This episode serves as a sort of “Dopamine Masterclass”. I discuss the immensely powerful chemical that we all make in our brain and body: dopamine. I describe what it does and the neural circuits involved. I explain dopamine peaks and baselines, and the cell biology of dopamine depletion. I include 14 tools for how to control your dopamine release for sake of motivation, focus, avoiding and combating addiction and depression, and I explain why dopamine stacking with chemicals and behaviors inevitably leads to states of underwhelm and poor performance. I explain how to achieve sustained increases in baseline dopamine, compounds that injure and protect dopamine neurons including caffeine from specific sources. I describe non-prescription supplements for increasing dopamine—both their benefits and risks—and synergy of pro-dopamine supplements with those that increase acetylcholine. 

#HubermanLab #Dopamine #Motivation

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Links:
Review on Dopamine: https://www.nature.com/articles/s41583-021-00455-7
Cold Exposure & Dopamine: https://link.springer.com/article/10.1007%2Fs004210050065

Timestamps:
00:00:00 Introduction & Tool 1 to Induce Lasting Dopamine
00:04:48 Sponsors: Roka, InsideTracker, Headspace
00:09:10 Upcoming (Zero-Cost) Neuroplasticity Seminar for Educators
00:09:58 What Dopamine (Really) Does
00:15:30 Two Main Neural Circuits for Dopamine 
00:18:14 How Dopamine Is Released: Locally and Broadly
00:22:03 Fast and Slow Effects of Dopamine
00:25:03 Dopamine Neurons Co-Release Glutamate
00:28:00 Your Dopamine History Really Matters 
00:30:30 Parkinson’s & Drugs That Kill Dopamine Neurons. My Dopamine Experience 
00:36:58 Tool 3 Controlling Dopamine Peaks & Baselines
00:40:06 Chocolate, Sex (Pursuit & Behavior), Nicotine, Cocaine, Amphetamine, Exercise
00:46:46 Tool 4 Caffeine Increases Dopamine Receptors
00:49:54 Pursuit, Excitement & Your “Dopamine Setpoint”
00:56:46 Your Pleasure-Pain Balance & Defining “Pain”
01:00:00 Addiction, Dopamine Depletion, & Replenishing Dopamine
01:07:50 Tool 5 Ensure Your Best (Healthy) Dopamine Release
01:15:28 Smart Phones: How They Alter Our Dopamine Circuits
01:19:45 Stimulants & Spiking Dopamine: Counterproductive for Work, Exercise & Attention
01:22:20 Caffeine Sources Matter: Yerba Mate & Dopamine Neuron Protection
01:24:20 Caffeine & Neurotoxicity of MDMA
01:26:15 Amphetamine, Cocaine & Detrimental Rewiring of Dopamine Circuits
01:27:57 Ritalin, Adderall, (Ar)Modafinil: ADHD versus non-Prescription Uses
01:28:45 Tool 6 Stimulating Long-Lasting Increases in Baseline Dopamine 
01:37:55 Tool 7 Tuning Your Dopamine for Ongoing Motivation
01:47:40 Tool 8 Intermittent Fasting: Effects on Dopamine 
01:53:09 Validation of Your Pre-Existing Beliefs Increases Dopamine
01:53:50 Tool 9 Quitting Sugar & Highly Palatable Foods: 48 Hours
01:55:36 Pornography
01:56:50 Wellbutrin & Depression & Anxiety
01:58:30 Tool 10 Mucuna Pruriens, Prolactin, Sperm, Crash Warning
02:01:45 Tool 11 L-Tyrosine: Dosages, Duration of Effects & Specificity
02:05:20 Tool 12 Avoiding Melatonin Supplementation, & Avoiding Light 10pm-4am
02:07:00 Tool 13 Phenylethylamine (with Alpha-GPC) For Dopamine Focus/Energy
02:08:20 Tool 14 Huperzine A
02:10:02 Social Connections, Oxytocin & Dopamine Release
02:12:20 Direct & Indirect Effects: e.g., Maca; Synthesis & Application
02:14:22 Zero-Cost & Other Ways To Support Podcast & Research

The Huberman Lab Podcast is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this podcast or materials linked from this podcast is at the user’s own risk. The content of this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice for any medical condition they may have and should seek the assistance of their health care professionals for any such conditions.

Title Card Photo Credit: Mike Blabac - https://www.blabacphoto.com

the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life.

a professor of neurobiology and ophthalmology at Stanford School of Medicine.

Today, we are going to talk all about dopamine

and what drives you to do the things that you do.

We're going to talk about motivation and desire and craving, but also how dopamine relates to satisfaction and our feelings of wellbeing.

