission.
30:05If you're interested in that,
30:07I'll post a link to a absolutely stellar review
30:09that was published in Nature Reviews Neuroscience
30:12called spatial and temporal scales of dopamine transmission.
30:15It is quite detailed,
30:16but they have beautiful diagrams
30:18and can walk you through all the things
30:20that I just described and get into even more detail.
30:22We'll put a link to that in the caption on YouTube.
30:26Right now, I want to share with you two anecdotes,
30:29one from my own life,
30:30and one from some fairly recent history
30:34that illustrate some of the core biology of dopamine
30:38and how profoundly it can shape our experience.
30:41The first one is a really tragic situation that occurred.
30:47This was in the 80s,
30:49there was a outbreak of what looked like Parkinsonian
30:54symptoms in a young population.
30:56So many of you heard of Parkinson's disease.
30:58Parkinson's disease is a disease in which people initially
31:02start to quake, can't generate smooth movements,
31:05they'll have issues with speech,
31:06sometimes cognition as well.
31:08There are examples like Michael J. Fox,
31:10which are kind of early onset.
31:12Parkinson's typically it hits people
31:15a little bit later in life.
31:16There's a genetic component.
31:19But there is this question,
31:22and there's always been this question
31:23whether or not certain lifestyle factors
31:25can also create Parkinson's?
31:27And some years ago there was a situation
31:31where street laboratories,
31:35illicit laboratories were trying to make a drug
31:38called MPPP, which is an opioid light compound.
31:41It's a bit like heroin,
31:44and heroin addicts seeking heroin went out and bought
31:48what they thought was MPPP.
31:51Unfortunately, it was not MPPP.
31:56I mean, it would have been tragic if it was anyway
31:58because they were drug addicts,
31:59but what they ended up taking turned out to be a lot worse.
32:02What they ended up taking was MPTP,
32:05and MPTP can arise in the synthesis of MPPP.
32:10So someone in a lab someplace,
32:12this was mainly in the Central Valley in California,
32:14but elsewhere as well.
32:16Somebody created MPTP,
32:20and what ended up happening was a large number
32:23of young people who were opioid addicts
32:26became completely boxed in paralyzed.
32:30Couldn't speak, couldn't blink,
32:32couldn't do anything.
32:34Couldn't function, couldn't move.
32:35So both aspects of dopamine transmission were disrupted.
32:40They had no motivation and drive.
32:43They couldn't generate any movement of any kind.
32:45They were literally locked in frozen.
32:48And sadly, this is irreversible.
32:51It's irreversible,
32:52because what MPTP does is it kills the dopaminergic neurons
32:58of the substantia nigra that nigrostriatal pathway
33:00that's involved in generating movement.
33:02And it kills the dopaminergic neurons
33:05of the so-called mesocorticolimbic pathway.
33:08I was in college when this whole MPTP thing happened.
33:11And I remember hearing this story.
33:13At the time, I had no understanding
33:15of what it is to have very high levels of dopamine
33:18or extremely depleted levels of dopamine.
33:20There was no reason why I should have that understanding.
33:22I mean, of course I had experienced different pleasures
33:24of different kinds and I've had lows in my life,
33:27but nothing to the extreme that I'm about to discuss.
33:33I got Giardia.
33:35And Giardia is a stomach bug that if any of you ever had it,
33:39it is terrible.
33:40It's terrible diarrhea.
33:42You end up very dehydrated very quickly.
33:43You drop a ton of weight and it is extremely unpleasant.
33:48I ended up going to the emergency room,
33:51and in the emergency room,
33:53I begged them for something to stop up my guts.
33:56And they gave it to me.
33:57They put a saline line into rehydrate me
33:59and they injected something into the saline bag.
34:02And within minutes I felt more sadness,
34:08more overwhelming sense of depression,
34:13basically, lower than I'd ever felt in my entire life.
34:16It was absolutely profound.
34:19I was crying endlessly without knowing why I was crying.
34:23I was miserable.
34:24And I asked them, what did you inject?
34:26And they said, "We injected Thorazine."
34:29Thorazine is an antipsychotic drug.
34:31It's actually used to block dopamine receptors.
34:34It's what's given to people who have schizophrenia.
34:37Often is given to people who have schizophrenia,
34:39because schizophrenia involves among other things
34:42elevated levels of dopamine.
34:45It was horrible.
34:47The experience of it was miserable,
34:50unlike anything I'd ever experienced.
34:53And so I actually said to them,
34:55"What did you give me?"
34:56They said, "Thorazine."
34:57And I said, "You have to give me l-DOPA.
35:00"You have to give me something to get my dopamine levels
35:03"back up again."
35:04And they did.
35:05They gave me an injection of l-DOPA into the bag,
35:07went straight to my bloodstream.
35:08And within minutes I felt fine again.
35:12It was incredible.
35:13And it really opened up my mind and my experience
35:16to what it is to have absolutely plummeted levels
35:19of dopamine.
35:20And there's nothing more miserable than that I'll tell you.
35:23And these poor souls who had this MPTP experience,
35:27unfortunately, they couldn't recover those cells.
35:29People who have severe Parkinson's
35:32are struggling with this as well,
35:33because in Parkinson's and in Lewy body dementia,
35:35the dopaminergic neurons often die.
35:37It's not just a problem with those neurons
35:39releasing enough dopamine.
35:40Later, we're going to talk about some approaches
35:43to maintaining dopaminergic neuron health
35:46and things that we can all do for that.
35:47But I will tell you these dopamine neurons
35:50that we all have are very precious for movement
35:52and mood and motivation.
35:54Having experienced what it is to have very, very low levels
35:58of dopamine or in this case to have my dopamine receptors
36:00blocked from Thorazine was eye-opening to say the least,
36:06and has given me tremendous sensitivity to the fact
36:09that dopamine is perhaps one of the most powerful molecules
36:13that any of us has inside of us.
36:16And the one that we ought to all think very carefully about
36:19how we leverage,
36:20because while most experiences and most things
36:24that we do, and take and eat and cetera,
36:27won't create enormous highs and enormous lows in dopamine.
36:31Even subtle fluctuations in dopamine really shape
36:34our perception of life and what we're capable of,
36:36and how we feel.
36:38And so we want to guard those and we want to understand them.
36:40So let's lean into that understanding about dopamine.
36:42And then let's talk about some tools
36:44that we can all use to leverage dopamine
36:46in order to keep that baseline in the appropriate,
36:49healthy place,
36:50and still be able to access those peaks in dopamine.
36:53Because those, after all are some of what makes life rich
36:57and worth living.
36:58So let's talk about the baseline of dopamine
37:00that we all have and the peaks in dopamine
37:03that we all can achieve through different activities
37:07and things that we ingest.
37:10All of us have different baseline levels of dopamine.
37:13Some of this is sure to be genetic.
37:17Some people just simply ride at a level a little bit higher.
37:21They're a little bit more excited,
37:22they're a little bit more motivated,
37:24or maybe they're a lot more excited or a lot more motivated.
37:28Some people are a little mellower,
37:30some people are a little less excitable.
37:32And some of that has to do with the fact
37:34that dopamine doesn't act alone.
37:36Dopamine has close cousins or friends in the nervous system.
37:41And I'll just name off a few of those close cousins
37:43and friends.
37:45Epinephrin also called adrenaline
37:48is the main chemical driver of energy.
37:52We can't do anything, anything at all,
37:55unless we have some level of epinephrin
37:57in our brain and body.
37:58It's released from the adrenal glands
38:00which right on top our kidneys.
38:01It's released from an area of the brainstem
38:03called locus coeruleus.
38:05And its release tends to wake up neural circuits
38:08in the brain and wake up various aspects
38:11of our body's physiology and give us a readiness.
38:15So it should come as no surprise
38:16that dopamine and epinephrin aka adrenaline
38:20hang out together.
38:22In fact, epinephrin and adrenaline are actually manufactured
38:26from dopamine.
38:28There's a biochemical pathway involving dopamine
38:30which is a beautiful pathway.
38:32If ever you want to look it up,
38:33you can just look up biochemistry of dopamine.
38:36But what you'll find is that,
38:38l-DOPA is converted into dopamine.
38:43Dopamine is converted to two noradrenaline.
38:47Norepinephrin, it's also called.
38:49And noredrenaline, norepinephrin is converted
38:52into adrenaline.
38:54So not only are dopamine and epinephrin aka adrenaline
38:58close cousins,
39:00they are actually family members.
39:02Okay?
39:03They're closely related.
39:04I'm not going to get too deep into epinephrin today.
39:06I'm not going to talk too much about those pathways,
39:08but anytime I'm talking about dopaminergic transmission
39:11or that you have a peak in dopamine,
39:13inevitably, that means that you have a peak
39:15and release of epinephrin as well.
39:17What dopamine does is dopamine really colors
39:21the subjective experience of an activity
39:24to make it more pleasureful,
39:26to make it something that you want more of.
39:28Epinephrin is more about energy.
39:30Epinephrin alone can be fear, paralysis, trauma.
39:35Not physical paralysis, but mental paralysis,
39:38you know, frozen in fear or being traumatized or scared.
39:43But the addition of dopamine to that chemical cocktail,
39:46if dopamine is released in the brain,
39:48well, then that epinephrin becomes one of excitement.
39:53Okay?
39:53I'm using a broad brush here,
39:54but essentially what you need to know is that,
39:56dopamine and epinephrin aka adrenaline are family members.
40:00And they tend to work together like a little gang
40:03to make you seek out certain things.
40:06So what sorts of activities?
40:08What sorts of things increase dopamine?
40:11And how much do they increase dopamine?
40:14Well, let's take a look at some typical things
40:17that people do out there or ingest out there
40:21that are known to increase dopamine.
40:23So let's recall that you have a baseline level of dopamine
40:26and that everybody does.
40:28And even within a family,
40:29you might have family members who are very excitable,
40:31happy and motivated,
40:33and others who are less excitable, happy and motivated.
40:36But your level of dopamine has everything
40:40to do with those genetics,
40:41but also with what you've experienced in the previous days
40:44and the previous months and so on.
40:48When you do or ingest certain things,
40:50your levels of dopamine will rise above baseline
40:53transiently.
40:55And depending on what you do or ingest,
40:58it will rise either more or less,
41:00and it will be very brief or a last a long time.
41:03So let's take a look at some of the typical things
41:05that people take and do and eat.
41:08Some are good for us,
41:09some are not good for us.
41:12And let's ask how much dopamine is increased above baseline?
41:15Now, of course, these are averages,
41:16but these are averages that have been measured
41:19in so-called micro dialysis studies in animals.
41:21So actually extracting from particular brain areas
41:24how much dopamine is released?
41:25Or from measuring the serum,
41:27the circulating levels of dopamine in humans.
41:32Chocolate.
41:34They didn't look at milk versus dark chocolate.
41:35But chocolate will increase your baseline level of dopamine
41:391.5 times.
41:41Okay?
41:42So it's a pretty substantial increase in dopamine.
41:44It's transient.
41:45It goes away after a few minutes or even a few seconds.
41:50I'll explain what determines the duration in a minute.
41:53But 1.5 times for chocolate.
41:56Sex.
41:57Both the pursuit of sex and the act of sex
42:02increases dopamine two times.
42:06So it's a doubling above baseline.
42:09Now, of course, there's going to be variation there,
42:11but that's the average increase in baseline dopamine
42:16caused by sex.
42:18Later, I will talk about how the different aspects
42:22of the so-called arousal art,
42:23the different aspects of sex,
42:25believe it or not have a differential impact on dopamine.
42:28But for now as a general theme or activity,
42:33sex doubles the amount of dopamine circulating
42:36in your blood.
42:39Nicotine.
42:40In particular, nicotine that is smoked
42:43like cigarettes and so forth,
42:45increases dopamine two and a half times above baseline.
42:49So there's a peak that goes up above baseline
42:53two and a half times higher.
42:57It is very short-lived.
42:59Anyone who's ever been a chain smoker
43:01or observed a chain smoker understands
43:03that the increase in dopamine from nicotine
43:06is very short-lived.
43:09Cocaine will increase the level of dopamine
43:12in the bloodstream two and a half times above baseline.
43:16And amphetamine another drug that increases dopamine
43:21will increase the amount of dopamine in the bloodstream
43:2510 times above baseline.
43:27A tremendous increase in dopamine.
43:30Exercise.
43:31Now, exercise will have a different impact
43:34on the levels of dopamine,
43:35depending on how much somebody subjectively enjoys
43:38that exercise.
43:40So if you're somebody who loves running,
43:43chances are it's going to increase your levels of dopamine
43:47two times above your baseline,
43:49not unlike sex.
43:53People who dislike exercise will achieve
43:55less dopamine increase or no increase in dopamine
43:59from exercise.
44:01And if you like other forms of exercise like yoga
44:03or weightlifting or swimming or what have you.
44:05Again, it's going to vary by your subjective experience
44:08of whether or not you enjoy that activity.
44:11This is important.
44:12And it brings us back to something
44:14that we talked about earlier.
44:15Remember that mesocorticolimbic pathway?
44:19Well, the cortical part is important.
44:21The cortical part actually has a very specific part,
44:25which is your prefrontal cortex.
44:27The area of your forebrain that's involved in thinking
44:30and planning and involved in assigning
44:34a rational explanation to something,
44:36and involved in assigning a subjective experience
44:39to something, right?
44:41So for instance, the pen that I'm holding right now,
44:43it's one of these Pilot V5s.
