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Controlling Your Dopamine For Motivation, Focus & Satisfaction | Andrew Huberman | YouTubeToText
YouTube Transcript: Controlling Your Dopamine For Motivation, Focus & Satisfaction
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Core Theme
This episode of the Huberman Lab Podcast delves into the complex role of dopamine, demystifying common myths and explaining its biological functions related to motivation, desire, satisfaction, and well-being, while also highlighting its connection to addiction and providing science-based tools for its regulation.
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- Welcome to the Huberman Lab Podcast,
where we discuss science and science-based tools
for everyday life.
[energetic music]
I'm Andrew Huberman,
and I'm a professor of neurobiology and ophthalmology
at Stanford School of Medicine.
Today, we are going to talk all about dopamine
and what drives you to do the things that you do.
We're going to talk about motivation and desire and craving,
but also how dopamine relates to satisfaction
and our feelings of wellbeing.
And of course, any discussion about dopamine
has to include a discussion about the potential
for dopamine induced addiction.
Indeed, dopamine lies at the heart of addiction
to all things.
But today we are mainly going to focus on,
how what we do and how we do it,
and how we conceptualize those things
leads to changes in this amazing molecule
in our brain and bodies that we call dopamine.
I'm going to teach you what dopamine is and what it is not.
There are a lot of myths about the molecule dopamine.
We often hear about so-called dopamine hits.
Today, we are going to dispel many common myths
about dopamine,
and we are going to talk about how dopamine actually works.
We're going to discuss the biology of dopamine,
the psychology.
We will discuss some neural circuits
and a really exciting aspect of dopamine biology
or so-called dopamine schedules.
In other words, we are going to discuss
how things like food, drugs, caffeine, pornography,
even some plant-based compounds can change
our baseline levels 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
is just up to the neck.
And the dopamine release continued to rise
and rise and rise,
and eventually reached 250% above baseline.
Now, what was interesting is after subjects got out
of this cold water,
that dopamine increase was sustained.
And I know nowadays many people are interested
in using cold water therapy as a way to increase metabolism
and fat loss,
but also to improve sense of well-being,
improve cognition, improve clarity of mind.
There's something really special about this very alert,
but calm state of mind
that seems to be the one that's optimal
for pretty much everything except sleep,
but for all aspects of work and for social engagement
and for sport that highly alert,
but calm state of mind really is the sweet spot
that I believe most of us would like to achieve.
And this cold water exposure done correctly
really can help people achieve that state of mind
through these increases in dopamine
that lasts a very long time.
So I will later detail the specifics of that study,
what it entailed in terms of how long,
the variations, the 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 zero cost to consumer information about science
and science related tools to the general public.
In keeping with that theme,
I'd like to thank the sponsors of today's podcast.
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I'd like to announce that there's an event
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This is an event put on by Logitech
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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
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The event is September 30th, 2021 at 3:00 p.m Eastern.
You can find the registration link in the caption
for this episode.
So let's talk about dopamine.
Most people have heard of dopamine,
and we hear all the time now about dopamine hits.
But actually there's no such thing as a dopamine hit.
And actually the way that your body uses dopamine
is to have a baseline level of dopamine.
Meaning an amount of dopamine that's circulating
in your brain and body all the time.
And that turns out to be important for how you feel
generally, whether or not you're in a good mood,
motivated, et cetera.
And you also can experience peaks in dopamine
above baseline.
Now, this has a very specific name
in the neurobiology literature,
so-called tonic and phasic release of dopamine.
And I'll explain what that means in a couple of minutes.
But if you remember nothing else from this episode,
please remember this,
that when you experience something or you crave something
really desirable, really exciting to you, very pleasurable.
What happens afterwards is your baseline level
of dopamine drops.
Okay?
So these peaks in dopamine,
they influence how much dopamine
will generally be circulating afterward.
And you might think, oh, a big peak in dopamine after that,
I'm going to feel even better
because I just had this great event.
Not the case.
What actually happens is that your baseline level
of dopamine drops.
And I will explain the precise mechanism for that.
Okay?
In the neuroscience literature,
we refer to this as tonic and phasic release of dopamine.
Tonic being the low level baseline
that's always there circulating,
released into your brain all the time.
And then phasic these peaks that ride above that baseline.
And those two things interact.
And this is really important.
I'm going to teach you the underlying neurobiology,
but even if you have no background in biology,
I promise to make it all clear.
I'll explain the terms and what they mean.
And I'm excited to teach you about dopamine,
because dopamine has everything to do with how you feel
right now as you're listening to this,
it has everything to do with how you will feel
an hour from now,
has everything to do with your level of motivation
and your level of desire,
and your willingness to push through effort.
If ever you've interacted with somebody
who just doesn't seem to have any drive they've given up,
or if you've interacted with somebody
who seems to have endless drive and energy,
what you are looking at there in those two circumstances
is without question a difference
in the level of dopamine circulating in their system.
There will be other factors too,
but the level of dopamine is the primary determinant
of how motivated we are, how excited we are,
how outward facing we are and how willing we are,
to lean into life and pursue things.
Dopamine is what we call a neuromodulator.
Neuromodulators are different than neurotransmitters.
Neurotransmitters are involved in the dialogue
between neurons nerve cells.
And neurotransmitters tend to mediate local communication.
Just imagine two people talking to one another at a concert,
that communication between them is analogous
to the communication carried out by neurotransmitters,
whereas neuromodulators influence the communication
of many neurons.
Imagine a bunch of people dancing
where it's a coordinated dance involving 10 or 20
or hundreds of people.
Neuromodulators are coordinating that dance.
In the nervous system what this means is that,
dopamine release changes the probability
that certain neural circuits will be active
and that other neural circuits will be inactive.
Okay?
So it modulates a bunch of things all at once,
and that's why it's so powerful at shifting
not just our levels of energy,
but also our mindset,
also our feelings of whether or not we can,
or cannot accomplish something.
So how does dopamine work and what does it do?
Well, first of all, it is not just responsible for pleasure,
it is responsible for motivation and drive.
Primarily, at the psychological level,
also for craving.
Those three things are sort of the same.
Motivation, drive and craving.
It also controls time perception,
and we will get deep into how dopamine
can modulate time perception,
and how important it is that everybody be able
to access increases in dopamine at different timescales.
This turns out to be important to not end up addicted
to substances,
but it also turns out to be very important to sustain effort
and be a happy person over long periods of time.
Which I think most everybody wants.
It certainly is adaptive in life to be able to do that.
Dopamine is also vitally important for movement.
I'll explain the neural circuits for dopamine and mindset,
and dopamine in movement in a moment,
but in diseases like Parkinson's or Lewy bodies 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 and speaking,
challenges in particular in initiating movement.
And because dopamine is depleted elsewhere
to people with Parkinson's and Lew's bod,
excuse me, Lewy body dementia also experience drops
in motivation and affect, meaning mood.
They tend to get depressed and so on.
When those people are properly treated,
they can, not always,
but they can recover some fluidity of movement,
some ability to initiate movement.
And almost without question,
those people feel better psychologically,
not just because they can move,
but also because dopamine impacts mood and motivation.
So what are the underlying neural circuits?
For those of you that are not interested in biology
and specific nomenclature,
you can tune out now if you want,
but it's actually pretty straightforward.
You have two main neural circuits in the brain
that dopamine uses in order to exert all its effects.
