Optimize & Control Your Brain Chemistry to Improve Health & Performance | Huberman Lab Podcast #80

- Welcome to the Huberman Lab Podcast,

where we discuss science and science-based tools

for everyday life.

[upbeat music]

I'm Andrew Huberman,

and I'm a professor of neurobiology and ophthalmology

at Stanford School of Medicine.

Today, we are going to discuss your brain chemistry

and how to control and optimize your brain chemistry

for all aspects of mental health,

physical health, and performance.

Many times before on the Huberman Lab Podcast,

and frankly, every time I'm a guest on another podcast,

I get questions about science and science-based tools

for things like enhancing sleep,

enhancing focus,

enhancing creativity,

improving relationships,

getting over grief and on and on,

all of which are valid questions

and for which there are protocols that are based in science

and that work the first time and every time.

However far more important than knowing a protocol

is understanding why a given protocol works.

That's why I'm always hammering on mechanism

and explaining the cells and circuits and chemicals,

at least to some detail,

so that people can understand not just what to do,

but why it works and therefore,

how to change a protocol

as their life circumstances change,

or as goals change.

Now today we are going to go even a layer deeper.

We're going to explore the foundations

of your biology in your brain and body

that allow any protocol to work

because as it turns out,

all of the protocols out there,

whether or not it's a breathing protocol

or a supplement or a prescription drug

or an exercise routine,

they all tap into and leverage

a core set of just a few biological mechanisms.

That's right,

beneath everything you are able to do and feel

and indeed beneath every protocol that allows you

to change for the better

and optimize your mental health,

physical health, and performance,

there's just a small subset of chemicals

that you're leveraging toward that change.

So today we are going to talk

about the four major pillars of neurochemistry

that allow you to, for instance,

be focused when you want to focus,

that allow you to relax

when you need to relax and de-stress,

that allow you to optimize your sleep,

that allow you to optimize your exercise routine

or to work through a pain point in relationship

or in career or in your relationship to yourself.

So what I can say for sure

is that by the end of this episode,

you will have a much richer understanding

about how your brain and nervous system

and indeed your entire body work.

And you'll have a much firmer understanding

as to which protocols and tools to reach for

given your particular goals in the moment,

in the day, across the week, across the month,

across the year, and indeed across your entire lifespan.

So what we're really going for today are principles,

deeper understanding of why any given protocol works

and we are also going to discuss specific protocols.

Some of those protocols I've discussed

on previous episodes of the Huberman Lab Podcast,

but I must say,

many of the protocols and tools that I will discuss

are brand new and based on research

that I have not discussed at all,

simply because the research papers came out only recently,

or these are papers that I only recently unearthed.

In fact, I'm going to share with you two recent studies

in a moment that are exceedingly important

for optimizing your sleep

and these are studies that, again,

I've never discussed in any episode on sleep

or on any other podcast.

So by the end of today's episode,

you're going to have far more knowledge

about your biology and psychology than you did at the start

and you'll be armed with many more tools

and most importantly,

principles so that you can navigate

not just the tools presented on this podcast,

but in the vast landscape of tools that are out there

for mental health, physical health and performance.

The Huberman Lab Podcast is proud to announce

that we've partnered with Momentous supplements.

We've done that for several reasons.

First of all,

the quality of their supplements is exceedingly high.

Second of all,

we wanted to have a location where you could find

all of the supplements discussed on the Huberman Lab Podcast

in one easy to find place.

You can now find that place at livemomentous.com/huberman.

In addition, Momentous supplements ship internationally,

something that a lot of other supplement companies

simply do not do.

So that's terrific whether or not you live in the US

or you live abroad.

Right now, not all of the supplements

that we discuss on the Huberman Lab Podcast are listed,

but that catalog of supplements

is being expanded very rapidly

and a good number of them that we've talked about,

some of the more prominent ones for sleep and focus

and other aspects of mental and physical health

are already there.

Again, you can find them at livemomentous.com/huberman.

Every so often, I come across a study or set of studies

that I get so excited about

that I start telling everybody in my immediate life

and I insist on also sharing it with you,

the listeners of this podcast,

because I find the information

to be so incredibly interesting and actionable.

The two studies that I'm going to discuss

both relate to sleep and sleep states

and how to access better sleep.

The first one was published in the journal Cell Reports,

Cell Press journal, excellent journal.

And the title of this paper is

"Rapid and Reversible Control of Human Metabolism

"by Individual Sleep States".

We will provide a link to this study in the show captions.

The first author is Nora Nowak, N-O-W-A-K.

And basically what they did is they measured

the different forms of metabolism that occur

while humans sleep.

As far as I know,

this is one of the first studies of this kind.

There are many studies of metabolism.

There are many studies of sleep.

This study focused on how different states of sleep

such as rapid eye movement sleep,

which is associated with dreaming

and high emotional content dreams

versus slow wave sleep,

which tends to be more focused on physical repair

of the body, more mundane dreams,

how those different states of mind during sleep

relate to different aspects of metabolism

and what they found was absolutely fascinating.

First of all,

they found that sleep states regulate more than 50%,

half of all the metabolite features detected

in human breath.

What does that mean?

Well, it turns out that you can figure out

what humans are metabolizing in particular,

more lipids or more carbohydrate,

whether or not they're relying more on glucose metabolism

based on the contents of their breath.

This is true during waking and during sleep.

And this is what allowed them

to do these incredible measurements

of what's being metabolized during sleep.

They measured close to 2000 metabolites in breath,

every 10 seconds across the entire night's sleep.

And what they found was that

there are major pathways related to lipid metabolism,

fat metabolism,

or to carbohydrate metabolism

or other forms of metabolism

that are up or down regulated as human beings transition

between slow wave sleep,

rapid eye movement sleep

and waking.

And you might say waking?

Well, yes, they also looked as people fell asleep

and as they emerged from sleep.

And believe it or not every so often during sleep,

you wake up, you didn't know this,

but you wake up in the middle of the night,

you look around and you go back to sleep.

You're not aware of it because you're still

in a rather sleep like state, although you are awake.

What they found was that sleep

and the various states of sleep

regulated individual metabolic pathways.

They found for instance,

that the switch from sleep to wakefulness

reduces fatty acid oxidation.

So that means while you're asleep,

you're oxidating more fatty acids.

And as you wake up, that becomes less the case.

And there's a switch in slow wave sleep

that increases fatty acid oxidation.

And there's this transition from rapid eye movement sleep

to other aspects of sleep

that brings about things like the so-called TCA cycle.

Some of you familiar with metabolism

will be familiar with the TCA cycle,

the so-called tricarboxylic acid cycle,

intermediates, that's fancy nerd speak

for specific aspects of metabolism being regulated

during this rapid eye movement sleep transition.

What does all this mean?

And how is this actionable?

Well, on many episodes of the Huberman Lab Podcast

such as the master sleep episode

and the episode that we're going

into in further depth today,

we're going to talk about sleep and how to optimize sleep.

It's been thought of,

but not really tamped down

that quality and depth of sleep and duration of sleep

is important for metabolism during the daytime.

And indeed that's the case.

If people are sleep deprived or they're not sleeping enough,

things like glucose metabolism, et cetera,

get really disrupted during the daytime.

But what this current study shows

is that the metabolism that you experience during sleep,

or to be more specific,

the range of different types of metabolism

that you experience during sleep

may serve to tune up

or to ensure that the specific aspects of metabolism

that you require during wakefulness are working properly.

In addition to that,

this study clearly shows that getting enough sleep

allows you to transition

through all the various forms of metabolism

and use all those different forms

of metabolites during sleep

in a way that's immensely beneficial

for the systems of your brain and body.

So the take home message here is that,

as the author state,

sleep and experiencing the different states of sleep,

slow wave sleep early in the night, predominantly,

plus rapid eye movement sleep toward the end of the night

is extremely important for optimizing metabolic circuits

for human performance and health.

In other words, by not getting sufficient duration sleep,

you're not allowing your body

and brain to transition through all the different aspects

of fuel utilization

and you're not teaching your brain and body

how to use similar types of fuels during wakefulness.

So again, all of this points to the fact

that we need to be getting sufficient quality

and duration of sleep.

So if you're sleep deprived, even by an hour or so,

you're going to get far less rapid eye movement sleep

because rapid eye movement sleep is what occurs

toward the end of a sleep night.

During the early part of the night,

far more slow wave sleep.

In getting less rapid eye movement sleep,

we know it makes you more emotionally labile,

but now we know it's also going to alter certain forms

of glucose metabolism

during the night

and during wakefulness.

So that all underscores the need to get sleep.

But then the question is how to get enough sleep

and how to make sure you get

into all these different sleep states.

And this is particularly important

for you so-called night owls.

There's a lot of controversy out there

as to whether or not different so-called chronotypes exist,

that is people who just naturally or genetically

want to be an early bird,

wake up early and go to bed early.

So these people that wake up at 4:00 AM

and would be most comfortable going to bed

by seven or 8:00 PM or 9:00 PM.

Then they are so called night owls,

people that would feel best or tend to feel best

when they go to sleep at 1:00 AM, 2:00 AM, even 3:00 AM,

and like to wake up later 8:00, 9:00, 10:00,

or even 11:00 AM or noon.

And then of course,

most people go to sleep somewhere

between 10:00 PM and midnight

and wake up somewhere between 5:00 AM and 7:00 AM,

or I suppose more typically 6:00 AM and 8:00 AM.

Now whether or not real chronotypes exist

or whether or not people simply select schedules

for sleep and wakefulness that they like

because of their social schedules

or the activities they enjoy.

For instance, some people like to really go out,

they like to go out dancing or hear music,

or spend time in venues that are only open late at night,

and don't even open until noon or after.

Other people like myself rarely go out at night

but I like to get up early.

I like to exercise.

I like to see the sunrise, et cetera.

So I don't know if I'm a morning person

or an evening person.

I just know the things I enjoy

tend to happen in the early part of the day.

And the things that I don't enjoy quite as much

tend to happen late at night.

Regardless of whether or not

there are real genetic propensities

to be a night owl or an early bird

or a sort of typical person right there in the middle,

it's very important that people

have some control over their sleep schedule

and even more important,

that people are able to get sufficient amount

of REM sleep and slow wave sleep,

for many reasons,

but including the reasons I discussed

in the previous study related to metabolism.