44:44I love these Pilot V5s.
44:45They don't sponsor the podcast.
44:46I just happen to like them.
44:47I liked the way that they write,
44:48how they feel.
44:50If I spent enough time thinking about it,
44:52or talking about it,
44:53I could probably get a dopamine increase
44:54just talking about this Pilot V5.
44:56And that's not because I have the propensity
44:58to release dopamine easily,
45:00it's that as we start to engage with something
45:02more and more and what we say about it,
45:05and what we encourage ourselves to think about it,
45:08has a profound impact on its rewarding
45:11or non rewarding properties.
45:13Now, it's not simply the case that you can lie to yourself,
45:15and you can tell yourself I love something
45:17and when you don't really love it,
45:18and it will increase dopamine.
45:20But what's been found over and over again,
45:22is that if people journal about something
45:24or they practice some form of appreciation for something,
45:27or they think of some aspect of something that they enjoy,
45:31the amount of dopamine that that behavior will evoke
45:35tends to go up.
45:37So for people that hate exercise,
45:38you can think about some aspect of exercise
45:41that you really enjoy.
45:42However, I will caution you against saying to yourself,
45:48I hate exercise or I hate studying or I hate this person,
45:52but I love the reward I give myself afterward.
45:55Later, we're going to talk about how rewards given afterward
45:59actually make the situation worse.
46:01They won't make you like exercise more or study more,
46:04they actually will undermine the dopamine release
46:07that would otherwise occur for that activity.
46:09So certain things chemicals have a universal effect.
46:13They make everybody's dopamine go up.
46:16So some people like chocolate,
46:17some people don't of course,
46:19but in general, it make has causes
46:21this increase in dopamine.
46:22But sex, nicotine, cocaine, amphetamine,
46:25those things cause increases in dopamine
46:28and everybody that takes them.
46:30Things like exercise, studying, hard work,
46:33working through a challenge in a relationship
46:35or working through something hard of any kind
46:38that is going to be subjective
46:40as to how much dopamine will be released.
46:42And we will return to that subjective component
46:45in a little bit.
46:46But now you have a sense of how much dopamine
46:50can be evoked by different activities
46:53and by different substances.
46:55One that you might be wondering about is caffeine.
46:57I'm certainly drinking my caffeine today,
46:59and I do enjoy caffeine in limited quantities.
47:03I drink yerba mate and I drink coffee and I love it.
47:08Does it increase dopamine?
47:10Well, a little bit.
47:11Caffeine will increase dopamine to some extent,
47:14but it is pretty modest compared to the other things
47:17that I described.
47:18Chocolate, sex, nicotine, cocaine, amphetamine and so on.
47:22However, there's a really interesting paper
47:25published in 2015.
47:26This is Volkow et al.
47:27You can look up it's very easy to find.
47:30That showed that regular ingestion of caffeine,
47:33whether or not it's from coffee or otherwise,
47:36increases up regulation of certain dopamine receptors.
47:40So caffeine actually makes you able to experience
47:46more of dopamines effects.
47:47Because as I mentioned before,
47:49dopamine is vomited out into the synapse
47:51or it's released volumetrically,
47:52but then it has to bind someplace
47:54and trigger those G protein-coupled receptors.
47:56And caffeine increases the number,
47:59the density of those G protein-coupled receptors.
48:03Now, sitting back and thinking about that,
48:06you might think, oh yeah, you know,
48:07sometimes I'll notice people,
48:09at least in the old days that used to be a cigarette
48:11and a cup of coffee.
48:13Or when people drink alcohol,
48:14oftentimes they'll smoke.
48:16And it's well-known that different compounds
48:19like alcohol and nicotine or caffeine and nicotine
48:23or certain behaviors and certain drugs can synergize
48:26to give bigger dopamine increases.
48:28And this is not terribly uncommon.
48:30There are a lot of people nowadays
48:32who for instance take pre-workout energy drinks.
48:34They'll drink,
48:35I won't name names,
48:36but they'll drink a canned energy drink
48:38or they'll drink a pre-workout
48:40and they'll try and get that big stimulation
48:42that stimulant effect for the dopamine,
48:44the norepinephrin, that family of molecules
48:47that works together to make you motivated.
48:48And then they'll also exercise to try and get even more
48:51of a dopaminergic experience out of that workout.
48:54Sometimes it's also to perform better as well, of course,
48:59but as we'll talk about in a few minutes,
49:01that aspect or that approach rather
49:04of trying to just get your dopamine
49:05as high as you possibly can,
49:07in order to get the most out of experience,
49:09turns out to not be the best approach.
49:11And what you'll find as we talk about dopamine schedules
49:16is that layering together multiple things,
49:19substances and activities
49:21that lead to big increases in dopamine,
49:24actually can create pretty severe issues
49:27with motivation and energy right after those experiences
49:30and even a couple of days later.
49:32So I'm not saying that people shouldn't take
49:34the occasional pre-workout if that's your thing,
49:35or drink a cup of coffee or two before working out
49:38now and again.
49:39Some people really enjoy that.
49:40I certainly do that every once in a while,
49:42but if you do it too often,
49:44what you'll find is that your capacity to release dopamine
49:48and your level of motivation and drive and energy overall
49:51will take a serious hit.
49:53Now, I've been alluding to this dopamine peaks
49:55versus dopamine baseline things
49:57since the beginning of the episode.
49:58I talked about tonic and phasic release and so forth.
50:02But now let's really drill into what this means,
50:04and how to leverage it for our own purposes.
50:08In order to do that, let's take a step back and ask,
50:10why would we have a dopamine system like this?
50:12Why would we have a dopamine system at all?
50:15Well, we have to remember what our species primary
50:19interest is?
50:20Our species like all species has a main interest,
50:25and that's to make more of itself.
50:26And it's just about sex and reproduction.
50:28It's about forging for resources.
50:31Resources can be food,
50:32it can be water can be salt,
50:34it can be shelter,
50:36it can be social connection.
50:39Dopamine is the universal currency of forging and seeking,
50:44right?
50:45We call sometimes talk about motivation and craving,
50:46but what we mean in the evolutionary adaptive context,
50:49what we mean is forging and seeking.
50:51Seeking water, seeking food, seeking mates.
50:54Seeking things that make us feel good
50:56and avoiding things that don't make us feel good.
50:58But in particular seeking things
50:59that will provide sustenance and pleasure in the short-term
51:03and will extend the species in the long-term.
51:07Once we understand that dopamine is a driver for us
51:10to seek things,
51:12it makes perfect sense as to why
51:14it would have a baseline level and it would have peaks.
51:17And that the baseline and peaks would be related
51:19in some sort of direct way.
51:21Here's what I mean by that.
51:23Let's say that you were not alive now,
51:26but you were alive 10,000 years ago.
51:28And you woke up and you looked and you realized
51:31you had minimal water and you had minimal food left.
51:36Maybe you have a child,
51:37maybe you have a partner,
51:38maybe you're in an entire village,
51:39but you realize that you need things.
51:42Okay?
51:45You need to be able to generate the energy
51:47to go seek those things.
51:49And chances are there were dangers in seeking those things.
51:52Yes, it could be saber-tooth tigers
51:53and things of that sort,
51:55but there are other dangers too.
51:56There's the danger of a cut to your skin
51:58that could lead to infection.
51:59There's the danger of storms,
52:00there's the danger of cold,
52:01there's the danger of leaving your loved ones behind.
52:04So you go out and forage, right?
52:07You could be hunting, you could be gathering,
52:08or you could be doing both.
52:10The going out and foraging process
52:13was we are certain driven by dopamine.
52:17I mean, there's no fossil record of the brain,
52:18but the circuits have existed.
52:20We know for tens of thousands,
52:21if not hundreds of thousands of years.
52:23And they are present in every animal, not just mammals,
52:27but even in little worms like C. elegans,
52:28it's the same process.
52:29It's mediated by dopamine.
52:32So dopamine drives you to go out and look for things.
52:35And then let's say you find a couple berries,
52:37and these ones are rotten,
52:38these ones are good.
52:39Maybe you hunt an animal and kill it,
52:41or you find an animal that was recently killed
52:43and you decide to take the meat.
52:46You are going to achieve,
52:48or I should say, experience some sort of dopamine release.
52:51You found the reward.
52:52That's great.
52:54But then it needs to return to some lower level.
52:57Why?
52:58Well, because if you just stayed there,
53:00you would never continue to forage for more.
53:03It doesn't just increase your baseline and then stay there.
53:06It goes back down.
53:08And what's very important to understand
53:09is that it doesn't just go back down
53:11to the level it was before,
53:13it goes down to a level below
53:16what it was before you went out seeking that thing.
53:19Now, this is counter-intuitive.
53:20We often think,
53:21Oh, okay, I'm going to pursue the win, right?
53:24Let's move this to modern day.
53:27I'm going to run this marathon,
53:28I'm going to train for this marathon.
53:29Then you run the marathon and you finish,
53:32you cross the finish line,
53:33you feel great.
53:34And you would think, okay, now I'm set for the entire year,
53:37I'm going to feel so much better,
53:38I'm going to feel this accomplishment in my body,
53:40it's going to be so great.
53:41That's not what happens.
53:42You might feel some of those things,
53:44but your level of dopamine has actually dropped
53:46below baseline.
53:48Now, eventually it will ratchet back up.
53:51But two things are really important.
53:52First of all, the extent to which it drops below baseline
53:55is proportional to how high the peak was.
53:59So if you cross the finish line pretty happy,
54:02it won't drop that much below baseline afterward.
54:06If you cross the finish line ecstatic,
54:08well, a day or two later,
54:10you're going to feel quite a bit lower
54:12than you would otherwise.
54:13You might not be depressed,
54:14because it depends on where that baseline was to begin with.
54:17But the so-called postpartum depression
54:19that people experience after giving birth
54:22or after some big win a graduation
54:25or any kind of celebration that postpartum drop
54:29in mood and affect and motivation is the drop
54:33in baseline dopamine.
54:35This is very important to understand,
54:36because this happens on very rapid timescales
54:38and it can last quite a long time.
54:41It also explains the behavior that most of us
54:45are familiar with,
54:46of engaging in something that we really enjoy.
54:48Going to a restaurant that we absolutely love,
54:51or engaging in some way with some person
54:53that we really, really enjoy.
54:55But if we continue to engage in that behavior
54:57over and over again,
54:59it kind of loses its edge.
55:01It starts to kind of feel less exciting to us.
55:06Some of us experienced that drop in excitement more quickly
55:10and more severely than others,
55:12but everyone experiences that to some extent.
55:16And this has direct roots in these evolutionarily
55:20conserved circuits.
55:22Some of you may be hearing this and think,
55:23no, no, no, no that's not how it works for me.
55:25I'm just riding higher and higher all the time.
55:27I love my kids,
55:28I love my job,
55:29I love school,
55:30I love wins,
55:31I don't want losses.
55:33I agree.
55:35We all feel good when we are achieving things,
55:37but oftentimes we are feeling good
55:40because we are layering in different aspects of life,
55:43consuming things and doing things
55:44that increase our dopamine.
55:46We're getting those peaks,
55:48but afterward the drop in baseline occurs,
55:52and it always takes a little while to get back
55:55to our stable baseline.
55:58We really all have a sort of dopamine set point.
56:01And if we continue to indulge in the same behaviors
56:04or even different behaviors that increase our dopamine
56:07in these big peaks over and over and over again,
56:10we won't experience the same level of joy
56:12from those behaviors or from anything at all.
56:16Now, that has a name.
56:17It's called addiction.
56:18But even for people who aren't addicted,
56:22even for people don't an attachment
56:24to any specific substance or behavior,
56:26this drop in bay below baseline after any peak in dopamine
56:30is substantial.
56:31And it governs whether or not we are going to feel motivated
56:34to continue to pursue other things.
56:37Fortunately, there's a way to work with this,
56:39such that we can constantly stay motivated,
56:42but also keep that baseline of dopamine
56:44at an appropriate, healthy level.
56:46A previous guest on the Huberman Lab Podcast
56:48was Dr. Anna Lembke.
56:49She's head of the Addiction Dual Diagnosis Clinic
56:52at Stanford.
56:53Has this amazing book,
56:54"Dopamine Nation: Finding Balance in the Age of Indulgence".
56:58If you haven't read the book,
56:59I highly encourage you to check it out.
57:01It's fantastic.
57:02The other terrific book about dopamine
57:04is the "Molecule of More",
57:05which is a similar in some regard,
57:08but isn't so much about addiction,
57:09it's more about other types of behaviors.
57:11Both books really focus on these dopamine schedules
57:15and the relationship between these peaks
57:16and baselines of dopamine.
57:20In Dr. Lembke's book,
57:21and when she was on the Huberman Lab Podcast
57:23and other podcasts,
57:24she's talked about this pleasure pain balance
57:26that when we seek something that we really like,
57:28or we indulge in it,
57:29like eating a little piece of chocolate,
57:31if we really liked chocolate,
57:32there's some pleasure.
57:33But then there's a little bit of pain
57:37that exceeds the amount of pleasure,
57:38and it's subtle,
57:40and we experience it as wanting more of that thing.
57:43Okay?
57:44So there's a pleasure pain balance,
57:45and I'm telling you that the pleasure and the pain
57:48are governed by dopamine to some extent.
57:50Well, how could that be?
57:51Right?
57:52I said before, when you engage in an activity
57:54or when you ingest something that increases dopamine,
57:56the dopamine levels go up,
57:58you know, to substantial degree
58:00with all the things I listed off.
