Welcome to the huberman Lab podcast, where we discuss science and science based tools for everyday life.
I major 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
Cast, 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 in that work the first time. And every time
however far more important than knowing a protocol, is understanding why a given protocol
works? That's why I'm always hammering on mechanism and explaining the cells and circuits and
chemicals at least two
Some detail so that people can understand, not just what to do, but why it works? And therefore, how to change
your 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 to
breathing protocol, or a
supplement, or a prescription drug or an exercise
routine,
They all tap into and leverage a core set of just a
few biological mechanisms. That's
right. Beneath everything you are able to do and feel and indeed beneath every protocol that allows you to change for the better and optimize your mental health, physical health, and performance. There's just a small subset of
chemicals that you're leveraging toward that
change. So today, we are going to talk about the four major pillars of neurochemistry that allow you to for instance, the
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
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 life span.
So what we're really going for today, our 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 our brand-new and base.
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
Currently 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, huberman Lab podcast is proud to announce that. We've partnered with Momentis supplements. We've done that for several reasons. First of all, the quality of their supplements is exceedingly High. Second of all, we wanted to have a location where you could find all of the supplements discussed on the huberman Lab
podcast in one easy to find place, you can now
find that place at live
momentous.com.
Hubermann in addition, momentous supplements, ship internationally,
something that a lot of other supplement companies, simply do not do so that's terrific whether or not you live in the u.s. or you live abroad right now. Not
all of the supplements that we discuss on the human Lab podcast are listed but that catalog of supplements is being expanded very rapidly and a good. Number of them that we've talked about some of the more prominent ones for sleep and
focus and other aspects of mental and physical
health are already there. Again, you can find them at live momentous.com hubermann 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 in the title of this paper is rapid and reversible control of human metabolism.
Mm by individual sleep States. We will
provide a link to the study in the show captions. The first author is Nora, no whack and owa
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 have sleep. This study focused on how different states of sleep such as rapid eye movement sleep, which is associated with dreaming and high emotional.
Sent 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 metabolites 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.
Go hydrate 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 2,000 metabolites in breath every 10
seconds across the entire
night 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
Things 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 emerge 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 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 your oxidative 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 try carbolic acid cycle,
intermediates that's
Nancy 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 human
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
enough 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, Etc, 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 required during wakefulness
are working properly in
To that, this study, clearly shows that getting enough sleep allows you to transition through all the various forms of metabolism and use all those
different forms of metabolites
during sleep in a way, that's immensely beneficial for the
systems of your brain and body.
So the take-home message here is that as the author State sleep and experiencing the different states of sleep slow-wave sleep early in the night predominantly
plus rapid. Eye movement sleep toward the end of the night is
extremely
A 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 rap,
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.
I towels,
there's a lot of controversy out there as to whether or not different so-called Chrono types 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 7:00 or 8:00 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 10:00 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 Chrono types exist or whether or not people will 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.
Time in venues that are only open late
at night. 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, Etc. 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 then happen, late at night,
regardless of whether or not. They're 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 there
for 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 the study in particular, whether or not
people can actually shift their schedule by a few hours or more. Some people out there contend that if you're a night owl, that's just going to be impossible or very, very challenging to do
turns out. It's not impossible and it's not even that challenging to do provided. You do the right things, just a brief overview of the study, and then I'll
give you the key.
Takeaways, it was a randomized control trial, it involved. A number of different people, both male and female. And what they did was they use non-pharmacological practical interventions.
In a real-world
setting, here. I'm paraphrasing. They
use targeted, light exposure, they used consistent sleep, wake times. They used fixed mealtimes, 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
is objectively measured as well as improved cognitive performance. That was objectively measure to improve
reaction times. Improved physical grip strength, which is actually measured, 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 do they have? People do. Well, I'm going to just going to list
this off and sort of Rapid Fire succession. They will provide
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 a 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 8 or even
seven am consistently. But they were also asked to maximize at
outdoor light exposure, during the mornings for reasons that if you listen to this podcast
before, if you've heard me talk
about before, you know that I'm
constantly talking
about, I'll probably go into the grave shouting.
Please get as much
light exposure from sunlight early in the
day as possible because it sets in motion. A huge number of things that are beneficial for your mental health, and physical health, including dopamine production timing, melatonin production correctly, reducing cortisol Peaks late in the day etcetera, Etc.