I'm very excited, therefore,

about a study that came out in sleep medicine.

This was a few years ago, but somehow I missed this one.

It was published in 2019.

And the title of this article is

"Resetting the Late Timing of 'Night Owls'

"Has a Positive Impact on Mental Health,

"Physical Health and Performance".

This is a study done in humans,

focusing specifically on people

that like to stay up late and sleep in,

but who desire to be able to get up and feel alert

in order to go to work or study

and they want to go to sleep a bit earlier.

And so there are a lot of questions

embedded in this study in particular,

whether or not people can actually shift their schedule

by a few hours or more.

Some people out there contend that if you're a night owl,

that's just going to be impossible

or very, very challenging to do.

Turns out it's not impossible

and it's not even that challenging to do

provided you do the right things.

Just a brief overview of the study

and then I'll give you the key takeaways.

It was a randomized control trial.

It involved a number of different people,

both male and female.

And what they did was they used non-pharmacological,

practical interventions in a real world setting,

here I'm paraphrasing.

They used targeted light exposure.

They used consistent sleep, wake times.

They used fixed meal times,

caffeine intake and exercise.

And this is one of the reasons I love this study so much

because I've done episodes

where I've talked about temperature,

exercise, feeding, and most importantly,

light exposure as a way to control

and shift your sleep wake cycles,

your so-called circadian timing and entrainment.

What did they find?

Well, they found "Significant improvements

"in terms of mood so far less depression and stress",

subjectively measured,

"as well as improved cognitive performance",

that was objectively measured.

So improved reaction times,

improved physical grip strength,

which is actually a measure not just of strength per se,

but also of nervous system function

and a number of things that people could do

in order to optimize their morning hours,

even though they were night owls previously.

What did they have people do?

Well, I'm going to just going to list this off

sort of rapid fire succession.

Then we'll provide a link to the study

if you want to learn more.

First of all, they told participants

to try and wake up two to three hours

before their typical wake up time,

two to three hours.

That seems brutal to me

and probably seems brutal to you

if you're somebody who typically wakes up at 10:00 AM

to try and get up at eight or even 7:00 AM consistently,

but they were also asked to maximize

outdoor light exposure during the mornings

for reasons that if you've listened to this podcast before,

if you've heard me talk about before,

you know, that I'm constantly talking about,

I'll probably go into the grave shouting,

please get as much light exposure

from sunlight early in the day as possible

because it sets in motion

a huge number of things that are beneficial

for your mental health and physical health,

including dopamine production,

timing melatonin production correctly,

reducing cortisol peaks late in the day,

et cetera, et cetera.

So they asked them to get a lot of outdoor light exposure.

They didn't give them a specific amount.

What they said,

maximize outdoor light exposure during the mornings,

the time before noon.

And again, they had them waking up two to three hours

before their habitual wake up time.

They were also told,

and this is very important

if you're going to shift your schedule earlier,

to try and keep sleep wake times fixed

between their work days and their weekends.

So not sleeping in on the weekends

or not having any sleep in days,

regardless of how well they slept the night before.

How fixed?

Within 15 to 30 minutes of their pre-designated time.

So if they were waking up at seven o'clock one day,

they set their alarm and they made sure they got out of bed

at seven o'clock every day plus or minus 30 minutes,

but never later than 7:30,

never earlier than 6:30.

Participants were also asked to try and go to sleep

two to three hours before their habitual bedtime.

So again, these are people that want to stay up late,

like 11:00 PM, perhaps,

but even as late as 1:00 AM or 2:00 AM.

And now they are asked to go to sleep

two to three hours before their habitual bedtime

and to wake up two to three hours earlier,

as I mentioned earlier.

They were also told,

and I love this because it fits with many of the things

we've talked about on this podcast before,

to try and limit light exposure during the evenings,

dim the lights or limit altogether artificial lights.

Lot of reasons for that,

I covered that in the Master Sleep episode,

I covered that in the Optimized Health Using Light episode.

You can find those at HubermanLab.com.

They're asking them to do that here.

And they asked participants to keep a regular schedule

for their daily meals,

not eating on the hour consistently,

you know, at 9:00 AM, noon, 3:00 PM, exactly.

But within again, about 15 to 30 minutes,

they're always eating at the same times.

That was also important.

And again, that's because we have these so-called

food in trained circadian clocks.

When you eat, tells your body when to be alert

and when you're not eating, when to be asleep.

And they were told to not drink any caffeine

after 3:00 PM in the afternoon.

Another theme that we've talked about on this podcast.

They were also told not to take naps after 4:00 PM.

Naps are an interesting feature of the sleep wake cycle.

To be very brief about this

and to pull from the episode

that I did with world sleep expert

from the University of California Berkeley, Matt Walker,

naps are great for many people,

but don't nap if it interferes with your nighttime sleep.

And in this study, they told them don't nap after 4:00 PM.

And if you are a napper, don't nap for more than 90 minutes.

10 minute naps are fine.

20 minute naps are fine.

Zero minute naps are fine,

but don't nap for more than 90 minutes.

And don't nap after 4:00 PM.

And to exercise during the morning.

Now this one can be a bit controversial

because I know a lot of the PTs out there

and a lot of the online, you know,

gym rats and people who,

and runners too, for that matter,

will say, well according to body temperature and research,

it's best to exercise in the afternoon.

Look, it's better to exercise sometime

as opposed to no time,

but if you're focused on how to shift your schedule earlier,

meaning get up earlier and go to sleep earlier,

this study had people exercise in the early part of the day,

certainly before 2:00 PM and ideally before noon.

So again, this is a really important study

because it combines a lot of different variables

to arrive at this very impressive shift

where people can get up two to three hours earlier

and then pretty consistently and reflexively

start going to bed two to three hours earlier,

feeling more alert during the day,

again, improvements in cognitive performance,

mood and physical performance, grip, strength, et cetera.

Very few studies are able to

or are willing to tackle so many variables

and combine them in one study.

This paper, I think, does a marvelous job of doing this

and is incorporating things that individually,

each have some support for them

in animal studies and previous human studies.

But as far as I know,

this is one of the few studies

that really combines all these different features

in one place,

eating times, keeping those consistent,

getting maximal sunlight exposure earlier in the day,

getting up at a consistent time,

going to sleep at a consistent time and on and on.

It's a really marvelous study for that reason.

And I think for any of you that are night owls

and any of you that want to reinforce your early waking

and early to bed times,

and I think for most all of you

who fall into that general middle category

of tend to go to sleep somewhere

between 10:00 PM and midnight,

'cause that's most people

and tend to wake up sometime between 6:00 AM and 8:00 AM,

well, maybe you want to become more of an early riser

or maybe you're going to travel

or the seasons are changing and you want to shift your time

or you have a new job, et cetera,

or something that's actually very common

in terms of relationship struggle.

You want to match your wake sleep times,

or maybe you want to offset your wake sleep times

from a significant other,

these sorts of approaches that I described here

and that are supported by the data in this paper

are absolutely powerful and science supported.

And I'm certain that if you were to apply them,

that you would see essentially the same effects

that were observed here.

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.

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Let's talk about how to optimize

and indeed how to control your brain chemistry

for a sake of health and performance.

Now in order to do that,

we all need to be on the same page

about some basic facts.

Some of those basic facts

involve learning some basic biology.

And I promise that even if you don't have a biology

or chemistry background,

everything I'm about to say should be accessible

and clear to you.

The important thing to know

is that your brain and your spinal cord

and the rest of your so-called nervous system

control all the organs of your body

and that all the organs of your body feed back,

meaning they communicate through chemicals and other means,

to your nervous system.

Now your nervous system plays a particularly important role

in generating everything from sleep

to wakefulness, creativity,

stress, calm, et cetera,

by way of a particular type of cell-cell interaction.

And that's called synaptic communication.

What is synaptic communication?

Well, in order to understand that

let's dial back a little bit further

and try and understand for a moment

what makes up your nervous system.

In its simplest form,

your nervous system is made of nerve cells

that we call neurons.

Neurons communicate with one another through chemicals.

They release certain chemicals that make other neurons

more or less likely to be electrically active.

What do we mean by electrically active?

We mean,

as it sounds,

electricity passing down through cells

and then literally causing electricity in other cells.

The simplest way to think about this

is maybe when you were a kid or maybe even still now,

you would wear socks and you'd shuffle along the floor

to generate some static electricity,

and then you'd touch someone [playful whirring]

and you'd shock them with your finger.

I'm a younger brother

so I'd occasionally do that to my sister.

I had friends, we would do that to one another.

I know it's kind of silly and childish,

yet, it illustrates the principle

that we can generate electricity and pass electricity

to other beings or in the case of neurons,

from one neuron to the next.

The way neurons do that,

is that in between the neurons,

they're little spaces,

those little spaces are called synapses

and neurons literally vomit,

well, they don't literally vomit,

but they release little packets

of so-called transmitter chemical

into that space we call a synapse.

It travels across the synapse.

It attaches to the cell on the other side,

the other neuron.

And then depending on what that chemical is,

it either makes that next neuron more electrically active

or less electrically active,

so called excitation,

it either excites the next neuron

to be electrically active also,

or it inhibits, it prevents the next neuron

from being electrically active.

So again, very simply,

we have nerve cells that communicate with one another

through electricity and chemicals

that inspire that electricity

and the little gaps between neurons are called synapses.

If you can understand that,

I'm certain you can make it through the rest of the episode

and that you'll get all the depth and important detail

that you need to know.

But I want to go just a little bit further

and explain that neurons don't just talk one-to-one.

There are trillions of neurons in your nervous system

that allow you to be happy, to be in love,

to be sad, to be in grief,

to remember things and so on.

And what you do at any moment,

what you feel and what you think

relates to which so-called neural circuits are active.

So a lot of times we think about brain areas

and we've all seen these pictures of the brain

where, you know, someone was in a fMRI scanner,

or they were in a brain scanner of some sort,

and they saw a picture of something

and a certain area of the brain lights up as it's called.

That lighting up of the brain really reflects

the activity of hundreds, if not thousands,

maybe even millions of neurons in that region.

Those images of brain areas lighting up

and indeed talking about brain areas lighting up,

can be a little bit or a lot misleading

because in fact, no single brain area

controls any one single perception

or behavior or feeling state.