And of course, any discussion about dopamine has to include a discussion about the potential for dopamine induced addiction.

But today we are mainly going to focus on how, what we do and how we do it and how we conceptualize those things leads to changes in this amazing molecule in our brain and bodies that we call dopamine.

I'm going to teach you what dopamine is and what it is not.

There are a lot of myths about the molecule dopamine.

We often hear about so-called dopamine hits.

Today, we are going to dispel many common myths about dopamine, and we are going to talk about how dopamine actually works.

We're going to discuss the biology of dopamine, the psychology.

We will discuss some neural circuits and a really exciting aspect of dopamine biology are so-called dopamine schedules.

In other words, we are going to discuss how things like food, drugs, caffeine, pornography, even some plant-based compounds can change our baseline levels of dopamine.

And in doing so, they change how much dopamine we are capable of experiencing from what could be very satisfying events or events that make us feel not so good because of things that we did or took prior.

So I promise you it's going to be a vast discussion, but I will structure it for you.

And you'll come away with a deep understanding of really what drives you.

You will also come away with a lot of tools, how to leverage dopamine, so that you can sustain energy drive and motivation for the things that are important to you over long periods of time.

Before we dive into the meat of today's discussion, I'd like to share with you a fascinating result that really underscores what dopamine is capable of in our brains and bodies and underscores the fact that just through behaviors, no drugs, nothing of that sort, just through behaviors, we can achieve terrifically high increases in dopamine that are very long and sustained in ways that serve us.

This is a result that was published in the European Journal of Physiology.

I'll go into it in more detail later, but essentially what it involved is having human subjects get into water of different temperatures.

So it was warm water, moderately cool water, and cold, cold water.

Had them stay in that water for up to an hour.

And they measured by way of blood draw, things like cortisol, norepinephrine and dopamine.

What was fascinating is that cold water exposure led to very rapid increases in norepinephrine and epinephrine, which is also just called adrenaline.

It also led to increases in dopamine and these increases in dopamine were very significant.

They kicked in around 10 or 15 minutes after submersion into the cold water.

And I should mention the head wasn't below water, it was just up to the neck.

And the dopamine release continued to rise and rise and rise and eventually reach 250% above baseline.

Now, what was interesting is after subjects got out of this cold water, that dopamine increase was sustained.

And I know nowadays many people are interested in using cold water therapy as a way to increase metabolism and fat loss, but also to improve sense of wellbeing, improve cognition, improve clarity of mind.

You know, there's something really special about this very alert, but calm state of mind.

That seems to be the 1 that's optimal for pretty much everything except sleep, but for all aspects of work and for social engagement and for sport, that highly alert but calm state of mind really is the sweet spot that I believe most of us would like to achieve.

And this cold water exposure done correctly really can help people achieve that state of mind through these increases in dopamine that last a very long time.

So I will later detail the specifics of that study, what it entailed in terms of how long the variations that different subjects experienced as well as how to limit the amount of stress hormone, cortisol that's released as a consequence of the cold water.

And we will also talk about compounds, supplements that people can take in order to increase their levels of dopamine should they choose.

Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.

It is however, part of my desire and effort to bring 0 cost to consumer information about science and science related tools to the general public.

In keeping with that theme, I'd like to thank the sponsors of today's podcast.

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I'd like to announce that there's an event that some of you may find very useful.

This is an event put on by Logitech that I will be speaking at.

It's called Rethink Education, the Biology of Learning, Reimagining Learning Through Neuroscience.

And at this event, I will be speaking, there will be other speakers as well.

And I will be talking about neuroplasticity and its applications for teaching and for learning.

I will describe what I call the plasticity super protocol that incorporates all of what we know about rapid learning, efficient learning, and the best ways to teach and learn.

It's geared towards educators of all kinds.

The event is September 30th, 2021 at 3 p.m.

You can find the registration link in the caption for this episode.

Most people have heard of dopamine and we hear all the time now about dopamine hits, but actually there's no such thing as a dopamine hit.

And actually the way that your body uses dopamine is to have a baseline level of dopamine, meaning an amount of dopamine that's circulating in your brain and body all the time.

And that turns out to be important for how you feel generally, whether or not you're in a good mood, motivated, et cetera.

And you also can experience peaks in dopamine above baseline.

This has a very specific name in the neurobiology literature, so-called tonic and phasic release of dopamine.

And I'll explain what that means in a couple of minutes.

But if you remember nothing else from this episode, please remember this, that when you experience something or you crave something really desirable, really exciting to you, very pleasurable, what happens afterwards is your baseline level of dopamine drops, okay?

So these peaks in dopamine, they influence how much dopamine will generally be circulating afterward.