So they asked them to get a lot of outdoor, light exposure. They didn't give them a specific amount where they said maximize
outdoor light exposure. During the mornings the time before noon, and again, they have them waking up to 23 hours before their habitual wake-up time.
They were also trying
Old and this is very important if you're going to shift your schedule earlier to try and keep sleep-wake times fixed between their workdays and their weekends.
So not sleeping in on the weekends we're 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 7:00 one day, they set their alarm and they made sure they got out of bed at
7:00 every day plus, or minus 30 minutes. But
Never later than 7:30 never earlier than 630.
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 lately, 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 to 23
hours. Earlier, as I mentioned earlier,
they were also told and I love this because it
fits with many of the things we 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 huberman, lab.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 our 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 and train, 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
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 or fine. 20-minute naps are fine. 0 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,
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, we'll say well according to body temperature and research, it's best to exercise in the afternoon. Look it's better to exercise some time 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 to 23 hours earlier and then pretty consistently and reflexively start going to bed, 2, to 3 hours, earlier, feeling more alert. During the day
again improvements in cognitive performance, mood and
physical performance, grip strength,
Etc. 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 it's
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 Awning 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
Enforce your
early waking and early to bed times. And I
think for most all of you who fall into that General middle category of tend
to go to sleep somewhere between 10:00 p.m. and midnight because that's most people intend 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 etcetera 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
you're awake 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
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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 feedback, 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 Etc, 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 Shuffle
Along the floor to generate some static electricity and the you touch someone and you shock them with your finger younger brother. So I'd occasionally do that to my sister I'd 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 little spaces, those little spaces are called synapses and neurons.
Ron's
literally vomit. Well, they don't literally bomb it 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
Inhibits it prevents
the next neuron from a 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. 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 121. There are
Trillions of neurons in your nervous system
that allow you to be happy to be in, love to be sad to be in grief to remember things and so on,
and what you do at any moment, what you feel, and what you think relates to which
so-called neural circuits are active.
So a lot of times we think about brain areas and we've all seen these pictures of the brain where,
you know, someone was in a fmri scanner or they were in a brain scanner of some sort. And they saw a picture of
Something and a certain area of the brain lights up as it's
called that lighting up of the brain, really reflects the activity of hundreds, if not
thousands, maybe even millions of neurons in that
region.
Those images of brain areas lighting up and indeed talking about brain areas. Lighting up can be a little bit or a lot
misleading because in fact no
single brain area controls any one single perception or behavior or feeling
State, rather, we have so-called 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.
Of lots of different brain areas that light up in particular sequences. And when I say, lay 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 are just
Seem to be spontaneously coming
to mind.
All of that can be controlled
to a considerable extent
by leveraging. The
so-called neuromodulators what our
neuromodulators. Neuromodulators our particular chemicals that make it likely that certain neural circuits
will be active and not others.
And the for
neuromodulators that we're going to talk about today that are of the utmost importance
for your goals are
Mean 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 norepinephrine, Etc. 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. 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
Eights of energy and the pursuit of particular goals. 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 to. 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 where 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 where the Baseline?
Well it's fair to say that most people are awake during the
daytime in a sleep 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 etcetera 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 your so-called diurnal, you're awake during the day. Pretty
much everybody follows a schedule in which from 0 to 9 hours after waking,
that is from the time you wake up until about 9:00.
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
to. 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 3 of the
24-hour cycle, which is from about. And again, about the zero proximate 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 will I chaos. What I mean, is that
during sleep. You have incredible peaks in the cetyl
choline and drops. In
acetylcholine, you have incredible peaks in
dopamine and drops and dopamine. Give
incredible Peaks and serotonin and drops. And 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
To 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 3, the levels of neuromodulators are all over the
place, but it's not
random right? I say it's chaos but it's
Sighs. According to the specific
reparative goals of sleep, the specific metabolic roles of sleep
etcetera. We're not going to focus too much on phase 3 today because phase 3 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.
Etc. And of course there are things that you can do in the late portion of phase 2 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,
are things to fall back
asleep. You're not really doing much
during sleep. So we are mainly going to focus on what we're calling Phase, 1 and Phase 2. Phase one being this dopamine
epinephrine dominated phase of our day and Phase 2 being this more.
