The Tim Ferriss Show - #521: Dr. Andrew Huberman — A Neurobiologist on Optimizing Sleep, Enhancing Performance, Reducing Anxiety, Increasing Testosterone, and Using the Body to Control the Mind
Episode Date: July 7, 2021Brought to you by Athletic Greens all-in-one nutritional supplement, Theragun percussive muscle therapy devices, and Helix Sleep premium mattresses. More on... all three below.Andrew Huberman, PhD (@hubermanlab), is a neuroscientist and tenured professor in the Department of Neurobiology at Stanford University’s School of Medicine. He has made numerous important contributions to the fields of brain development, brain function, and neural plasticity. Andrew is a McKnight Foundation and Pew Foundation fellow and recipient of the 2017 Cogan Award for his discoveries in the study of vision. Work from the Huberman Laboratory at Stanford Medicine has been consistently published in top journals including Nature, Science, and Cell.Andrew is host of the Huberman Lab podcast, which he launched in January of this year. The show aims to help viewers and listeners improve their health with science and science-based tools. New episodes air every Monday on YouTube and all podcast platforms. Please enjoy!This episode is brought to you by Helix Sleep! Helix was selected as the #1 overall mattress of 2020 by GQ magazine, Wired, Apartment Therapy, and many others. With Helix, there’s a specific mattress to meet each and every body’s unique comfort needs. Just take their quiz—only two minutes to complete—that matches your body type and sleep preferences to the perfect mattress for you. They have a 10-year warranty, and you get to try it out for a hundred nights, risk free. They’ll even pick it up from you if you don’t love it. And now, to my dear listeners, Helix is offering up to 200 dollars off all mattress orders plus two free pillows at HelixSleep.com/Tim.*This episode is also brought to you by Theragun! Theragun is my go-to solution for recovery and restoration. It’s a famous, handheld percussive therapy device that releases your deepest muscle tension. I own two Theraguns, and my girlfriend and I use them every day after workouts and before bed. The all-new Gen 4 Theragun is easy to use and has a proprietary brushless motor that’s surprisingly quiet—about as quiet as an electric toothbrush.Go to Theragun.com/Tim right now and get your Gen 4 Theragun today, starting at only $199.*This episode is also brought to you by Athletic Greens. I get asked all the time, “If you could only use one supplement, what would it be?” My answer is usually Athletic Greens, my all-in-one nutritional insurance. I recommended it in The 4-Hour Body in 2010 and did not get paid to do so. I do my best with nutrient-dense meals, of course, but AG further covers my bases with vitamins, minerals, and whole-food-sourced micronutrients that support gut health and the immune system. Right now, Athletic Greens is offering you their Vitamin D Liquid Formula free with your first subscription purchase—a vital nutrient for a strong immune system and strong bones. Visit AthleticGreens.com/Tim to claim this special offer today and receive the free Vitamin D Liquid Formula (and five free travel packs) with your first subscription purchase! That’s up to a one-year supply of Vitamin D as added value when you try their delicious and comprehensive all-in-one daily greens product.*If you enjoy the podcast, would you please consider leaving a short review on Apple Podcasts/iTunes? It takes less than 60 seconds, and it really makes a difference in helping to convince hard-to-get guests. I also love reading the reviews!For show notes and past guests, please visit tim.blog/podcast.Sign up for Tim’s email newsletter (“5-Bullet Friday”) at tim.blog/friday.For transcripts of episodes, go to tim.blog/transcripts.Discover Tim’s books: tim.blog/books.Follow Tim:Twitter: twitter.com/tferriss Instagram: instagram.com/timferrissFacebook: facebook.com/timferriss YouTube: youtube.com/timferrissPast guests on The Tim Ferriss Show include Jerry Seinfeld, Hugh Jackman, Dr. Jane Goodall, LeBron James, Kevin Hart, Doris Kearns Goodwin, Jamie Foxx, Matthew McConaughey, Esther Perel, Elizabeth Gilbert, Terry Crews, Sia, Yuval Noah Harari, Malcolm Gladwell, Madeleine Albright, Cheryl Strayed, Jim Collins, Mary Karr, Maria Popova, Sam Harris, Michael Phelps, Bob Iger, Edward Norton, Arnold Schwarzenegger, Neil Strauss, Ken Burns, Maria Sharapova, Marc Andreessen, Neil Gaiman, Neil de Grasse Tyson, Jocko Willink, Daniel Ek, Kelly Slater, Dr. Peter Attia, Seth Godin, Howard Marks, Dr. Brené Brown, Eric Schmidt, Michael Lewis, Joe Gebbia, Michael Pollan, Dr. Jordan Peterson, Vince Vaughn, Brian Koppelman, Ramit Sethi, Dax Shepard, Tony Robbins, Jim Dethmer, Dan Harris, Ray Dalio, Naval Ravikant, Vitalik Buterin, Elizabeth Lesser, Amanda Palmer, Katie Haun, Sir Richard Branson, Chuck Palahniuk, Arianna Huffington, Reid Hoffman, Bill Burr, Whitney Cummings, Rick Rubin, Dr. Vivek Murthy, Darren Aronofsky, and many more.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.