Rather, we have so-called neuro circuits,

chains of neurons,

chains of specific neurons that is,

that create different states of mind

that lead to specific behaviors

that lead to specific emotional states.

And those neural circuits are made up

of lots of different brain areas that light up

in particular sequences.

And when I say light up, excuse me,

what I mean is that particular brain areas either excite

or prevent the excitation,

that is they inhibit other brain areas

in a particular sequence.

Much like keys on a piano played in a particular sequence,

makes up a particular song,

particular brain areas activated or made silent

in a particular sequence

leads to a particular behavior

like getting up out of a chair

or a particular feeling state

like being particularly happy one day when you wake up

or particularly depressed,

whether or not that depression is caused by a life event

or whether not it arises spontaneously.

So we have neurons, we have synapses

and we have neural circuits.

And vitally important is the fact that

which neural circuits are active

and which neural circuits are likely to be less active

at any given moment,

depends on two major categories of chemicals.

It depends on hormones

and it depends on so-called neuromodulators.

Now we're mainly going to focus on neuromodulators today

because those are the things

that if you can learn to control them,

and indeed there are tools to control them,

then you can control which neural circuits

are more likely or less likely to be active

in you at any given moment.

And in doing so,

you can control whether or not

you are going to be alert and focused or deeply asleep.

You can control whether or not

you are going to be in a creative state

or whether or not you're going to be in a state of mind

more fit, more capable that is

of doing focused work or math

or more so-called linear types of work

where there's a correct answer.

There's a specific thing to follow

and you're simply going to plug and chug as it were

through a particular set of steps

in order to accomplish something.

Or for instance,

whether or not you're going to be in a more relaxed

and creative state where you're thinking about new ideas

or new ideas just seem to be spontaneously coming to mind.

All of that can be controlled

to a considerable extent

by leveraging these so-called neuromodulators.

What are neuromodulators?

Neuromodulators are particular chemicals

that make it likely

that certain neuro circuits will be active and not others.

And the four neuromodulators

that we're going to talk about today

that are of the utmost importance for your goals

are dopamine,

epinephrine also called adrenaline,

serotonin and acetylcholine.

That's dopamine, epinephrine,

serotonin and acetylcholine.

Today, I'm going to teach you

how each of those different categories

of neuromodulators work

and the things that you can do

to control those neuromodulators,

that is increase them or decrease them

through behavioral tools and supplementation,

in ways that allow you to access

the brain and body states that you want

at the times that you want.

Just very quickly.

I want to talk about how neuromodulators are able to work,

regardless of whether or not it's dopamine

or serotonin or epinephrine, et cetera.

There are many features of how neuromodulators work,

but for sake of today's discussion,

we only need to focus on two of those features.

And those are fast-acting features

and longer slower features

or what we call baseline features.

What am I talking about when I say faster or baseline?

Well, consider that at any given moment,

whether or not you're asleep or awake,

whether or not it's morning or afternoon or night,

you have some amount of dopamine

being released in your brain and body,

some amount of serotonin,

some amount of epinephrine

and some amount of acetylcholine.

It is rarely, if ever the case,

that you have zero dopamine or zero serotonin.

You know, so often we hear about someone

being dopamine depleted

or these days, you hear a lot about that anyways.

Or you'll hear that people's serotonin is bottomed out.

In reality, none of these neuromodulators

ever disappear completely,

but they tend to be present at different levels

or different relative levels.

Another important thing to point out

is that they don't work alone.

In fact, as you'll soon learn,

dopamine and epinephrine are close cousins

that collaborate in terms of creating states

of focus and motivation, for instance,

or in creating states of energy

and the pursuit of particular goals.

When I say they're close cousins,

what I mean is that they tend to impact

some of the same neural circuits.

And believe it or not,

dopamine and epinephrine are chemically related, too.

I'll just tell you right now

that epinephrine is actually derived from dopamine,

chemically epinephrine, that is adrenaline,

is made from the molecule dopamine.

Now dopamine and serotonin can also work together

to impact certain circuits in the brain.

But in large part,

they operate on separate circuits.

And acetylcholine,

which you'll soon learn is involved

in states of focus and can actually open up,

it can literally create states in the mind

in which your brain is more plastic

and able to change and learn more quickly.

Well, acetylcholine can do that on its own,

but rarely does it do it on its own.

More typically, it gets assistance

from some of the other neuromodulators.

Now that might seem like it complicates the picture,

but it actually makes the picture far simpler

because what we can say for sure

is that the fast actions of dopamine

or the fast actions of epinephrine,

serotonin or acetylcholine

are actions that occur on the order of seconds or minutes

or up to about an hour or so.

Whereas the slower actions of those neuromodulators

tend to occur on the order of hours, days, or even weeks.

Now perhaps surprisingly,

I'd like to focus on the slow actions

of the neuromodulators first,

because those slow actions of the neuromodulators

are happening in you and in me and in everyone right now,

and they set the backdrop,

the context in which the various tools

to manipulate dopamine, epinephrine, serotonin,

or acetylcholine will work.

What do I mean by the context

or the backdrop or the baseline?

Well, it's fair to say that most people

are awake during the daytime and asleep at night.

I do realize that there are people

who are going to be doing shift work

or they're raising young children,

or that might have a sick person at home

that they're tending to, et cetera,

or even have insomnia, they're tending to them.

So schedules of sleep and wakefulness will vary,

but in general, everybody,

regardless of whether or not you're nocturnal

or you're, so-called, diurnal, your awake during the day,

pretty much everybody follows a schedule in which

from zero to nine hours after waking,

that is from the time you wake up

until about nine hours later,

the neuromodulators,

dopamine and epinephrine,

tend to be at their highest levels that they will be

at any point in the 24-hour period,

in any period of the day.

So we can call this zero to nine hour period

phase one of the day, just for simplicity.

And I've referred to this before in a previous episode,

but not in this exact context.

From nine to about 16 hours is what we would call phase two.

And that's when dopamine and epinephrine levels

tend to subside a bit

compared to the earlier phase one part of the day

and serotonin levels start to increase.

And then phase three of the 24-hour cycle,

which is from about,

and again about the zero approximates,

from about 17 hours after waking

until about 24 hours after waking

is phase three of the day.

And during that time,

there is chaos in terms of which

neuromodulators are most present in the brain.

And by chaos, what I mean is that during sleep,

you have incredible peaks in acetylcholine

and drops in acetylcholine.

You have incredible peaks in dopamine

and drops in dopamine.

You have incredible peaks in serotonin

and drops in serotonin.

Most often, you are not going to see

much if any release of epinephrine, adrenaline,

and that's because epinephrine,

also called adrenaline,

tends to wake us up and put us into action mode behaviors

and that's simply not happening during sleep.

But for the other three neuromodulators,

across the night,

it's sort of chaos.

You've got peaks and drops and peaks and drops

in different combinations

than you would ever see in wakefulness.

And this plays important roles in dreaming,

important roles

in some of the reparative functions of sleep.

The point is that during that phase three,

the levels of neuromodulators are all over the place,

but it's not random, right?

I say it's chaos, but it's organized

according to the specific reparative goals of sleep,

the specific metabolic roles of sleep, et cetera.

We're not going to focus too much on phase three today

because phase three of the 24-hour cycle,

that 17 to 24-hour period,

is one in which you ought to be deeply asleep,

whether or not you're nocturnal or diurnal, right?

17 hours after waking, you ought to be asleep.

And there are a lot of episodes of this podcast.

And indeed, today, I started talking about

two particular studies related to sleep,

and there are a lot of tools to enhance sleep, et cetera.

And of course there are things that you can do

in the late portion of phase two of the day

in order to enhance your transition time

into and depth of sleep.

But you can't really do much during sleep, right?

You're not taking supplements.

You're not doing breathing practices.

There are things to fall back asleep,

but you're not really doing much during sleep.

So we're mainly going to focus

on what we're calling phase one and phase two.

Phase one, being this dopamine

epinephrine dominated phase of our day.

And phase two being this more serotonergic

or serotonin dominated portion of the day.

And then you might say,

well, what about acetylcholine?

You forgot about acetylcholine?

Well, we didn't forget about acetylcholine.

Acetylcholine is under control

more in terms of what we happen to be doing

at any given moment,

whether or not we're focusing or not focusing,

whether or not we're learning or not learning.

And here I'm referring to acetylcholine

specifically in the context of the brain and thinking,

because as some of you

are probably shouting out there, right,

if you're an exercise physiologist

or you know anything about how the brain controls movement,

acetylcholine is used at the nerve to muscle synapse, right?

So neurons don't just control other neurons electrically.

The way you are able to move in fact

is because neurons are controlling

the electric activity of muscles,

literally the contraction of muscle fibers,

and that control is exerted

through the release of acetylcholine.

So acetylcholine is working at muscles, as well,

but we're not focused on that today.

We're focused on what we can do

during phase one of the day

and what we can do during phase two of the day

to control the specific neuromodulators,

dopamine, epinephrine, serotonin, and acetylcholine,

toward particular end goals.

And as I've been harping on for the last five

or 10 minutes or so,

it is important to understand

that in the early phase one part of the day,

again, zero to nine hours,

dopamine and epinephrine already

dominate the neuromodulator landscape.

That is they are already elevated

and then they will taper off in phase two.

Whereas in phase two of the day,

serotonin tends to dominate

more than dopamine and epinephrine.

And so if you think about that,

what it means is that if your goal

is to increase serotonin

in order to get some particular effect

on your mental performance

or physical performance or health,

or if your goal is to increase your dopamine or epinephrine,

to get some particular effect on your mental health,

physical performance, et cetera,

well, then you need to consider

what the background level of dopamine

or epinephrine or serotonin happens to be

because in doing so,

you will know which tool to select

and how hard you need to push on that tool, right?

If your levels of dopamine are already riding pretty high,

because it's the early part of the day,

well then it doesn't take a whole lot more

to get dopamine to a level in which it can,

for instance, change your level of motivation.

Whereas if you are in the late part of the day,

let's say eight or 9:00 PM,

and you have a lot of serotonin

swimming around in your system

and you really need to be focused and alert,

well, you can do that by leveraging the dopamine

and epinephrine system

and indeed the acetylcholine system too,

but you're going to have to resort to tools

that can do that far more potently

and that can do that in a much more sustained way

if you're going to access the state that you want.