Serotonergic or serotonin dominated portion of the day and then you might say, well, what about acetylcholine? 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 your exercise
Or, you know, anything about how the brain controls
movement acetylcholine is used at the nerve to
muscle synapse, right? So neurons, don't just control other neurons electrically. The way you are able to move. In fact is because neurons are controlling the electric activity of muscles, literally the contraction of muscle fibers and that control is exerted through the release of acetylcholine. So acetylcholine is working at muscles as well but we're not focused on that today.
We're focused on what we can do.
During phase 1 of the day and what we can do during phase 2 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, 0 to 9 hours,
dopamine and epinephrine already, dominate
that neuromodulator landscape. That is
they are already elevated.
It. And then they will taper
off in Phase 2
whereas in Phase 2 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 norepinephrine to get some
particular effect on your mental health, physical
Formants, Etc.
Well, then you need to consider what the
background level of dopamine norepinephrine, 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.
Ocean. Whereas, if you are in the late part of the day, let's say 8 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
potent, Lee. 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
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,
In these
Baseline levels of neuromodulators
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, their 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 steer
roid
hormones, like estrogen and like testosterone and corticosteroids. And here, of course, I'm referring to the steroid hormones for what they are. They are indeed steroid hormones. But I'm not talking about steroids that people inject for sports performance or 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
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, 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 S. These are extremely fast. Actions corticosteroid also
Can have fast actions and slow actions. But
since this isn't a discussion about hormones per se and we've done entire
episodes, like the optimized testosterone and estrogen episode, you can find that at huberman lab.com or the
interview with be
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.
Atoning epinephrine and acetylcholine. And in general,
testosterone tends to collaborate with an 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 to saucer and go up, and this
is true for both males and four females in general when
corticosteroids like cortisol and some related.
Steroid hormones,
increase epinephrine levels, go up and in general, when hormones like oxytocin or prolactin are increased levels of Serotonin go up. We can't draw a direct link between any one hormone system and acetylcholine, acetylcholine, kind of sits
off in a category of its own in that way.
But again, in general testosterone, and dopamine tend
to collaborate in the same direction, cortisol and epinephrine tend to collaborate in the same direction.
Oxytocin and prolactin which are hormones and serotonin tend to collaborate in the same direction.
And then we have
poor old lonely acetylcholine off on its own. But it's not poor. And lonely 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.
Is certain categories of hormones
of the sort that I mentioned testosterone estrogen, oxytocin prolactin so on,
but oftentimes the
effects of those manipulations in hormones
that are going to be most. Salient are not going to be due to the Direct effects of those hormones. Sometimes it could be, but oftentimes, it's going to be due to their effects on the brain and nervous system by way of how those
hormones impact neuromodulators. So for instance,
there are various things
People can do both men and women to
increase their testosterone, and estrogen in the appropriate.
Ratios, I talked about one such approach previous episode, and that is to get sunlight
onto a large portion of one skin. Each day, believe it or not, this actually works
and it works because your skin is actually an
endocrine organ. Are hormone secreting, organ, the beautiful
study. I've covered it on this podcast before. We will provide a link to the study again, but
Had people spend at least 20 minutes or so closer to 30 minutes each day trying to maximize sunlight
exposure to as much of their skin as they could. In terms of still maintaining decent exposure. Meaning not over exposing themselves in a
cultural way, meaning wearing enough clothes that they were decent, but still getting a lot of sun exposure, 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 where I should say increases,
In
libido or observed as well. They subjectively reported more passion, Etc. 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 0 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, etcetera, originated, 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 module ettore way. So yes, I said, it hormones modulate neuromodulators sort
of set 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 amount of dopamine, or 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-coital e 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 our we say, I wasn't consulted, the design phase meaning. I didn't design these circuits. And if anyone tells you that they did, you should back away quickly because
none of us design these circuits. This is the way that Evolution and nature created these systems.
And they tend to work in a bit of a
seesaw fashion prolactin up, dopamine down, right? Dopamine up
prolactin down in general. That is the way they work. So if we are to take a look at how each of these neuromodulator systems functions on its own, while understanding that they never
truly function on their own,
we can start to really make sense of the landscape of tools that are available to us and which tools are going to be most
powerful to select. If our goal is for instance, to be focused or
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 and 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 in, to some extent prescription drug base 2, 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 state's of body and mind that you
want. Now, once again, painting with a
somewhat broad brush, but nonetheless,
Inaccurate 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
To have a dopamine fast etcetera.