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Optimal minimum.
At this altitude, I can run flat out for a half mile before my hands start shaking.
Can I ask you a personal question?
Now would have seen an appropriate time.
What if I did the opposite?
I'm a cybernetic organism living tissue over metal endoskeleton.
The Tim Ferriss Show.
Hello, boys and girls, ladies and germs. This is Tim Ferriss. Welcome to another episode of The Tim Ferriss Show, where it is my job to interview world-class performers from all
different disciplines to tease out the habits, routines, influences, life lessons, and so on
that you can apply to your own lives. My guest today is Andrew Huberman. That's H-U-B-E-R-M-A-N
PhD. You can find him on Twitter and Instagram at Huberman Lab. Andrew is a neuroscientist and
tenured professor in the Department of Neurobiology at Stanford University School of Medicine.
He has made numerous important contributions to the fields of brain development, brain function,
and neuroplasticity. Andrew is a McKnight Foundation and Pew Foundation Fellow and a recipient of the 2017 Kogan, that's C-O-G-A-N,
award for his discoveries in the study of vision. Work from the Huberman Laboratory at Stanford
Medicine has been consistently published in top journals, including Nature, Science, and Cell.
Andrew is the host of the Huberman Lab podcast, which he launched in January of this
year. The show aims to help viewers and listeners improve their health with science and science-based
tools. New episodes air every Monday on YouTube and all podcast platforms. As mentioned, you can
find him on Instagram and Twitter at Huberman Lab. You can find him on the web at hubermanlab.com.
Andrew, many people have been trying to matchmake for five or six years,
and finally, here we are. Welcome to the show. Oh, thanks so much for having me here. Yes,
we've crossed paths near misses for a long time, and it's great to finally sit down and chat.
I thought I would start right in your wheelhouse and use a headline to introduce the subject of
vision. Scientific American interviewed you not long ago,
and they titled the piece, quote, Vision and Breathing May Be the Secrets to Surviving 2020,
end quote. So breathing, I think for a lot of folks might seem self-evident. Stop that. You
have a lot of problems on your hands. Or if you do it incorrectly, we can certainly dive into that
later on. Vision, I think, will jump out as perhaps odd to a lot of folks. Why vision? Why is vision perhaps a secret or a key to surviving 2020 or any year for that matter? is perhaps the strongest lever by which we can shift our state of mind and body.
And that might at first come as a surprise because we think of vision as this thing that
we have to see colors and motion and recognize faces, et cetera.
But the two little goodies in the front of our skull, our eyes, are actually part of
our central nervous system.
So a lot of people don't realize this,
but your neural retina,
the little light sensing piece of the eyes
in the back of the eye,
kind of lines it like a pie crust,
are actually two pieces of your brain
that were deliberately squeezed out
during early development.
So they're the only two pieces of your brain
that are outside the cranial vault, as we say.
And those little pieces of brain have an enormous impact on the state of the rest of your brain. So it's fair to say that what you see and how you view the world literally has an
incredible impact on your state of mind, respiration, breathing also on your state of mind and body but the reason is the following our
visual system is not just for seeing objects shapes and colors etc our eyes have two functions
so much in the same way that our ears are responsible for hearing but also there's a
balance mechanism in there our eyes are responsible for detecting shapes and colors, et cetera, but also for telling
the rest of the brain whether or not to be more alert or more relaxed.
And the most fundamental way that our eyes do that is communicating time of day, the
presence or absence of sunlight to our central circadian clock.
And then the central circadian clock, which is really just an aggregation of neurons,
communicates to the rest of the brain and body whether or not, for instance, metabolism should be higher, metabolism should be low,
whether or not we should feel like moving or feel like lying down and not moving at
all.
But there are a number of ways in which the visual system works on fast time scales to
adjust our inner state.
And one of the most simple ways that it does that is one that normally happens when we're
stressed or relaxed,
but we don't recognize it. So for instance, if we are very relaxed, our pupils change or the shape
of our lens changes such that we actually have dilated vision. We see the entire environment
we're in, so-called panoramic vision. When we are stressed or we are excited about something,
the pupils dilate, the shape of
our lens changes, literally the optics of our eye changes, and the information about
the outside world that's delivered to the rest of our brain and body changes.
The aperture of our experience, our entire experience shrinks.
We get so-called soda straw view of the world.
We're looking through soda straws, essentially, when we are alert or stressed. And we've experienced this, but we don't normally notice it happening.
So much like breathing, our experience of life, whether or not we're alert or stressed,
excited or calm, changes our patterns of breathing. We're all accustomed to that.
