Welcome to the Huberman Lab Podcast,

where we discuss science

and science-based tools for everyday life.

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.

I’m trying to get 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 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’re 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 will 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.

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.

The title of this paper is

A Rapid and Reversible Control of Human Metabolism

by Individual Sleep States.

We will provide a link to the 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 tricarbolic 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 authors 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 a.m.

and would be most comfortable going to bed

by 7 or 8 p.m. or 9 p.m.

Then there are so-called night owls,

people that would feel best or tend to feel best

when they go to sleep at 1 a.m., 2 a.m., even 3 a.m.

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

or even 11 a.m. or noon.

And then of course, most people go to sleep

somewhere between 10 p.m. and midnight

and wake up somewhere between 5 a.m. and 7 a.m.

or I suppose more typically 6 a.m. and 8 a.m.

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 controlled 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, quote,

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 just going to list this off

in sort of a 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 a.m.

to try and get up at eight or even 7 a.m. 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,

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,

but 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 p.m. perhaps, but even as late as 1 a.m. or 2 a.m.,

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 Optimize 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 a.m., noon, 3 p.m. 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-entrained 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 p.m. in the afternoon.

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

They were also told not to take naps after 4 p.m.

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 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 p.m.

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 p.m.

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 early and go to sleep earlier,

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

certainly before 2 p.m. 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 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 p.m. and midnight

because that’s most people,

and tend to wake up sometime between 6 a.m. and 8 a.m.,

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.

In keeping with that theme,

I’d like to thank the sponsors of today’s podcast.

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Let’s talk about how to optimize

and indeed how to control your brain chemistry

for 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

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,

there are 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 will 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 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 neural 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 or 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’re going to be alert and focused,

or deeply asleep.

You can control whether or not

you’re 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 neural 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, you’re 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 will 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 these are 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 when I 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.

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 exercise physiologists

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’re 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’re in the late part of the day,

let’s say eight or 9 p.m.

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’re 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 corticosterones,

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,

because 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.

Corticosteroin 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 corticosteroins 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 need 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, prolactin, and 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 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 overexposing 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 at 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 designed 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,

which all of 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 and 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,

although 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 wellbeing, 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

because 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.

It was lying down.

It couldn’t see.

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 an ability to measure the amounts

of neuromodulator at a given location in the brain,

had I been able to do that experiment on them

in that moment, I would have 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 it 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.

Daria Rose, Dr. Daria Rose, I should say,

has a podcast called the Daria 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 staring into 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, it turns out that regular ingestion of caffeine

at safe and appropriate levels about 100 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

because 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 p.m.

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 if you’re not,

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 a 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 A-S-E, that’s an enzyme,

they will take these inhibitors that prevent

the breakdown of dopamine and other so-called catecholamines

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 teramine,

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, R-modafinil.

I covered all of those in the episode on ADHD,

and you can find that at 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 supplements increase 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 prurines.

This is actually the outside of a velvety bean

that has been extracted and put into a supplement.

Mucuna prurines 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 prurines.

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 1,000 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 100 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 their 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

or, 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 phenolethylamine.

This relates to the so-called PEA molecule, P-P-E-A.

And phenolethylamine increases dopamine

and some metabolites related to dopamine

in ways that really increase energy

and feelings of wellbeing and motivation.

And again, it’s fast acting.

So my particular protocol, the one I use,

is I’ll take phenolethylamine 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 phenolethylamine 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 were 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 it’s 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.

It comes from a study published in the year 2000.

I’ll link to this study.

I love this study, by the way.

I 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 Sromick 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.

I had them sitting there 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 catecholamines.

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 kinds of sustained increases.

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

We have 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

and 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 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 it’s 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 guests 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.

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-reviewed 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’ve 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 p.m. and 4 a.m.

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’re 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 focus 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 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 just 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 they 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 chocowilling 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,

weightlifting, 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 bi-directional 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 will 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 combined 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’ve 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.

Increased 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 of 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 acetylcholine.

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 huperzine.

Alpha-GPC is in the choline pathway

such that more acetylcholine is synthesized

after you ingest it.

That’s the general logic or framework of how it works.

Whereas huperzine is mainly in the enzymatic pathway.

It tends to adjust how much acetylcholine is broken down

and lead to net increases in acetylcholine.

I will often take 300 milligrams of alpha-GPC

prior to workouts or prior to cognitive work bouts.