The first one is a pathway that goes from this area
in the what's called the ventral tegmentum.
That's a fancy, but ventral just means bottom,
and tegmentum actually means floor.
So it's at the bottom of the brain,
and it's the ventral part of the floor.
So it's really low in the back of the brain,
the ventral tegmentum.
And it goes from the ventral tegmentum
to what's called the ventral striatum
and the prefrontal cortex.
Now, that's a lot of language,
but basically what we call this is the,
mesocorticolimbic pathway.
This is the pathway by which dopamine influences motivation,
drive and craving.
It involves structures that some of you may have heard
of before.
Things like nucleus accumbens and the prefrontal cortex.
This is the pathway that really gets disrupted
in addictions where in particular drugs that influence
the release of dopamine like cocaine and methamphetamine.
We'll talk about those drugs today.
They tap into this pathway.
But if you are pursuing a partner,
a boyfriend or girlfriend,
if you're pursuing a degree in school,
if you're pursuing a finish line in a race,
you are tapping into this so-called
mesecorticolimbic 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 nigropstriatal pathway,
it means that the neurons are in substantial nigra
and they connect to the striatum, nigrostriatal pathway.
So while it's a lot of language there, some logic there.
Okay?
So we've got these two pathways.
One, mainly for movement, right?
This is the substantia nigra to dorsal striatum.
And we've got this other pathway,
the so-called mesocorticolimbic pathway,
that's for reward, reinforcement and motivation.
I want you to remember that there are two pathways.
If you don't remember the two pathways in detail,
that's fine.
But please remember that there are two pathways,
because that turns out to be important later.
Now, the other thing to understand about dopamine is that,
the way that dopamine is released in the brain and body
can differ.
Meaning it can be very local,
or it can be more broad.
Now, most of you have probably heard of synapses.
Synapses are the little spaces between neurons,
and basically neurons nerve cells communicate
with one another by making each other electrically active,
or by making each other less electrically active.
So here's how this works.
You can imagine one nerve cell and another nerve cell
with a little gap between them,
a little synapse.
And the way that one nerve cell causes
the next nerve cell to fire.
What we call fire really means to become electrically active
is that it vomits out these little packets,
what we call vesicles.
They're little bubbles filled with a chemical,
when that chemical enters the synapse,
it some of it docks or parks on the other side,
in the other neuron.
And by virtue of electrical changes in the,
what we call the postsynaptic neuron,
that chemical will make that neuron more electrically active
or less electrically active.
Dopamine can do that like any other neurotransmitter
or neuromodulator.
So it can have one neuron influence another neuron.
But dopamine can also engage
in what's called a volume metric 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,
and then there's volumetric release.
So volumetric release is like dumping all this dopamine out
into the system.
So dopamine is incredible because it can change the way
that our neural circuits work at a local scale
and at a very broad scale.
And for those of you that are only interested in tools,
like how do I get more dopamine?
Let me tell you this part is really important
because if you were to take a drug or supplement
that increases your level of dopamine,
you are influencing both the local release of dopamine
and volumetric release.
This relates back to the baseline of dopamine
and the big peak above baseline.
And that turns out to be important.
And I'll just allude to why it's important.
Many drugs and indeed many supplements
that increase dopamine will actually make it harder
for you to sustain dopamine release
over long periods of time.
And to achieve those peaks that most of us are craving
when we are in pursuit of things.
Why?
Because if you get both volume metric release,
the dumping out of dopamine everywhere,
and you're getting local release,
what it means is that the difference between the peak
and baseline is likely to be smaller.
And this is very important,
how satisfying or exciting or pleasureful
a given experience is,
doesn't just depend on the height of that peak,
it depends on the height of that peak relative
to the baseline.
So if you increase the baseline and you increase the peak,
you're not going to achieve more and more pleasure
from things.
I'll talk about how to leverage this information
in a little bit,
but just increasing your dopamine.
Yes, it will make you excited for all things.
It will make you feel very motivated,
but it will also make that motivation very short-lived.
So there's a better way to increase your dopamine.
There's a better way to optimize
this peak to baseline ratio.
For now what we've talked about is two main neural circuits,
one for movement,
and one for motivation and craving with dopamine.
And we've talked about two main modes of communication
between neurons with dopamine.
One is this local synaptic release.
One is more volume metric release.
And in the back of your mind,
you can relate this back to,
again, this baseline versus peaks above baseline.
So that's a description of what we would call
the spatial effects or the spatial aspects of dopamine.
I said this connects to that,
that connects to this.
You can get local or more broad volumetric release.
What about the duration of release
or the duration of action for dopamine?
Well, dopamine is unique among chemicals in the brain,
because dopamine unlike a lot of chemicals in the brain
works through what are called G protein-coupled receptors.
And for those of you that are about to pass out
from the amount of detail,
just hang in there with me.
It's really not complicated.
There are two ways that neurons can communicate
or mainly two ways.
There are third and fourth,
but mostly neurons communicate by two modes.
One, are what we call fast electrical synapses
ionotropic conduction.
All right?
You don't need to know what that means,
but basically one neuron activates another neuron
and little holes open up in that neuron,
and ions rush in.
Sodium is the main ion salt
by which one neuron influences the electrical activity
of another neuron because sodium ions contain a charge.
Okay?
There are other things like chloride and potassium.
If you're interested in looking this up,
just look up ionic conductances in the action potential,
or I could do a post on it some time
and we could go into detail.
But just understand that when neurons
want to influence each other,
they can do it by way of this fast ionotropic conduction.
This is a really quick way for one neuron
to influence the next.
Dopamine doesn't communicate that way.
Dopamine is slower.
It works through what are called G protein-coupled
receptors.
So what happens is dopamine is released
in these little vesicles that I've mentioned before,
get vomited out into the synapse.
Some of that dopamine will bind
to the so-called postsynaptic neuron,
it'll bind to the next neuron,
and then it sets off a cascade.
It's kind of like a bucket brigade of one thing,
getting handed off to the next,
to the next, to the next.
It's G protein-coupled receptors.
And anytime you hear about these GPCRs
or G protein-coupled receptors,
pay attention because they're really interesting.
They're slow,
but they also can have multiple cascades of effects.
They can impact even gene expression at some level.
They can change what a cell actually becomes.
They can change how well or how poorly that cell
will respond to the same signal in the future.
So dopamine works through the slower process.
These G protein-coupled receptors.
And so its effects tend to take a while in order to occur.
This aspect of dopamine transmission is important
because it now underscores two things.
One, there's two pathways for dopamine to communicate.
One for movement,
one for motivation and craving.
There's two spatial scales at which dopamine can operate
synaptically or volumetrically.
And dopamine can have slow effects,
really slow effects,
or even very long lasting effects.
And it even can control gene expression.
It can actually change the way that cells behave.
One thing that's not often discussed about dopamine,
but is extremely important to know
is that dopamine doesn't work on its own.
Neurons that release dopamine co-release glutamate.
Glutamate is a neurotransmitter
and it's a neurotransmitter that is excitatory,
meaning it stimulates neurons to be electrically active.
So now even if you don't know any cell biology,
you should start to gain a picture
that dopamine is responsible for movement,
motivation and drive.
It does that through two pathways,
but also the dopamine stimulates action in general,
because it releases this excitatory neurotransmitter.