You know, our breathing speeding up or holding our breath in anticipation. But as well, our inner state drives changes in our visual system, the aperture of whether
or not we see the big picture or we have a very contracted view of the world.
But both those things, breathing and vision also run in reverse, meaning if we change
our pattern of breathing, we change our inner state.
If our state changes, our breathing changes.
So it's reciprocal.
It's bidirectional.
Likewise with vision, when we are excited or stressed, the aperture of our visual window
shrinks.
We get that soda straw view of the world.
When we are relaxed, the aperture of our vision expands.
But as well, it runs in both directions.
If we expand our view of the world, literally force our visual field, or just
it's very easy, actually, you can do it no matter where you are right now. If you just try and
expand your visual field, not by looking around or moving your head or eyes, but by trying to see
yourself in the environment that you're in. So you literally dilate your views. You could see the
ceiling and the floor and the walls if you're inside, or if you're outdoors, seeing as big an
aperture of your visual field or your visual environment as possible.
So you're directing your attention to, even though you might remain looking straight ahead,
you're just directing your attention to as wide a peripheral view, horizontally and vertically
as possible.
Is that what you mean?
That's right.
Exactly.
So essentially, if you keep your head and eyes mostly stationary, you don't have to be rigid about rock steady. But if you look forward and you expand your field of view, so you kind of relax your eyes so that you can see as much of your environment around you as possible to the pointal and believe it or not, the stress mechanisms that
drive your internal state towards stress. This is why when you go to a vista or you view a horizon,
it's very relaxing because you naturally go into panoramic vision. When you are indoors,
you're looking at your phone, you're looking at a computer or a camera or something of that sort,
or you're talking to somebody or an intense conversation, you may not notice it, but your entire visual field shrinks to a much smaller aperture. And that drives an increase
in alertness in internal state. And we sometimes call that stress if it's a negative experience.
If it's a positive experience, we might call that love or obsession or fascination. But
the important thing to realize is that both vision and breathing have a profound
and very rapid effect on our internal state of mind and body. And it runs in both directions.
Our internal state that could be triggered by a text message or hearing something that somebody
says drives changes in our breathing and our vision, but our breathing and our vision can
also drive changes in our internal state. And so that article in scientific American was a discussion about how we can
leverage the visual system and the respiration,
the breathing system in order to take control over our internal state,
because it's not just that 2020 was stressful.
It's that our internal state determines everything.
It doesn't just determine if we feel like we're having a hard time falling
asleep or we're having a hard time focusing, for instance. It also determines how we batch time,
how we analyze where we are in the world in terms of our lifespan. A good example of this would be
when we are very stressed, we find sliced time. This is why when people are in a car accident or
something, they might report that things were in slow motion. They're actually, your frame rate increases.
Whereas when you're very relaxed, your frame rate slows down.
And when we are relaxed, we get so-called perspective.
We are able to say, well, this too shall pass, or I can place this stressful event in a context.
So one thing that's just fundamental to how our nervous system works
is that we are constantly placing our experience, both our immediate and past experience, as well
as our anticipation of the future into some sort of larger context. And our visual system, literally
how we are viewing the world at that moment dictates how we create perspective in terms of
states of mind. Sounds a little bit abstract,
but it's actually, it boils right down to optics of the eye
and very concrete things like how you move your eyes
and how you view the world.
This is super fascinating to me
because I've thought a lot about breathing
and how, on one hand,
breathing is a function of the autonomous nervous systems. When you're asleep, you don't
have to consciously inhale and exhale, but simultaneously it's this almost API into your
autonomic nervous system because while you're awake, you can control and direct and modify
your breathing for that directionality. But I've never thought about it from the visual perspective.
And just a quick bit of trivia that is out of left field, but nonetheless came to me
that people might find interesting, is that the dilation, this hyperdilation of pupils
is, I don't know how much it is associated with arousal or sexual arousal.
But for those who have ever heard the word belladonna, it is a plant.
The reason it's called belladonna, beautiful woman in Italian, is that it used to be
turned into a tincture. And it is a psychotropic, and it is also very dangerous. I don't recommend
people consume it. But many, many years ago, hundreds of years ago, women in certain parts
of Europe would create a tincture and put it into their eyes to hyper dilate their pupils because it was thought to be very, very attractive. Hence,
beautiful woman. Could you speak to how one can think about using their visual apparatus or
stimulating or not stimulating their eyes, their visual system for, say, sleep?
If one wants to optimize for sleep, what are some considerations? And it could be that,
it could be other inputs, but I'd just be curious to know how this fits into sleep for you personally.
Our light viewing behavior has perhaps the strongest effect on our levels of alertness
and our capacity to fall asleep and get a good night's sleep. And this is because at the
fundamental layer of our biology, every cell in our body needs information about time of day.