But when I say often,

I tend to do this anywhere from three to four times a week,

typically not every day.

Although there are people,

including people who are trying to offset

age-related cognitive decline,

that will take 300 milligrams of alpha-GPC

three times a day every day,

which closely mimics some of the studies

that have been done on humans

looking at offsetting age-related cognitive decline

using things like alpha-GPC.

I should point out that there have been a few studies,

a few, not many,

but these studies emphasize that people

who take a lot of alpha-GPC chronically over time

may be at increased risk for stroke.

I think the data are still out on that

and we need more data.

But for me, in terms of thinking

about the risk-benefit profiles,

taking 300 milligrams of alpha-GPC

most certainly does increase my ability of focus.

I’ve noticed that.

I tend to take it alongside caffeine and phenylethylamine.

So I take that in combination

either before workouts or work bouts,

really sharpens my focus.

And again, I’m doing that three, maybe four times per week.

And I’m careful to do that in the early part of the day

so that it does not disrupt my sleep.

Although I have taken alpha-GPC

in the second half of the day

and I had no trouble sleeping at all.

I don’t know what the exact half-life is

of the given form that’s typically in supplementation.

It’s actually hard to get that information,

but typically the focus effects wear off

after about two, maybe four hours maximum.

Now, one thing that I don’t think

has ever been discussed before,

certainly not on this podcast,

is that if you take alpha-GPC even semi-regularly,

you may notice that a particular feature

of your blood work will increase.

And that’s TMAO, which is sometimes associated

with increased cardiovascular risk.

This may, again, may relate to some of the potential risk

of very high levels of alpha-GPC ingestion over many years,

increasing stroke risk.

Again, those studies looked at people

who’ve been taking it for up to a decade.

But in any case, one way to prevent the increase in TMAO

if you’re taking alpha-GPC at all

is to take 600 milligrams of garlic

because it contains something called allicin.

This was a trick that was handed off to me

by Dr. Kyle Gillette,

who again was a guest on this podcast some time ago

talking about hormones and hormone health.

Turns out that ingestion of 600 milligrams of allicin

alongside or even just same day as alpha-GPC

can really clamp those TMAO levels

that would otherwise increase if you’re taking alpha-GPC.

And indeed, I’ve done the blood work

and that turns out to be the case.

I saw a spike in TMAO.

I started taking 600 milligrams of garlic

and those TMAO levels came down.

And last as it relates to acetylcholine,

but certainly not least,

just as acetylcholine can increase focus,

focus can increase acetylcholine.

I talked a lot about this in the episode on focus,

but there are behavioral tools that you can use

to enhance focus.

Things like staring at a particular visual target

at the same distance at which you’re going to perform

some work and doing that for 30 to 60 seconds,

narrowing in a very deliberate way your visual field

and then moving into a focused work about.

That behavioral practice of narrowing your visual aperture

will increase the amount of acetylcholine transmission

in particular neural circuits

that will then make it easier to focus.

How do we know that?

Well, I covered in that episode

some of the peer-reviewed studies

that relate to protocols that are now actively

being deployed in schools in China and elsewhere,

where kids are doing deliberate visual focus exercises

in order to increase their mental focus.

And while they’re not doing micro dialysis

or brain imaging on those kids in real time,

the cognitive effects and indeed the performance effects

in terms of academic ability and output

are pretty impressive.

So acetylcholine increases focus.

We talked about some dietary

and some supplementation based ways to improve acetylcholine

or I should say increase acetylcholine.

And that does in fact lead to increases

in one’s ability to focus.

This is why a lot of the prescription drugs

for the treatment of Alzheimer’s,

age-related cognitive decline,

and indeed even some of the drugs

that tap into treatments for ADHD

also involve the acetylcholine system.

So there’s nothing surprising or heretical here,

but it is important to point out

that your behavioral ability to focus

is also related to your ability to access

and deploy acetylcholine.

So never do we want purely pharmacologic treatments

to be the only way that people are increasing

a given neuromodulator.

I always say behaviors first,

then nutrition, then supplementation.

And then if there’s a need, certainly a clinical need,

then prescription drugs, et cetera,

of course administered through a physician.

So let’s discuss serotonin.

Serotonin, as I mentioned earlier,

is associated with brain and body states

of well-being, of comfort, of satiety,

and therefore it should come as no surprise

that a lot of the prescription drug treatments

for things like depression

involve increasing levels of serotonin

in the brain and body.