Dopamine is not about pleasure. Dopamine is about motivation, craving and pursuit for goals or four things that are outside our
immediate possession and experience, the
motivation in pursuit of a mate, the motivation and pursued to mate the motivation of pursuit of food. The motivation and
pursuit of a career goal, etc, etc.
Things we do not yet have but that we want and we get into
Sort of uh 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, Etc. Putting people in jail, or keeping people out of jail etcetera, that's done with their mouths. Now, with their bodies athletes
in a state of
motivated training or in motivated competition use their bodies.
All, this is obvious, of course, but perhaps,
what is not so obvious, is that
one molecule not working alone, but predominantly one molecule dopamine is responsible for
all of those motivated states,
which again, underscores the power
of these neuromodulators.
So dopamine, we can think of 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 nor adrenaline 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
If
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 and very
Close juxtaposition because they do, indeed collaborate with one another.
But for sake of today's discussion, we can just think of epinephrine is 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, its
released at Great levels in our brain and body when we are stressed and that actually protects us against infections of multiple.
Mine's 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 contentedness being happy
feeling fairly relaxed
feeling soothed and to some extent, even some relief from pain or
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 a motivated, no
motivation to seek out things like food or sex or work or Etc. 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, where you 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 content - 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 met,
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 systems 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.
Thing that we call Neural plasticity 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 acetyl, choline can also be
Released and can encourage the learning and neural
plasticity associated with calm States.
For instance, if somebody has a newborn child, we know that they are flooded with
oxytocin, which is actually even been called The Love hormone or though. It does many things in addition to control feelings of romantic attachment and attachment to Children, Etc, 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
Just on that child not just its well-being, but they narrow, all, they're thinking all their Vision, all
their hearing to that child and their 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. They were, 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 you brought over this couple,
they had a newborn his baby had been born, maybe two or three weeks before and
it was
Seated. Not seated. It was lying down. It couldn't see. There's like a potato bug, you barely holds head
up, but it was lying in a little bassinet on the floor as we ate dinner and it was
almost Hilaire. 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 micro
dialysis which is a ability to measure the amounts of neuromodulator to given location 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,
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.
Rules could be its own entire podcast episode, and that we've done it near entire
episodes. On each of these tools are 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
Chiral 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 etcetera.
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 were 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.
Getting burned typically early days. 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. Diarrhoea 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
It 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 giving your electric bill etcetera, 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
ERD for this is a particular type of dopamine, receptor that dopamine receptor for the genes for dopamine receptor, for 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.
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 for,
but a different category, 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
Every of the neurons and cells, that Express those dopamine receptors. How do you do that? Well,
turns out, that regular ingestion of caffeine at safe and appropriate levels about 100, to 250, mg is going to
increase the number of D2 and D3. Dopamine receptors. I talked a little bit about this in a previous episode
again, will 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. All
Those occur to 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 in sensitive 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 passed to and certainly not for 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.
Like variability across the night according to different
stages of sleep. It should be even more obvious as to why disrupting the architecture of sleep will be bad for you.
So limit that caffeine intake, too 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 mate. Is there 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
indirect
Pathway to dopamine synthesis.
Us and tyrosine Foods. Include things like certain Meats. Parmesan cheese, very high entire scene. 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. Any time you hear a sec? 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 these derivatives of tyrosine called it Terror mean that
generates What's called the cheese effect which is people get
potent migraines, headaches blood pressure goes up, y, 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
Is
that dopamine or limits? Its action. And so they have an excess of dopamine and dopamine it has effects on blood pressure, Etc. So the cheese effect is something to avoid. If you are somebody who's taking drugs that tap into or manipulate the dopamine pathway other for Parkinson's or depressions, obviously, you're going to want to be careful about adjusting up or down levels of dopamine to potently. So mind, the cheese effect. If you're taking an MAO inhibitor, a lot of information about this
online for most people eating foods like Parmesan cheese,
In foods like certain meats and certain vegetables also
can increase tyrosine levels which will increase dopamine
synthesis. So these are ways of modulating more 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 to ways to spike your dopamine to enhance your state of motivation.
The 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 to. In fact, I recommend nobody do ever, which are things like cocaine, methamphetamine, Etc. They are incredibly destructive for lives because of the way that they so potently increase dopamine and then the crash and dopamine that occurs later. I mean, they can indeed and often do ruin lives. So we're leaving those off the table.