It's no coincidence that we have a collection of neurons over the roof of our mouth the so-called
suprachiasmatic nucleus that's our central circadian clock it informs every cell in our
body about time of day but it is deep in our brain it has no access to light so there are
a collection of neurons in the eye the so-called melanopsin ganglion cells or sometimes called
intrinsically sensitive photosensitive ganglion cells these or sometimes called intrinsically sensitive, photosensitive ganglion
cells. These are just neurons in the back of your eye, remembering, of course, that the eye is
actually part of the brain that's outside the skull. And those neurons communicate to the central
clock when it's daytime and when it's night. So the simple behavior that I do believe everybody
should adopt, including many blind people. We've talked
about why that is, is to view ideally sunlight for two to 10 minutes every morning upon waking.
So when you get up in the morning, you really want to get bright light into your eyes because
it does two things. First of all, it triggers the timed release of cortisol, a healthy level of cortisol into your system, which acts as a wake up signal and will promote wakefulness and the ability to focus throughout the day.
It also starts a timer for the onset of melatonin, this sleepiness hormone or the hormone of darkness, as they say.
Melatonin is inhibited by light. So by viewing light first
thing in the day, you set in motion these two timers, one for wakefulness that starts immediately
and one for sleepiness that starts later. The key thing here is that people are hearing a lot
nowadays about avoiding blue light. Blue light is so terrible. Well, it turns out that blue light
is exactly the wavelength of light that triggers activation of these cells. And that's exactly what you want early in the day.
So people generally will say, well, maybe I should just look at my computer or my phone first thing in the day.
Well, it turns out that these cells are very hard to activate early in the day and very easy to activate at night.
So it's kind of like the biology is encouraging us, if you will, to take on the right behaviors, which are to get outside. Even if there's cloud cover,
there's a lot more light energy, a lot more photons coming through cloud cover than you're
going to get off your phone or a computer. And early in the day, two to 10 minutes outside
without sunglasses is going to be really beneficial for a huge range of biological
functions and brain state.
I have made a practice, I'm in the middle of nowhere in the country right now, of getting up
and not necessarily doing a full workout, but just jumping rope for literally two to five minutes,
two to 10 minutes outside facing the sun, where the sun is rising. And there's certainly an effect,
I mean, I am moving. So
there's an effect on cortisol. And as you noted, it's like cortisol gets this ridiculously bad
rap across the board. And it's like, guys, if you don't have cortisol, you're dead.
If you like having, storing glycogen and breaking it down into glucose and so on,
it's important to have some cortisol. There's a tremendous, for me, mood-elevating effect of this exposure.
And I'm just, I really have never familiarized myself
with the mechanism by which that would be the case.
And certainly if it's placebo,
I'm happy to just take placebo.
But do you have any explanation
for why that exposure can have such a mood-elevating effect?
Yeah, it's definitely not placebo.
That morning light exposure is going to also trigger
the activation of dopamine release,
dopamine being this essentially feel-good neuromodulator.
The best way to conceptualize dopamine is that,
yes, it's part of the reward system,
but it's really the molecule of motivation
and positive anticipation.
That's really what it's about.
And I should mention that the cortisol
is going to be released in a pulse once every 24 hours, no matter what. That's coming, as we call
it, it's an intrinsic rhythm, but you can time it by viewing light and or by getting exercise early
in the day. There are actually data to just kind of emphasize what happens when you don't do this.
There are really nice data from my colleague, David Spiegel's lab. He actually co-published this with the great Bob Sapolsky
a few years ago. David's our associate chair of psychiatry at Stanford. And they showed that if
that cortisol pulse shows up later in the day, and especially if it's around 8 or 9 p.m.,
then it's associated with depression. By shifting that cortisol pulse earlier in the day,
you ameliorate some of the symptoms of depression.
And because of the dopamine release,
you get this overall mood enhancement.
There are four things that really time our circadian biology
and these mood mechanisms properly and align us for sleep.
And the most powerful timekeeper, as they say,
zeitgeber, because Germans discovered this mechanism initially. So the most powerful timekeeper, zeitgeber,
time giver, there it is. I knew you'd do it better than I would, is light. When you view light,
light is the most powerful stimulus for your biology and central circadian clock.
Then it's exercise. So it's your protocol of jumping rope, facing the sun. You're layering
on timekeepers. You're giving more signals to the central clock and the rest of your body about
when to be active. And you're also indirectly signaling when you will want to be asleep later.
Then it's feeding. I know a lot of people fast through the early part of the day now.
That's very fashionable. And I do that as well. But were you to eat early in the day, that can also help. And then the other one is social cues.
So interacting with people early in the day or with your dog early in the day, I have a dog,
I live alone with my dog. So that's how I interact with the world socially. But those things are
going to create wake up signals and your body will start to anticipate them and your brain will start to anticipate them
such that if you miss it for a day, you're still going to wake up and feel that alertness
signal early in the day.