That said, anytime you talk about

prescription drugs for serotonin,

we also want to acknowledge

that there are often side effects

associated with increasing serotonin,

in particular if serotonin levels go too high.

That is, if the dosages of those treatments go too high,

people will, for instance, feel reduced appetite,

reduced libido, increased lethargy, et cetera,

and there’s a so-called serotonergic syndrome.

All of that can and should be considered

with a well-trained physician,

so because they’re prescription drugs,

controlling the dosage, deciding what dosage to take,

deciding which SSRI to take,

and whether or not to come off those drugs,

how to come off those drugs.

Again, all of that should be handled

with a licensed physician.

That said, there are behavioral tools,

nutritional tools, and supplementation tools

that can tap into the serotonin system,

not to the same degree in potency,

but nonetheless in ways that can still impact

our feelings of well-being in positive ways.

So let’s focus first on the behavioral tools,

and some of these might make people chuckle a little bit,

but I want to point out that a lot of these tools

are quite potent.

In fact, they are power tools for modulating serotonin,

and we know that based on human neuroimaging studies,

human and animal microdialysis studies,

and other studies that really have evaluated

circulating levels of serotonin

and the particular brain circuits that release serotonin

when people do certain things.

What sorts of things?

Well, for instance, physical contact,

in particular with loved ones.

This can be romantic love, this can be children,

so your own children, or your spouse,

even if it’s not sexual contact,

friend-to-friend contact, even friend-to-animal contact.

You know, as a former dog owner,

I hope to have another dog soon,

because unfortunately Costello passed away,

but there is something really comforting and wonderful

about petting your dog, and certainly,

given that many of the studies on serotonin

and these other neuromodulators were done on animal models,

we also know that serotonin is being evoked in the dog,

and of course in the child,

and in the significant other, et cetera.

So things like holding hands, believe it or not,

hugs, cuddling, et cetera,

can increase serotonin transmission,

and they make people feel good.

This shouldn’t really come as a surprise.

There’s also gratitude,

and we did an entire episode about gratitude.

There’s a lot of misunderstanding about gratitude.

Oftentimes when people hear gratitude,

they think, oh, gratitude,

this is just being thankful for what you have,

and it’s kind of a weak sauce effect,

meaning, you know, it’s kind of like,

maybe a little serotonin goes up,

or maybe there’s a little bit of increased feelings

of well-being.

Nothing could be further from the truth.

It turns out, first of all,

that receiving, not giving gratitude,

is what has the most potent effects on increasing serotonin

and activity of the brain circuits that involve serotonin

and that lead to increases in feelings of well-being.

So it’s interesting.

Receiving much more than giving gratitude

is what activates those serotonergic pathways.

So the takeaway from that is both give

and receive gratitude,

and of course, do it in an authentic way.

The other thing about gratitude

that’s somewhat counterintuitive

is that observing others giving and receiving gratitude

is immensely powerful for evoking serotonin

and the activity of serotonergic circuits

in you, the observer.

So receiving and observing gratitude

turns out to be the most potent way

to increase serotonin in the brain and body.

And these, again, are dramatic effects

that are quite long lasting,

and not the sorts of effects

that are going to lead to side effects,

at least there’s no reason to think they would.

Now, what about nutritional approaches

to increasing serotonin?

Well, just as we have tyrosine as an amino acid precursor

upstream of dopamine synthesis,

we have the amino acid tryptophan,

which is upstream of serotonin synthesis.

And one simply has to go online

and put in tryptophan-containing foods,

and you will discover that there are a lot of foods

that are enriched in tryptophan

that can lead to net increases

in the amount of serotonin available in the brain and body.

The most kind of famous or infamous of these

is white meat turkey, the so-called tryptophan effect,

where people get very sleepy after eating white meat turkey,

and it is indeed highly enriched in tryptophan.

Although typically the getting sleepy after eating turkey

is most often associated with the Thanksgiving meal,

and the Thanksgiving meal, at least in the US,

is often associated with people vastly overeating.

And so I do want to point out

that if you fill your gut with food,

no matter what that food is,

there’s going to be a diversion of blood to your gut

that’s going to make you feel sleepy

because there’s a diversion of blood away from other tissues.

So if you eat a lot, you’re going to get sleepy, period,

whether or not you eat turkey or some other substance.