58:04Where's the pain coming from?
58:06Well, the pain is coming from the lack of dopamine
58:09that follows.
58:10And you now know what that lack of dopamine reflects.
58:16How do you know?
58:17Well, earlier we were talking about how dopamine
58:19is released between neurons.
58:22And I mentioned two ways.
58:23One, is into the synapse where it can activate
58:25the postsynaptic neuron.
58:26And the other was what I called volumetric release
58:28where it is distributed more broadly.
58:31It's released out over a bunch of neurons.
58:35In both cases it's released from these things
58:37we call synaptic vesicles,
58:39literally little bubbles, tiny, tiny little bubbles
58:42that contain dopamine.
58:43Prrr! They get vomited out into the area
58:45or into the synapse.
58:47Well, those vesicles get depleted.
58:52For the synaptic physiologists out there,
58:54we call this the readily releasable pool of dopamine.
58:58We can only deploy dopamine that is ready to be deployed.
59:03That's packaged in those little vesicles and ready to go.
59:05It's like when you order a product and they say out of stock
59:08until two months from now.
59:10Well, it's not ready to be released.
59:12Same thing with dopamine.
59:13There's a pool of dopamine that synthesized,
59:16and you can only release the dopamine
59:20that's been synthesized.
59:20It's the readily releasable pool.
59:23The pleasure pain balance doesn't only hinge
59:27on the readily releasable pool of dopamine,
59:29but a big part of the pleasure pain balance
59:33hinges on how much dopamine is there?
59:36And how much is ready and capable of being released
59:39into the system?
59:41So now we've given some meat to this thing
59:45that we call the pleasure pain balance,
59:47and now it should make perfect sense
59:49why if you take something or do something
59:52that leads to huge increases in dopamine,
59:55afterward your baseline should drop
59:58because there isn't a lot of dopamine around
1:00:01to keep your baseline going.
1:00:04Fortunately, most people do not experience
1:00:07or pursue enormous increases in dopamine
1:00:10leading to the severe drops in baseline.
1:00:14Many people do, however,
1:00:15and that's what we call addiction.
1:00:17When somebody pursues a drug or an activity
1:00:20that leads to huge increases in dopamine.
1:00:22And now you understand that afterward
1:00:24the baseline of dopamine drops
1:00:26because of depletion of dopamine,
1:00:28that readily releasable pool.
1:00:30The dopamine is literally not around to be released,
1:00:33and so people feel pretty lousy
1:00:35and many people make the mistake of then going and pursuing
1:00:39the dopamine evoking the dopamine releasing activity
1:00:42or substance again thinking mistakenly
1:00:46that it's going to bring up their baseline.
1:00:48It's going to give them that peak again.
1:00:50Not only does it not give them a peak,
1:00:52their baseline gets lower and lower
1:00:54because they're depleting dopamine more and more and more.
1:00:57And we've seen this over and over again
1:00:59when people get addicted to something
1:01:01then they're not achieving much pleasure at all.
1:01:05You can even see this with video games.
1:01:08People will play a video game,
1:01:09they love it,
1:01:10it's super exciting to them,
1:01:12and then they'll keep playing and playing and playing,
1:01:15and either one of two things happens typically both.
1:01:19First of all,
1:01:20I always say addiction is a progressive narrowing
1:01:23of the things that bring you pleasure.
1:01:25So oftentimes what will happen is the person
1:01:27only has excitement and can achieve dopamine release
1:01:31to the same extent doing that behavior
1:01:33and not other behaviors.
1:01:35And so they start losing interest in school,
1:01:37they start losing interest in relationships.
1:01:39they start losing interest in fitness and wellbeing
1:01:42and depletes their life.
1:01:44And eventually what typically happens is,
1:01:47they will stop getting dopamine release
1:01:50from that activity as well,
1:01:52and then they drop into a pretty serious depression
1:01:55and this can get very severe and people
1:01:57have committed suicide from these sorts of patterns
1:02:00of activity.
1:02:01But what about the more typical scenario?
1:02:04What about the scenario of somebody
1:02:06who is really good at working during the week,
1:02:10they exercise during the week,
1:02:11they drink on the weekends?
1:02:13Well, that person is only consuming alcohol
1:02:16maybe one or two nights a week,
1:02:18but oftentimes that same person will be spiking
1:02:22their dopamine with food during the middle of the week.
1:02:25Now, we all have to eat and it's nice to eat foods
1:02:27that we enjoy.
1:02:28I certainly do that.
1:02:29I love food in fact.
1:02:31But let's say they're eating foods
1:02:34that really evoke a lot of dopamine release
1:02:36in the middle of the week,
1:02:37they're drinking one or two days on the weekend,
1:02:39they are one of these work, hard play hard type.
1:02:42So they're swimming a couple miles in the ocean
1:02:45in the middle of the week as well.
1:02:47They're going out dancing once on the weekend.
1:02:49Sounds like a pretty balanced life as I describe it.
1:02:53Well, here's the problem.
1:02:56The problem is that dopamine is not just evoked
1:03:00by one of these activities,
1:03:01dopamine is evoked by all of these activities.
1:03:04And dopamine is one currency of craving motivation
1:03:08and desire and pleasure.
1:03:11There's only one currency.
1:03:13So even though if you look at the activities,
1:03:16you'd say, well, it's just on the weekends
1:03:18so this thing is only a couple of times a week.
1:03:20If you looked at dopamine simply as a function,
1:03:23as a chemical function of peaks and baseline,
1:03:26it might make sense why this person
1:03:28after several years of work hard, play hard
1:03:31would say, yeah, you know I'm feeling kind of burnt out.
1:03:34I'm just not feeling like I have the same energy
1:03:35that I did a few years ago.
1:03:37And of course there are age-related reasons
1:03:39why people can experience drops in energy,
1:03:42but oftentimes what's happening
1:03:45is not some sort of depletion and cellar metabolism
1:03:48that's related to aging.
1:03:49What's happening is they're spiking their dopamine
1:03:51through so many different activities throughout the week,
1:03:54that their baseline is progressively dropping.
1:03:57And in this case it can be very subtle.
1:03:59It can be very, very subtle.
1:04:00And that's actually a very sinister function of dopamine
1:04:06we could say.
1:04:07Which is that it can often drop in imperceptible ways,
1:04:10but then at once it reaches a threshold of low dopamine,
1:04:15we just feel like,
1:04:16hmm, we can't really get pleasure from anything anymore.
1:04:18What used to work doesn't work anymore.
1:04:20So it starts to look a lot like the more severe addictions
1:04:23or the more acute addictions to things like cocaine
1:04:26and amphetamine which lead to these big increases,
1:04:28these big spikes in dopamine,
1:04:29and then these very severe drops in the baseline.
1:04:33Now, of course, we all should engage in activities
1:04:37that we enjoy.
1:04:38I certainly do,
1:04:39everybody should.
1:04:39A huge part of life is pursuing activities and things
1:04:42that we enjoy.
1:04:44The key thing is to understand this relationship
1:04:47between the peaks and the baseline,
1:04:48and to understand how they influence one another.
1:04:50Because once you do that,
1:04:52you can start to make really good choices in the short run
1:04:55and in the long run to maintain your level of dopamine
1:04:58baseline.
1:04:59Maybe even raise that level of dopamine baseline
1:05:02and still get those peaks and still achieve those feelings
1:05:06of elevated motivation, elevated desire and craving.
1:05:10Because again, those peaks and having a sufficiently
1:05:15healthy high level of dopamine baseline
1:05:17are what drove the evolution of our species,
1:05:19and they're really what drive the evolution of anyone's life
1:05:21progression too.
1:05:22So they're a good thing.
1:05:23Dopamine is a good thing.
1:05:25Just very briefly, because it was also covered
1:05:27in the interview episode I did with Anna Lembke
1:05:31about addiction.
1:05:32Some of you might be asking,
1:05:34what should I do if I experience a drop
1:05:36in my baseline level of dopamine
1:05:38because of engagement with some activity or some substance
1:05:42that led to big peaks?
1:05:45Just to put some color and example on this,
1:05:48a few episodes ago I talked about a friend
1:05:50who I've known a long time.
1:05:52So it actually the child of a friend
1:05:53who has basically become addicted to video games,
1:05:57he decided actually after seeing that episode with Anna
1:06:00to do a 30-day complete fast from phone,
1:06:04from video games and from social media of all kinds.
1:06:07He's now at day 29 has really accomplished this,
1:06:11not incidentally, his levels of concentration,
1:06:13his overall mood are up.
1:06:14He's doing far far better.
1:06:16What he did is hard.
1:06:18In particular first 14 days is really hard,
1:06:20but the way that you replenish the releasable pool
1:06:23of dopamine is to not engage in these dopaminergic
1:06:27seeking behaviors.
1:06:29Because remember typically people arrive at a place
1:06:31where they want to stop engaging in these behaviors
1:06:34or ingesting substances when that dopamine is depleted,
1:06:37when they're not getting the same lift.
1:06:38In his case, he was feeling depressed.
1:06:40He thought he had ADHD.
1:06:41They were starting to treat it as ADHD.
1:06:44And certainly there are people out there who have ADHD,
1:06:47but what he found was that his levels of concentration
1:06:49are back.
1:06:50He does not need to be treated for ADHD.
1:06:52And actually the psychiatrist wondered if he did prior
1:06:55to this video game, social media fast.
1:06:58He's feeling good.
1:06:58He's exercising again.
1:07:00I'm not making this up.
1:07:01This is really a very specific,
1:07:04but very relevant example of how the dopamine system
1:07:08can replenish itself.
1:07:10Of course, if there's a clinical need for ADHD treatment,
1:07:13by all means pursue that.
1:07:14But I think a lot of ADHD does go misdiagnosed
1:07:19because of this depletion in dopamine
1:07:21that occurs because of overindulgence in other activities
1:07:24in the drop in baseline.
1:07:25So for anyone that's experienced a real drop in baseline
1:07:28who has addictive tendencies,
1:07:31whether or not their behaviors or substances,
1:07:32that is always going to be the path forward.
1:07:37Is going to be either cold turkey
1:07:38or through some sort of tapering to limit interactions
1:07:42with the, what would otherwise be the dopamine evoking
1:07:45behavior or substance.
1:07:47So let's talk about the optimal way to engage in activities
1:07:51or to consume things that evoke dopamine.
1:07:55And by no means am I encouraging people to take drugs
1:07:57of abuse.
1:07:58I would not do that,
1:07:59I am not doing that.
1:08:00But some of the things on these lists
1:08:03of dopamine evoking activities are things like chocolate,
1:08:07coffee, even if it's indirect.
1:08:10Sex and reproduction,
1:08:11provided it's healthy consensual context appropriate,
1:08:15age appropriate, species appropriate of course,
1:08:17is central to our evolution and progression as a species.
1:08:21So certain things like cocaine, amphetamine,
1:08:24I will put in the classification of bad.
1:08:26I'm willing to do that.
1:08:27And other things are part of life,
1:08:29food, exercise if that evokes your dopamine.
1:08:32How are we supposed to engage with these dopamine evoking
1:08:35activities in ways that are healthy and beneficial for us?
1:08:38How do we achieve these peaks,
1:08:40which are so central to our wellbeing and experience of life
1:08:43without dropping our baseline?
1:08:45And the key lies in intermittent release of dopamine.
1:08:50The real key is to not expect or chase high levels
1:08:56of dopamine release every time we engage
1:08:58in these activities.
1:09:01Intermittent reward schedules are the central schedule
1:09:05by which casinos keep you gambling.
1:09:08The central schedule by which elusive partners
1:09:12or potential partners keep you texting and pursuing
1:09:16on either side of the relationship.
1:09:18Intermittent schedules are the way that the internet
1:09:22and social media and all highly engaging activities
1:09:27keep you motivated and pursuing.
1:09:31And we can take this back to our evolutionary adaptive
1:09:35scenario where you are out there looking for water,
1:09:38looking for food,
1:09:40not every trail, not every pursuit, not every hunch
1:09:44about where the animals will be?
1:09:46Where the food will be?
1:09:47Where the berries will be?
1:09:49Not every single one of those played out.
1:09:54There's something called dopamine reward prediction error.
1:09:56When we expect something to happen,
1:09:58we are highly motivated to pursue it.
1:10:01If it happens great, we get the reward.
1:10:04The reward comes in various chemical forms
1:10:06including dopamine,
1:10:07and we are more likely to engage in that behavior again.
1:10:11This is the basis of casino gambling.
1:10:13This is how they keep you going back
1:10:14again and again and again,
1:10:15even though on average the house really does win.
1:10:20You can transplant that example to any number
1:10:23of different pleasureful activities.
1:10:24If you're not a gambler and that doesn't appeal to you,
1:10:27I have to imagine there's something that appeals to you,
1:10:29something that you do repeatedly because you enjoy it.
1:10:31And almost inevitably it's because there's an intermittent
1:10:35schedule.
1:10:37There's a intermittent schedule by which dopamine
1:10:40sometimes arrives,
1:10:41sometimes a little bit, sometimes a lot,
1:10:43sometimes a medium amount.
1:10:44Okay?
1:10:45That intermittent reinforcement schedule
1:10:48is actually the best schedule to export to other activities.
1:10:53How do you do that?
1:10:54Well, first of all, if you are engaged in activities
1:10:59school, sport, relationship, et cetera,
1:11:01where you experience a win,
1:11:04you should be very careful about allowing yourself
1:11:06to experience huge peaks in dopamine,
1:11:09unless you're willing to suffer the crash that follows
1:11:13and waiting a period of time for it to come back up.