So this is not something that you have to do every day, but ideally you do it every
day because it's like setting a clock or a watch properly.
And I should mention that for people that live in areas with very dense cloud cover,
you can use light boxes and things of that sort, but irrespective of that in the morning and during
the day, and anytime you want to be alert, you want to flip on as many overhead lights as possible.
This is because these cells in the eye that trigger activation and alertness of the rest
of the brain and nervous system reside in the lower portion of the eye. They view the upper
visual field. Now, the inverse
of all this is also important. As you approach the evening or nighttime and you want to go to sleep,
that is a time to start avoiding bright lights of any color, not just blue light. And if possible,
to place whatever lights are present in your environment lower in your visual field. So this
would be desk lamps. Most people don't have floor lighting, dim the lights. If you want to wear blue blockers or do
something of that sort, that's fine. But I think people have taken the blue blocker thing a little
too far by wearing them all day. That's actually going to disrupt your circadian clocks. So in the
evening, you really want to avoid bright light of any kind. And again, it's an averaging. If you do
this every once in a while,
you go to the bathroom in the middle of the night, or you have an emergency and things
are really bright for one night, it's not going to screw you up. However, there was a paper
published in the journal Cell a few years ago by my good friend and colleague at the National
Institutes of Mental Health. His name is Samer Hattar. He's the head of the chronobiology unit
at the National Institutes of Mental Health. And what Samer's lab showed is that
bright light exposure of any wavelength between the hours of about 11 p.m. and 4 a.m. cause a
serious disruption in the dopamine system such that in subsequent days, you have a disruption
in a lowering of mood, difficulty in learning. There's a cascade of things that happen.
In other words, we get punished for light viewing at the wrong times of the circadian cycle,
and we get rewarded for light viewing at the correct times of the circadian cycle.
Let's talk about the latter portion of the day. Before I get to that, though, just for my understanding, if one, say, wants to target going to bed
or more accurately feeling sleepy enough to go to bed easily with rapid onset at say 10 p.m.,
is there a preferred time to get that exposure early in the day in the sense that if I'm doing
my 10 minutes of jumping rope facing the sun,
is it best to have it a certain distance temporarily from when I want to go to sleep?
Yes, it's about 14 to 16 hours prior to when you want to sleep is the ideal time to get that morning light exposure. And if we want to get a little bit technical about this, we can, and I'll do my
best to make it clear because there's also a way that you can use this mechanism to shift your
circadian clock to avoid jet lag and shift work. I'll just ask you, so what's your typical wake
up time? Not getting up in the middle of the night and using the restroom necessarily,
and then going back to sleep. But when do you finally get up and get out of bed? What time is that typically? I would say when I'm living my best life and not being Marty from Back to
the Future, it's usually seven o'clock, let's just say. Okay. So if seven o'clock is your average
wake-up time, then we can be pretty sure that two hours prior to your natural wake-up time
is what's called your
temperature minimum. It's when your body temperature was lowest. That temperature minimum,
and I should be clear, we don't need to know your actual temperature. No one needs to know
their actual temperature minimum, but you can count on the fact that two hours before waking up,
your body temperature is close to or at its lowest point.
And to be clear, this would be if you are waking without an alarm clock, right?
That would be if you're following natural rhythms.
Correct.
So if you view light, I should mention that you have to do this light viewing behavior
with your eyes.
That might seem obvious, but some years ago, there was a paper published in the journal
Science, which is one of the three apex journals, Science, Nature, Cell.
And it stated that light presented to the back of the knee of humans could shift their circadian
clocks. And that paper was retracted by the same authors that published the study. There was a
technical flaw. Humans have no extraocular photoreception. So we need to tell the cells of the body
what time of day it is,
essentially where we are in time
by light viewing behavior with the eyes.
Blind people do this a little bit differently.
Some blind people actually still retain
these so-called melanopsin cells.
People without eyes at all,
maybe from a burn victim or something,
they are going to use social cues
and exercise and other things. But most everybody on the planet does this through light viewing behavior.
So when I say get light, what I mean is get light in your eyes, obviously never so bright that it's
going to damage your eyes. You'll know if a light's too bright because you'll want to close
your eyelids. That's a simple rule of thumb. But the key thing here is that if you view light, in particular bright light,
in the hour or two before that temperature minimum, so for you, Tim, that would be
between around 3 a.m. or 4 a.m., it's going to have the quality of delaying your circadian clock.
What it'll effectively do is make you want to stay awake later,
and it will make you want to sleep in later the following nights. However, if you view light
in the hour or so immediately after that so-called temperature minimum, so for you,
this would be 6 a.m. or 7 a.m., it's going to shift your clock in the other direction. You're
going to want to go to bed a little bit earlier and you're going to
want to wake up a little bit earlier the next night.