Nonetheless, there are a number of foods

that contain a lot of tryptophan,

and that some people will leverage

in order to try and increase

the total amount of circulating serotonin available to them

in order to have a modest increase

in overall mood and wellbeing.

So what are some of these foods?

These are things like milk, in particular, whole milk.

So full fat milk.

I know a number of people choose not to drink milk

because their lactose intolerance.

I’m raising my hand because I’m one such person.

Although when I was a kid, I did enjoy milk.

Canned tuna, turkey, as we mentioned before,

high in tryptophan.

Oats, I am a consumer of oatmeal, so that resonates with me.

Cheese, and here I read,

although not as high in tryptophan

as meat and other dairy sources,

certain cheeses like cheddar cheeses

can be rich in tryptophan.

Certain nuts and seeds, certain breads.

Chocolate, I know a number of people

will be relieved to hear that.

I know chocolate lovers are always looking

for an excuse to eat chocolate.

I confess I’ve never really liked chocolate,

except, dare I say, I like the smooth 100% chocolates.

I know many people gag when they hear 100%.

I actually really like them.

And some fruits can be highly enriched in tryptophan,

things like bananas and apples and things of that sort,

although not nearly to the degree of things

like turkey, canned tuna, and milk.

I’m sure there are other excellent sources of tryptophan

from the diet, including vegan sources,

so please peruse the internet to try and find the sources

that are compatible with your nutritional program,

if indeed your goal is to increase tryptophan.

Now, there are supplements that can increase tryptophan

and can do so quite potently.

One of the ones that has received increasing attention

as of lately is Cysis Quadrangularis, complicated name,

when taken in dosages of about 300 to 600 milligrams

can pretty dramatically increase serotonin levels.

In fact, anywhere from 30% to 39% increases

in circulating serotonin.

That’s a big increase,

and I can provide a link to that study.

The study was focused not so much on serotonin,

but was focused mainly on treatment of obesity and appetite

and weight loss, and it should come as no surprise

that serotonin, if increased,

might lead to decreases in appetite.

A cautionary note, Cysis Quadrangularis

may need to be cycled.

How quickly to cycle it,

meaning do you do two weeks on, two weeks off,

whether or not you need to do more rapid cycling,

like two days on, two days off, is a matter of debate.

There are not a lot of data on this just yet.

There are a lot of opinions about this on the internet,

but again, not a lot of quality peer-reviewed data.

Nonetheless, Cysis Quadrangularis has been shown

to potently increase serotonin in humans,

and for people that are seeking to increase serotonin,

maybe in particular for sake of appetite and weight control,

that might be a useful compound.

I know many people also take 5-HTP,

one of the precursors to serotonin,

in dosages of anywhere from 300 to 500 milligrams.

Typically, people are doing this in anticipation of sleep,

meaning in the final hour of wakefulness

before going to sleep.

I myself have tried 5-HTP prior to sleep,

and all I can tell you is that it led to very deep sleep

for about one to three hours,

and then I woke up and I could not fall back asleep.

I ran that experiment twice

before I decided to abandon 5-HTP as a sleep aid,

and that’s why I’ve never put it into our sleep kit,

or at least my sleep kit.

And when I refer to the sleep kit,

that’s something you can find at hubermanlab.com.

This is a zero-cost resource

where you can see behavioral tools

and also supplementation tools

that can improve the transition time into

and the depth of sleep,

and none of those rely on 5-HTP supplementation.

That said, I know a number of people

use 5-HTP supplementation outside of sleep,

or I should say during the daytime,

to try and increase serotonin,

and it will indeed increase circulating serotonin.

But again, people vary in their sensitivity

to these sorts of things.

Some people might find, for instance,

that 300 milligrams of 5-HTP is just far too much.

It blunts their appetite, might even reduce libido.

There aren’t a lot of very well-controlled studies

looking at this,

and so it has to be figured out on an individual basis

if you decide to approach it at all.

Now, one molecule that I’ve found

to be particularly interesting and useful,

and this is one that I haven’t talked about

yet on this podcast,

is inositol, in particular, myoinositol.

Myoinositol can have the effect of increasing serotonin

and other neurochemicals,

but primarily, at least in terms of the neuromodulators

discussed today, serotonin.

I’ve been taking 900 milligrams of myoinositol

every third night or so

as a test of its ability to improve sleep,

and I have to say, the depth and quality of sleep

that I’ve been obtaining on myoinositol

is pretty remarkable.