It tends to make certain neurons that are nearby
or even that are far away,
because of volumetric release,
it tends to make those more active.
So dopamine is really stimulating.
And indeed we say that dopaminergic transmission
or dopamine tends to stimulate sympathetic arousal.
Sympathetic doesn't have anything to do with sympathy.
It's just simply means that it tends
to increase our levels of alertness.
It tends to bring an animal or a human
into a state of more alertness, readiness
and desire to pursue things outside the confines
of its skin.
So if I were to just put a really simple message
around dopamine it would be,
there's a molecule in your brain and body
that when released tends to make you look outside yourself,
pursue things outside yourself,
and to crave things outside yourself.
The pleasure that arrives from achieving things
also involves dopamine,
but is mainly the consequences of other molecules.
But if ever you felt lethargic and like just lazy
and you had no motivation or drive,
that's a low dopamine state.
If ever you felt really excited, motivated,
even if you're a little scared to do something.
Maybe you did your first skydive,
or you're about to do your first skydive,
or you're about to do some public speaking
and you really don't want to screw it up,
you are in a high dopamine state.
Dopamine is a universal currency in all mammals,
but especially in humans for moving us toward goals
and how much dopamine is in our system at any one time
compared to how much dopamine was in our system
a few minutes ago,
and how much we remember enjoying a particular experience
of the past.
That dictates your so-called quality of life
and your desire to pursue things.
This is really important.
Dopamine is a currency,
and it's the way that you track pleasure.
It's the way that you track success.
whether or not you are doing well or doing poorly.
And that is subjective,
but if your dopamine is too low,
you will not feel motivated.
If your dopamine is really high,
you will feel motivated.
And if your dopamine is somewhere in the middle,
how you feel depends on whether or not
you had higher dopamine a few minutes ago or lower dopamine.
This is important,
your experience of life and your level of motivation
and drive depends on how much dopamine you have relative
to your recent experience.
This is again, something that's just not accounted
for in the simple language of dopamine hits.
Okay?
A simple way to envision dopamine hits
is every time you do something you like,
you to piece of chocolate,
dopamine hit.
You look at your Instagram,
dopamine hit.
You see someone you like,
dopamine hit.
All these things described as dopamine hits
neglect the fact that if you scroll social media
and you see something you really like,
dopamine hit.
Sure there's an increase in dopamine,
but then you get to something else and you go,
hmm, not that interesting.
However, had you arrived at that second thing first,
you might think that it was really interesting.
If you had arrived to that second Instagram post
three days later or four days later,
you might find it extremely interesting.
Again, how much dopamine you experience from something
depends on your baseline level of dopamine
when you arrive there,
and your previous dopamine peaks.
Okay?
That's super important to understand,
and it's completely neglected by the general language
of dopamine hits.
This is why when you repeatedly engage in something
that you enjoy,
your threshold for enjoyment goes up and up and up.
So I want to talk about that process.
And I want to explain how that process works,
because if you understand that process,
and you understand some of these schedules and kinetics
as we call them around dopamine,
you will be in a terrific position
to use any dopamine enhancing tools that you decide to use.
You'll be in an excellent position to modulate
and control your own dopamine release
for optimal motivation and drive.
I realized that was a lot of information
about the biology of dopamine,
sort of like trying to make you drink
from the fire hose of dopamine biology.
However, I realized that some people
probably want even more information
about the biology of dopamine transmission.
If you're interested in that,
I'll post a link to a absolutely stellar review
that was published in Nature Reviews Neuroscience
called spatial and temporal scales of dopamine transmission.
It is quite detailed,
but they have beautiful diagrams
and can walk you through all the things
that I just described and get into even more detail.
We'll put a link to that in the caption on YouTube.
Right now, I want to share with you two anecdotes,
one from my own life,
and one from some fairly recent history
that illustrate some of the core biology of dopamine
and how profoundly it can shape our experience.
The first one is a really tragic situation that occurred.
This was in the 80s,
there was a outbreak of what looked like Parkinsonian
symptoms in a young population.
So many of you heard of Parkinson's disease.
Parkinson's disease is a disease in which people initially
start to quake, can't generate smooth movements,
they'll have issues with speech,
sometimes cognition as well.
There are examples like Michael J. Fox,
which are kind of early onset.
Parkinson's typically it hits people
a little bit later in life.
There's a genetic component.
But there is this question,
and there's always been this question
whether or not certain lifestyle factors
can also create Parkinson's?
And some years ago there was a situation
where street laboratories,
illicit laboratories were trying to make a drug
called MPPP, which is an opioid light compound.
It's a bit like heroin,
and heroin addicts seeking heroin went out and bought
what they thought was MPPP.
Unfortunately, it was not MPPP.
I mean, it would have been tragic if it was anyway
because they were drug addicts,
but what they ended up taking turned out to be a lot worse.
What they ended up taking was MPTP,
and MPTP can arise in the synthesis of MPPP.
So someone in a lab someplace,
this was mainly in the Central Valley in California,
but elsewhere as well.
Somebody created MPTP,
and what ended up happening was a large number
of young people who were opioid addicts
became completely boxed in paralyzed.
Couldn't speak, couldn't blink,
couldn't do anything.
Couldn't function, couldn't move.
So both aspects of dopamine transmission were disrupted.
They had no motivation and drive.
They couldn't generate any movement of any kind.
They were literally locked in frozen.
And sadly, this is irreversible.
It's irreversible,
because what MPTP does is it kills the dopaminergic neurons
of the substantia nigra that nigrostriatal pathway
that's involved in generating movement.
And it kills the dopaminergic neurons
of the so-called mesocorticolimbic pathway.
I was in college when this whole MPTP thing happened.
And I remember hearing this story.
At the time, I had no understanding
of what it is to have very high levels of dopamine
or extremely depleted levels of dopamine.
There was no reason why I should have that understanding.
I mean, of course I had experienced different pleasures
of different kinds and I've had lows in my life,
but nothing to the extreme that I'm about to discuss.
I got Giardia.
And Giardia is a stomach bug that if any of you ever had it,
it is terrible.
It's terrible diarrhea.
You end up very dehydrated very quickly.
You drop a ton of weight and it is extremely unpleasant.
I ended up going to the emergency room,
and in the emergency room,
I begged them for something to stop up my guts.
And they gave it to me.
They put a saline line into rehydrate me
and they injected something into the saline bag.
And within minutes I felt more sadness,
more overwhelming sense of depression,
basically, lower than I'd ever felt in my entire life.
It was absolutely profound.
I was crying endlessly without knowing why I was crying.
I was miserable.
And I asked them, what did you inject?
And they said, "We injected Thorazine."
Thorazine is an antipsychotic drug.
It's actually used to block dopamine receptors.
It's what's given to people who have schizophrenia.
Often is given to people who have schizophrenia,
because schizophrenia involves among other things
elevated levels of dopamine.
It was horrible.
The experience of it was miserable,
unlike anything I'd ever experienced.
And so I actually said to them,
"What did you give me?"
They said, "Thorazine."
And I said, "You have to give me l-DOPA.
"You have to give me something to get my dopamine levels
"back up again."
And they did.
They gave me an injection of l-DOPA into the bag,
went straight to my bloodstream.
And within minutes I felt fine again.
It was incredible.
And it really opened up my mind and my experience
to what it is to have absolutely plummeted levels
of dopamine.