And you might think, oh, a big peak in dopamine, after that, I'm going to feel even better because

What actually happens is that your baseline level of dopamine drops.

And I will explain the precise mechanism for that.

Okay, in the neuroscience literature, we refer to this as tonic and phasic release of dopamine.

Tonic being the low level baseline that's always there circulating released into your brain all the time.

And then phasic, these peaks that ride above that baseline.

I'm going to teach you the underlying neurobiology, but even if you have no background in biology, I promise to make it all clear.

I'll explain the terms and what they mean.

And I'm excited to teach you about dopamine because dopamine has everything to do with how you feel right now, as you're listening to this.

It has everything to do with how you will feel an hour from now has everything to do with your level of motivation and your level of desire and your willingness to push through effort.

If ever you've interacted with somebody who just doesn't seem to have any drive, they've given up, or if you've interacted with somebody who seems to have endless drive and energy, what you are looking at there in those 2 circumstances is without question, a difference in the level of dopamine circulating in their system.

There will be other factors too, but the level of dopamine is the primary determinant of how motivated we are, how excited we are, how outward facing we are, and how willing we are to lean into life and pursue things.

Dopamine is what we call a neuromodulator.

Neuromodulators are different than neurotransmitters.

Neurotransmitters are involved in the dialogue between neurons, nerve cells, and neurotransmitters tend to mediate local communication.

Just imagine 2 people talking to 1 another at a concert.

That communication between them is analogous to the communication carried out by neurotransmitters.

Whereas neuromodulators influence the communication of many neurons.

Imagine a bunch of people dancing where it's a coordinated dance involving 10 or 20 or hundreds of people.

Neuromodulators are coordinating that dance.

In the nervous system, what this means is that dopamine release changes the probability that certain neural circuits will be active and that other neural circuits will be inactive, okay?

So it modulates a bunch of things all at once.

And that's why it's so powerful at shifting, not just our levels of energy, but also our mindset, also our feelings of whether or not we can or cannot accomplish something.

So how does dopamine work and what does it do?

Well, first of all, it is not just responsible for pleasure.

It is responsible for motivation and drive, primarily at the psychological level, also for craving.

Those 3 things are sort of the same, motivation, drive, and craving.

And we will get deep into how dopamine can modulate time perception and how important it is that everybody be able to access increases in dopamine at different timescales.

This turns out to be important to not end up addicted to substances, but it also turns out to be very important to sustain effort and be a happy person over long periods of time, which I think most everybody wants.

It certainly is adaptive in life to be able to do that.

Dopamine is also vitally important for movement.

I'll explain the neural circuits for dopamine and mindset and dopamine in movement in a moment, but in diseases like Parkinson's or Lewy's body's dementia, which is similar to Parkinson's in many ways, there's a depletion or death of dopamine neurons at a particular location in the brain, which leads to shaky movements, challenges in speaking challenges in particular in initiating movement.

And because dopamine is depleted elsewhere too, people with Parkinson's and Louie's, excuse me, Louie body dementia, also experience drops in motivation and affect, meaning mood, they tend to get depressed and so on.

When those people are properly treated, they can, not always, but they can recover some fluidity of movement, some ability to initiate movement.

And almost without question, those people feel better psychologically, not just because they can move, but also because dopamine impacts mood and motivation.

So what are the underlying neural circuits?

For those of you that are not interested in biology and specific nomenclature, you can tune out now if you want, but it's actually pretty straightforward.

You have 2 main neural circuits in the brain that dopamine uses in order to exert all its effects.

The first 1 is a pathway that goes from this area in the what's called the ventral tegmentum.

That's a fancy, but ventral just means bottom and tegmentum actually means floor.

So it's at the bottom of the brain and it's the ventral part of the floor.

So it's really low in the back of the brain, the ventral tegmentum.

And it goes from the ventral tegmentum to what's called the ventral striatum and the prefrontal cortex.

Now that's a lot of language, but basically what we call this is the mesocortico-limbic pathway.

This is the pathway by which dopamine influences motivation, drive, and craving.

It involves structures that some of you may have heard of before, things like nucleus accumbens and the prefrontal cortex.

This is the pathway that really gets disrupted in addictions where in particular drugs that influence the release of dopamine like cocaine and methamphetamine, we'll talk about those drugs today, they tap into this pathway.

But if you are pursuing a partner, a boyfriend, or girlfriend, if you're pursuing a degree in school, if you're pursuing a finish line in a race, you are tapping into this so-called mesocortico-limbic pathway.

This is the classic reward pathway in all mammals.

The other pathway emerges from an area in the brain called the substantia nigra, so-called because the cells in that area are dark and the substantia nigra connects to an area of the brain called the dorsal striatum.