In fact, I’ve used it alone

and in combination with the Magnesium 3-Nate

Apigenin Theanine Sleep Kit that I’ve talked about

and that’s included in that, again, zero-cost kit

that’s available as a PDF on our website.

So myoinositol is known to increase

circulating levels of serotonin.

It has been explored extensively in both animal models

and in humans for its daytime use for treating anxiety.

It does seem to reduce anxiety,

and for all sorts of things.

It’s been explored for bipolar disorder.

We’re going to do an episode

about bipolar disorder coming up.

It’s been explored for the treatment of migraine.

It’s been explored for ADHD.

It’s been explored for a huge number

of different conditions of brain and body.

Again, I’ve been using the 900 milligrams of myoinositol

in the 30 to 60 minutes before sleep to improve my sleep,

and it has been doing that very dramatically,

especially when I take it alongside

the rest of those sleep kit supplements.

A quick note about myoinositol

for sake of increasing serotonin.

If you look at the human studies on myoinositol

that are out there,

and in particular focus on the human studies,

what you’ll find is that the dosages

that are often used are tremendously high.

It’s like five grams, eight grams,

18 grams of myoinositol taken throughout the day.

I don’t know how people stomach that,

and in fact, many people drop out of those studies

because of gastric discomfort,

and yet I also wonder how people tolerate it

because it has somewhat of a sedative effect in it,

this kind of anti-anxiety effect,

and I can’t even imagine,

given my experience with 900 milligrams,

what one would experience taking multiple

or many more grams per day,

so I certainly am not encouraging that,

and the only reason I mentioned myoinositol

is that it has a known effect of increasing serotonin.

At least in my experience,

it does not lead to this falling deeply asleep

and waking back up.

Actually, to the contrary,

if I wake up in the middle of the night

to use the bathroom

or I wake up in the middle of the night

for whatever other reason,

I find it far easier to fall back asleep

if I’ve taken 900 milligrams of inositol prior to sleep,

so for me, it’s proving to be a quite useful compound.

I’m not aware of having any serotonergic deficiency overall.

I don’t consider myself depressed,

and of course, I should mention that no supplement,

either added or withdrawn from your protocol,

should ever be used as a direct replacement

for prescription drug treatments

that your physician has given you.

You should always talk to your physician

anytime you remove or add something

to your drug protocol or prescription protocol, of course.

So we’ve got behavioral protocols

that, as silly as it feels to say,

have been shown to potently increase serotonin,

things like physical contact, cuddling,

holding hands with people that you love, of course, right?

I think if they were people that you despised,

it would have the opposite effect for obvious reasons,

but also receiving gratitude and observing gratitude,

very potent increases in serotonin,

and things like Cysis Quadrangularis,

things like 5-HTP may have their uses, right?

They’re very potent at increasing serotonin,

but they do seem to have the need to cycle them,

and they are nuanced.

Some people respond well to them,

others, like myself, don’t,

and of course, always be on the lookout

for dramatic or even subtle decreases in appetite or libido

or things that you might not want

if you are going to be tinkering

with your serotonergic levels and pathways.

And then myo-inositol actually is proving

to be quite useful to me.

And whether or not that’s because of its effects

on serotonin or through some of its other effects

on maybe reducing anxiety,

which certainly I experience

if I wake up in the middle of the night,

I don’t like waking up in the middle of the night,

but on myo-inositol, I sort of seem to not really care

that I woke up and I fall right back asleep.

So the direct source of the positive effects

that I’m getting aren’t clear,

but nonetheless, I thought I’d pass it along

as a useful tool because it is out there

and it is available over the counter

and provided you’re taking the appropriate safety steps

in considering whether or not to use it or not,

I think it might be a useful tool.

And of course,

as with all the other neuromodulators we discussed,

you have both a baseline of serotonin

and the ability to give or provide yourself peaks

of serotonin through these various protocols.

The dietary interventions of the sort that I mentioned,

meaning eating foods that are enriched in tryptophan,

those are mainly going to adjust

your baseline levels of tryptophan.

For instance, if you really want to be sleepy,

sure, you could eat some white meat turkey

in hopes that that tryptophan will convert to serotonin

and make you sleepy, et cetera.

But in general,

those are going to be pretty long lasting effects,

especially given the fact that not all of the tryptophan

you will ingest is going to be converted

into serotonin in your brain.

It’s going to have other effects on other tissues

and organs of your body.