And there's nothing more miserable than that I'll tell you.
And these poor souls who had this MPTP experience,
unfortunately, they couldn't recover those cells.
People who have severe Parkinson's
are struggling with this as well,
because in Parkinson's and in Lewy body dementia,
the dopaminergic neurons often die.
It's not just a problem with those neurons
releasing enough dopamine.
Later, we're going to talk about some approaches
to maintaining dopaminergic neuron health
and things that we can all do for that.
But I will tell you these dopamine neurons
that we all have are very precious for movement
and mood and motivation.
Having experienced what it is to have very, very low levels
of dopamine or in this case to have my dopamine receptors
blocked from Thorazine was eye-opening to say the least,
and has given me tremendous sensitivity to the fact
that dopamine is perhaps one of the most powerful molecules
that any of us has inside of us.
And the one that we ought to all think very carefully about
how we leverage,
because while most experiences and most things
that we do, and take and eat and cetera,
won't create enormous highs and enormous lows in dopamine.
Even subtle fluctuations in dopamine really shape
our perception of life and what we're capable of,
and how we feel.
And so we want to guard those and we want to understand them.
So let's lean into that understanding about dopamine.
And then let's talk about some tools
that we can all use to leverage dopamine
in order to keep that baseline in the appropriate,
healthy place,
and still be able to access those peaks in dopamine.
Because those, after all are some of what makes life rich
and worth living.
So let's talk about the baseline of dopamine
that we all have and the peaks in dopamine
that we all can achieve through different activities
and things that we ingest.
All of us have different baseline levels of dopamine.
Some of this is sure to be genetic.
Some people just simply ride at a level a little bit higher.
They're a little bit more excited,
they're a little bit more motivated,
or maybe they're a lot more excited or a lot more motivated.
Some people are a little mellower,
some people are a little less excitable.
And some of that has to do with the fact
that dopamine doesn't act alone.
Dopamine has close cousins or friends in the nervous system.
And I'll just name off a few of those close cousins
and friends.
Epinephrin also called adrenaline
is the main chemical driver of energy.
We can't do anything, anything at all,
unless we have some level of epinephrin
in our brain and body.
It's released from the adrenal glands
which right on top our kidneys.
It's released from an area of the brainstem
called locus coeruleus.
And its release tends to wake up neural circuits
in the brain and wake up various aspects
of our body's physiology and give us a readiness.
So it should come as no surprise
that dopamine and epinephrin aka adrenaline
hang out together.
In fact, epinephrin and adrenaline are actually manufactured
from dopamine.
There's a biochemical pathway involving dopamine
which is a beautiful pathway.
If ever you want to look it up,
you can just look up biochemistry of dopamine.
But what you'll find is that,
l-DOPA is converted into dopamine.
Dopamine is converted to two noradrenaline.
Norepinephrin, it's also called.
And noredrenaline, norepinephrin is converted
into adrenaline.
So not only are dopamine and epinephrin aka adrenaline
close cousins,
they are actually family members.
Okay?
They're closely related.
I'm not going to get too deep into epinephrin today.
I'm not going to talk too much about those pathways,
but anytime I'm talking about dopaminergic transmission
or that you have a peak in dopamine,
inevitably, that means that you have a peak
and release of epinephrin as well.
What dopamine does is dopamine really colors
the subjective experience of an activity
to make it more pleasureful,
to make it something that you want more of.
Epinephrin is more about energy.
Epinephrin alone can be fear, paralysis, trauma.
Not physical paralysis, but mental paralysis,
you know, frozen in fear or being traumatized or scared.
But the addition of dopamine to that chemical cocktail,
if dopamine is released in the brain,
well, then that epinephrin becomes one of excitement.
Okay?
I'm using a broad brush here,
but essentially what you need to know is that,
dopamine and epinephrin aka adrenaline are family members.
And they tend to work together like a little gang
to make you seek out certain things.
So what sorts of activities?
What sorts of things increase dopamine?
And how much do they increase dopamine?
Well, let's take a look at some typical things
that people do out there or ingest out there
that are known to increase dopamine.
So let's recall that you have a baseline level of dopamine
and that everybody does.
And even within a family,
you might have family members who are very excitable,
happy and motivated,
and others who are less excitable, happy and motivated.
But your level of dopamine has everything
to do with those genetics,
but also with what you've experienced in the previous days
and the previous months and so on.
When you do or ingest certain things,
your levels of dopamine will rise above baseline
transiently.
And depending on what you do or ingest,
it will rise either more or less,
and it will be very brief or a last a long time.
So let's take a look at some of the typical things
that people take and do and eat.
Some are good for us,
some are not good for us.
And let's ask how much dopamine is increased above baseline?
Now, of course, these are averages,
but these are averages that have been measured
in so-called micro dialysis studies in animals.
So actually extracting from particular brain areas
how much dopamine is released?
Or from measuring the serum,
the circulating levels of dopamine in humans.
They didn't look at milk versus dark chocolate.
But chocolate will increase your baseline level of dopamine
1.5 times.
Okay?
So it's a pretty substantial increase in dopamine.
It's transient.
It goes away after a few minutes or even a few seconds.
I'll explain what determines the duration in a minute.
But 1.5 times for chocolate.
Sex.
Both the pursuit of sex and the act of sex
increases dopamine two times.
So it's a doubling above baseline.
Now, of course, there's going to be variation there,
but that's the average increase in baseline dopamine
caused by sex.
Later, I will talk about how the different aspects
of the so-called arousal art,
the different aspects of sex,
believe it or not have a differential impact on dopamine.
But for now as a general theme or activity,
sex doubles the amount of dopamine circulating
in your blood.
Nicotine.
In particular, nicotine that is smoked
like cigarettes and so forth,
increases dopamine two and a half times above baseline.
So there's a peak that goes up above baseline
two and a half times higher.
It is very short-lived.
Anyone who's ever been a chain smoker
or observed a chain smoker understands
that the increase in dopamine from nicotine
is very short-lived.
Cocaine will increase the level of dopamine
in the bloodstream two and a half times above baseline.
And amphetamine another drug that increases dopamine
will increase the amount of dopamine in the bloodstream
10 times above baseline.
A tremendous increase in dopamine.
Exercise.
Now, exercise will have a different impact
on the levels of dopamine,
depending on how much somebody subjectively enjoys
that exercise.
So if you're somebody who loves running,
chances are it's going to increase your levels of dopamine
two times above your baseline,
not unlike sex.
People who dislike exercise will achieve
less dopamine increase or no increase in dopamine
from exercise.
And if you like other forms of exercise like yoga
or weightlifting or swimming or what have you.
Again, it's going to vary by your subjective experience
of whether or not you enjoy that activity.
This is important.
And it brings us back to something
that we talked about earlier.
Remember that mesocorticolimbic pathway?
Well, the cortical part is important.
The cortical part actually has a very specific part,
which is your prefrontal cortex.
The area of your forebrain that's involved in thinking
and planning and involved in assigning
a rational explanation to something,
and involved in assigning a subjective experience
to something, right?
So for instance, the pen that I'm holding right now,
it's one of these Pilot V5s.
I love these Pilot V5s.
They don't sponsor the podcast.
I just happen to like them.
I liked the way that they write,
how they feel.
If I spent enough time thinking about it,
or talking about it,
I could probably get a dopamine increase
just talking about this Pilot V5.