Of course prescription drugs that many people in 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 and use of things like, modafinil are modafinil. I
covered all of those in the
episode on ADHD and you can find that huberman lab.com. And the other places, this podcast is found prescription drugs aside
because they require a prescription and a discussion. That's in-depth inappropriate with your physician health care. Provider
there are supplements that can vary, 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
Haitian. 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.
Option are mucuna pruriens this is actually the outside of a velvety beam
that has been extracted and put into a supplement.
Mucuna, pruriens is
actual l-dopa,
it's 99% l-dopa, which is a prescription
drug that is given for Parkinson's. And for other purposes, we're increasing, dopamine is
important. I don't recommend mucuna pruriens, I'm not saying that no one should take it, but I don't take it and I don't recommend it because it tends to so potently and acutely, increase, dopamine that there's a
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 our 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
Work out,
I'll take it in dosages of anywhere. From 500 mg to 1000. Mg people vary
tremendously in their sensitivity
to supplementing l-tyrosine. I know people that can take 2 G. I know people that can barely take 100 mg. I know people that the best dose for them is 0 mg. 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 2 hours. And then there's kind of a tapering off, some people experience
a little bit of an
emotional or end 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 uses more fast-acting but more potent, which is phenol a flaming. This relates to the so-called PE a molecule ppea and phenylethylamine increases dopamine.
And some metabolites related to dopamine in ways that really increase energy and feelings of well-being
and motivation. And again, it's fast acting. So my particular protocol, the one I use is
I'll take phenylethylamine
at dosages of about 300 to 600 mg
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 finally claiming 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 their 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
And we know based on
hundreds, if not thousands of studies that things like winning at some sort of competition or succeeding in reaching a goal, can certainly increase. Dopamine, we talk a lot about this, in the episode on dopamine, motivation and
drive, but leaving that aside, there are certain behavioral, protocols, that are unrelated to
your overall goals and motivations that can increase dopamine in a
very sustained way. And without question the most potent behavioral tool for doing
That is going to be
deliberate, cold, exposure,
deliberate, cold, exposure, has been
talked about a
lot here and elsewhere, in terms of its ability to do things, like reduce inflammation
as a way to test and improve
resilience, because uncomfortable,
cold provided its applied safely, as a great way to learn to be more resilient because you're essentially staying or forcing yourself to stay in a circumstance where your system is flooded with adrenaline.
But
One lesser-known
aspect of deliberate cold exposure
is one that's been demonstrated quite convincingly in. Humans comes from a study published in the year 2000. I'll link to this
study, I love this study. By the way, covered it many times on this podcast because I love it so much and I think it's truly important
and that's the study from ceramic at all, 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 put
People in the cold water and I should mention the water that they use in the study wasn't that cold, they had a bunch of different conditions but they had people that got into for instance, 60,
°F water for up to two hours at them sitting there. And I'm 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, °F water to get these kind 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 publish just this last
year that getting into much colder water of say 50 degrees or 55 degrees or even 45 degrees
Fahrenheit
can potently increase dopamine and epinephrine as well. And that you don't need to expose yourself
to that cold water for nearly as long. So
perhaps,
Even as short as one minute or even 30 seconds exposure, to really cold water can lead to these potent.
Long-lasting increases in dopamine,
many people will ask which protocols to follow for instance. Will a
cold shower suffice. Very likely. Yes. If your shower gets cold enough, do you need ice floating in the bath? No, it's all about the temperature. Not whether or not. There's ice present or not. How long
to stay in there. There are a lot of details that we don't have time to go into this episode. Please see the episode
on the use of deliberate cold for health.
And performance. You'll find that huberman lab.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 Coldwater immersion if you
can't, you use cold
shower. But you want to use a temperature that is safe.
Meaning, you're not gonna 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 it.
Opted, 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
Hebrew and Lab podcast was dr. Anna Lemke, our director of the Dual diagnosis addiction clinic. At Stanford, she is an amazing book called dopamine Nation, all about dopamine and both its uses healthy and its perils in things like addiction.
Describes a patient of hers that use deliberate cold exposure to try and maintain dopamine levels
while coming off of drugs that
were increasing dopamine. So potently that they were
putting him down the path of addiction.
So the use of cold water for increasing dopamine is a real tool. It's
I would say a power tool. In fact,
it's the kind of thing that if you want to increase dopamine for sake of motivation, it might be your first go to provided. You're also doing the things to maintain dopamine,
Baseline like sunlight exposure.