Nonetheless, if you want to increase serotonin,

providing the appropriate baseline context

is going to be useful.

And again, this is a general theme

of all four of these neuromodulators,

dopamine, epinephrine, acetylcholine, and serotonin.

You want to make sure that you have sufficient

baseline levels of those things

through things like diet, regular behaviors,

and then you have the opportunity to use supplementation.

And if it’s appropriate for you,

prescription drugs and certain behavioral protocols

to try and get these potent increases,

these acute increases in whichever the neuromodulators

you happen to want to leverage for your particular goals.

So that brings us to the end of at least this exploration

of the neuromodulators, dopamine, epinephrine,

acetylcholine, and serotonin.

Some of you who are regular listeners of this podcast

might be saying, well, we’ve heard all this before, right?

You had an episode on dopamine,

you had an episode on anxiety,

you had an episode on sleep.

And indeed that’s true,

but what I’ve tried to provide today is a framework

that cuts through all those episodes,

and at the same time builds out a new,

and what I believe to be a really important theme

and principle, which is that whether or not

you’re using nutritional tools, or supplementation,

or prescription drugs, or any other sort of protocol

to try and create a desired effect of focus,

or energy, motivation, relaxation,

you’re playing with the same neurochemical ingredients.

Just as in the realm of nutrition,

you have macronutrients,

you have proteins, carbohydrates, and fats

that can be adjusted in different ratios

and arranged at different times

in order to achieve certain desired effects.

Well, when it comes to your neurochemistry

and your ability to perform mentally, to perform physically,

and your overall wellbeing,

you are dealing with a small handful

of especially potent molecules.

And I acknowledge that there are many neuromodulators,

there are indeed many neurotransmitters,

glutamine, glycine, GABA, et cetera,

but today we focused on the main four,

meaning the most potent and most widespread neuromodulators

in the brain and body that give you access

to particular brain states and body states

of the sort that most people desire.

So what I’m hoping is that rather than decide

that any one tool is the most useful,

or that any one neurochemical is most useful,

for that matter,

that the information that I’ve provided today

allows you a kit of versatile tools

that allows you to figure out what levels of dopamine

and augmentation of dopamine

are appropriate and necessary for you,

what levels of acetylcholine

and tools for manipulating acetylcholine

are going to be most useful for you,

and so on and so forth.

Because at least at this stage in time,

that is June 2022,

there is no simple at-home test.

In fact, there is no simple laboratory test

that allows us to know whether or not

our dopamine levels are high

and our serotonin levels are low.

We can look at somebody and their behavior,

we can look at ourselves and our own mood and behavior,

and we can infer what those levels may or may not be,

but unfortunately we don’t have a really good test

of dopamine levels or serotonin levels

that would allow us to say,

okay, this person or I need to increase dopamine twofold

in order to achieve the kind of motivation that we want.

Unfortunately, that doesn’t exist.

Rather, we are confronted with a situation

where we understand generally

what these different neuromodulators do,

the different mental states and physical states

that they tend to put us into, and we reviewed those,

and we know that there are really potent tools

to adjust those neuromodulators,

if not alone, but in certain combinations.

That is, ingestion of caffeine will tap into

and support dopamine and epinephrine.

Increasing dopamine and epinephrine

alongside increasing acetylcholine

will allow us to access certain brain states,

that is, focused, alert, energized brain states,

great for learning and plasticity of all kinds,

whereas augmenting serotonin

is going to put us into a more relaxed state

and so on and so forth.

And I’d like you to keep in mind

that there is no negotiating the fact

that we all have different phases of our 24-hour cycle

during which those very same neuromodulators

tend to be naturally higher or naturally lower,

and I reviewed that at the beginning of the episode.

So my wish for you is that you will take this information,

experiment with it as you see fit for you and in a safe way,

and as you go forward to really try and gain intuition

and understanding as to not just how these protocols work,

but how any protocol that you might encounter,

supplement-based, drug-based, behavioral-based,

how those might tap

into these different major neuromodulator systems,

and from that, to be able to better predict and evaluate

whether or not they’re going to be useful to you,

detrimental to you,

or whether or not they should be used in combinations

that would be more useful to you.

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So I’d like to thank you once again for joining me today

in our discussion about these incredibly powerful molecules

we call neuromodulators and the things we can do and take

in order to control them so that we can enhance

our mental health, physical health, and performance.

And last, but certainly not least,

thank you for your interest in science.

♪♪