And that's not because I have the propensity
to release dopamine easily,
it's that as we start to engage with something
more and more and what we say about it,
and what we encourage ourselves to think about it,
has a profound impact on its rewarding
or non rewarding properties.
Now, it's not simply the case that you can lie to yourself,
and you can tell yourself I love something
and when you don't really love it,
and it will increase dopamine.
But what's been found over and over again,
is that if people journal about something
or they practice some form of appreciation for something,
or they think of some aspect of something that they enjoy,
the amount of dopamine that that behavior will evoke
tends to go up.
So for people that hate exercise,
you can think about some aspect of exercise
that you really enjoy.
However, I will caution you against saying to yourself,
I hate exercise or I hate studying or I hate this person,
but I love the reward I give myself afterward.
Later, we're going to talk about how rewards given afterward
actually make the situation worse.
They won't make you like exercise more or study more,
they actually will undermine the dopamine release
that would otherwise occur for that activity.
So certain things chemicals have a universal effect.
They make everybody's dopamine go up.
So some people like chocolate,
some people don't of course,
but in general, it make has causes
this increase in dopamine.
But sex, nicotine, cocaine, amphetamine,
those things cause increases in dopamine
and everybody that takes them.
Things like exercise, studying, hard work,
working through a challenge in a relationship
or working through something hard of any kind
that is going to be subjective
as to how much dopamine will be released.
And we will return to that subjective component
in a little bit.
But now you have a sense of how much dopamine
can be evoked by different activities
and by different substances.
One that you might be wondering about is caffeine.
I'm certainly drinking my caffeine today,
and I do enjoy caffeine in limited quantities.
I drink yerba mate and I drink coffee and I love it.
Does it increase dopamine?
Well, a little bit.
Caffeine will increase dopamine to some extent,
but it is pretty modest compared to the other things
that I described.
Chocolate, sex, nicotine, cocaine, amphetamine and so on.
However, there's a really interesting paper
published in 2015.
This is Volkow et al.
You can look up it's very easy to find.
That showed that regular ingestion of caffeine,
whether or not it's from coffee or otherwise,
increases up regulation of certain dopamine receptors.
So caffeine actually makes you able to experience
more of dopamines effects.
Because as I mentioned before,
dopamine is vomited out into the synapse
or it's released volumetrically,
but then it has to bind someplace
and trigger those G protein-coupled receptors.
And caffeine increases the number,
the density of those G protein-coupled receptors.
Now, sitting back and thinking about that,
you might think, oh yeah, you know,
sometimes I'll notice people,
at least in the old days that used to be a cigarette
and a cup of coffee.
Or when people drink alcohol,
oftentimes they'll smoke.
And it's well-known that different compounds
like alcohol and nicotine or caffeine and nicotine
or certain behaviors and certain drugs can synergize
to give bigger dopamine increases.
And this is not terribly uncommon.
There are a lot of people nowadays
who for instance take pre-workout energy drinks.
They'll drink,
I won't name names,
but they'll drink a canned energy drink
or they'll drink a pre-workout
and they'll try and get that big stimulation
that stimulant effect for the dopamine,
the norepinephrin, that family of molecules
that works together to make you motivated.
And then they'll also exercise to try and get even more
of a dopaminergic experience out of that workout.
Sometimes it's also to perform better as well, of course,
but as we'll talk about in a few minutes,
that aspect or that approach rather
of trying to just get your dopamine
as high as you possibly can,
in order to get the most out of experience,
turns out to not be the best approach.
And what you'll find as we talk about dopamine schedules
is that layering together multiple things,
substances and activities
that lead to big increases in dopamine,
actually can create pretty severe issues
with motivation and energy right after those experiences
and even a couple of days later.
So I'm not saying that people shouldn't take
the occasional pre-workout if that's your thing,
or drink a cup of coffee or two before working out
now and again.
Some people really enjoy that.
I certainly do that every once in a while,
but if you do it too often,
what you'll find is that your capacity to release dopamine
and your level of motivation and drive and energy overall
will take a serious hit.
Now, I've been alluding to this dopamine peaks
versus dopamine baseline things
since the beginning of the episode.
I talked about tonic and phasic release and so forth.
But now let's really drill into what this means,
and how to leverage it for our own purposes.
In order to do that, let's take a step back and ask,
why would we have a dopamine system like this?
Why would we have a dopamine system at all?
Well, we have to remember what our species primary
interest is?
Our species like all species has a main interest,
and that's to make more of itself.
And it's just about sex and reproduction.
It's about forging for resources.
Resources can be food,
it can be water can be salt,
it can be shelter,
it can be social connection.
Dopamine is the universal currency of forging and seeking,
right?
We call sometimes talk about motivation and craving,
but what we mean in the evolutionary adaptive context,
what we mean is forging and seeking.
Seeking water, seeking food, seeking mates.
Seeking things that make us feel good
and avoiding things that don't make us feel good.
But in particular seeking things
that will provide sustenance and pleasure in the short-term
and will extend the species in the long-term.
Once we understand that dopamine is a driver for us
to seek things,
it makes perfect sense as to why
it would have a baseline level and it would have peaks.
And that the baseline and peaks would be related
in some sort of direct way.
Here's what I mean by that.
Let's say that you were not alive now,
but you were alive 10,000 years ago.
And you woke up and you looked and you realized
you had minimal water and you had minimal food left.
Maybe you have a child,
maybe you have a partner,
maybe you're in an entire village,
but you realize that you need things.
Okay?
You need to be able to generate the energy
to go seek those things.
And chances are there were dangers in seeking those things.
Yes, it could be saber-tooth tigers
and things of that sort,
but there are other dangers too.
There's the danger of a cut to your skin
that could lead to infection.
There's the danger of storms,
there's the danger of cold,
there's the danger of leaving your loved ones behind.
So you go out and forage, right?
You could be hunting, you could be gathering,
or you could be doing both.
The going out and foraging process
was we are certain driven by dopamine.
I mean, there's no fossil record of the brain,
but the circuits have existed.
We know for tens of thousands,
if not hundreds of thousands of years.
And they are present in every animal, not just mammals,
but even in little worms like C. elegans,
it's the same process.
It's mediated by dopamine.
So dopamine drives you to go out and look for things.
And then let's say you find a couple berries,
and these ones are rotten,
these ones are good.
Maybe you hunt an animal and kill it,
or you find an animal that was recently killed
and you decide to take the meat.
You are going to achieve,
or I should say, experience some sort of dopamine release.
You found the reward.
That's great.
But then it needs to return to some lower level.
Why?
Well, because if you just stayed there,
you would never continue to forage for more.
It doesn't just increase your baseline and then stay there.
It goes back down.
And what's very important to understand
is that it doesn't just go back down
to the level it was before,
it goes down to a level below
what it was before you went out seeking that thing.
Now, this is counter-intuitive.
We often think,
Oh, okay, I'm going to pursue the win, right?
Let's move this to modern day.
I'm going to run this marathon,
I'm going to train for this marathon.
Then you run the marathon and you finish,
you cross the finish line,
you feel great.
And you would think, okay, now I'm set for the entire year,
I'm going to feel so much better,
I'm going to feel this accomplishment in my body,
it's going to be so great.
That's not what happens.
You might feel some of those things,
but your level of dopamine has actually dropped
below baseline.
Now, eventually it will ratchet back up.