GE 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's available for it to be released by any number of the tools I provided thus far,
and those are
sufficient number of B
vitamins. So, it turns out that B vitamins in particular B6,
Or vitamin B6, can potently reduce
prolactin levels and again, prolactin and dopamine tend to work in kind of push-pull fashion, that said
you should be cautious about taking excessive levels of B6. It
is a vitamin that if you take too much, you're 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 peripheral. 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,
Etc 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.
Sure, 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 Etc is to avoid bright
light exposure to your eyes, not just blue light, but all colors
of light in Phase 3, that is 17 to
24 hours after waking up because that's really, when you should be asleep or trying to get a sleep. If you're having trouble sleeping
work from Samurai guitars lab, the director of the
chronobiology unit, the National Institutes of mental health. Again in previous huberman, laptop.
Podcast
guest, tell us that bright light exposure in
Phase 3 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 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,
that'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.
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 at
focus. And of course, keep in mind those things that can suppress do
Oppa mean 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 returned 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 that 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. 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.
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.
Has that you're after. So next, I'd like to talk about
epinephrine also called adrenaline,
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 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 in
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 were kind of hood, I'd
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 amphetamines or cocaine or
any
Amulet their pupils tend to be
huge. Their eyes tend to be wide open. They don't blink very often
and the opposite is true when people take sedatives.
So it all starts to make sense. When you think about the basic actions of these things
for many people, increasing adrenaline, or epinephrine. Might seem like a
crazy idea. Most people probably associate this molecule with stress and then it 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
A 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
really want to bounce out of bed. I try and push
myself to do that. I'm
always impressed by these choco willing types that are up at 4:30 or up at five and already into action. I tend to be kind of
thinking about thinking about
maybe being in action early in the day but I try and push myself to get into action which itself
can increase epinephrine. I should mention that any physical activity, any physical activity walking,
running weight, lifting swimming even talking for that matter. Is going to increase levels of epinephrine. Locus coeruleus is a brain structure. That is tightly coupled with behaviors in a 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.
Post awaking, 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 of 100 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 we'll 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 exercised, 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 two more 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 excel in a very deep and repetitive way. If you were to do
that right now, does it matter. If you do it through your nose or mouth,
although, ideally you would do the inhale through your nose and 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.
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 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 and 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, Etc. That's really the domain of
And should really be worked out with your cardiologist with a physician etcetera.
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
Later, 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 we're, 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
In 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 in our visual system. In 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 Masala, switches in the forebrain and extends connections out
to many different brain areas.
He has 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 or nose, Etc. What
do I mean by Fidelity? Well, we are constantly being bombarded with
sensory information through all of our various
Is and acetylcholine release from this area. In the back of the brain, has the ability to increase the extent to which say a 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, turns out there been a lot of studies including
many quality, peer reviewed studies
carried out in humans. Looking at what happens when you increase
Reese, 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
Low plasticity, the circuits literally change. So this
is great. The work of Michael silver at Berkeley. The work of Mike, Mirza Nick at UCSF.
The work of Michael kill guard down in
Texas, all of those laboratory. See this
again, and again and again,
increase acetylcholine before, and during learning. And there's a much higher probability that the
learning will quote, unquote, sink in that, the information will be retained because those neural circuits change.
Now ways to increase
acetylcholine in
a potent. Way include again nutrition. And
Implementation.
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
and own.
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 post-trauma, 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 calling 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 cooling, to synthesize enough Baseline acetyl, choline
in the realm of supplementation, there are some excellent
tools.
For increasing, acetylcholine in the acute short term
meaning over the course of about 30
minutes out to about two hours or maybe even four hours and the
number of different molecules that can do
that that are available without a prescription. At least in the u.s. is pretty vast.
The most common of those
molecules is actually nicotine nicotine addict.
Acetylcholine receptors are abundant
throughout the body and brain. They're in various brain circuits, they are on
muscle and yes smoking nicotine.
Neither 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 choose
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 information.
Find 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 insisted, 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 a see.
So Colleen 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 mg of
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 mg of
alpha GPC three times a day every day
which closely mimic. 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
doubt that there have been a few studies, a
few, not many, but
this 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 mg of alpha GPC, most certainly does increase my ability
to focus. I've noticed that I tend to take it alongside caffeine and phenol Ethel aiming. So I take that in combination either.