So again, it's really important to understand

what the backdrop of these neuromodulators is,

the so-called baseline

and that they vary across the day

if you are going to be able to leverage tools

to optimize your brain chemistry.

Anyone that tells you do this protocol

in order to increase your dopamine,

do this protocol,

or take this supplement to increase your serotonin,

they can be telling you the absolute truth,

but if you don't consider the backdrop

over which that supplement

or behavior is going to have its effect,

well, then you can't really predict the effect it will have.

But if you can understand these backdrop baseline elements

to how neuromodulators work,

well, then you're in a terrific position

to leverage the best tools

in the immediate and short-term

and that is on the order of seconds, minutes and hours.

Before we dive into the more pointed,

directed effects of specific tools on neuromodulators,

I'd like to just briefly mention hormones

because they are also important

for understanding the background and the context

and these baseline levels of neuromodulators.

Now here, I'm going to paint with a bit of a broad brush,

but what I will say is accurate,

even though it might not be exhaustive.

What I mean by that is everything I'm about to say is true,

but it doesn't cover every example in detail

and nuanced possibility out there.

Hormones have many different effects on the brain and body

and not unlike neuromodulators,

some of those effects are very fast.

Some of them are very slow.

In fact, certain hormones,

for instance, the steroid hormones,

like estrogen and like testosterone

and corticosteroids

and here, of course,

I'm referring to the steroid hormones for what they are.

They are indeed steroid hormones,

but I'm not talking about steroids

that people inject for sports performance

or for physical augmentation.

I'm talking about the steroid hormones

that you make naturally

because indeed you make these naturally.

Well, the steroid hormones

can actually control gene expression.

They can change the identity of cells

and the genes and proteins that cells express.

This is why during puberty, for instance,

testosterone and estrogen are released into the body,

growth hormone is released into the body

and bodies and voices and personalities

and brains change tremendously

because literally there is a transformation

of the breast tissue,

of the testicular tissue,

of the ovarian tissue, of the bones, of the muscles,

of the tissues and cells that control hair growth.

Gene expression changes in all those cell types.

And the child becomes an adolescent,

becomes a young adult, right?

That's what puberty really is.

In fact, puberty is perhaps

the most dramatic transformation that we go through

in our entire lifespan in terms of our aging,

'cause indeed it reflects a very rapid,

I should mention, period of aging

and transformation of the identity of cells.

So steroid hormones and other hormones

can have very slow long-lasting actions in that way.

They can also have very fast actions.

So for instance,

adrenaline, epinephrine, released from the adrenal glands

can immediately make your heart beat faster,

can immediately change the circumference

of your blood vessels and arteries and capillaries

and change the way blood flows.

It can change the way you see the world, literally.

It does change the way you see the world

through your visual system.

And that all happens on the order

of hundreds of milliseconds or seconds,

these are extremely fast actions.

Corticosteroid also can have fast actions and slow actions.

But since this isn't a discussion about hormones per se,

and we've done entire episodes

like the Optimize Testosterone and Estrogen episode.

You can find that at HubermanLab.com.

Or the interview with the incredibly knowledgeable

and clear and

really wonderful tutor of actionable information,

Dr. Kyle Gillette, who is also on this podcast,

you can learn a lot about hormones there.

Today, we want to think about hormones

as they relate to these neuromodulators,

the dopamine, serotonin, epinephrine and acetylcholine,

and in general,

testosterone tends to collaborate with

and increase the action of dopamine.

That's not always the case, but in general,

when testosterone goes up, dopamine goes up

and sometimes even vice versa.

When dopamine goes up, testosterone go up.

And this is true for both males and for females.

In general, when corticosteroids

like cortisol and some related steroid hormones increase,

epinephrine levels go up.

And in general, when hormones like oxytocin

or prolactin are increased,

levels of serotonin go up.

We can't draw a direct link

between any one hormone system and acetylcholine.

Acetylcholine kind of sits off

in a category of its own in that way.

But again, in general, testosterone and dopamine

tend to collaborate in the same direction.

Cortisol and epinephrine tend to collaborate

in the same direction.

Oxytocin and prolactin, which are hormones,

and serotonin tend to collaborate in the same direction.

And then we have poor old, lonely acetylcholine

off on its own, but it's not poor and lonely.

It actually has incredibly potent effects on its own.

So it's really that it just doesn't mean much help

from the hormone systems

or at least not the steroid hormone systems

in order to have its tremendous effects.

Now a lot of what people think about

and will do when trying to improve mental health

and physical health

is they will try and increase

or decrease certain categories of hormones

of the sort that I mentioned,

testosterone, estrogen, oxytocin, and prolactin, so on.

But oftentimes, the effects of those manipulations

in hormones that are going to be most salient

are not going to be due to the direct effects

of those hormones.

Sometimes it could be.

But oftentimes it's going to be due to their effects

on the brain and nervous system

by way of how those hormones impact neuromodulators.

So for instance,

there are various things that people can do,

both men and women,

to increase their testosterone and estrogen

in the appropriate ratios.

I talked about one such approach in a previous episode,

and that is to get sunlight

onto a large portion of one's skin each day.

Believe it or not, this actually works.

And it works because your skin

is actually an endocrine organ,

a hormone secreting organ.

It's a beautiful study.

I've covered it on this podcast before.

We will provide a link to this study again,

but it had people spend at least 20 minutes or so,

closer to 30 minutes, each day,

trying to maximize sunlight exposure

to as much of their skin as they could

in terms of still maintaining decent exposure,

meaning not over exposing themselves in a cultural way,

meaning wearing enough clothes that they were decent,

but still getting a lot of sun exposure,

a couple of times per week or more.

What they found was that people's testosterone

and estrogen levels went up.

Feelings of well-being went up.

Feelings of well, or I should say increases in libido

were observed, as well.

They subjectively reported more passion, et cetera,

testosterone and estrogen did indeed both go up.

And again, I want to highlight that increases in estrogen,

not just testosterone,

are related to increases in libido in both men and women.

This is why you never want

to crush your estrogen down to zero,

whether or not you're male or female,

if you want to maintain some sort of healthy libido

and general feelings of well-being, unrelated to libido.

Well, many of those effects

we know are not due to direct effects

of testosterone and estrogen,

but rather are due to the effects

of testosterone and estrogen on the neuromodulators,

dopamine and serotonin,

because much of libido and feelings of well-being

and feelings of relaxation,

but also desire, motivation, et cetera,

originate because of the activation of neural circuits

that dopamine controls and promotes

and that serotonin promote and control.

So this is very important to understand

as we move toward more specific discussion

of the chemicals that we call neuromodulators,

because hormones are controlling those neuromodulators

in a very slow modulatory way.

So yes, I said it,

hormones modulate neuromodulators.

I sort of said it twice on purpose.

And this is a dramatic and potent effect.

So I'll just give you one more example.

The hormone prolactin tends to be antagonistic.

It tends to reduce amounts of dopamine

or at least when prolactin levels are high,

dopamine levels tend to be lower.

You observe this after the birth of a new child,

you observe this post coitally after mating,

in all species, humans and animals.

When prolactin is elevated,

serotonin tends to be elevated.

And when prolactin is elevated,

levels of dopamine and the effects of dopamine

tend to subside.

Now as I move toward explaining

what each of the four categories of neuromodulators do,

this will start to make more and more sense

as to why this would be.

I always say I wasn't consulted in the design phase,

meaning I didn't design these circuits.

And if anyone tells you that they did,

you should back away quickly

because none of us design these circuits.

This is the way that evolution

and nature created these systems.

And they tend to work in a bit of a seesaw fashion,

prolactin up, dopamine down, right?

Dopamine up, prolactin down.

In general, that is the way they work.

So if we are to take a look at how each of these

neuromodulator systems functions on its own,

while understanding that

they never truly function on their own,

we can start to really make sense

of the landscape of tools that are available to us

and which tools are going to be most powerful to select

if our goal is for instance, to be focused

or if our goal is to be less stressed

or if our goal is to be highly motivated

and highly focused for sake of learning.

All of that is indeed possible

if you understand these four neuromodulators

and you understand that while there are many tools

ranging from pharmacologic to behavioral

that can tap into these neuromodulator systems,

that can kind of press on the gas of dopamine,

pull back on serotonin and so on,

but that there are particular tools,

both behavioral and supplementation-based,

and to some extent,

prescription drug based, too,

and we'll touch on a few of those.

If you understand that and why they work,

well, then you can create a sort of kit,

a grab bag of things that you can use in any context

or I should say that you can look to

depending on the context you're in

and create the states of body and mind that you want.

Now once again, painting with a somewhat broad brush,

but nonetheless, an accurate brush,

we can say that dopamine,

when elevated above baseline,

tends to increase states of motivation,

both mental and physical motivation,

drive and to some extent focus.

I've said it many times before, and I'll say it again,

there's a lot of misconception about dopamine.

Many people out there think that dopamine

is all about pleasure.

You hear about dopamine hits or people chasing dopamine

or the need to have a dopamine fast, et cetera.

Dopamine is not about pleasure.

Dopamine is about motivation, craving and pursuit

for goals or for things that are outside

our immediate possession and experience.

The motivation and pursuit of a mate.

The motivation and pursuit to mate.

The motivation and pursuit of food.

The motivation and pursuit of a career goal,

et cetera, et cetera,

things we do not yet have, but that we want

and we get into sort of a forward center of mass

and a pursuit of, and that pursuit can be physical.

That pursuit can be cognitive.

It can be both cognitive and physical.

And it can involve talking about something, right?

Because in some professions,

pursuit of things involves talking.

I think about lawyers,

they talk a lot in pursuit of winning cases

and money, et cetera,

putting people in jail or keeping people out of jail,

et cetera, that's done with their mouths,

not with their bodies.

Athletes in a state of motivated training

or in motivated competition use their bodies.

All this is obvious of course,

but perhaps what is not so obvious

is that one molecule not working alone,

but predominantly one molecule, dopamine,

is responsible for all of those motivated states,

which again, underscores the power of these neuromodulators.

So dopamine, we can think of

at least in the context of today's discussion

as controlling and indeed promoting motivation,

drive and pursuit

and to some extent, focus.