Now,
if you hear this,
you're probably thinking,
well,
my clock is always more or less in the same place.
How come it doesn't jump around?
I wake up,
I view light.
How come I'm not going to bed earlier and earlier every night and waking up
earlier and earlier?
The reason is there's a second time of day,
which is in the evening as the sun sets, where your circadian clock is also vulnerable again to these shifts. And typically,
because most of us are viewing light in the late afternoon, all of us are naturally having our
clock shifted so that we want to get up earlier and go to bed earlier the next night and morning.
But we're also delaying our clock a little bit in the afternoon.
Now we can make this all very simple. The simple thing to do is within 30 minutes of waking up,
get bright light exposure in your eyes and not from a phone or from a screen because it won't be sufficiently bright. Get it from sunlight. And if you can't get it from sunlight, you can use
one of these light pads. I don't use one of these expensive wake up clocks or something like that.
I bought an led drawing pad. It's like a trace table. It's like the artist's cheat mechanism.
It actually says on it, I forget the company, but it says 930 locks. You can find these very
inexpensively online and that's going to work great. I just set it at my desk in the morning.
If it's very overcast and I'll work. Now it is important to get outside because even though your windows or the windshield
of your car is optically clear, it filters out a lot of that blue light that's important for
setting your circadian clock. So two to 10 minutes of light viewing early in the day.
And then you can do yourself a great favor as well by going outside in the evening or late
afternoon as the sun is approaching this,
what we call low solar angle, because that will also send another signal to the brain
that it's evening.
So there's a morning stimulus and an evening stimulus.
This only takes a few minutes each day.
And what's key to understand is that the cells in the, of your body, they're going to have
all these rhythms of liver function and metabolic function. Your brain is going to have its rhythms of alertness
and anxiety and sleepiness providing multiple signals. So for you exercise in light in the
morning, and then in the afternoon, a little bit of light is going to tell your system in a
redundant way, but in a powerful way, these are the times to be awake. These are the times to be
asleep. And then if you like, we can talk about evening behavior,
but that temperature minimum is worth knowing
because if ever you are traveling, for instance, to Europe,
what you can do is in the two or three days before,
you can just set your alarm,
wake up around your temperature minimum,
maybe an hour before,
turn on some bright lights in your home.
So you get bright light exposure and
you will start to shift your clock forward. That nine hour jump can be accomplished in about two
days if you do this correctly. And the reverse is also true. You could shift your clock earlier if
you like. And when you land in Europe, if we want to get down into the weeds, when you land in Europe,
you have to be cognizant of what your clock is back home. Remember your temperature
minimum. It's much more important than where you are in your new environment. That temperature
minimum is an anchor point. Remember, light viewed in the hour or two before that temperature minimum
will make you want to go to sleep later and wake up later. Light viewed after that temperature
minimum will make you want to go to sleep earlier and wake up earlier. Let's talk about something that is a perennial topic, and that is sleep aids. Specifically,
I'd love to get your opinion on various supplements or prescription medications,
for that matter, that people might use. There's a huge list of things that people could use.
On the prescription side, certainly you've got the Ambien and the trazodones and so on. Then on the supplemental side, you've got melatonin,
very, very popular. You have California poppy. I mean, there's an infinitely long list of various
supplements. I would love to hear your thoughts on at least two of these. One is melatonin because of its popularity. And then
the second is actually phosphatidylserine, so PS for short, and using it to blunt cortisol
release after going to bed. And I would just be curious to know if you have any opinions on those or any others
that you would advise against or advocate for or use personally. Sure. So I'll say why I'm not a
fan of melatonin. When I was a graduate student, I worked on the melatonin system and the circadian
system. And one of the most powerful effects of melatonin is to suppress puberty. The melatonin system is closely linked up with GABA inhibitory neurons in the hypothalamus.
It effectively keeps puberty from happening.
So the melatonin rhythms of young children, pre-pubertal children, are not as phasic,
right?
They're pretty constant.
And that's one of the reasons they don't go into puberty. There are
many other reasons they don't go into puberty until certain triggers are set. But melatonin
has strong effects on the sex steroid hormones, the pathways related to estrogen and testosterone.
And I think it was the one experiment that I did where we took, we were working on these little,
they're called Siberian hamsters, these little hamsters who in long days, because they are seasonally breeding animals, in long
days, these Siberian hamsters have testicles. Well, that at least for Siberian hamsters are
pretty impressive size. If however, you inject those animals with melatonin or you put them
into short days. So you increase the amount of darkness and you decrease the amount of light.
Remembering, of course, that light inhibits melatonin.
Their testicles shrink to the size of a grain of rice.
So I don't know if this was my male ego or something, but I saw that experiment and I
thought, wow, this is powerful stuff, this melatonin stuff.