For 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 is 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 have been taking it for up to a day.
Kate. 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 Alison. 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 Allison
alongside or even just same day as Alpha. GPC can really clamp those TM.
AO 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 acetyl. Choline 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 in a
Killer 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 it 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 microdialysis 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 Bates 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
Choline,
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 is a need certainly, a clinical need
then, prescription drugs Etc, 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 serotonin levels, go too high. That is if the dosage is of those treatments that go too high
people will, for instance feel
reduced, appetite reduced libido, increased lethargy Etc.
Ha and
there's a so-called serotonergic syndrome all of that can and should be
considered with a well trained physician. So because their 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
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 is 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 out of another dog soon, because, unfortunately Costello passed away, but there is something really comforting in 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 Etc.
So things like holding hands, believe you're not hugs cuddling. Etc. 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 often times 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 me, 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. This is 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 somewhat counterintuitive is that observing others giving and receiving gratitude is immensely powerful for a
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. So called tryptophan effect where people get very sleepy after eating white meat turkey, and it is
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 u.s. 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
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
well-being. 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 they're 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 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 a hundred percent, 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, can 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,
Supplements that can increase tryptophan and can do so quite potently,
one of the ones that has received increasing attention and as of lately, is cissus quadrangle Eros. Complicated name. When taken in dosages of about 300 to 600, mg can pretty dramatically increase serotonin levels. In fact, anywhere, from 30 percent to 39 percent
increases in circulating serotonin, that's a big increase and I can provide a link
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 sisters, quadrangle Eris 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 a lot of opinions about this on
the internet. But again, not a lot of quality peer review data. Nonetheless. This is
quadrangle Eris has been shown to put Lee 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 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 huberman. Lab.com, this is
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 increased circulating serotonin. But again, people vary in their sensitivity, to these sorts of things, some people might find for instance, that
Mg
of 5-HTP is just far too much, it blunts their appetite might even reduced 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, myo-inositol
myo-inositol can have the effect of increasing serotonin and other
Goals. But primarily at least, in terms of the neuromodulators discussed today, serotonin, I've been
taking 900 milligrams of myo-inositol 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 my own and also tall is pretty remarkable. In fact, I've used it alone and in combination with the Magnesium, three and eight apigenin theanine sleep kit that I've talked about in that's included in that again, zero cost kit.
It that's available as a PDF, on
our website. So
myo-inositol 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 myo-inositol 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 myo-inositol
for sake of increasing serotonin.
If you look at the human studies on my own
acetal, 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.
Lehigh things like 5, G, 8 g, 18 grams of myo-inositol 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 just comfort. And yet I also wonder how people tolerate it because it has somewhat of a sedative effect in its kind of anti-anxiety effect. And I can't even imagine given my experience with 900 mg. What one would experience taking multiple or many more grams per day? So I certainly am not in
Urging that. And
the only reason I mentioned myo-inositol is that it
has a known effect of increasing serotonin at least in my experience, it does not lead to this falling deeply sleeping waking back up, actually to the contrary. If I wake up in the middle of the night to use the bathroom where I wake up with the middle of night, for whatever other reason I find it far, easier to fall back asleep. If I've taken 900 milligrams, inositol prior to sleep. So for me it's proving to be a quite useful compound. I'm not aware of having any
Energy 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 is given, you should always talk to your physician. Any time 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, cissus quadrangle Eris things like 5-HTP may have their uses right there very potent at increasing serotonin but they do seem to
have the need to cycle them and they are new on some people respond well to them.
Other 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 may be reducing anxiety. Which certainly experience if I wake up in the middle and I don't like waking up in the middle the night. But on my own,
Satellizer 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 or unclear. But nonetheless I thought I'd pass 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
I'd 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 and hopes that that tryptophan will convert to serotonin and make you sleepy
etcetera. 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
Inverted 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 supplements
in tation. 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 yet? An episode on dopamine, you had an episode on anxiety, you had an episode on sleep and it,
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 well-being, you are dealing with a small handful of especially potent
molecules and
Knowledge, that there are
many neuromodulators. There are indeed many neurotransmitters
glutamine glycine gab
etcetera, but today we focused on the main for 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 to anyone tool is the most
useful, or that anyone,
Eagle 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 20, 22. 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 in 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 to fold 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 n
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
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 our review 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
Aced
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 if
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