Epinephrine and a closely related molecule

called norepinephrine

and again, I want to emphasize

that epinephrine is adrenaline

and adrenaline is epinephrine.

Norepinephrine is noradrenaline

and noradrenaline is norepinephrine,

but today we're going to just simply talk about

epinephrine and norepinephrine.

That category of neuromodulator

is mainly responsible for generating our energy,

our level of fuel

and baseline level of

forward center of mass, as I like to call it.

You can also think of it as how high your RPM are.

Now we're not a car

and the car analogy sort of falls apart

as we go further into the biology,

but it's a decent one for now.

When epinephrine levels are high,

we tend to feel agitated,

we tend to feel like we want to move,

we tend to feel like we can't shut down our thinking

and our anticipation of what's going to happen next.

And when epinephrine levels are very, very low,

we actually have less physical energy.

We tend to have less mental energy

in terms of generating thoughts very quickly

and so on and so forth.

And as I mentioned before,

dopamine and epinephrine are closely related

so much so that we know for a fact

that epinephrine is actually manufactured

from the molecule dopamine.

So that's why I'm talking about these two neuromodulators

in very close juxtaposition

because they do indeed collaborate with one another.

But for sake of today's discussion,

we can just think of epinephrine as increasing energy,

adrenaline increases energy in our state of readiness.

It also, I should mention, activates our immune system.

Contrary to popular belief

that stress inhibits our immune system,

epinephrine is deployed,

it's released at great levels in our brain and body

when we are stressed.

And that actually protects us

against infections of multiple kinds,

at least in the short-term.

That and all the details of that

and tools related to that

were covered in our episode on the immune system,

if you want to check that out.

Now the neuromodulator serotonin

creates a number of different states in the brain and body,

but for sake of today's discussion,

we're going to think about the predominant states

that it creates

and those are states of contentness,

being happy, feeling fairly relaxed,

feeling soothed and to some extent,

even some relief from pain or lack of pain.

Serotonin is associated with a feeling of satiety

of having enough of what we already have.

Now when serotonin is very, very high,

people can even be sedate.

They can be completely amotivated,

no motivation to seek out things

like food or sex or work or et cetera.

Whereas when serotonin levels are very low,

people can actually exhibit agitation

and high levels of stress.

So the levels matter here,

but again, for sake of today's conversation,

when we leverage serotonin,

we are really leveraging a neuromodulator

that tends to increase the activity

of neural circuits in the brain and body

that make us feel relaxed and happy.

And it tends to decrease the activity of neural circuits

that make us rabidly in pursuit of things

that we don't have, right.

The opposite of content and sated

is motivation, desire and hunger and thirst

for things that we don't have.

So serotonin is the molecule of peace.

It is the molecule of contentness.

It is the molecule of having enough,

at least for the time being

or the feeling that we have enough for the time being.

Now acetylcholine is a fourth category of neuromodulator

that as I mentioned earlier, is somewhat not totally,

but somewhat distinct from any direct control

by the major hormone systems of the body,

or at least the major steroid hormone systems.

And acetylcholine we can say

is mainly associated with states of focus.

And we can go a step further and say

that it's mainly associated with steps of focus

as they relate to learning and encoding new information,

so called neuroplasticity.

Now neuroplasticity,

or the brain and nervous system's ability to change

in response to experience

can be impacted by an enormous number

of different chemicals, not just acetylcholine,

but acetylcholine has a particularly potent ability

to open up the thing that we call neuroplasticity

to allow plasticity to happen in one moment

whereas in a previous moment,

it could not occur

because acetylcholine had not been released in the brain

or in the spinal cord.

So acetylcholine is involved in focus and in learning,

but it is not necessarily always associated

with learning in the context of highly motivated,

really ramped up states.

It can be,

but acetylcholine can also be released

and can encourage the learning

and neuroplasticity associated with calm states.

For instance, if somebody has a newborn child,

we know that they are flooded with oxytocin,

which has actually even been called the love hormone

or it does many things in addition to control feelings

of romantic attachment

and attachment to children, et cetera.

It does all of that, but it does a lot more, as well.

But when people have a new child,

they also tend to be hyper-focused on that child,

not just its well-being,

but they narrow all their thinking,

all their vision,

all their hearing to that child

and there are obvious adaptive reasons

for wanting to do that.

I recall a family dinner we had.

Gosh, this was over 10 years ago.

We had a couple over.

My mom was in the habit of inviting people over

who didn't have places to go on the holidays,

'cause that's just who she is

and I think it's quite nice.

So she brought over this couple, they had a newborn,

I think this baby had been born

maybe two or three weeks before

and it was seated or not seated [laughs].

It was lying down.

I couldn't see it.

It was like a potato bug.

It could barely hold its head up.

But it was lying in a little bassinet on the floor

as we ate dinner.

And it was almost hilarious, it actually was hilarious.

We laughed a lot about this,

that the entire meal,

they were basically staring at this baby.

They were so clearly in love with the baby

and so flooded with oxytocin and also prolactin

that they couldn't take their focus off this baby.

It was actually really wonderful and endearing to see.

But in addition to that,

I'd be willing to bet

had I been able to do a little bit of microdialysis,

which is a ability to

measure the amounts of neuromodulator

given location in the brain,

had I been able to do that experiment on them

in that moment, I would've found that levels

of acetylcholine were exceedingly high

because they were so hyper-focused on this child,

not just in love with, but focused on that child.

And without a doubt,

the neural circuits related to focus

and plasticity were heavily engaged

again for obvious adaptive reasons related to child rearing

and learning the coos and cries

and pain signals and pleasure signals of one's offspring.

So we have dopamine associated with motivation,

drive and pursuit and to some extent, focus.

We have epinephrine and norepinephrine associated

with energy of having a forward center of mass,

mentally and or physically.

We have serotonin,

which is associated with a peaceful,

content, sated state of being.

And we have acetylcholine,

which is associated with focus

and in particular focus as it relates to learning

and encoding new information.

So let's say you want to be more motivated.

You want to be more in pursuit of goals.

And you want to have more energy and to be more focused.

There are many ways to go about that.

In fact, there's a near infinite cloud of opportunities,

everything from prescription drugs to illicit drugs,

which I certainly do not recommend,

supplements, nutrition.

You can listen to particular music.

You can do all sorts of cognitive behavioral,

nutritional supplementation tricks.

Or you can just understand

that what you're really after are increases in dopamine

above baseline that you control

and there are ways to control them that are quite potent

and science tells us which tools

are going to be the most potent

and the most versatile for you.

So I'm going to share those tools with you now

with the caveat that each one of those tools

could be its own entire podcast episode,

and that we've done near entire episodes

on each of these tools or small collections of these tools.

So I'm going to cover these in somewhat superficial manner.

We can provide links to previous episodes

that relate to each of these tools in detail,

but I'll give you enough detail about them

that would allow you to incorporate them into your routine

should you choose.

Let's say you want to increase dopamine

for sake of increasing motivation.

The first thing to do is

to understand what the natural behavioral tools are

for increasing dopamine

and to do those as consistently as possible.

Again, these are tools that you'll want to do

nearly every day, if not every day.

And I know I'm sounding like a broken record on this one,

but here again, we come to sunlight

and I should say,

not just the desire to,

but really the need

for viewing the maximum amount of sunlight

that one can reasonably get

given schedules and locations in the world,

time of year, et cetera,

in the early part of the day,

within the first hour of waking, ideally,

but certainly in the first three hours of your day,

you are going to want to maximize sunlight exposure

to your eyes.

Never look at the sun or any other light so bright

that it's painful to look at.

And yes, of course blinking is fine,

but no, take sunglasses off,

go outside once the sun is out

and get some natural light in your eyes.

And if it's appropriate

or I should say in a way that's appropriate,

maximize the amount of sunlight exposure to your skin,

but please don't get burned.

Please do wear sunscreen if you're prone to getting burned.

Typically early day sunlight is not going to burn you,

at least not most people,

unless you're extremely fair-skinned.

So don't get burned.

Do what you need to in order to protect yourself from burn.

There's some emerging controversy about sunscreen

and which ones are safe and which ones aren't safe.

We have not done an episode on that yet,

but I find it to be an important and interesting topic.

Darya Rose, Dr. Darya Rose, I should say,

has a podcast called The Darya Rose Podcast

and did an episode all about sunscreens,

which are safe, which are not safe,

by interviewing an expert on that

so I refer you to that podcast as it relates to sunscreen.

But get some natural light exposure in your eyes.

And if you wake up before the sun comes out,

turn on as many bright lights inside

as you can turn on reasonably

given your electric bill, et cetera.

Get a lot of bright sunlight exposure early in the day

and get a lot of sunlight exposure to your skin

in the early part of the day,

in a way that doesn't burn you,

meaning burn your skin or blind you, please.

Please don't do anything that harms your vision

like stare into a bright light, that's painful.

What does that do?

Well, it sets in motion a number

of different biological cascades.

Some are very fast.

There are fast actions of sunlight

that will trigger for instance,

dopamine release from different parts of your brain

and your endocrine system.

And we now know that it increases levels of genes

related to thyroid hormone

and actually increases certain dopamine receptors.

So there's a wonderful paper.

We will provide a link to this paper

that shows that sunlight exposure

can actually increase the amount of so-called DRD4.

This is a particular type of dopamine receptor,

the dopamine receptor four.

The genes for dopamine receptor four

are actually under photic control.

So if you get sunlight exposure to your eyes

and it does have to be to your eyes

in the early part of the day,

you increase the amount of dopamine receptor that you have,

which allows whatever circulating dopamine

happens to be there

to have a greater effect on motivation

and I should say also on mood and feelings

of being in pursuit and generally,

in craving and pursuit of things in life.

Now there's another way to increase the effect

of whatever dopamine happens to be circulating

in your brain and body.

And this again, relates to increasing the number

or the efficacy of the receptors for dopamine.

Now here we're not talking about the dopamine receptor four,

but a different category of dopamine receptors,

the D2 and D3 receptors,

which are expressed multiple places in your brain and body

and bind dopamine,

meaning dopamine parks in them like a parking spot

and allows dopamine

to generally increase the activity of the neurons

and cells that express those dopamine receptors.

How do you do that?