And it turns out in females of the same species, they leave estrus, they stop
cycling. They don't have menstrual cycles. They have estrus cycles. And there are powerful effects
of melatonin on the reproductive axis. Now, humans are not seasonal breeders and we have a more
robust sex steroid hormone axis than that. But especially for children, but also for adults,
it just seems to me that melatonin has a number of
other effects that are worth considering, enough effects that I tend to avoid it.
Now, I should also say that most of the concentrations of melatonin that are in
supplements are 10 to 1,000 times what the endogenous internal levels would naturally be.
So people taking melatonin are seeing dramatic effects, but you're taking super physiological
levels of melatonin.
We all kind of balk when we hear about people taking, you know, a thousand milligrams of
testosterone cypionate a week, which unfortunately certain people do.
But this is the equivalent of super dosing sleep hormones.
And these are hormones that have other issues and other roles,
I should say, in the body. So that's why I veer away from melatonin. Also, there are three things
that I personally have found to be much more beneficial that seem to have very good safety
margins. Of course, everyone needs to check with their physician, but those three things are magnesium threonate, T-H-R-E-O-N-A-T-E, or by glycinate, magnesium by glycinate. Magnesium threonate and magnesiumrate is a great laxative. It goes by another name too. You can imagine what it might be. That will remind
you that it's a great laxative. What it's not great at inducing sleep. Magnesium threonate or
magnesium biglycinate, so 200 to 400 milligrams about 30 minutes before sleep, is a powerful
sleep aid. People with heart issues might not want to take it or might want to check
with their doctor, but I take a cocktail of magnesium threonate and then two other things.
One is very commonly known, which is theanine, T-H-E-A-N-I-N-E, 200 to 400 milligrams of theanine
can create a kind of a hypnotic state, help you fall asleep. Basically falling asleep requires
turning off your thoughts. And the only people
that should really avoid theanine, I think are people who suffer from sleepwalking or night
terrors. It can create very vivid dreams. And then the third thing is apigenin, A-P-I-G-E-N-I-N,
which is a derivative of chamomile, but it acts as a chloride channel agonist. So it essentially
helps shut down the forebrain by hyperpolarizing neurons and all this kind of stuff for the
aficionados if they want to know. So that cocktail of 50 milligrams of apigenin,
300 to 400 milligrams of magnesium threonate or biglycinate, and 200 to 400 milligrams of theanine
for me has been the best way to consistently fall asleep quickly
and stay asleep most, if not the entire night, which for me is about seven, eight hours.
And of course, I'm not a physician.
I'm a scientist.
Everyone needs to figure out what's right for them.
But many, many people who I've recommended this to have told me that in combination with
the morning light viewing, that their sleep has been completely
transformed. They thought they were so-called insomniacs, but they actually were just having
a hard time turning off their thoughts and probably their cortisol was drifting too late in the day.
So to that cortisol point, this is fascinating. And I just find it endlessly interesting that
different forms of magnesium can be so target-specific with respect to different tissues in the body. So, so fascinating. sleep to help blunt cortisol release, but I do cycle. I use it as needed, really, if there's a
lot of rumination or I've had a particularly stressful day. But do you have any thoughts on
whether or not you would ever do that personally or if you'd be too concerned about
side effects or long-term side effects? I suppose that could be a larger issue if you're just never
cycling off. But do you have any thoughts on using different compounds to blunt cortisol release if you're
over-ruminating and want to sort of minimize that, in this case, stress response while
you're trying to sleep?
I have not tried PS.
I use ashwagandha from time to time if I'm in a particularly long bout of stress.
One of the things that I think
is relevant here is that we hear about stress as terrible, but of course, short-term stress
buffers the immune system. It actually activates the spleen to release killer cells and things of
that sort. We are more robust in fighting off infection in the short term from pulses and
cortisol. But I would say we can define long-term stress as if you are having sleep disruption
or you're feeling like you're in that wired and tired mode,
we don't really have a technical name for this,
for more than two or three days,
you're starting to enter the realm of long-term stress
and that's where buffering cortisol can really help
and that's where I start to take some ashwagandha
late in the day.
There's good evidence it can buffer cortisol. I do cycle it, so I'm not going to take it
every night or every day. I would probably stop after a week or so and then just go back to my
normal regimen, which doesn't include ashwagandha, but I always have some on hand. I have to say that
I certainly use and enjoy the benefits of supplements, many of them, in fact. But the practice that for me has really helped reduce stress and allowed me to fall asleep more easily and control my state of mind late in the evening is this practice that some people call yoga n a day, and it doesn't have to be done every day,
and lying down and doing a sort of body scan.
It involves some long exhale breathing,
which is very relaxing to the nervous system,
and really allowing the mind to enter
one of these pseudo sleep states.
We know from work in my laboratory
and work that I'm doing with David Spiegel's laboratory,
as well as work from other labs,
that that state of shallow nap or shallow sleep done in waking allows the brain to,
and the person to get better at turning off their thoughts and falling asleep in the evening.