1:11:17What would this look like in the practical sense?
1:11:19Well, let's say you are somebody
1:11:20who really does enjoy exercise,
1:11:22or let's say you're somebody who kind of likes exercise,
1:11:24but forces yourself to do it,
1:11:26but you make it pleasureful by giving yourself
1:11:28your favorite cup of coffee first,
1:11:30or maybe taking a pre-workout drink
1:11:32or taking an energy drink
1:11:34or listening to your favorite music.
1:11:35And then you're in the gym
1:11:36and you're listening to your music.
1:11:37That all sounds great, right?
1:11:39Well, it is great except that by layering together
1:11:42all these things to try and achieve that dopamine release,
1:11:44and by getting a big peak in dopamine,
1:11:46you're actually increasing the number of conditions required
1:11:50to achieve pleasure from that activity again.
1:11:53And so there is a form of this where sometimes
1:11:56you do all the things that you love
1:11:58to get the optimal workout.
1:11:59You listen to your favorite music,
1:12:00you got your favorite time of day,
1:12:02you have your pre-workout drink,
1:12:03if that's your thing.
1:12:04You do all the things that give you that best experience
1:12:08of the workout for you.
1:12:10But there's also a version of this where sometimes
1:12:13you don't do the dopamine enhancing activities.
1:12:17You don't ingest anything to increase your dopamine.
1:12:19You just do the exercise.
1:12:22You don't do the exercise and expect dopamine to arrive
1:12:27through some what we call exogenous source as well.
1:12:30You might think, well, that sounds lame.
1:12:31I want to continue to enjoy exercising.
1:12:35Ah, well, that's exactly the point.
1:12:37If you want to maintain motivation for school, exercise,
1:12:40relationships or pursuits of any duration in kind,
1:12:44the key thing is to make sure that the peak in dopamine,
1:12:47if it's very high, doesn't occur too often.
1:12:51And if something does occur very often
1:12:54that you vary how much dopamine you experience
1:12:57with each engagement in that activity.
1:13:00Now, some activities naturally have this intermittent
1:13:03property woven into them, right?
1:13:05We sometimes have classes that we like
1:13:07and other classes we don't like.
1:13:09We don't always get straight A's,
1:13:11sometimes we don't get rewarded with the outcome
1:13:13that we would like.
1:13:14We don't always have the perfect relationship outcome,
1:13:18but understand that your ability to experience motivation
1:13:21and pleasure for what comes next
1:13:23is dictated by how much motivation and pleasure
1:13:26and dopamine you experienced prior.
1:13:29The reason I can't give a very specific protocol
1:13:32like delete dopamine or lower dopamine every third time,
1:13:36is that that wouldn't be intermittent.
1:13:38The whole basis of intermittent reinforcement
1:13:40is that you don't really have a specific schedule
1:13:44of when dopamine is going to be high,
1:13:46and when dopamine is going to be low
1:13:48and when dopamine is going to be medium.
1:13:49That's a predictable schedule,
1:13:51not a random intermittent schedule.
1:13:53So do like the casinos do certainly works for them
1:13:57and for activities that you would like to continue to engage
1:14:00in over time,
1:14:01whatever those happen to be.
1:14:04Start paying attention to the amount of dopamine
1:14:07and excitement and pleasure that you achieve with those,
1:14:09and start modulating that somewhat at random.
1:14:12That might be removing some of the dopamine
1:14:15releasing chemicals that you might take prior.
1:14:18Maybe you remove them every time,
1:14:21but then every once in a while you introduce them,.
1:14:23Maybe it involves sometimes doing things socially
1:14:27that you enjoy doing socially,
1:14:28sometimes doing the same thing, but alone.
1:14:31There are a lot of different ways to do this.
1:14:34There are a lot of different ways to approach this,
1:14:36but now knowing what you know about peaks and baselines
1:14:39in dopamine and understanding how important
1:14:42it is not just to achieve peaks,
1:14:43but to maintain that baseline at a healthy level,
1:14:46it should be straightforward for you to implement
1:14:48these intermittent schedules.
1:14:50For those of you that are begging for more specificity,
1:14:54we can give you a tool.
1:14:55One would be, you can flip a coin before engaging
1:14:59in any of these types of activities
1:15:00and decide whether or not you are going to allow
1:15:03other dopamine supportive elements
1:15:07to go for instance, into the gym with you.
1:15:09Are you going to listen to music or not?
1:15:11If you enjoy listening to music,
1:15:12well then flip a coin,
1:15:13and if it comes up heads,
1:15:14bring the music in,
1:15:15if it comes up tails, don't.
1:15:17Okay?
1:15:17It sounds like you're undercutting your own progress,
1:15:19but actually you are serving your own progress
1:15:23both short-term and long-term by doing that.
1:15:25Now, the smartphone is a very interesting tool
1:15:28for dopamine in light of all this.
1:15:32It's extremely common nowadays to see people texting
1:15:35and doing selfies and communicating in various ways,
1:15:39listening to podcasts, listening to music,
1:15:41doing all sorts of things while they engage
1:15:43in other activities or going to dinner
1:15:45and texting other people or making plans,
1:15:47sharing information.
1:15:48That's all wonderful,
1:15:49it gives depth and richness and color to life,
1:15:52but it isn't just about our distracted nature
1:15:56when we're engaging with the phone,
1:15:59it's also a way of layering in dopamine.
1:16:02And it's no surprise that levels of depression
1:16:06and lack of motivation are really on the increase.
1:16:11Everything that we've talked about until now
1:16:14sets up an explanation or interpretation
1:16:17of why interacting with digital technology
1:16:21can potentially lead to disruptions
1:16:23or lowering in baseline levels of dopamine.
1:16:28I can use a personal example for this.
1:16:30I happen to really enjoy working out,
1:16:32I've always really enjoyed it.
1:16:33But in recent years I noticed that,
1:16:37if I was bringing my phone to my workouts,
1:16:39then not only was I a little bit more distracted
1:16:42and not focusing on what I was doing
1:16:43as much as I could have or should have,
1:16:45but also I started to lose interest in what I was doing.
1:16:49It wasn't as pleasureful,
1:16:50I would feel like it just didn't have the same
1:16:53kind of oomph.
1:16:53And I was beginning to question my motivation.
1:16:56As I started learning more about this relationship
1:16:59between the peaks and the bass lines in dopamine.
1:17:02What I realized was that some time ago
1:17:04I probably experienced a incredible increase
1:17:07in the amount of dopamine during one of my workouts,
1:17:09because I enjoy working out and I enjoy listening to music.
1:17:13I also enjoy listening to podcasts,
1:17:15I also enjoy communicating with people.
1:17:17Those are all wonderful pursuits,
1:17:18but I had layered in too many of them too many times.
1:17:22And then it essentially wasn't working for me anymore.
1:17:25Much in the same way a drug wouldn't work for somebody
1:17:28who takes it repeatedly because their baseline of dopamine
1:17:30is dropping.
1:17:31So at least for this calendar year,
1:17:33I've made a rule for myself,
1:17:35which is I don't allow my phone into my workouts at all.
1:17:40No music, at least not from the phone.
1:17:42It can be in the room.
1:17:44I might listen to a podcast in the room,
1:17:46but I don't listen to anything
1:17:49or engage in anything on my phone.
1:17:50No texting whatsoever.
1:17:51And most of the time I just don't even bring it with me
1:17:53for that period of time.
1:17:54It's only a short period of time.
1:17:56I'm not training that often.
1:17:59This is something that I think has been misinterpreted
1:18:03as people can't be alone now.
1:18:06People talk about, oh, you know,
1:18:07they can't walk across the street or they can't go anywhere,
1:18:12ride the bus,
1:18:13can't be on the plane without being in contact.
1:18:15They can't handle just their thoughts.
1:18:17I don't think that's really what's going on.
1:18:19I think what's happened is that we achieved
1:18:22the great dopamine increase
1:18:23that comes from this incredible thing
1:18:25which I personally enjoy being able to communicate by phone,
1:18:29by text and exchange pictures and send links
1:18:31and these kinds of things, social media.
1:18:33But then what happens is it doesn't have that same
1:18:36fulfilling aspect to it.
1:18:38And it tends to remove the excitement
1:18:41and the pleasure of the very activities
1:18:43that we are engaged in.
1:18:44So I know this is a hard one for many people,
1:18:46but I do invite you to try removing multiple
1:18:51sources of dopamine release
1:18:52or what used to be multiple sources of dopamine release
1:18:56from activities that you want to continue to enjoy,
1:18:58or that you want to enjoy more.
1:19:00And now you understand the biological mechanisms
1:19:03that would underlie a statement like that.
1:19:05It takes a little bit of working with,
1:19:07I know it can be challenging in the first week
1:19:10or so of not engaging with the phone
1:19:12during any kind of workout.
1:19:14That actually was really tough,
1:19:16but now I'm back to a place where I enjoy it that much more.
1:19:19I also feel as if I conquered something
1:19:20in terms of the circuitry related to dopamine.
1:19:23I now understand why something
1:19:25that I enjoyed so much had become less pleasureful for me.
1:19:29And there's a deep, deep satisfaction
1:19:31that comes from understanding,
1:19:32okay, there wasn't anything wrong with me
1:19:34or what I was doing or anything at all.
1:19:38It was just there was something wrong with the approach
1:19:40I was taking,
1:19:41which was layering in all these sources of dopamine
1:19:43and dropping my baseline.
1:19:45For this very same reason,
1:19:46I caution people against using stimulants every time
1:19:50they study or every time they work out
1:19:54or every time that they do anything
1:19:57that they would like to continue to enjoy
1:19:59and be motivated at.
1:20:00There's one exception which is caffeine,
1:20:02because as I mentioned before,
1:20:04if you like caffeine,
1:20:06that actually could be a good thing
1:20:07for your dopamine system,
1:20:08because it does upregulate these D2, D3 receptors.
1:20:11So it actually makes whatever dopamine
1:20:13is released by that activity,
1:20:16more accessible or more functional within the biochemistry
1:20:19and the pathways of your brain and body.
1:20:23However, a number of energy drinks
1:20:25and particular pre-workouts contain things
1:20:28that are precursors to dopamine,
1:20:30and on their own, even if you didn't engage in the activity
1:20:33would cause the release of dopamine to a substantial degree.
1:20:36They do cause the release of dopamine
1:20:38to a substantial degree.
1:20:40And over time that will deplete your dopamine.
1:20:44So energy drinks, pre-workout drinks,
1:20:48drugs of various kinds that people take to study
1:20:51and pay attention.
1:20:52We talked about some of these for the ADHD episode,
1:20:54things like Adderall, Ritalin, armodafinil or modafinil
1:20:58taken repeatedly over time will reduce
1:21:01the level of satisfaction and joy
1:21:03that you get from the activities
1:21:05you engage in while under the influence of those compounds.
1:21:10I'm not trying to demonize those compounds
1:21:11for their clinical use.
1:21:13What I'm saying is taking stimulants
1:21:14and then engaging in activities
1:21:16that you would like to continue to feel pleasureful
1:21:19is undercutting the process.
1:21:20And inevitably might not happen tomorrow,
1:21:23might not happen in a month,
1:21:24but inevitably you will have challenges with motivation
1:21:27and drive related to those activities.
1:21:30Now, some people can keep it right in check.
1:21:32They can just do the one can have the energy drink
1:21:34or they only do their pre-workout before really hard days,
1:21:38for instance.
1:21:39More power to you.
1:21:42I actually do that sometimes, frankly.
1:21:44But people who are trying to get into that peak
1:21:47super motivated, driven, driven state,
1:21:49really focused every time they engage in an activity,
1:21:52you are absolutely undercutting the process
1:21:55and you are undermining your ability to stay motivated
1:21:57and focused.
1:21:58So just as we talked about intermittent reward schedules
1:22:03a moment ago,
1:22:05intermittent spiking of dopamine if you do it at all
1:22:09is definitely the way to go,
1:22:10and chronically trying to spike your dopamine
1:22:13in order to enhance your motivation, focus and drive
1:22:15will absolutely undermine your motivation focus and drive
1:22:19in the long run.
1:22:20Ingestion of caffeine is somewhat of an exception
1:22:24among the other examples of things
1:22:26I've mentioned to avoid before
1:22:29what would otherwise be dopamine increasing activities.
1:22:32Because again, caffeine can increase the density
1:22:37and the efficacy of these dopamine receptors.
1:22:41It turns out that the source of caffeine could also matter
1:22:45while coffee or tea or other forms of caffeine
1:22:48will have this effect of increasing dopamine receptors.
1:22:52Yerba mate something I've talked about before
1:22:55on this podcast has some interesting properties.
1:22:58First of all, it contains caffeine.
1:22:59It's also high in antioxidants.
1:23:02It also contains something called GLP-1
1:23:04which is favorable for management of blood sugar levels.
1:23:10Yerba mate turns out has also been shown
1:23:13to be neuroprotective specifically for dopaminergic neurons.
1:23:17Now, I should mention this is just a couple of studies,
1:23:20so we don't want to conclude too much from these studies
1:23:23more needs to be done.
1:23:24But they showed that in a model of damage
1:23:27to dopamine neurons, ingestion of yerba mate,
1:23:31and some of the compounds within yerba mate
1:23:33can actually serve to preserve the survival
1:23:35of dopamine neurons in both the movement related pathway
1:23:38and the motivation pathway.