This is not surprisingly called the nigrostriatal pathway.

For those of you who have never done any neuroanatomy, I'm going to teach you a little trick right now.

Everything in neuroanatomy, the first part of a word tells you where the neurons are.

And then the second part tells you where they are connecting to.

So when I say nigrostriatal pathway, it means that the neurons are in the substantia nigra and they connect to the striatum, nigrostriatal pathway.

So while it's a lot of language, there is some logic there.

Okay, So we've got these 2 pathways, 1 mainly for movement, right?

This is the substantia nigra to dorsal striatum.

And we've got this other pathway, the so-called mesocortical limbic pathway that's for reward, reinforcement, and motivation.

I want you to remember that there are 2 pathways.

If you don't remember the 2 pathways in detail, that's fine, but please remember that there are 2 pathways because that turns out to be important later.

Now, the other thing to understand about dopamine is that the way that dopamine is released in the brain and body can differ.

Meaning it can be very local or it can be more broad.

Now, most of you have probably heard of synapses.

Synapses are the little spaces between neurons and basically neurons, nerve cells, communicate with 1 another by making each other electrically active or by making each other less electrically active.

You can imagine 1 nerve cell and another nerve cell with a little gap between them, a little synapse.

And the way that 1 nerve cell causes the next nerve cell to fire, what we call fire really means to become electrically active is that it vomits out these little packets, what we call vesicles.

They're little bubbles filled with a chemical.

When that chemical enters the synapse, it's some of it docks or parks on the other side in the other neuron.

And by virtue of electrical changes in what we call the post-synaptic neuron, that chemical will make that neuron more electrically active or less electrically active.

Dopamine can do that like any other neurotransmitter or neuromodulator.

So it can have 1 neuron influence another neuron, but dopamine can also engage in what's called a volumetric release.

Volumetric release is like a giant vomit that gets out to 50 or a hundred or even thousands of cells.

So there's local release, what we call synaptic release.

So volumetric release is like dumping all this dopamine out into the system.

So dopamine is incredible because it can change the way that our neural circuits work at a local scale and at a very broad scale.

And for those of you that are only interested in tools, like how do I get more dopamine?

Let me tell you, This part is really important because if you were to take a drug or supplement that increases your level of dopamine, you are influencing both the local release of dopamine and volumetric release.

This relates back to the baseline of dopamine and the big peak above baseline.

And I'll just allude to why it's important.

Many drugs and indeed many supplements that increase dopamine will actually make it harder for you to sustain dopamine release over long periods of time.

And to achieve those peaks that most of us are craving when we are in pursuit of things.

Because if you get both volumetric release, the dumping out of dopamine everywhere, and you're getting local release, what it means is that the difference between the peak and baseline is likely to be smaller.

And this is very important, how satisfying or exciting or pleasurable a given experience is, doesn't just depend on the height of that peak.

It depends on the height of that peak relative to the baseline.

So if you increase the baseline and you increase the peak, you're not going to achieve more and more pleasure from things.

I'll talk about how to leverage this information in a little bit, but just increasing your dopamine, yes, it will make you excited for all things.

It will make you feel very motivated, but it will also make that motivation very short lived.

So there's a better way to increase your dopamine.

There's a better way to optimize this peak to baseline ratio.

For now, what we've talked about is 2 main neural circuits, 1 for movement and 1 for motivation and craving with dopamine.

And we've talked about 2 main modes of communication between neurons with dopamine.

And in the back of your mind, you can relate this back to again, this baseline versus peaks above baseline.

So that's a description of what we would call the spatial effects or the spatial aspects of dopamine.

I said, this connects to that, that connects to this, you can get local or more broad volumetric release.

What about the duration of release or the duration of action for dopamine.

Well, dopamine is unique among chemicals in the brain because dopamine, unlike a lot of chemicals in the brain, works through what are called G protein coupled receptors.

And for those of you that are about to pass out from the amount of detail, just hang in there with me.

There are 2 ways that neurons can communicate

There are a third and a fourth, but mostly neurons communicate by 2 modes.

are what we call fast electrical synapses, ionotropic conduction, all right?

You don't need to know what that means, but basically 1 neuron activates another neuron and little holes open up in that neuron and ions rush in.

Sodium is the main ion, salt, by which 1 neuron influences the electrical activity of another neuron because sodium ions contain a charge.

Okay, there are other things like chloride and potassium.

If you're interested in looking this up, just look up.

See all Andrew Huberman transcripts on Youtube

Controlling Your Dopamine For Motivation, Focus & Satisfaction | Huberman Lab Podcast #39