But two things are really important.
First of all, the extent to which it drops below baseline
is proportional to how high the peak was.
So if you cross the finish line pretty happy,
it won't drop that much below baseline afterward.
If you cross the finish line ecstatic,
well, a day or two later,
you're going to feel quite a bit lower
than you would otherwise.
You might not be depressed,
because it depends on where that baseline was to begin with.
But the so-called postpartum depression
that people experience after giving birth
or after some big win a graduation
or any kind of celebration that postpartum drop
in mood and affect and motivation is the drop
in baseline dopamine.
This is very important to understand,
because this happens on very rapid timescales
and it can last quite a long time.
It also explains the behavior that most of us
are familiar with,
of engaging in something that we really enjoy.
Going to a restaurant that we absolutely love,
or engaging in some way with some person
that we really, really enjoy.
But if we continue to engage in that behavior
over and over again,
it kind of loses its edge.
It starts to kind of feel less exciting to us.
Some of us experienced that drop in excitement more quickly
and more severely than others,
but everyone experiences that to some extent.
And this has direct roots in these evolutionarily
conserved circuits.
Some of you may be hearing this and think,
no, no, no, no that's not how it works for me.
I'm just riding higher and higher all the time.
I love my kids,
I love my job,
I love school,
I love wins,
I don't want losses.
I agree.
We all feel good when we are achieving things,
but oftentimes we are feeling good
because we are layering in different aspects of life,
consuming things and doing things
that increase our dopamine.
We're getting those peaks,
but afterward the drop in baseline occurs,
and it always takes a little while to get back
to our stable baseline.
We really all have a sort of dopamine set point.
And if we continue to indulge in the same behaviors
or even different behaviors that increase our dopamine
in these big peaks over and over and over again,
we won't experience the same level of joy
from those behaviors or from anything at all.
Now, that has a name.
It's called addiction.
But even for people who aren't addicted,
even for people don't an attachment
to any specific substance or behavior,
this drop in bay below baseline after any peak in dopamine
is substantial.
And it governs whether or not we are going to feel motivated
to continue to pursue other things.
Fortunately, there's a way to work with this,
such that we can constantly stay motivated,
but also keep that baseline of dopamine
at an appropriate, healthy level.
A previous guest on the Huberman Lab Podcast
was Dr. Anna Lembke.
She's head of the Addiction Dual Diagnosis Clinic
at Stanford.
Has this amazing book,
"Dopamine Nation: Finding Balance in the Age of Indulgence".
If you haven't read the book,
I highly encourage you to check it out.
It's fantastic.
The other terrific book about dopamine
is the "Molecule of More",
which is a similar in some regard,
but isn't so much about addiction,
it's more about other types of behaviors.
Both books really focus on these dopamine schedules
and the relationship between these peaks
and baselines of dopamine.
In Dr. Lembke's book,
and when she was on the Huberman Lab Podcast
and other podcasts,
she's talked about this pleasure pain balance
that when we seek something that we really like,
or we indulge in it,
like eating a little piece of chocolate,
if we really liked chocolate,
there's some pleasure.
But then there's a little bit of pain
that exceeds the amount of pleasure,
and it's subtle,
and we experience it as wanting more of that thing.
Okay?
So there's a pleasure pain balance,
and I'm telling you that the pleasure and the pain
are governed by dopamine to some extent.
Well, how could that be?
Right?
I said before, when you engage in an activity
or when you ingest something that increases dopamine,
the dopamine levels go up,
you know, to substantial degree
with all the things I listed off.
Where's the pain coming from?
Well, the pain is coming from the lack of dopamine
that follows.
And you now know what that lack of dopamine reflects.
How do you know?
Well, earlier we were talking about how dopamine
is released between neurons.
And I mentioned two ways.
One, is into the synapse where it can activate
the postsynaptic neuron.
And the other was what I called volumetric release
where it is distributed more broadly.
It's released out over a bunch of neurons.
In both cases it's released from these things
we call synaptic vesicles,
literally little bubbles, tiny, tiny little bubbles
that contain dopamine.
Prrr! They get vomited out into the area
or into the synapse.
Well, those vesicles get depleted.
For the synaptic physiologists out there,
we call this the readily releasable pool of dopamine.
We can only deploy dopamine that is ready to be deployed.
That's packaged in those little vesicles and ready to go.
It's like when you order a product and they say out of stock
until two months from now.
Well, it's not ready to be released.
Same thing with dopamine.
There's a pool of dopamine that synthesized,
and you can only release the dopamine
that's been synthesized.
It's the readily releasable pool.
The pleasure pain balance doesn't only hinge
on the readily releasable pool of dopamine,
but a big part of the pleasure pain balance
hinges on how much dopamine is there?
And how much is ready and capable of being released
into the system?
So now we've given some meat to this thing
that we call the pleasure pain balance,
and now it should make perfect sense
why if you take something or do something
that leads to huge increases in dopamine,
afterward your baseline should drop
because there isn't a lot of dopamine around
to keep your baseline going.
Fortunately, most people do not experience
or pursue enormous increases in dopamine
leading to the severe drops in baseline.
Many people do, however,
and that's what we call addiction.
When somebody pursues a drug or an activity
that leads to huge increases in dopamine.
And now you understand that afterward
the baseline of dopamine drops
because of depletion of dopamine,
that readily releasable pool.
The dopamine is literally not around to be released,
and so people feel pretty lousy
and many people make the mistake of then going and pursuing
the dopamine evoking the dopamine releasing activity
or substance again thinking mistakenly
that it's going to bring up their baseline.
It's going to give them that peak again.
Not only does it not give them a peak,
their baseline gets lower and lower
because they're depleting dopamine more and more and more.
And we've seen this over and over again
when people get addicted to something
then they're not achieving much pleasure at all.
You can even see this with video games.
People will play a video game,
they love it,
it's super exciting to them,
and then they'll keep playing and playing and playing,
and either one of two things happens typically both.
First of all,
I always say addiction is a progressive narrowing
of the things that bring you pleasure.
So oftentimes what will happen is the person
only has excitement and can achieve dopamine release
to the same extent doing that behavior
and not other behaviors.
And so they start losing interest in school,
they start losing interest in relationships.
they start losing interest in fitness and wellbeing
and depletes their life.
And eventually what typically happens is,
they will stop getting dopamine release
from that activity as well,
and then they drop into a pretty serious depression
and this can get very severe and people
have committed suicide from these sorts of patterns
of activity.
But what about the more typical scenario?
What about the scenario of somebody
who is really good at working during the week,
they exercise during the week,
they drink on the weekends?
Well, that person is only consuming alcohol
maybe one or two nights a week,
but oftentimes that same person will be spiking
their dopamine with food during the middle of the week.
Now, we all have to eat and it's nice to eat foods
that we enjoy.
I certainly do that.
I love food in fact.
But let's say they're eating foods
that really evoke a lot of dopamine release
in the middle of the week,
they're drinking one or two days on the weekend,
they are one of these work, hard play hard type.
So they're swimming a couple miles in the ocean
in the middle of the week as well.
They're going out dancing once on the weekend.
Sounds like a pretty balanced life as I describe it.
Well, here's the problem.
The problem is that dopamine is not just evoked
by one of these activities,
dopamine is evoked by all of these activities.
And dopamine is one currency of craving motivation
and desire and pleasure.