1:23:41So perhaps you need that incentive
1:23:44in order to ingest your yerba mate,
1:23:46perhaps you don't need any incentive.
1:23:48In my case, I don't need any incentive.
1:23:49I already enjoy yerba mate as my principle
1:23:52source of caffeine,
1:23:53although I do drink coffee as well.
1:23:55But if one were going to consume caffeine,
1:23:57you might consider consuming that caffeine
1:24:00in the form of yerba mate both for sake of upregulating
1:24:02dopamine receptors and getting more of a dopamine increase.
1:24:07And of course, for the similar properties of caffeine
1:24:10if that's what you're seeking.
1:24:12And in addition to that,
1:24:14because your yerba mate does appear
1:24:16to have some sort of neuroprotective
1:24:18and a particular dopamine neuron protective properties.
1:24:22Now, that doesn't mean that caffeine is always beneficial.
1:24:24And actually there's one instance related to dopamine
1:24:27where caffeine can be particularly dangerous.
1:24:30And this relates to MDMA so-called ecstasy.
1:24:33MDMA is under investigation in various clinical trials
1:24:37for its potential to treat trauma and depression.
1:24:41It's also of course, a drug that's used recreationally.
1:24:44It's still illegal at least in the United States.
1:24:50Whether or not MDMA is neurotoxic
1:24:52has been very controversial.
1:24:53Early on it was thought that it is neurotoxic
1:24:56that it can destroy serotonergic neurons.
1:24:59There were other papers that came out
1:25:01which argued that's not the case.
1:25:04And that's in particular because one of the early papers
1:25:07published in science magazine claiming
1:25:10that MDMA was neurotoxic.
1:25:13That paper was retracted.
1:25:14It turns out that that study had mistakenly
1:25:17used methamphetamine instead,
1:25:19and methamphetamine is known to be neurotoxic.
1:25:23I think most of the data point to the idea
1:25:25that MDMA might not be neurotoxic,
1:25:28but in any case, caffeine has been shown to increase
1:25:32the toxicity of MDMA receptors.
1:25:34And you might say, "Well, how could that be?"
1:25:36Well, now you understand why that could be.
1:25:39Caffeine increases the density and efficacy
1:25:42of these dopamine receptors, D2 and D3 receptors.
1:25:45MDMA is a potent drug for increasing concentrations
1:25:50of dopamine as well as serotonin and other neuromodulators.
1:25:53And it appears that caffeine ingestion by upregulating
1:25:57these receptors,
1:25:58can lead to more toxicity of MDMA.
1:26:02So caffeine can be a beneficial substance in one context,
1:26:06and actually can be a detrimental
1:26:08if not dangerous substance in another context.
1:26:11Two substances that greatly increase dopamine,
1:26:14namely amphetamine and cocaine can cause long-term problems
1:26:20with the dopaminergic pathways.
1:26:22And this is largely based on a study
1:26:24that was published some years ago, 2003,
1:26:27but still holds a lot of merit.
1:26:29This is a paper published in proceeds
1:26:31in the National Academy of Sciences,
1:26:33a very high tier stringent journal.
1:26:36First author is Kolb, K-O-L-B.
1:26:38And the title of the paper pretty much tells the story.
1:26:42Amphetamine or cocaine limits the ability
1:26:45of later experience to promote structural plasticity
1:26:47in the neocortex and nucleus accumbens.
1:26:49Neocortex is the outer shell of the brain more or less.
1:26:54And the nucleus accumbens is part of that,
1:26:56mesolimbic dopamine pathway for motivation drive
1:26:59and reinforcement.
1:27:01Neuroplasticity of course, is the brain's ability to change
1:27:04in response to experience.
1:27:05And neuroplasticity is the basis of learning and memory
1:27:09and essentially remodeling of our neural circuitry
1:27:13in positive ways of all kinds.
1:27:15And this study was really one of the first to show
1:27:18that ingesting amphetamine and cocaine
1:27:21because of the high peak in dopamine
1:27:25that it creates and the low dopamine state,
1:27:28the baseline drop that it creates afterwards,
1:27:31limits plasticity and learning subsequent
1:27:34to taking amphetamine and cocaine.
1:27:36It was at least in this study shown
1:27:38to be a long lasting effect.
1:27:40I doubt it's a permanent effect,
1:27:41but this should serve as a serious cautionary note
1:27:45that amphetamine and cocaine not only can cause a drop
1:27:48in baseline dopamine,
1:27:49but can actually put the brain into a state
1:27:51in which it cannot learn and modify itself to get better
1:27:55at least for some period of time.
1:27:57In a previous episode on ADHD,
1:28:00I talked about the widespread use of drugs
1:28:02like Adderall, Ritalin, modafinil and armodafinil,
1:28:05all of which lead to very large increases in dopamine,
1:28:07and for people with ADHD can really improve their symptoms.
1:28:12But of course there's a lot of non-prescription,
1:28:15non-clinical use of those compounds as well.
1:28:18And it stands to reason that the use of those substances
1:28:21to increase dopamine could very well provide
1:28:25the same sort of blockade of neuroplasticity
1:28:27that cocaine and amphetamine do.
1:28:28Because when you look at the amount of dopamine increase
1:28:32that's triggered by those compounds,
1:28:33it's really comparable.
1:28:35So again, a cautionary note against spiking one's dopamine
1:28:39too much on a regular basis,
1:28:41unless there's a valid clinical need for doing that.
1:28:45So we've been focusing a lot for the last few minutes
1:28:48on the kind of darker side of dopamine
1:28:50and how getting big peaks in dopamine can be detrimental,
1:28:54but I want to acknowledge the truth,
1:28:56which is that dopamine feels great.
1:28:59Being in pursuit and motivated and craving things
1:29:01feels wonderful.
1:29:03And I don't want to demonize dopamine.
1:29:05What I'm trying to do today is to illustrate
1:29:07how dopamine works in your brain
1:29:09so that you can continue to engage
1:29:12in dopamine evoking activities.
1:29:15And certainly there is a place for ingesting things
1:29:18that can increase dopamine provided that they are safe
1:29:21for us in the short and long-term.
1:29:25There are activities that we can do that will give us
1:29:28healthy, sustained increases in dopamine,
1:29:31both the peaks when they happen and to maintain
1:29:35or even increase our baseline levels of dopamine.
1:29:37So how do we do that?
1:29:39What are some of these activities?
1:29:41Well, in recent years,
1:29:43there's been a trend toward more people
1:29:45doing so-called cold exposure.
1:29:47In part, this was popularized by Wim Hof,
1:29:51the so-called 'Iceman' getting into cold showers,
1:29:54taking ice baths, exposing oneself to cold water
1:29:57of various kinds can in fact increase our levels of dopamine
1:30:01as well as the neuromodulator norepinephrine.
1:30:05This is not a new phenomenon.
1:30:08In the 1920s, a guy by the name of Vincent Priessnitz
1:30:12was one of the first people to popularize and formalize
1:30:15cold water therapies.
1:30:17He was an advocate of cold water exposure
1:30:20in order to boost the immune system
1:30:22and increase feelings of wellbeing.
1:30:24And actually this practice dates back long
1:30:26before Vincent's popularized it.
1:30:30And Wim Hof is the more recent iteration of this.
1:30:33First of all, some of the safety parameters.
1:30:35Let's establish those first.
1:30:36Getting to very, very cold water.
1:30:38You know, 30 degree Fahrenheit
1:30:39or even low 40 degree Fahrenheit
1:30:42can put somebody into a state of cold water shock.
1:30:44I mean, people can die doing that.
1:30:46So obviously you want to approach this with some caution,
1:30:49but for most people getting into 60 degree water
1:30:52or 50 degree water,
1:30:54or if you're acclimated and comfortable with it,
1:30:57you know, 40 degree water or 45 degree water
1:30:59can have tremendously beneficial results
1:31:03on your neuromodulator systems, including dopamine.
1:31:07What temperature of water you can tolerate
1:31:09will depend on how cold water adapted you are,
1:31:12and how familiar you are with the experience
1:31:15of getting into cold water.
1:31:17And when I say comfortable with,
1:31:18I should mention, there is never a case
1:31:21in which getting into cold water does not evoke
1:31:25a release of epinephrin.
1:31:27So the quickening of the breath, the widening of the eyes,
1:31:30the feeling as if you can't catch your breath
1:31:32and even some physical pain at the level of the skin
1:31:35that happens almost every time,
1:31:37or every time that you get into cold water,
1:31:39even if your cold water adapted.
1:31:41What almost everybody knows and understands is that,
1:31:44that wall, as I like to refer to it is coming.
1:31:47That's always the first experience
1:31:48of getting into cold water.
1:31:50There's no real way around that.
1:31:52Now, this study that I mentioned earlier,
1:31:55human physiological responses to immersion into water
1:31:58of different temperatures,
1:31:59really interesting study that was done and published
1:32:02in the university of, excuse me,
1:32:04the European Journal of Applied Physiology.
1:32:06I can provide a link to that study in the show caption.
1:32:09It's a really interesting study.
1:32:11They looked at people getting exposed to water
1:32:14that was warm, moderately cold or very cold.
1:32:16It was 32 degrees Celsius, 20 degrees Celsius,
1:32:19or 14 degrees Celsius.
1:32:21You can just put those online and do the conversion,
1:32:23or you can do the conversion to Fahrenheit if you like.
1:32:25But in any case, what they looked at were the concentrations
1:32:29of things like epinephrin and dopamine and so on.
1:32:34And what they found was really interesting.
1:32:36First of all, upon getting into cold water,
1:32:42the changes in adrenaline and noradrenaline,
1:32:46epinephrin and norepinephrine were immediate and fast,
1:32:49and these were huge increases.
1:32:52So that's the getting into the cold water
1:32:53that everybody experiences
1:32:55these huge increases in adrenaline.
1:32:57But then what was interesting is they observed
1:32:59that dopamine levels started to rise somewhat slowly
1:33:03and then continued to rise and reach levels
1:33:06as high as 2.5 times above baseline.
1:33:10That's a remarkably high increase.
1:33:12Remember if we go back to our examples of chocolate, sex,
1:33:17a doubling above baseline,
1:33:19nicotine two and a half times above baseline, cocaine.
1:33:23The increase in dopamine from a cold water exposure
1:33:27of this kind was comparable to what one sees from cocaine,
1:33:31except, except in this case,
1:33:33it wasn't a rise and crash.
1:33:36It was actually a sustained rise in dopamine
1:33:40that took a very long time up to three hours
1:33:42to come back down to baseline.
1:33:44Which is really remarkable,
1:33:46and I think this explains some of the positive,
1:33:49mental and physical effects that people report subjectively
1:33:52after doing cold water exposure.
1:33:55One question that many of you are probably asking
1:33:57is just how cold should the water be?
1:33:59Well, you could mimic what was done in this study
1:34:01and do 14 degrees Celsius.
1:34:03But for some people that won't be cold enough,
1:34:05for some people that will be too cold.
1:34:07They did look at the release of stress hormones
1:34:10like cortisol in addition to the release of things
1:34:12like epinephrin and adrenaline.
1:34:13And it's interesting that they noted that in all cases,
1:34:17but especially at that coldest temperature,
1:34:19there was an increase in cortisol,
1:34:20but that it was transient,
1:34:22That eventually people's cortisol,
1:34:23the stress hormone subsided a bit.
1:34:26There are basically two different approaches
1:34:28to remaining in the cold when it's uncomfortable.
1:34:31One is to try and relax yourself.
1:34:34Two, try and practice slow breathing,
1:34:36to try and dilate your gaze.
1:34:38I've talked about this before in previous podcasts,
1:34:40you go into panoramic vision to essentially try
1:34:41and calm yourself so that it's not as stressful
1:34:45in the cold.
1:34:46Other people however, take the approach of trying to ramp up
1:34:51their level of internal autonomic arousal,
1:34:53meaning to get really energized
1:34:55and kind of lean into the friction of the cold.
1:34:58And they find that easier.
1:34:59Other people distract themselves,
1:35:01they recite the alphabet,
1:35:02or they do something, anything to try
1:35:05and distract themselves from the discomfort.
1:35:08To be totally honest,
1:35:09it does not matter for sake of dopamine release.
1:35:12Because the dopamine release is triggered
1:35:14and then continues even after you get out of the cold water.
1:35:17Now, in this study, it was long exposure to cold water.
1:35:22It was an hour.
1:35:23That's a long period of time.
1:35:25And I do warn you against getting into cold water
1:35:28that's so cold that it will make your temperature drop
1:35:32and make you hyperthermic for an hour.
1:35:33That actually could be dangerous for a lot of people.
1:35:35You might have a hard time reheating,
1:35:37and hypothermia is not a good thing.
1:35:39They had people monitoring subjects in these studies
1:35:43and paying attention to their core body temperature.
1:35:45They were able to reheat them afterwards.
1:35:47It's well-established now that getting into cold water,
1:35:51whether or not it's a shower,
1:35:52an ice bath circulating cold water, a stream, et cetera,
1:35:56that can evoke the norepinephrine release immediately,
1:35:59and the long arc of that dopamine release.
1:36:01Why would that be good?
1:36:02Up until now, I've basically said getting increases
1:36:05in dopamine are detrimental to your baseline.
1:36:09Well, this does appear to raise the baseline of dopamine
1:36:12for substantial periods of time.
1:36:13And most people report feeling a heightened level of calm
1:36:18and focus after getting out of cold water.