Well, turns out that regular ingestion of caffeine

at safe and appropriate levels,

about a hundred to 250 milligrams

is going to increase the number of D2

and D3 dopamine receptors.

I talked a little bit about this on a previous episode.

Again, we'll provide links to these studies,

but this is an important finding,

I believe, because this is not about the acute,

the immediate effects of caffeine on alertness,

although those occur, too.

When you drink caffeine,

it's going to increase your levels of adrenaline

and so-called epinephrine,

which will increase your energy levels.

It's going to decrease levels of something called adenosine,

which builds up while you're sleepy.

It's going to make you feel less sleepy, more alert,

more energetic.

That's sort of obvious.

But what's less obvious is that it's increasing the number

and efficacy of dopamine receptors

so that whatever dopamine happens to be around

in your system is going to have more of a potent effect.

So how much caffeine should you drink?

That's going to vary from person to person.

Some people are very sensitive to caffeine, others are not.

I tend to be fairly insensitive to caffeine,

'cause I've been drinking it for a long period of time.

But you know, after one or two cups of espresso or coffee,

I feel like I've had enough.

I tend to drink my caffeine early in the day,

which is what I'm going to recommend that you do,

not drinking caffeine past two and certainly not 4:00 PM,

if you're on a typical schedule

and you want to be able to sleep that night,

even if you can fall asleep.

Having too much caffeine in your system is not good

because it disrupts the architecture of sleep.

And now knowing about all the metabolic variability

across the night, according to different stages of sleep,

it should be even more obvious

as to why disrupting the architecture of sleep

would be bad for you.

So limit that caffeine intake to early in the day

and don't go ballistic.

Certainly don't go ballistic in any case,

but for most people anywhere

from 100 to 400 milligrams of caffeine

is going to have this effect.

And this effect again is a slow accumulating effect

by drinking caffeine consistently day-to-day.

I get my caffeine mainly from Yerba Mate tea.

I want to emphasize that it's probably a good idea

to stay away from the smoked mates.

There's some evidence those can be carcinogenic,

but I brew my own Yerba Mate tea,

or sometimes I'll drink coffee or espresso,

or sometimes both frankly,

as long as I'm hydrating enough and I'm getting enough salt,

then I tend to feel fine with that much caffeine.

The other way to increase dopamine

and to make sure that your baseline levels of dopamine

are high enough is to make sure

that you're eating sufficient numbers

of tyrosine-rich foods.

You can look up which foods include tyrosine.

Tyrosine is a precursor to dopamine.

It's an amino acid that is in direct pathway

to dopamine synthesis

and tyrosine foods include things like

certain meats, Parmesan cheese,

very high in tyrosine, for instance.

In fact, there's something called the cheese effect,

believe it or not.

I don't want to go too far off topic,

but the cheese effect is kind of interesting

because certain people will take antidepressants

that are so called MAO inhibitors,

monoamine oxidase inhibitors.

Anytime you hear ASE, that's an enzyme.

They will take these inhibitors

that prevent the breakdown of dopamine

and other so-called catacholamines,

which allow more dopamine to be in circulation.

But if these people eat certain cheeses,

including Parmesan cheese, and there are other foods,

of course that include not just tyrosine,

but one of the derivatives of tyrosine,

called tyramine,

that generates what's called the cheese effect,

which is people get potent migraines,

headaches, blood pressure goes up.

Why, well, because they've got a lot of tyrosine

in their system and dopamine in their system.

And they've got less of the enzyme

that removes that dopamine or limits its action

and so they have an excess of dopamine

and dopamine has effects on blood pressure, et cetera.

So the cheese effect is something to avoid

if you are somebody who's taking drugs

that tap into or manipulate the dopamine pathway,

either for Parkinson's or depressions,

obviously you're going to want to be careful

about adjusting up or down levels of dopamine too potently.

So mind the cheese effect

if you're taking an MAO inhibitor.

There's a lot of information about this online.

For most people, eating foods like Parmesan cheese,

eating foods like certain meats and certain vegetables

also can increase tyrosine levels,

which will increase dopamine synthesis.

So these are ways of modulating, more or less,

the baseline of dopamine that you are able to produce

and the ways that dopamine can have its action

by way of binding to receptors more potently.

Now there are other ways to increase dopamine

in a more acute or directed way,

ways to spike your dopamine,

to enhance your state of motivation, mood, focus and so on.

And in thinking about the vast landscape of tools

that can do that,

we have one category of tools,

which are the really, really bad things

that I don't recommend anybody do.

In fact, I recommend nobody do ever,

which are things like cocaine, methamphetamine, et cetera.

They are incredibly destructive for lives

because of the way that they so potently increase dopamine

and then the crash in dopamine that occurs later.

I mean, they can indeed and often do ruin lives.

So we're leaving those off the table.

There are of course, prescription drugs that many people,

especially people who have clinically diagnosed ADHD,

attention deficit hyperactivity disorder,

rely on and in fact benefit from in many cases,

things like Ritalin, Adderall, Vyvanse.

Nowadays, there's also a lot of interest in use

of things like Modafinil, Armodafinil.

I covered all of those in the episode on ADHD.

And you can find that on HubermanLab.com

and the other places this podcast is found.

Prescription drugs aside because they require a prescription

and a discussion that's in-depth

and appropriate with your physician, healthcare provider.

There are supplements that can very potently

increase dopamine as well,

perhaps not to the extent

that some of those other prescription drugs can,

but certainly to a degree that will impact

and increase dopamine and motivation

and the other states dopamine is associated with.

And the two main categories of supplements

that are very effective in raising dopamine

and here I should provide the caveat

that anytime you're going to add or remove anything

from your supplementation protocols,

please talk to a physician

who is knowledgeable on these topics.

If you're somebody who has,

or is taking drugs for depression or mania,

please be very cautious about manipulating your dopamine

in any case.

I don't just say that to protect us,

I say that to protect you.

But if we were to look at the supplement landscape

and ask which supplement increased dopamine,

there are a vast number of them,

but the three main ones,

the most effective ones that are readily available out there

without a prescription are mucuna pruriens.

This is actually the outside of a velvety bean

that has been extracted and put into a supplement.

Mucuna pruriens is actual L-dopa.

It's 99% L-dopa, which is a prescription drug

that is given for Parkinson's and for other purposes

where increasing dopamine is important.

I don't recommend mucuna pruriens.

I'm not saying that no one should take it,

but I don't take it.

And I don't recommend it

because it tends to so potently

and acutely increase dopamine,

that there's a pretty substantial crash afterwards.

So I avoid it and I don't generally suggest

that anyone take it unless there's really a clinical need,

or they're working very closely with somebody

that can really monitor that.

The other two supplements that can increase dopamine

in a short-term way,

but in a significant way,

are L-tyrosine

so you can buy that as a supplement amino acid.

I sometimes take this.

I would say, I probably take it about once a week maximum

for work bouts or workouts.

I'll take it in dosages of anywhere

from 500 milligrams to a thousand milligrams.

People vary tremendously in their sensitivity

to supplementing L-tyrosine.

I know people that can take two grams.

I know people that can barely take a hundred milligrams.

I know people that the best dose for them

is zero milligrams.

So there's a lot of variation there depending on sensitivity

and they're natural baseline levels of dopamine

and whether or not they're doing a lot of other things

to support dopamine,

but nonetheless, taking L-tyrosine will lead

to fairly substantial increases in dopamine

within about 15 to 45 minutes

and it lasts for about 30 minutes to two hours

and then there's kind of a tapering off.

Some people experience a little bit of an emotional

and or I should say energetic crash, some people don't.

And then the other supplement that I certainly use,

and that I know a number of other people use

is more fast-acting, but more potent,

which is phenylethylamine.

This relates to the so-called PEA molecule,

PEA, P-E-A,

and phenylethylamine increases dopamine

and some metabolites related to dopamine

in ways that really increase energy

and feelings of well-being and motivation.

And again, it's fast-acting.

So my particular protocol,

the one I use is I'll take phenylethylamine

at dosages of about 300 to 600 milligrams

along with some L-tyrosine,

or I'll take it on its own with a molecule,

or I should say a compound

that we'll talk about a little bit later

as it relates to acetylcholine, Alpha-GPC,

but tyrosine and phenylethylamine taken alone or together

will make you feel more motivated and more alert,

more willing and able to lean into

particular motivated behaviors,

whether or not they're physical or cognitive.

If you'd like to learn more about these compounds

and their supplementation and their effects,

I encourage you to check out

the ever valuable website, examine.com.

It's zero cost to access,

and they provide references and some more details

about these sorts of compounds and other related compounds.

Now if we are going to look at behavioral tools

for potently increasing dopamine,

that too is a vast landscape.

And we know based on hundreds, if not thousands of studies

that things like winning at some sort of competition

or succeeding in reaching a goal

can certainly increase dopamine.

We talk a lot about this in the episode

on dopamine, motivation and drive,

but leaving that aside,

there are certain behavioral protocols

that are unrelated to your overall goals and motivations

that can increase dopamine in a very sustained way.

And without question,

the most potent behavioral tool for doing that

is going to be deliberate, cold exposure.

Deliberate cold exposure has been talked about a lot here

and elsewhere in terms of its

ability to do things like reduce inflammation

as a way to test and improve resilience

because uncomfortable cold,

provided its applied safely

is a great way to learn to be more resilient

because you're essentially staying or forcing yourself

to stay in a circumstance

where your system is flooded with adrenaline.

But one lesser known aspect of deliberate cold exposure

is one that's been demonstrated

quite convincingly in humans,

comes from a study published in the year 2000.

I'll link to this study.

I love this study by the way.

Covered it many times on this podcast

because I love it so much and I think it's truly important.

And that's the study from Srámek et al,

entitled, "Human physiological responses

"to immersion into water of different temperatures".

I'm not going to go into this into a ton of detail

for sake of time,

but basically what they show is that

putting people into cold water,

and I should mention the water that they used

in this study wasn't that cold.

They had a bunch of different conditions,

but they had people that got into, for instance,

60 degree Fahrenheit water for up to two hours,

had them sitting there,

had them in a lawn chair up to their neck,

had very long sustained increases in dopamine transmission

and dopamine circulation in their brain and body.

And also some of the other catacholamines,

as I mentioned before,

dopamine tends to collaborate with epinephrine

and vice versa.