There's only one currency.
So even though if you look at the activities,
you'd say, well, it's just on the weekends
so this thing is only a couple of times a week.
If you looked at dopamine simply as a function,
as a chemical function of peaks and baseline,
it might make sense why this person
after several years of work hard, play hard
would say, yeah, you know I'm feeling kind of burnt out.
I'm just not feeling like I have the same energy
that I did a few years ago.
And of course there are age-related reasons
why people can experience drops in energy,
but oftentimes what's happening
is not some sort of depletion and cellar metabolism
that's related to aging.
What's happening is they're spiking their dopamine
through so many different activities throughout the week,
that their baseline is progressively dropping.
And in this case it can be very subtle.
It can be very, very subtle.
And that's actually a very sinister function of dopamine
we could say.
Which is that it can often drop in imperceptible ways,
but then at once it reaches a threshold of low dopamine,
we just feel like,
hmm, we can't really get pleasure from anything anymore.
What used to work doesn't work anymore.
So it starts to look a lot like the more severe addictions
or the more acute addictions to things like cocaine
and amphetamine which lead to these big increases,
these big spikes in dopamine,
and then these very severe drops in the baseline.
Now, of course, we all should engage in activities
that we enjoy.
I certainly do,
everybody should.
A huge part of life is pursuing activities and things
that we enjoy.
The key thing is to understand this relationship
between the peaks and the baseline,
and to understand how they influence one another.
Because once you do that,
you can start to make really good choices in the short run
and in the long run to maintain your level of dopamine
baseline.
Maybe even raise that level of dopamine baseline
and still get those peaks and still achieve those feelings
of elevated motivation, elevated desire and craving.
Because again, those peaks and having a sufficiently
healthy high level of dopamine baseline
are what drove the evolution of our species,
and they're really what drive the evolution of anyone's life
progression too.
So they're a good thing.
Dopamine is a good thing.
Just very briefly, because it was also covered
in the interview episode I did with Anna Lembke
about addiction.
Some of you might be asking,
what should I do if I experience a drop
in my baseline level of dopamine
because of engagement with some activity or some substance
that led to big peaks?
Just to put some color and example on this,
a few episodes ago I talked about a friend
who I've known a long time.
So it actually the child of a friend
who has basically become addicted to video games,
he decided actually after seeing that episode with Anna
to do a 30-day complete fast from phone,
from video games and from social media of all kinds.
He's now at day 29 has really accomplished this,
not incidentally, his levels of concentration,
his overall mood are up.
He's doing far far better.
What he did is hard.
In particular first 14 days is really hard,
but the way that you replenish the releasable pool
of dopamine is to not engage in these dopaminergic
seeking behaviors.
Because remember typically people arrive at a place
where they want to stop engaging in these behaviors
or ingesting substances when that dopamine is depleted,
when they're not getting the same lift.
In his case, he was feeling depressed.
He thought he had ADHD.
They were starting to treat it as ADHD.
And certainly there are people out there who have ADHD,
but what he found was that his levels of concentration
are back.
He does not need to be treated for ADHD.
And actually the psychiatrist wondered if he did prior
to this video game, social media fast.
He's feeling good.
He's exercising again.
I'm not making this up.
This is really a very specific,
but very relevant example of how the dopamine system
can replenish itself.
Of course, if there's a clinical need for ADHD treatment,
by all means pursue that.
But I think a lot of ADHD does go misdiagnosed
because of this depletion in dopamine
that occurs because of overindulgence in other activities
in the drop in baseline.
So for anyone that's experienced a real drop in baseline
who has addictive tendencies,
whether or not their behaviors or substances,
that is always going to be the path forward.
Is going to be either cold turkey
or through some sort of tapering to limit interactions
with the, what would otherwise be the dopamine evoking
behavior or substance.
So let's talk about the optimal way to engage in activities
or to consume things that evoke dopamine.
And by no means am I encouraging people to take drugs
of abuse.
I would not do that,
I am not doing that.
But some of the things on these lists
of dopamine evoking activities are things like chocolate,
from a dopaminergic drug which Macuna Pruriens is.
And then they feel a low or a reduction in drive
and excitement and enthusiasm after the drug wears off.
Just like they would with other dopamine
increasing compound.
For that reason, many people have turned
to the use of L-tyrosine.
L-tyrosine is an amino acid precursor to l-DOPA.
So it lies further up the dopamine synthesis pathway.
And nowadays it's very common because all L-tyrosine
is sold over the counter in the United States
that people will take L-tyrosine as a way
to get more energized alert and focused.
Indeed, there are data that L-tyrosine will accomplish that.
L-tyrosine is typically taken in capsule form
or powder form anywhere from 500 to 750
to a 1000 milligrams.
It is a potent stimulus for increasing dopamine.
And the timescale for increasing dopamine
is about 30 to 45 minutes after ingestion.
Dopamine levels start to peak.
The classic study that really nailed down
the fact that tyrosine has this effect
was published way back in 1983,
Journal of Clinical Endocrinology and Metabolism
that directly compared L-tyrosine supplementation
with tryptophan ingestion on plasma dopamine and serotonin.
Tryptophan being a precursor to serotonin.
And indeed what they found is that ingestion of L-tyrosine
can increase the amount of dopamine circulating in the blood
and in the brain too, of course.
The L-tyrosine ingestion induced dopamine
increases within 45 minutes and they were short-lasting
after about 30 minutes the effect had dissipated,
meaning the levels of dopamine had dropped down to baseline.
And even though they didn't look at levels
of baseline dopamine past that time point,
the expectation based on everything we know
about dopamine biology is that it would then drop
below baseline due to the depletion
of the readily reservable pool of dopamine vesicles
that we talked about way back at the beginning
of this episode.
The nice thing about this study is it does show specificity
of effect because ingestion of tryptophan
did not increase dopamine instead it increased serotonin.
So there's really specificity of these pathways
that rule out any placebo type effects.
I'm not suggesting that anybody, everybody
increase their dopamine levels by way of tyrosine
or Macuna Pruriens.
For those of you that are seeking to increase
your dopamine levels without prescription drugs,
those are the most direct route to that.
Of course, if you have a pre-existing
dopaminergic condition,
so schizophrenia or psychosis of any kind,
bipolar, anxiety,
things like Macuna Pruriens and L-tyrosine
will not be good for you.
And if you don't, you should just understand and expect
that it's going to lead to an increase in dopamine.
You'll certainly feel an elevated state
for some of you that might be agitating,
for some of you that might be really pleasureful,
and then you will feel a crash afterwards.
How deep is that crash will really depend on your biology
and where your dopamine baseline began.
So I personally am not a fan of using things
like Macuna Pruriens at all for myself
for the reasons I mentioned earlier,
just too intense and too much of a crash.
I do use L-tyrosine from time to time
for enhancing focus and motivation,
but I want to emphasize from time to time.
So I might use it once a week, occasionally twice a week,
but I've never been one to take L-tyrosine regularly
in order to focus or train or do any kind of mental work.
I just don't want to rely on any exogenous substance
in order to get my dopamine circuits activated.
And I don't want to experience the drop in dopamine
that inevitably occurs some period of time afterwards.
I should also mention things that can reduce
your levels of baseline dopamine.
One that is rarely discussed is melatonin.
I have talked before on this podcast about melatonin,
why I am not a fan of using melatonin
in order to enhance sleep.