1:36:22So cold water exposure turns out
1:36:23to be a very potent stimulus for shifting
1:36:26the entire milieu,
1:36:27the entire environment of our brain and body
1:36:30and allowing many people to feel much, much better
1:36:34for a substantial period of time
1:36:36after getting out of the ice bath or cold water of any kind
1:36:40than they did before.
1:36:42Now, you might ask how often to do this?
1:36:44Some people do this every day.
1:36:46It can be very stimulating.
1:36:47So typically doing it early in the day,
1:36:50it's going to be better.
1:36:50I don't necessarily recommend doing it right before sleep,
1:36:53but some people do it in the afternoon.
1:36:55And some people will indeed do that seven days a week,
1:36:58other people three days a week,
1:36:59other people every once in a while.
1:37:01What I can say is once you become cold water adapted,
1:37:05once it no longer has the same impact of novelty
1:37:09and feeling a bit like a,
1:37:10I don't want to say a shock to your system,
1:37:12'cause you don't want to go into cold water shock,
1:37:13but once it is comfortable for you,
1:37:17then it will no longer evoke this release.
1:37:20There really does seem to be something in the pathway
1:37:22from cold water exposure through the norepinephrine pathway
1:37:25and into the mesolimbic brainstem
1:37:27that causes this release in dopamine.
1:37:29But nonetheless, it's a basically zero cost.
1:37:32I mean, you need access to water of some sort,
1:37:34cold water shower, et cetera,
1:37:35but basically zero cost way of triggering a long lasting
1:37:39increase in dopamine without ingesting anything,
1:37:41no pharmacology whatsoever.
1:37:42Please again, approach it with a safety and caution in mind,
1:37:46but it is a very potent stimulus.
1:37:47Again, 250% of a rise in baseline,
1:37:51two and a half times rise in baseline rivals
1:37:53that of cocaine which is really remarkable.
1:37:56Now, I'd like to talk about the positive aspects
1:37:58of rewards for our behavior,
1:38:00and the negative aspects of rewards for our behavior.
1:38:03And from that, I will suggest a protocol
1:38:06by which you can achieve a better relationship
1:38:09to your activities and to your dopamine system.
1:38:12In fact, it will help tune up your dopamine system
1:38:14for discipline, hard work and motivation.
1:38:20Hard work is hard.
1:38:22Generally, most people don't like working hard.
1:38:26Some people do,
1:38:27but most people work hard in order to achieve some end goal.
1:38:32End goals are terrific and rewards are terrific
1:38:34whether or not they are monetary social or any kind.
1:38:39However, because of the way that dopamine relates
1:38:43to our perception of time,
1:38:46working hard at something for sake of a reward
1:38:50that comes afterward,
1:38:52can make the hard work much more challenging
1:38:55and make us much less likely to lean into hard work
1:38:58in the future.
1:38:59Let me give you a couple examples by way of data
1:39:02and experiments.
1:39:03There's a classic experiment done actually at Stanford
1:39:07many years ago in which children in nursery school
1:39:12and kindergarten drew pictures,
1:39:14and they drew pictures cause they like to draw.
1:39:17The researchers took kids that liked to draw
1:39:20and they started giving them a reward for drawing.
1:39:23The reward generally was a gold star
1:39:25or some thing that a young child would find rewarding.
1:39:30Then they stopped giving them the gold star.
1:39:33And what they found is the children
1:39:35had a much lower tendency to draw on their own.
1:39:41No reward.
1:39:42Now, remember this was an activity
1:39:44that prior to receiving a reward,
1:39:46the children intrinsically enjoyed and selected to do.
1:39:50No one was telling them to draw.
1:39:52What this relates to is so-called intrinsic
1:39:54versus extrinsic reinforcement.
1:39:57When we receive rewards,
1:39:58even if we give ourselves rewards for something,
1:40:02we tend to associate less pleasure with the actual activity
1:40:05itself that evoked the reward.
1:40:07Now, that might seem counterintuitive,
1:40:09but that's just way that the way
1:40:10that these dopaminergic circuits work.
1:40:13And now understanding these peaks in baselines in dopamine
1:40:16which I won't review again,
1:40:18this should make sense.
1:40:20If you get a peak in dopamine from a reward,
1:40:24it's going to lower your baseline
1:40:25and the cognitive interpretation
1:40:29is that you didn't really do the activity
1:40:31because you enjoyed the activity.
1:40:32You did it for the reward.
1:40:34Now, this doesn't mean all rewards of all kinds are bad,
1:40:37but it's also important to understand
1:40:39that dopamine controls our perception of time.
1:40:42When and how much dopamine we experience
1:40:46is the way that we carve up
1:40:48what we call our experience of time.
1:40:50When we engage in an activity,
1:40:52let's say school or hard work of any kind
1:40:55or exercise because of the reward
1:40:58we are going to give ourselves a receive at the end,
1:41:00the trophy, the sundae, the meal, whatever it happens to be.
1:41:06We actually are extending the time bin
1:41:10over which we are analyzing or perceiving that experience.
1:41:16And because the reward comes at the end,
1:41:19we start to dissociate the neural circuits
1:41:22for dopamine reward that would have normally been active
1:41:26during the activity.
1:41:28And because it all arrives at the end over time,
1:41:32we have the experience of less and less pleasure
1:41:35from that particular activity while we're doing it.
1:41:39Now, this is the antithesis of growth mindset.
1:41:43My colleague at Stanford, Carol Dweck, as many of you know,
1:41:45has come up with this incredible theory and principle,
1:41:49and actually goes beyond theory and principle
1:41:50called "Growth Mindset",
1:41:52which is this striving to be better to be in this mindset
1:41:55of I'm not there yet,
1:41:56but striving itself is the end goal.
1:42:00And that of course delivers you to tremendous performance.
1:42:03It's been observed over and over and over again,
1:42:05that people that have growth mindset,
1:42:06kids that have growth mindset end up performing very well
1:42:09because they're focused on the effort itself.
1:42:11And all of us can cultivate growth mindset.
1:42:15The neural mechanism of cultivating growth mindset
1:42:18involves learning to access the rewards from effort
1:42:22and doing.
1:42:23And that's hard to do because you have to engage
1:42:27this prefrontal component of the mesolimbic circuit.
1:42:30You have to tell yourself, okay, this effort is great,
1:42:33this effort is pleasureful.
1:42:35Even though you might actually be in a state
1:42:36of physical pain from the exercise,
1:42:38or I can recall this from college,
1:42:40just feeling like I wanted to get up from my desk,
1:42:42but forcing myself to study,
1:42:43forcing myself and forcing myself.
1:42:45What you find over time is that you can start to associate
1:42:48a dopamine release.
1:42:49You can evoke dopamine release from the friction
1:42:53and the challenge that you happen to be in.
1:42:55You completely eliminate the ability to generate
1:42:59those circuits and the rewarding process of being able
1:43:02to reward friction while in effort,
1:43:06if you are focused only on the goal that comes at the end.
1:43:09Because of the way that dopamine marks time.
1:43:12So if you say, oh, I'm going to do this very hard thing,
1:43:15and I'm going to push and push and push and push
1:43:17for that end goal that comes later.
1:43:20Not only do you enjoy the process of what you're doing less,
1:43:25you actually make it more painful
1:43:27while you're engaging in it.
1:43:28You make yourself less efficient at it,
1:43:30because if you were able to access dopamine while in effort,
1:43:33dopamine has all these incredible properties
1:43:35of increasing the amount of energy in our body,
1:43:37and in our mind, our ability to focus
1:43:39by way of dopamines conversion into epinephrin.
1:43:43But also you're undermining your ability to lean back
1:43:47into that activity the next time.
1:43:48The next time you need twice as much coffee
1:43:51and three times as much loud music,
1:43:53and four times as much energy drink
1:43:55and the social connection just to get out the door
1:43:58in order to do the run or to study.
1:44:00So what's more beneficial in fact can serve
1:44:04as a tremendous amplifier on all endeavors
1:44:07that you engage in.
1:44:09Especially hard endeavors is to A,
1:44:12not start layering in other sources of dopamine
1:44:15in order to get to the starting line,
1:44:17not layering in other sources of dopamine
1:44:19in order to be able to continue,
1:44:21but rather to subjectively start to attach
1:44:24the feeling of friction and effort
1:44:27to an internally generated reward system.
1:44:30And this is not meant to be vague,
1:44:32this is a system that exists in your mind,
1:44:35that exists in the minds of humans
1:44:37for hundreds of thousands of years,
1:44:38by which you're not just pursuing the things
1:44:41that are innately pleasureful,
1:44:43food, sex, warmth, water when you're thirsty.
1:44:47But the beauty of this mesolimbic reward pathway
1:44:51that I talked about earlier is that,
1:44:53it includes the forebrain.
1:44:54So you can tell yourself the effort part is the good part.
1:44:59I know it's painful,
1:45:00I know this doesn't feel good,
1:45:01but I'm focused on this.
1:45:02I'm going to start to access the reward.
1:45:04You will find the rewards,
1:45:07meaning the dopamine release inside of effort
1:45:10if you repeat this over and over again.
1:45:11And what's beautiful about it is that,
1:45:14it starts to become reflexive for all types of effort.
1:45:17When we focus only on the trophy,
1:45:19only on the grade,
1:45:20only on the win as the reward,
1:45:23you undermine that entire process.
1:45:25So how do you do this?
1:45:27You do this in those moments of the most intense friction.
1:45:31You tell yourself this is very painful
1:45:34and because it's painful,
1:45:36it will evoke an increase in dopamine release later,
1:45:40meaning it will increase my baseline in dopamine,
1:45:43but you also have to tell yourself
1:45:46that in that moment you are doing it by choice
1:45:50and you're doing it because you love it.
1:45:53And I know that sounds like lying to yourself,
1:45:56and in some ways it is lying to yourself,
1:45:58but it's lying to yourself in the context of a truth
1:46:01which is that you want it to feel better.
1:46:05You want it to feel even pleasureful.
1:46:07Now, this is very far and away different
1:46:10from thinking about the reward that comes at the end,
1:46:14the hot fudge sundae for after you cross the finish line
1:46:17and you can replace hot fudge sundae
1:46:18with whatever reward happens to be appealing to you.
1:46:22We revere people who are capable of doing
1:46:24what I'm describing.
1:46:25David Goggins comes to mind is a really good example.
1:46:28Many of you are probably familiar with David Goggins,
1:46:30former Navy SEAL who essentially
1:46:32has made a post-military career out of explaining
1:46:38and sharing his process of turning the effort
1:46:40into the reward.
1:46:42There are many other examples of this too, of course.
1:46:46Throughout evolutionary history,
1:46:48there's no question that we revered people
1:46:50who were willing to go out and forage and hunt and gather
1:46:53and caretake in ways that other members
1:46:57of our species probably found exhausting
1:47:00and probably would have preferred to just put their feet up
1:47:02or soaked them in a cool stream
1:47:04rather than continue to forage.
1:47:06The ability to access this pleasure from effort
1:47:10aspect of our dopaminergic circuitry
1:47:13is without question the most powerful aspect of dopamine
1:47:17and our biology of dopamine.
1:47:19And the beautiful thing is it's accessible to all of us.
1:47:23But just to highlight the things that can interfere with,
1:47:25and prevent you from getting dopamine release
1:47:29from effort itself,
1:47:32don't spike dopamine prior to engaging in effort.
1:47:35And don't spike dopamine after engaging in effort,
1:47:39learn to spike your dopamine from effort itself.
1:47:43One straightforward example of learning to attach dopamine
1:47:47to effort and strain as opposed to a process
1:47:51or a reward that naturally evokes dopamine release
1:47:55is so-called intermittent fasting.
1:47:57I know this is very popular nowadays.
1:47:59Some people like to do intermittent fasting,
1:48:01some people don't.
1:48:02Some people have a 12 hour feeding window every 24 hours,
1:48:05some people do long fasts of two to three days even.
1:48:08I personally don't monitor a feeding window
1:48:11with a lot of precision.
1:48:12I tend to skip one meal a day,
1:48:14either breakfast or lunch,
1:48:15and then I eat the other two meals of the day
1:48:16depending on which meal I skipped.
1:48:18So it's either breakfast, lunch
1:48:19and maybe a little something in the evening,
1:48:22or I'll skip breakfast and do lunch and dinner and so on.
1:48:25Many people are now eating this way in part,
1:48:28because many people find it easier to not eat at all
1:48:32than to eat a smaller portion of some food.
1:48:36And that has everything to do with the dopamine reward
1:48:39evoking properties of food.
1:48:42When we ingest food or when we are about to ingest food,
1:48:45our dopamine levels go up.
1:48:47And typically when we ingest food,
1:48:49if it evokes some dopamine release,
1:48:51then we tend to want even more food.
1:48:52Remember dopamine's main role is one of motivation
1:48:56and seeking.
1:48:56And what dopamine always wants more of is more dopamine.
1:49:01More activity or thing that evokes more dopamine release.
1:49:05Well, let's just look at fasting
1:49:07from the perspective of dopamine schedules
1:49:10and dopamine release and peaks and baselines.
1:49:14Typically, when we eat we get dopamine release,
1:49:18especially when we eat after being very hungry.
1:49:21If you've ever gone camping,
1:49:22or you're very, very hungry,
1:49:24the food tastes that much better.
1:49:26And that's actually because of the way
1:49:28that deprivation states increase the way
1:49:32that dopaminergic circuits work.