Now you don't need to put yourself

into 60 degree Fahrenheit water

to get these kind of sustained increases.

And you certainly don't need to do it for two hours.

We have a strong reason to believe

based on subsequent studies,

in fact, published just this last year,

that getting into much colder water

of say 50 degrees or 55 degrees

or even 45 degrees Fahrenheit

can potently increase dopamine and epinephrine, as well.

And that you don't need to expose yourself

to that cold water for nearly as long.

So perhaps even as short as one minute or even 30 seconds

exposure to really cold water,

can lead to these potent long-lasting increases in dopamine.

Many people will ask which protocols to follow.

For instance, will a cold shower suffice?

Very likely, yes, if your shower gets cold enough.

Do you need ice floating in the bath?

No, it's all about the temperature

not whether or not there's ice present or not.

How long to stay in there?

There are a lot of details

that we don't have time to go into this episode.

Please see the episode on the Use of Deliberate Cold

for Health and Performance.

You'll find that at HubermanLab.com.

We have a newsletter related to this.

It gets into a lot of detailed protocols,

but in general, we can say

that the way to evoke dopamine and epinephrine release

using cold water is to

ideally you would do cold water immersion.

If you can't, you'd use cold shower,

but you want to use a temperature that is safe,

meaning you're not going to have a heart attack,

but that is uncomfortable

such that you really want to get out

and then staying in for anywhere from one minute

to 10 minutes, depending on how cold adapted you are,

and then getting out

and drying off and going about your day,

unless you have some other protocol

that you're trying to extract from the cold.

So this is a cold exposure protocol

specifically aimed at increasing dopamine.

For some people out there, you might think

this is kind of silly using cold water to increase dopamine.

But when you look at the data in humans

on the effect of cold water exposure

to stimulate long-lasting, very significant increases

in dopamine and epinephrine,

I think you'll agree that this is a really potent tool

that provided its given safely and gone about safely,

is giving you the kinds of increases in dopamine

that you would seek using prescription pharmacology.

Now it shouldn't be used as a replacement

for prescription pharmacology,

although people have done that to success.

One of the previous guest on the Huberman Lab Podcast

was Dr. Anna Lembke, our director

of the Dual Diagnosis Addiction Clinic at Stanford.

She has an amazing book called "Dopamine Nation",

all about dopamine and both its uses, healthy,

and its perils in things like addiction.

And she describes a patient of hers

that used deliberate cold exposure

to try and maintain dopamine levels

while coming off of drugs

that were increasing dopamine so potently

that they were putting him down the path of addiction.

So the use of cold water for increasing dopamine

is a real tool.

It's, I would say, a power tool.

In fact, it's the kind of thing that if you want

to increase dopamine for sake of motivation,

it might be your first go-to

provided you're also doing the things

to maintain dopamine baseline

like sunlight exposure in particular,

making sure you're getting sufficient amounts

of tyrosine-containing foods and so on.

And now just very briefly,

I want to point to a few quick tools

that good peer review data tell us

can be leveraged in order to make sure

that you have sufficient dopamine when you want it

or that it's available for it to be released

by any number of the tools I provided thus far.

And those are sufficient number of B vitamins.

So it turns out that B vitamins,

in particular B6 or vitamin B6,

can potently reduce prolactin levels.

And again, prolactin and dopamine tend to work

in kind of push pull fashion.

That said you should be cautious

about taking excessive levels of B6.

It is a vitamin that if you take too much,

you'll likely excrete it through your urine,

but there is evidence that having

excessively high levels of B6

or supplementing with excessively high levels of B6

can cause some peripheral neuropathy,

some death of nerves in the periphery.

If you want to know what dosage levels are relevant there

just simply look it up online.

There's a lot of information about this.

But you do want to make sure

that you're getting enough B6, B12, et cetera,

such that you can keep prolactin levels in check.

And if you suspect that you have a dopamine deficiency,

please talk to your doctor

and talk to them about ways you might adjust

that prolactin down and thereby dopamine up.

The other way to ensure that dopamine levels stay high

or put differently,

that you don't quash whatever dopamine

you have in your system

is to really avoid bright light exposure to your eyes

between the hours of 10:00 PM and 4:00 AM

or another way of putting this

because I realize people sleep

at different times, et cetera,

is to avoid bright light exposure to your eyes,

not just blue light, but all colors of light

in phase three, that is 17 to 24 hours after waking up

because that's really when you should be asleep

or trying to get asleep, if you're having trouble sleeping.

Work from Samer Hattar's lab,

the director of the chronobiology unit

at the National Institutes of Mental Health,

again, a previous Huberman Lab Podcast guest,

tell us that bright light exposure

in phase three of your circadian cycle,

17 to 24 hours after waking,

can have dramatic effects in reducing dopamine levels

by way of activating a neural circuit

involving something called the habenula.

I don't want to get into too many details right now,

but really try and keep the lights dim

in the middle of the night or off,

if you can do that safely.

It's really going to help

if you're turning on your phone brightly,

if you are turning on bright lights,

it's not just going to negatively impact melatonin,

the hormone that helps you fall and stay asleep.

It's also going to negatively impact dopamine levels,

not just that night, but the subsequent day.

So that more or less summarizes our coverage

of ways to use behavior and supplementation and nutrition

to increase dopamine

and dopamine receptor efficacy and number,

and to keep sufficient amounts of dopamine

in your system day-to-day for motivation, mood and focus.

And of course, keep in mind those things

that can suppress dopamine,

the bright light exposure,

elevated prolactin, and so on.

My hope is that by understanding those tools

and how they work

and understanding that dopamine does certain things

and not others

that you can assemble a versatile kit of behaviors

and other things that you can do

in order to adjust your dopamine levels

according to your particular goals.

I want to just briefly return to the fact, however,

that all of that is riding on that phase one,

phase two background,

meaning, it's probably going to take less cold water exposure,

or I should say less time doing cold water exposure

early in the day

to get a big increase in dopamine

than it would later in the day.

Because later in the day, your baseline levels of dopamine

are lower and you've got more serotonin circulating.

That should make sense to you now as to why that's the case.

And does that mean

that you should really modify your protocols dramatically?

Probably not, but you might keep that in mind

that if, for instance, you need to be in a highly motivated,

focused state in the late part of the day,

for whatever reason,

it might take a few or more of these tools

in combination in order to accomplish that.

Whereas if you're somebody who feels pretty good

during the day, but you're kind of lacking motivation

and you want to increase dopamine levels

and you don't yet need to,

or want to resort to prescription drugs or supplementation,

well, then you might layer in a couple behavioral protocols

paying attention to of course,

the things that you might be doing

that would also potentially suppress dopamine.

So again, that kit of tools is designed

for you to play with, if you choose,

if it's safe for you to apply them, then do that.

Consider doing them individually,

not trying to hit all the tools all at once, right?

I mean, why throw all those tools

at your dopamine system at once?

Better would be to have those tools in your kit

and be able to deploy them depending on

whether or not you're on travel,

whether or not you're eating well or less well,

whether or not you're sleeping well or less well.

That's highly individual

and I'd like to think that in having those tools in hand,

you'll be able to adjust them and apply them in the ways

that allow you to access the dopamine increases

that you're after.

So next I'd like to talk about epinephrine,

also called adrenaline.

I want to point out that epinephrine

is released both in the brain and the body.

In fact, there's a barrier between brain and body

that prevents the epinephrine that's released

from your adrenal glands,

from crossing the blood brain barrier.

So your brain has a separate site

called the locus coeruleus.

This is a collection of neurons in the back of the brain

that kind of sprinkler the rest of the brain

with epinephrine

and essentially wakes up

whatever neural circuits happen to see, or I should say,

wake up any circuits where that epinephrine

happens to arrive, right,

and generally increase the excitability of those networks.

That's why we say epinephrine increases energy.

I'm not talking about caloric energy,

although that's distantly related to this,

but really energy and the desire to move,

the feeling that we can think,

the feeling that we can be alert.

In fact, if you look at somebody

and their eyelids are wide open,

in large part,

that's because of a lot of adrenaline in their system.

If their pupils are really big

and their eyes are really wide open,

in general, that means they have

a lot of epinephrine circulating there,

whereas when we're tired and we're kind of hood-eyed

and we're sort of sleepy,

or our pupils are really small,

in general, that's because levels of epinephrine

and also dopamine, remember they work together,

levels of epinephrine and dopamine tend to be lower.

This is also why when people take any drug,

like again, not recommending this,

amphetamine or cocaine or any stimulant,

their pupils tend to be huge.

Their eyes tend to be wide open.

They don't blink very often.

And the opposite is true when people take sedatives.

So it all starts to make sense

when you think about the basic actions of these things.

For many people, increasing adrenaline or epinephrine

might seem like a crazy idea.

Most people probably associate this molecule with stress

and then would like to be less stressed.

And we've done entire episodes about stress,

how to master stress, how to leverage stress,

how to conquer stress.

There are a lot of great tools to do that

that are behavioral, supplementation-based.

Please see the episode on Mastering Stress for those tools,

but there are people, including me,

that want to increase our levels of epinephrine

at least early in the day.

I'm somebody who wakes up rather slowly.

In fact, right after waking up,

I rarely want to bounce out of bed.

I try and push myself to do that.

I'm always impressed by these chakra-willy types

that are up at 4:30 or up at five and already into action.

I tend to be kind of thinking about

thinking about maybe being in action early in the day,

but I try and push myself to get into action,

which itself can increase epinephrine.

I should mention that any physical activity,

any physical activity,

walking, running, weight lifting, swimming,

even talking for that matter

is going to increase levels of epinephrine.

Locus coeruleus is a brain structure

that is tightly coupled with behaviors

in a bidirectional way.

That is, when you are in action,

you increase the amount of epinephrine released

from locus coeruleus.

You wake up the brain.

And conversely, when locus coeruleus is active,

the brain wakes up, so it's reciprocal.

It goes both directions.

So I saw a funny tweet actually earlier today,

it was something like

going to the gym gives you energy,

but you need energy to go to the gym.

Sounds like a pyramid scheme to me,

which made me chuckle.

But of course overlooks the fact that,

indeed, if you have energy,

you are more likely to be willing

to get into physical movement

or cognitive movement and thinking hard

or thinking a lot about something.