It can help one get to sleep,
but not stay asleep.
Dr. Matt Walker sleep expert
from University of California, Berkeley.
I think I don't want to put words in his mouth,
but in our discussion about melatonin on this podcast
when Matt was a guest in his book and on other podcasts,
Matt has generally stated that the use of melatonin
except for treatment of jet lag
is generally not a good idea.
And I agree.
I think that melatonin is not often thought about
as impacting the dopamine pathway,
but there's at least one study published in 2001
first author is Nishiyama just as it sounds.
It's spelled just as it sounds.
Acute effects of melatonin administration
on cardiovascular autonomic regulation in healthy men.
So the study wasn't specifically about dopamine,
but they looked at norepinephrine and dopamine levels,
and they found a statistically significant decrease
in dopamine 60 minutes after melatonin administration.
I've talked before about how viewing bright lights
between the hours of 10:00 p.m and 4:00 a.m
has been shown in studies by Dr. Samer Hattar,
David Bersin, excellent circadian scientists
to reduce levels of dopamine for several days
after that light exposure.
So dim the lights at night,
if you can avoid exogenous melatonin,
meaning if you don't have to take melatonin
and you can find a better alternative
that would be a good idea
if you want to maintain healthy levels of dopamine.
Now, there is one compound that you are all familiar with,
and you've probably actually taken without realizing it,
that increases dopamine.
And that's something called PEA for phenethylamine,
technically beta phenethylamine.
And PEA is found in various foods.
Chocolate just happens to be one in enriched in PEA
and can increase synaptic levels of dopamine.
I personally take PEA from time to time
as a focus and work aid in order to do intense
bouts of work.
Again, I don't do that too often.
This might be once a week or once every two weeks.
I might use it for training,
but typically I don't,
it's usually for mental work.
And I will take 500 milligrams of PEA
and I'll take 300 milligrams of Alpha-GPC.
That's something that I personally do.
That's what's right for me,
it's within my margins of safety for my health.
Again, you have to check with your doctor and decide
what's right for you.
It leads to a sharp but very transient increase in dopamine
that lasts about 30 to 45 minutes.
And at least in my system I've found to be much more
regulated and kind of even than something like L-tyrosine
and certainly much more regulated and even
and lower dopamine release than something
like Macuna Pruriens.
One of the lesser talked about compounds that's out there,
but that's gaining popularity for increasing dopamine
and as a so-called nootropic is something
called huperzine A.
Huperzine A is a compound sold over the counter
at least in the United States
that can increase acetylcholine transmission,
a different neuromodulator entirely.
But what's interesting is that huperzine A somehow
by way of interactions between the cholinergic system
and the dopaminergic system leads to increases in dopamine
in the medial prefrontal cortex and hippocampus.
Hippocampus, of course, being an area of the brain
associated with learning and memory.
And prefrontal cortex being associated
with the mesolimbic pathway, decision-making focus,
et cetera.
And so I think the reason why we're seeing an increase
in popularity of companies including huperzine A
and nootropic compounds is both for the cholinergic
stimulating properties,
but also for stimulating dopamine release.
I personally have never tried huperzine A.
You can go to www.examine.com or put huperzine A
into PubMed if you'd like to search around
and see some of the science behind it.
Again, I'm not recommending anyone take these things.
In fact, I recommend against anyone just diving in,
and starting to consume things without gaining knowledge
about how they function,
whether or not they're right for you.
But nonetheless, I think in the years to come,
we are going to see a lot more of L-tyrosine,
PEA phenethylamine and huperzine as a way of tapping
into the dopaminergic and cholinergic circuits
certainly along with things like Alpha-GPC
as non-prescription, short-lived
somewhat milder alternatives to things
that really spike dopamine,
things like Adderall, Ritalin, modafinil, armodafinil
and similar.
And I can't help but share with you one more result.
It's not related to pharmacology.
It's related to behaviors and social interactions.
And that's the very interesting
and I would say important finding
that was made a few years ago by my colleague, Rob Malenka,
who's in our department of psychiatry at Stanford,
showing that oxytocin and social connection
is actually directly stimulating the dopamine pathway.
I think for many years,
all of us including me would hear and thought
that oxytocin was in the serotonergic pathway
that it was about pair bonding,
and it was about some of these neuromodulators
that were more associated with things related
to feeling good with what we have in the present moment.
That's typically what we think of when we think
of the opioid system or the serotonergic system.
The dopamine system is really about seeking and reward,
but in a paper published in 2017 in the journal Science,
excellent journal.
The papers titled gaining of social reward by oxytocin,
excuse me, in the ventral tegmental area.
You now know what the ventral tegmental area,
it's that area of the mesolimbic pathway.
What this paper essentially showed is that,
oxytocin social connection and pair bonding itself
triggers dopamine release.
And as everyone read this result, we all realized,
ah, this makes total sense that for the evolution
of our species,
indeed for any species where social connections
are important,
it's also important to go seek social connections.
And so, while it's fun to think about pharmacology
and underlying neurocircuitry and cold water baths
and all these different things related to dopamine schedules
and reward mechanisms and attaching reward to effort
and all the various things that we've talked about today
in terms of science and tools and protocols,
I'd be remiss if I didn't include description of this result
and just emphasize that social connections,
close social connections in particular
that evoke oxytocin release.
So those are romantic type,
those are parent-child type,
those are friendship related,
and those can even be just friends at a distance related,
right?
It doesn't actually require skin contact
to get oxytocin release,
but oxytocin release is central to stimulating
the dopamine pathways.
So the take home message there is quite simple,
engage in pursue quality, healthy social interactions.
I know I've covered a lot of material today.
I've really tried hard to focus on things
that lie directly within the dopamine pathway
and circuitries,
as well as things that directly stimulate
those pathways and circuitries.
What I haven't talked about are all the things
that indirectly serve the dopamine pathways.
And out there on the internet
and indeed in the scientific literature,
you will find for instance,
that things like Maca root can increase dopamine.
Things like the gut microbiome can influence dopamine.
And indeed they can,
but they do that through indirect mechanisms.
By creating a environment,
a milieu in which dopamine and dopamine circuits
can flourish.
Maca is a good example of that.
It will reduce cortisol and through some indirect pathways
related to cortisol can increase dopamine.
But it's not a direct increase in dopamine.
And so as a consequence, it's rather subtle
compared to the various compounds and behaviors
that I talked about today.
Indeed cold water exposure leads to huge increases
in dopamine as we talked about before,
and very sustained ones at that.
I realize in giving you a lot of information about science
and mechanism all the way from psychological biological
to circuitry and synaptic transmission,
volumetric transmission and so forth,
that it might seem overwhelming.
The most important thing is to understand,
or that these dopamine pathways
really are under your control.
And the locus of control resides in the fact
that your previous levels of dopamine
are influencing your levels of dopamine right now.
And your current levels of dopamine
and where you take them next,
will influence your dopamine levels in the next days
and weeks to come.
So I hope both with the mechanisms that you now have in hand
plus some of the tools to tap into the dopaminergic system,
both behavioral, pharmacologic prescription,
and non-prescription, et cetera,
that you'll feel that you have more control
over your dopamine system.
And certainly that you have a better understanding
of your dopamine system so that you can modulate
and adjust your levels of dopamine in the ways
that serve you best.
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And last but certainly not least,
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