1:49:35Our perception of dopamine is heightened
1:49:38when the receptors for dopamine
1:49:40have not seen much dopamine lately,
1:49:42they haven't bound much dopamine.
1:49:43So when you fast, fast, fast, fast, fast,
1:49:45and then you finally eat,
1:49:47it evokes more dopamine release.
1:49:49So this is the big reward that comes at the end.
1:49:52Even bigger because you deprived yourself.
1:49:56This is true for all rewarding behaviors and activities
1:49:59by the way.
1:50:00The longer you restrict yourself from that activity,
1:50:03the greater the dopamine experience when the dopamine
1:50:06is finally released,
1:50:06because of an upregulation of the receptors for dopamine.
1:50:10but I just spent five minutes or more telling you
1:50:13that you should avoid too much reward at the end,
1:50:16and you should actually focus on the dopamine
1:50:19that you can consciously evoke from the deprivation strain
1:50:24and effort.
1:50:25And in fact, this is what happens for many people
1:50:28that start doing fasting and take a liking to it.
1:50:31Many people say that their state of mind
1:50:34when they fast is clearer,
1:50:35that they actually start to enjoy the period of fasting.
1:50:39In fact, some people start pushing out their eating window
1:50:41or skipping entire days of eating more and more
1:50:44in order to get deeper into that state of mind
1:50:47where surely it's not just dopamine,
1:50:50but dopamine is released.
1:50:51They will track their clock.
1:50:53Oh, I've been fasting 12 hours, 16 hours, et cetera.
1:50:56They are starting to attach dopamine release
1:50:58or create dopamine release from the deprivation,
1:51:01not from the food reward itself.
1:51:03And this I think makes it an interesting practice.
1:51:06And one that certainly has been practiced by for centuries
1:51:10in different cultures and different religions
1:51:12of deliberately restricting food,
1:51:14not just to increase the rewarding properties
1:51:16of food itself,
1:51:18but also to increase the rewarding properties
1:51:20of deprivation.
1:51:22And I should emphasize that a lot of the subjective aspects
1:51:25of the knowledge of the benefits of fasting
1:51:27serve as reinforcing dopamine amplifying aspects to fasting,
1:51:33meaning if somebody does intermittent fasting
1:51:36and they are deep into their fast
1:51:38and they're telling themselves,
1:51:39oh, my blood lipid profiles are probably improving.
1:51:41And my glucose management is probably improving.
1:51:44My insulin sensitivity is going up,
1:51:46and I'm going to live longer.
1:51:47All these things that have some basis from animal studies
1:51:51and some basis or not from human studies,
1:51:53it's all kind of still an emerging literature,
1:51:55but it does seem to be pointing in that direction
1:51:57that fasting can encourage things like autophagy,
1:52:01the engulfment of dead cells and things of that sort.
1:52:04Well, as people tell themselves these things,
1:52:07they are enhancing the rewarding properties
1:52:10of the behavior of fasting.
1:52:12And so this is a salient example
1:52:15of where knowledge of knowledge can actually help us
1:52:18change these deep primitive circuits related to dopamine.
1:52:23And this illustrates how the forebrain,
1:52:25which carries knowledge and carries interpretation
1:52:28and rational thought can be used to shape the very circuits
1:52:32that are involved in generating reward
1:52:35for what would otherwise just be kind of primitive
1:52:37behaviors, hardwired behaviors.
1:52:39And that's the beauty of these dopamine circuits.
1:52:41That's the beauty of dopamine.
1:52:42It's not just attached to the more primitive of food, sex,
1:52:47heat, et cetera.
1:52:49It's also attached to the things
1:52:51that we decide are good for us and are important for us.
1:52:54So telling yourself that exercise or fasting
1:52:57or studying or listening better
1:53:00or any kind of behavior is good for you
1:53:01will actually reinforce the extent
1:53:04to which it is good for you at a chemical level.
1:53:08And a somewhat eerie example of what I just mentioned
1:53:11was a study that was published last year
1:53:13in the journal Neuron, Cell Press journal,
1:53:15excellent journal.
1:53:16That showed that hearing something
1:53:20that reinforces one's prior beliefs
1:53:22actually can evoke dopamine release.
1:53:25So the dopamine pathway is so vulnerable
1:53:28to subjective interpretation
1:53:30that it actually makes it such that when we see something
1:53:33or hear something that validates a belief
1:53:35that we already have,
1:53:36that itself can increase dopamine release.
1:53:40Along the lines of how dopamine and dopamine schedules
1:53:44and our perception of things can shape the way
1:53:46that we experience things as pleasureful or not.
1:53:49There are beautiful studies mainly looking at sugar appetite
1:53:53and our sense of pleasure from sweet things,
1:53:55but also for savory foods, et cetera.
1:53:58And essentially the results that come out
1:54:00of this are the following.
1:54:01If you ingest something that you like,
1:54:03it tastes good to you,
1:54:05but then you ingest something that's even sweeter
1:54:07or even more savory.
1:54:09And then you go back to the food that you ate previously.
1:54:13Well, you don't like it as much,
1:54:15and that might seem like a duh, obviously.
1:54:18But that shift in perception can be blocked
1:54:22by blocking the shift in dopamine.
1:54:25And so this really speaks to these peaks and valleys
1:54:28in dopamine that I mentioned before
1:54:29and how your experience of anything is going to depend
1:54:33on your prior experience of other things
1:54:35that evoke dopamine.
1:54:36Big dopamine release makes it more challenging
1:54:39to experience more big dopamine release.
1:54:43So dopamine is one of those things
1:54:44that you don't want too high or too low for too long.
1:54:47It's all about staying in that dynamic range
1:54:50and that's going to be different for everybody.
1:54:52So for the very savory foods that are now everywhere,
1:54:57those highly savory foods
1:54:59or I think they call them highly palatable foods
1:55:02are making more bland foods, whole foods,
1:55:06meaning foods that aren't processed.
1:55:07It's making those tastes less good at least for a while.
1:55:10And all it takes is a short period of time, even just days,
1:55:13two days or so of not consuming any highly palatable foods
1:55:17and suddenly broccoli with just a little bit of seasoning
1:55:22tastes delicious to you.
1:55:23All right?
1:55:24So again, this just speaks to the fact that dopamine
1:55:27is this universal currency.
1:55:29It establishes value based on,
1:55:31not just what you're experiencing in the moment,
1:55:33but what you experienced in the days and minutes before.
1:55:36Now, that you understand how your previous level
1:55:39of dopamine relates to your current level of dopamine,
1:55:42and how your current level of dopamine will influence
1:55:46your future level of dopamine,
1:55:48it should become obvious why things like pornography,
1:55:52not just the accessibility of pornography,
1:55:54but the intensity of pornography can negatively shape
1:55:59real world romantic and sexual interactions.
1:56:02This is a serious concern.
1:56:04The discussion is happening now.
1:56:06The underlying neurobiological mechanisms
1:56:08you now understand.
1:56:09And this isn't to pass judgment on whether
1:56:11or not people like or don't like pornography,
1:56:14that's an ethical discussion,
1:56:15and it's a moral discussion that has to be decided
1:56:18for each individual by virtue of age, et cetera.
1:56:22But again, any activity that evokes
1:56:26a lot of dopamine release will make it harder
1:56:29to achieve the same level and certainly the greater level
1:56:33of dopamine through a subsequent interaction.
1:56:36So yes, indeed many people are addicted to pornography
1:56:40and yes, indeed many people who regularly indulge
1:56:44in pornography experienced challenges
1:56:46in real-world romantic interactions.
1:56:49You now understand the mechanisms behind
1:56:50what I'm telling you.
1:56:52Now, there are circumstances in which increasing levels
1:56:55of dopamine is desirable and advantageous
1:56:57and clinically helpful.
1:56:59Good example of this would be the drug Welbutrin
1:57:01also called bupropion which increases dopamine
1:57:04and norepinephrine.
1:57:06Wellbutrin bupropion was developed
1:57:07as an alternative treatment for depression
1:57:10because some people who take the so-called SSRI,
1:57:12selective serotonin reuptake inhibitors
1:57:15which as the name suggests increased serotonin
1:57:17suffer from serotonin related side effects.
1:57:21Things like decreased appetite, decreased libido,
1:57:24or sometimes increased appetite or other side effects
1:57:28that they don't want.
1:57:30And Wellbutrin seems to avoid the sexual side effects.
1:57:34It can blunt at appetite and these sorts of things
1:57:38because of the increase in norepinephrine and dopamine
1:57:41increases levels of motivation and craving,
1:57:44but also can create a state of elevated alertness
1:57:49that can sometimes get in the way of healthy eating
1:57:52and things of that sort.
1:57:52So one has to work with their clinician as psychiatrist.
1:57:56It is a prescription drug in order
1:57:58to find the dosage of Welbutrin that's correct for them.
1:58:01In addition, things like Welbutrin bupropion
1:58:04can increase anxiety because of the way that dopamine
1:58:06and norepinephrine are stimulating
1:58:09and tend to place people into heightened levels
1:58:10of alertness.
1:58:11Nonetheless, many people have gained terrific relief
1:58:14from depression from Wellbutrin bupropion,
1:58:17and many of those same people had serious trouble
1:58:19with some of the SSRI.
1:58:21So it does seem to be a very useful drug
1:58:23in certain contexts,
1:58:24both for depression and for the treatment of smoking
1:58:26for people desiring to quit smoking.
1:58:29And of course there are a lot of people out there
1:58:31who are seeking to increase their baseline levels
1:58:33of dopamine without taking any prescription
1:58:36pharmaceutical compounds.
1:58:38And nowadays there exist a lot of supplements to do that.
1:58:42The two most common ones that are directly
1:58:44within the dopamine pathway are Macuna Pruriens
1:58:48which is actually a velvety bean whose contents are l-DOPA.
1:58:54Believe it or not, the content of this being
1:58:56is the precursor to dopamine.
1:58:58So Macuna Pruriens is sold over the counter
1:59:01at least in the United States.
1:59:03And it literally is the precursor to dopamine.
1:59:07Meaning if you take it,
1:59:08you will experience very large increases in dopamine.
1:59:11Those increases are transient and very, very intense.
1:59:14And in fact, if you look at the constellation of effects
1:59:17of Macuna Pruriens,
1:59:19what you find is that they're pretty striking
1:59:21and they look a lot like if not identical to l-DOPA.
1:59:25The most obvious of those is in the context
1:59:28of Parkinson's disease.
1:59:29There are at least five studies that have shown
1:59:31that Macuna Pruriens can reduce the symptoms
1:59:35of Parkinson's disease,
1:59:36much in the same way that l-DOPA can reduce
1:59:39the symptoms of Parkinson's disease.
1:59:41And that shouldn't come as any surprise
1:59:42given what I just told you that is essentially l-DOPA.
1:59:46It also can reduce a particular hormone called prolactin.
1:59:50Dopamine and prolactin tend to be in somewhat
1:59:52push pull fashion.
1:59:53When dopamine is up,
1:59:54prolactin is down and vice versa.
1:59:57Prolactin is involved in milk letdown in women.
1:59:59It's involved in setting the refractory period
2:00:02for sex after ejaculation in males.
2:00:06The reason mating can occur and then not occur
2:00:08after a ejaculation is because of an increase in prolactin.
2:00:11Macuna Pruriens is often used a blunt prolactin,
2:00:14and they're actually a couple of studies showing
2:00:17that it can indeed do that.
2:00:19Macuna Pruriens has a number of other effects
2:00:21that lie in the sex and reproduction pathway
2:00:24that are worth noting.
2:00:27Sperm concentration, sperm quality
2:00:29is actually greatly increased by Macuna Pruriens.
2:00:32These are kind of curious effects until you understand
2:00:34a little bit more about the biology of dopamine
2:00:36which I'll mention in a moment,
2:00:37but there are several studies,
2:00:40four in fact that describe how Macuna Pruriens
2:00:45can increase sperm count, sperm quality,
2:00:48and sperm motility.
2:00:49So for those of you seeking to conceive children,
2:00:51Macuna Pruriens might be an interesting choice
2:00:54if you're interested in exploring
2:00:56non-prescription compounds.
2:00:58However, I should mention that any time
2:01:01you consume a substance that increases dopamine
2:01:06by mimicking dopamine or acting as a direct precursor
2:01:09to dopamine,
2:01:10there's almost inevitably a crash or a reduction
2:01:15in the baseline in dopamine that we referred to previously.
2:01:18So many people who take Macuna Pruriens
2:01:20feel really elevated, really motivated, really alert,
2:01:24all the sorts of things that one would expect
2:01:26from a dopaminergic drug which Macuna Pruriens is.
2:01:30And then they feel a low or a reduction in drive
2:01:34and excitement and enthusiasm after the drug wears off.
2:01:38Just like they would with other dopamine
2:01:40increasing compound.
2:01:42For that reason, many people have turned
2:01:45to the use of L-tyrosine.
2:01:47L-tyrosine is an amino acid precursor to l-DOPA.
2:01:50So it lies further up the dopamine synthesis pathway.
2:01:54And nowadays it's very common because all L-tyrosine
2:01:57is sold over the counter in the United States
2:02:00that people will take L-tyrosine as a way
2:02:02to get more energized alert and focused.
2:02:06Indeed, there are data that L-tyrosine will accomplish that.
2:02:10L-tyrosine is typically taken in capsule form
2:02:13or powder form anywhere from 500 to 750
2:02:16to a 1000 milligrams.