But also it is absolutely scientifically proven

that being in action

increases levels of epinephrine.

This is why exercising early in the day

gives you more energy for rest of day.

You still might experience a little bit of a crash

in the afternoon,

especially if you're getting up extra early,

or if you're drinking caffeine too close to waking.

I've talked about this before.

If you drink too much caffeine close to waking,

you're going to have an afternoon crash.

Better to push that caffeine intake out

about 90 to 120 minutes after waking.

I know this is really painful for certain people,

but caffeine does increase epinephrine.

Caffeine does other things to limit sleepiness.

And by pushing it out 90 to 120 minutes after waking,

you will avoid the afternoon crash to a large degree.

And if you get up and you exercise

or even do any movement of any kind,

a hundred jumping jacks or a walk, if you can't do that,

anything like that will increase

the total amount of epinephrine that you secrete

into your bloodstream and in your brain

and will get you more energy,

not just in that moment, but throughout the day.

So keep that in mind.

Exercise does indeed give you energy.

It burns caloric energy,

but it gives you neural energy

by way of increasing epinephrine transmission

from locus coeruleus.

And presumably if the exercise is intense enough,

adrenaline, epinephrine release,

from the adrenals within your body, as well.

So we have exercise and we have caffeine

as potent tools for increasing epinephrine

and thereby, energy.

Another potent tool that's purely behavioral,

but is known to work,

based on excellent studies in humans.

And actually my laboratory has been doing

similar types of studies

that are soon to be published, we hope,

is so-called cyclic hyperventilation.

Some of you may be familiar with Wim Hof breathing.

There's also Tummo breathing, which is very similar,

Kundalini breathing.

All of those styles of breathing

involve cyclic hyperventilation,

deep inhales, and either passive exhales or active exhales,

but repeating, inhale, exhale, inhale, exhale,

in a very deep and repetitive way.

If you were to do that right now,

doesn't matter if you do it through your nose or mouth,

although ideally you would do the inhale through your nose

and the exhale through your mouth,

if you did that for 25 repetitions,

25 inhales and exhales, you would feel more alert.

You'd also feel more warm, why?

Because you increased epinephrine, adrenaline release

in the brain and body.

It works the first time and it works every time

to increase epinephrine and thereby energy.

And in fact, there are protocols

and great scientific studies

of using cyclic hyperventilation

for periods of minutes, if not longer,

where for instance, you would do 25 big inhales and exhales

followed by a brief breath hold with your lungs empty,

then repeat 25, then brief breath hold,

excuse me, exhale, hold your lungs empty.

And then repeat again for a third round, if you like.

If you do that over and over, you're going to be very alert.

You're going to have more energy.

You're going to feel like

you want to move around a lot more.

In fact, you might even feel agitated.

So people with a lot of anxiety

or prone to panic attack might want to be cautious

in how they train and embark on that type of breathing,

might want to approach it a little more carefully

or avoid it altogether.

But for most people,

cyclic hyperventilation is simply going to

get you more energized and feeling like you want to move,

feeling like you can think more clearly,

and you'll be more wide-eyed and alert

because you are releasing adrenaline.

And the cold water exposure protocol

that I talked about earlier

and that's covered in our episode on cold

and in the newsletter on cold.

Well that, as I mentioned earlier,

potently increases dopamine, but also epinephrine.

So that's another terrific tool,

whether or not it's applied by cold shower or cold immersion

or some other thing like cryo,

that is going to make you more alert

because it releases adrenaline.

Now we can't really say that there are foods

to increase epinephrine.

Rather, there are foods that include a lot of tyrosine

that will increase dopamine.

And remember, dopamine is the molecule

from which epinephrine is synthesized.

So we can't really point to a particular food

or categories of food for increasing epinephrine.

I think caffeine and things like it

will increase epinephrine.

There are of course prescription drugs

that will increase epinephrine.

And of course,

there are all sorts of so-called beta blockers

that will block the receptors for epinephrine

to make you feel calm for public speaking

or for various heart conditions, et cetera.

That's really the domain of physicians

and should really be worked out with your cardiologist,

with a physician et cetera.

I think the tools of exercise

and should you want very potent increases in adrenaline,

high intensity exercise,

as well as the tools of caffeine, cyclic hyperventilation

and deliberate cold exposure,

really combine to give you a nice little kit,

I would say a versatile kit,

of ways to increase epinephrine

for sake of having more physical and mental energy.

So next is the neuromodulator acetylcholine.

And as I mentioned earlier,

acetylcholine is associated with states of focus

and those states of focus

can be high energy states of focus.

So the ones that are accompanied by

high levels of dopamine and epinephrine

and where we're really excited about

and really lasered in on something,

or they can be the calmer, more relaxed states of focus

like reading a book or practicing music

or listening very carefully to somebody

in a way that's relaxed and calm.

And yet nonetheless,

where we have a narrow cognitive

and typically a narrow visual aperture,

and typically also a narrow auditory aperture.

That is our auditory system and our visual system

and our thinking can be very broad.

It can be all over the place.

Or it can be very narrow.

And it can be very focused.

Acetylcholine is released from two major sites in the brain,

nucleus basalis, which is in the forebrain

and extends connections out to many different brain areas

to offer the opportunity to release acetylcholine locally

and more or less in a chemical way,

highlight those particular neurons and synapses

for strengthening, for plasticity later.

And it is released from sites in the back of the brain

in a way that can increase

the so-called fidelity of information coming in

through our eyes, our ears, our nose, et cetera.

What do I mean by fidelity?

Well, we are constantly being bombarded

with sensory information through all of our various senses

and acetylcholine released from this area

in the back of the brain,

has the ability to increase the extent to which

say, visual information

or just visual and auditory information

would make it through to our consciousness

whereas all the other types of sensory information

that are coming in are filtered out.

So your brain, because it's taking in all this information

needs to decide what to pay attention to.

And in this way, we can say that acetylcholine

has a lot to do, not just with "focus", in air quotes,

but literally attention,

which neural signals become relevant to our consciousness.

There's a whole discussion to be had there

and we don't have time for that.

Rather, I'd like to focus on what are the tools

that one can use

to maintain healthy baselines of acetylcholine

and increase acetylcholine for sake of learning

any type of information, physical, cognitive, or otherwise.

Now it turns out there have been a lot of studies,

including many quality peer reviewed studies

carried out in humans,

looking at what happens

when you increase acetylcholine levels in the brain

and you accompany that with the attempt to learn.

And what you find almost always

is that people experience increased focus,

that when measured the neuronal responses

become more specific,

so less broad scale activity in the brain

and more specific neural circuit activity

and that this triggers immediate and long-lasting changes

in the way those circuits work,

even when acetylcholine is not being deployed,

so-called neuroplasticity, the circuits literally change.

So this is great.

The work of Michael Silver at Berkeley,

the work of Mike Merzenich at UCSF,

the work of Michael Kilgard down in Texas,

all of those laboratories

see this again and again, and again.

Increase acetylcholine before and during learning.

And there's a much higher probability

that the learning will quote, unquote,

"sink in", that the information will be retained

because those neural circuits change.

Now ways to increase acetylcholine in a potent way

include again, nutrition and supplementation.

It is important to have baseline levels of acetylcholine

be sufficiently high, as well.

And for that really the ideal situation

is to regularly ingest foods that provide enough

of the precursors for acetylcholine to be made.

If you go online and you were to do a search

of which foods contain a lot of choline,

which is related to the synthesis of acetylcholine,

you would get some interesting information back.

For instance, beef liver

is the most potent source of choline.

I know nowadays there's kind of a growing micro trend

if you will, of ingesting beef liver,

even raw liver, which to be honest,

the thought of ingesting raw liver of any kind

activates my area postrema,

which is the area of the brain that triggers nausea.

In fact, I'm starting to salivate a bit,

not because I'm hungry,

but I think the whole concept makes me ill.

Nonetheless, cooked liver

or raw liver for that matter,

or liver of any kind seems to contain a lot of choline.

I realize most people,

most people are not going to be running out

and ingesting large amounts of beef liver.

Eggs contain a lot of choline.

Beef contains choline.

Soybeans contain choline.

So there are vegan or non-meat sources,

chicken, fish, mushrooms, kidney beans,

these sorts of things contain a lot of choline

and there are other vegetables that contain choline.

So depending on your dietary preferences and needs,

you can select certain foods to ingest,

to get enough choline to synthesize

enough baseline acetyl choline.

In the realm of supplementation,

there are some excellent tools

for increasing acetylcholine

in the acute short-term,

meaning over the course of about 30 minutes

out to about two hours or maybe even four hours.

And the number of different molecules that can do that,

that are available without a prescription,

at least in the US, is pretty vast.

The most common of those molecules is actually nicotine.

Nicotinic acetylcholine receptors

are abundant throughout the body and brain.

They're in various brain circuits.

They are on muscle and yes,

smoking nicotine either by vaping or cigarette

will activate those nicotinic receptors.

But of course, smoking is a terrible thing.

It will also activate things like lung cancer.

So I definitely don't recommend that.

It also activates addiction because of the ways

that it triggers activation of the dopamine circuit.

So I think that triggering activation

of acetylcholine-related pathways by ingesting nicotine

by way of inhalants is generally a bad idea.

However, some people will chew Nicorette

or other nicotine type gums.

I've never done that,

but I have friends who actually rely on that.

These are typically former smokers

that are trying not to smoke,

but still want to get some of the focus enhancement

that they experience from nicotine.

Some people are very sensitive to nicotine,

and this is important.

Some people are very sensitive to ingested nicotine.

So nowadays there are nicotine-dipped toothpicks,

there of course, is nicotine gum

and other sources of nicotine.

Some people can take that and feel fine.

Some people take it and feel absolutely terrible.

I confess, I've never actually tried nicotine

in any of those forms so I don't know how they work for me,

but some people do use them as cognitive enhancers.

In fact, I know one Nobel prize winning neuroscientist,

who's quite well known in our field

for chewing Nicorette all day long.

He insists that it really helps him with his focus

and he is exceedingly smart and productive,

although I'm sure there are other reasons for that.

Supplements that I have used and do use

for increasing acetylcholine

are things like Alpha GPC or Huperzinene.

Alpha GPC

is in the choline pathway,

such that more acetylcholine is synthesized