2:02:18It is a potent stimulus for increasing dopamine.
2:02:21And the timescale for increasing dopamine
2:02:23is about 30 to 45 minutes after ingestion.
2:02:26Dopamine levels start to peak.
2:02:28The classic study that really nailed down
2:02:31the fact that tyrosine has this effect
2:02:34was published way back in 1983,
2:02:36Journal of Clinical Endocrinology and Metabolism
2:02:39that directly compared L-tyrosine supplementation
2:02:42with tryptophan ingestion on plasma dopamine and serotonin.
2:02:48Tryptophan being a precursor to serotonin.
2:02:51And indeed what they found is that ingestion of L-tyrosine
2:02:55can increase the amount of dopamine circulating in the blood
2:02:58and in the brain too, of course.
2:03:02The L-tyrosine ingestion induced dopamine
2:03:04increases within 45 minutes and they were short-lasting
2:03:07after about 30 minutes the effect had dissipated,
2:03:10meaning the levels of dopamine had dropped down to baseline.
2:03:13And even though they didn't look at levels
2:03:16of baseline dopamine past that time point,
2:03:19the expectation based on everything we know
2:03:21about dopamine biology is that it would then drop
2:03:24below baseline due to the depletion
2:03:27of the readily reservable pool of dopamine vesicles
2:03:29that we talked about way back at the beginning
2:03:31of this episode.
2:03:33The nice thing about this study is it does show specificity
2:03:35of effect because ingestion of tryptophan
2:03:38did not increase dopamine instead it increased serotonin.
2:03:42So there's really specificity of these pathways
2:03:44that rule out any placebo type effects.
2:03:48I'm not suggesting that anybody, everybody
2:03:51increase their dopamine levels by way of tyrosine
2:03:53or Macuna Pruriens.
2:03:55For those of you that are seeking to increase
2:03:57your dopamine levels without prescription drugs,
2:03:59those are the most direct route to that.
2:04:01Of course, if you have a pre-existing
2:04:04dopaminergic condition,
2:04:05so schizophrenia or psychosis of any kind,
2:04:08bipolar, anxiety,
2:04:11things like Macuna Pruriens and L-tyrosine
2:04:14will not be good for you.
2:04:15And if you don't, you should just understand and expect
2:04:19that it's going to lead to an increase in dopamine.
2:04:23You'll certainly feel an elevated state
2:04:25for some of you that might be agitating,
2:04:27for some of you that might be really pleasureful,
2:04:29and then you will feel a crash afterwards.
2:04:31How deep is that crash will really depend on your biology
2:04:35and where your dopamine baseline began.
2:04:38So I personally am not a fan of using things
2:04:41like Macuna Pruriens at all for myself
2:04:43for the reasons I mentioned earlier,
2:04:45just too intense and too much of a crash.
2:04:48I do use L-tyrosine from time to time
2:04:50for enhancing focus and motivation,
2:04:52but I want to emphasize from time to time.
2:04:55So I might use it once a week, occasionally twice a week,
2:04:58but I've never been one to take L-tyrosine regularly
2:05:01in order to focus or train or do any kind of mental work.
2:05:04I just don't want to rely on any exogenous substance
2:05:08in order to get my dopamine circuits activated.
2:05:12And I don't want to experience the drop in dopamine
2:05:15that inevitably occurs some period of time afterwards.
2:05:18I should also mention things that can reduce
2:05:21your levels of baseline dopamine.
2:05:23One that is rarely discussed is melatonin.
2:05:27I have talked before on this podcast about melatonin,
2:05:30why I am not a fan of using melatonin
2:05:33in order to enhance sleep.
2:05:35It can help one get to sleep,
2:05:36but not stay asleep.
2:05:37Dr. Matt Walker sleep expert
2:05:39from University of California, Berkeley.
2:05:41I think I don't want to put words in his mouth,
2:05:43but in our discussion about melatonin on this podcast
2:05:48when Matt was a guest in his book and on other podcasts,
2:05:51Matt has generally stated that the use of melatonin
2:05:54except for treatment of jet lag
2:05:56is generally not a good idea.
2:05:58And I agree.
2:05:59I think that melatonin is not often thought about
2:06:03as impacting the dopamine pathway,
2:06:04but there's at least one study published in 2001
2:06:08first author is Nishiyama just as it sounds.
2:06:12It's spelled just as it sounds.
2:06:14Acute effects of melatonin administration
2:06:16on cardiovascular autonomic regulation in healthy men.
2:06:19So the study wasn't specifically about dopamine,
2:06:21but they looked at norepinephrine and dopamine levels,
2:06:24and they found a statistically significant decrease
2:06:28in dopamine 60 minutes after melatonin administration.
2:06:32I've talked before about how viewing bright lights
2:06:36between the hours of 10:00 p.m and 4:00 a.m
2:06:38has been shown in studies by Dr. Samer Hattar,
2:06:40David Bersin, excellent circadian scientists
2:06:44to reduce levels of dopamine for several days
2:06:47after that light exposure.
2:06:48So dim the lights at night,
2:06:50if you can avoid exogenous melatonin,
2:06:53meaning if you don't have to take melatonin
2:06:56and you can find a better alternative
2:06:58that would be a good idea
2:06:58if you want to maintain healthy levels of dopamine.
2:07:01Now, there is one compound that you are all familiar with,
2:07:04and you've probably actually taken without realizing it,
2:07:07that increases dopamine.
2:07:08And that's something called PEA for phenethylamine,
2:07:13technically beta phenethylamine.
2:07:16And PEA is found in various foods.
2:07:19Chocolate just happens to be one in enriched in PEA
2:07:23and can increase synaptic levels of dopamine.
2:07:26I personally take PEA from time to time
2:07:29as a focus and work aid in order to do intense
2:07:34bouts of work.
2:07:35Again, I don't do that too often.
2:07:36This might be once a week or once every two weeks.
2:07:39I might use it for training,
2:07:40but typically I don't,
2:07:41it's usually for mental work.
2:07:43And I will take 500 milligrams of PEA
2:07:46and I'll take 300 milligrams of Alpha-GPC.
2:07:49That's something that I personally do.
2:07:50That's what's right for me,
2:07:51it's within my margins of safety for my health.
2:07:54Again, you have to check with your doctor and decide
2:07:56what's right for you.
2:07:57It leads to a sharp but very transient increase in dopamine
2:08:02that lasts about 30 to 45 minutes.
2:08:05And at least in my system I've found to be much more
2:08:09regulated and kind of even than something like L-tyrosine
2:08:13and certainly much more regulated and even
2:08:15and lower dopamine release than something
2:08:18like Macuna Pruriens.
2:08:20One of the lesser talked about compounds that's out there,
2:08:22but that's gaining popularity for increasing dopamine
2:08:26and as a so-called nootropic is something
2:08:28called huperzine A.
2:08:30Huperzine A is a compound sold over the counter
2:08:33at least in the United States
2:08:35that can increase acetylcholine transmission,
2:08:38a different neuromodulator entirely.
2:08:40But what's interesting is that huperzine A somehow
2:08:43by way of interactions between the cholinergic system
2:08:46and the dopaminergic system leads to increases in dopamine
2:08:51in the medial prefrontal cortex and hippocampus.
2:08:53Hippocampus, of course, being an area of the brain
2:08:55associated with learning and memory.
2:08:57And prefrontal cortex being associated
2:08:59with the mesolimbic pathway, decision-making focus,
2:09:01et cetera.
2:09:02And so I think the reason why we're seeing an increase
2:09:04in popularity of companies including huperzine A
2:09:07and nootropic compounds is both for the cholinergic
2:09:11stimulating properties,
2:09:12but also for stimulating dopamine release.
2:09:15I personally have never tried huperzine A.
2:09:17You can go to www.examine.com or put huperzine A
2:09:20into PubMed if you'd like to search around
2:09:22and see some of the science behind it.
2:09:24Again, I'm not recommending anyone take these things.
2:09:26In fact, I recommend against anyone just diving in,
2:09:28and starting to consume things without gaining knowledge
2:09:31about how they function,
2:09:32whether or not they're right for you.
2:09:33But nonetheless, I think in the years to come,
2:09:36we are going to see a lot more of L-tyrosine,
2:09:39PEA phenethylamine and huperzine as a way of tapping
2:09:43into the dopaminergic and cholinergic circuits
2:09:46certainly along with things like Alpha-GPC
2:09:48as non-prescription, short-lived
2:09:50somewhat milder alternatives to things
2:09:54that really spike dopamine,
2:09:56things like Adderall, Ritalin, modafinil, armodafinil
2:09:59and similar.
2:10:00And I can't help but share with you one more result.
2:10:02It's not related to pharmacology.
2:10:04It's related to behaviors and social interactions.
2:10:08And that's the very interesting
2:10:10and I would say important finding
2:10:12that was made a few years ago by my colleague, Rob Malenka,
2:10:15who's in our department of psychiatry at Stanford,
2:10:17showing that oxytocin and social connection
2:10:20is actually directly stimulating the dopamine pathway.
2:10:24I think for many years,
2:10:26all of us including me would hear and thought
2:10:30that oxytocin was in the serotonergic pathway
2:10:33that it was about pair bonding,
2:10:35and it was about some of these neuromodulators
2:10:37that were more associated with things related
2:10:40to feeling good with what we have in the present moment.
2:10:43That's typically what we think of when we think
2:10:45of the opioid system or the serotonergic system.
2:10:48The dopamine system is really about seeking and reward,
2:10:50but in a paper published in 2017 in the journal Science,
2:10:53excellent journal.
2:10:56The papers titled gaining of social reward by oxytocin,
2:11:00excuse me, in the ventral tegmental area.
2:11:02You now know what the ventral tegmental area,
2:11:04it's that area of the mesolimbic pathway.
2:11:06What this paper essentially showed is that,
2:11:08oxytocin social connection and pair bonding itself
2:11:13triggers dopamine release.
2:11:15And as everyone read this result, we all realized,
2:11:18ah, this makes total sense that for the evolution
2:11:21of our species,
2:11:22indeed for any species where social connections
2:11:25are important,
2:11:26it's also important to go seek social connections.
2:11:29And so, while it's fun to think about pharmacology
2:11:31and underlying neurocircuitry and cold water baths
2:11:34and all these different things related to dopamine schedules
2:11:38and reward mechanisms and attaching reward to effort
2:11:41and all the various things that we've talked about today
2:11:43in terms of science and tools and protocols,
2:11:46I'd be remiss if I didn't include description of this result
2:11:49and just emphasize that social connections,
2:11:53close social connections in particular
2:11:55that evoke oxytocin release.
2:11:57So those are romantic type,
2:11:59those are parent-child type,
2:12:01those are friendship related,
2:12:02and those can even be just friends at a distance related,
2:12:06right?
2:12:07It doesn't actually require skin contact
2:12:08to get oxytocin release,
2:12:11but oxytocin release is central to stimulating
2:12:14the dopamine pathways.
2:12:15So the take home message there is quite simple,
2:12:19engage in pursue quality, healthy social interactions.
2:12:24I know I've covered a lot of material today.
2:12:26I've really tried hard to focus on things
2:12:28that lie directly within the dopamine pathway
2:12:31and circuitries,
2:12:32as well as things that directly stimulate
2:12:34those pathways and circuitries.
2:12:37What I haven't talked about are all the things
2:12:39that indirectly serve the dopamine pathways.
2:12:42And out there on the internet
2:12:44and indeed in the scientific literature,
2:12:46you will find for instance,
2:12:47that things like Maca root can increase dopamine.
2:12:50Things like the gut microbiome can influence dopamine.
2:12:53And indeed they can,
2:12:54but they do that through indirect mechanisms.
2:12:57By creating a environment,
2:12:59a milieu in which dopamine and dopamine circuits
2:13:02can flourish.
2:13:03Maca is a good example of that.
2:13:04It will reduce cortisol and through some indirect pathways
2:13:08related to cortisol can increase dopamine.
2:13:10But it's not a direct increase in dopamine.
2:13:13And so as a consequence, it's rather subtle
2:13:15compared to the various compounds and behaviors
2:13:17that I talked about today.
2:13:18Indeed cold water exposure leads to huge increases
2:13:23in dopamine as we talked about before,
2:13:25and very sustained ones at that.
2:13:28I realize in giving you a lot of information about science
2:13:31and mechanism all the way from psychological biological
2:13:34to circuitry and synaptic transmission,
2:13:36volumetric transmission and so forth,
2:13:38that it might seem overwhelming.
2:13:40The most important thing is to understand,
2:13:42or that these dopamine pathways
2:13:43really are under your control.
2:13:45And the locus of control resides in the fact
2:13:49that your previous levels of dopamine
2:13:51are influencing your levels of dopamine right now.
2:13:54And your current levels of dopamine
2:13:55and where you take them next,
2:13:57will influence your dopamine levels in the next days
2:13:59and weeks to come.
2:14:00So I hope both with the mechanisms that you now have in hand
2:14:04plus some of the tools to tap into the dopaminergic system,
2:14:06both behavioral, pharmacologic prescription,
2:14:09and non-prescription, et cetera,
2:14:10that you'll feel that you have more control
2:14:12over your dopamine system.
2:14:13And certainly that you have a better understanding
2:14:15of your dopamine system so that you can modulate
2:14:18and adjust your levels of dopamine in the ways
2:14:20that serve you best.
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2:15:18Today and on previous podcast episodes
2:15:20we talked a bit about supplements.
2:15:22Supplements certainly aren't necessary,
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