So I use both behavioral tools and pharmacology, which of course is really what supplementation is.
I don't have any problem with buffering cortisol a little bit in the short term, so doing that for a week or two,
but I wouldn't suggest that people suppress their cortisol long-term unless there's a
real clinical need to do that. Long-term being longer than two weeks. Just a quick thanks to one of our sponsors and we'll be right back to the show.
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You mentioned long exhales in the context of the yoga nidra practice.
Is it fair to refer to that yoga nidra practice as also non-sleep deep rest or NSDR or those separate phenomena?
Yeah, so yoga nidra is one of several what we call NSDR, non-sleep deep rest protocols.
Admittedly, I coined the term NSDR because scientists like acronyms almost as much as
the military likes acronyms. And I did it deliberately not to rob the beautiful history
and community that is yoga nidra and the yoga communities of anything, but rather because
many people are averse to doing anything that has a name like Yoga Nidra. And yet it's such
a powerful tool. It's a zero cost tool that has enormous effects on not just accessing sleep and
calm, but enhancing rates of neuroplasticity, something that we could talk more about.
Also, David Spiegel, again, our associate chair of
psychiatry at Stanford and close collaborator and friend of mine, is a world expert in clinical
hypnosis. We are part of a, just in full disclosure, we both sit on the advisory board of a
company called Reveri, R-E-V-E-R-I.com. Reveri is a zero cost app on Android and Apple that has short hypnosis protocols, anywhere from 10 minutes to 15 minutes.
Hypnosis and yoga nidra both fall under the umbrella of NSDR, non-sleep deep rest. And
these are protocols that people can use to deliberately access states of deep rest for
sake of, again, falling asleep more easily, reducing stress, but also for enhancing rates
of learning of neuroplasticity.
And because these are zero cost tools,
and because they're grounded
in excellent peer-reviewed research,
I feel comfortable mentioning them.
And what you find is that if people who are not familiar
with meditation or mindfulness,
or maybe they're not from West LA or the Bay area.
If they hear yoga, Nidra, they think magic carpets and they think, and they hear hypnosis
and they think that somebody is going to control their brain.
NSDR is my attempt to create a more friendly language, which is because all of these things
are really just the same thing.
They really involve two things.
One self-directing a state of calm.
That's something that we never learn how to do unless we have a need to do it. We suffer some trauma, we have
chronic stress, we start taking a mindfulness class. Self-inducing a state of calm through
respiration and vision is the hallmark of yoga nidra and hypnosis, and frankly, of all meditative
practices. Our thoughts follow our vision and breathing. And I can explain why that is in a
moment. In addition, these NSDR type practices involve not just self-directing calm, but they
also involve directing our focus to something. We generally have a hard time falling asleep
because we think we have to turn off our thoughts completely like a switch. But the transition to
sleep involves allowing our thoughts to become fragmented. And then we become relaxed. And then the brain enters
the state where space and time are very fluid and not under our conscious control. And those are
things that we can teach ourselves. So yoga nidra scripts are found all over YouTube. There's some
great apps out there. The zero cost ones that I use are any of the stuff by Kamini, K-A-M-I-N-I,
Desai, D-E-S-A-I. I like her voice very much. Some people, like my sister, loves Liam Gillen's
voice, another zero cost yoga nidra tool, Liam Gillen, double L-G-I-L-L-E-N. You have to find
a voice that you like. The Reverie app is David's voice. He has a very
hypnotic voice. And there are scripts in there for smoking cessation, stress and anxiety, sleep,
et cetera. These I really want to emphasize in addition to being zero cost are very powerful
tools if done regularly. There are two papers that were published in the last two years from
Cell Reports and Cell Press Journal, excellent journal, showing that a 20-minute non-sleep deep rest protocol after a bout of intense focus or intense attempt to learn anything, skill learning or cognitive learning, accelerates plasticity by about 50%.
So you are learning faster, much faster, and retention of that information lasts much longer.
And that's because these are sleep-like states.
And we know that neuroplasticity, the brain's ability to change in response to experience,
is triggered by high focus, by deliberate periods of very high focus.
But the actual rewiring of neurons, the formation of new synapses and the reordering of the
circuitry that leads to that
skill or that cognitive ability becoming reflexive, that happens in states of deep rest.
And non-sleep deep rest, NSDR, whether it's hypnosis or yoga nidra or a shallow nap of
about 20, 30 minutes, those things will all accelerate learning.
Let's hop around just a little bit.
Yoga Nidra first on the NSDR study that you mentioned and the increase in plasticity,
which I'm assuming was measured by retention, recall, et cetera, but perhaps it wasn't.
If you could send afterwards a link to that study, I'll put it in the show notes for
listeners who might be interested.
We've touched on breathing in a
few different capacities. I have a term in front of me that seems kind of self-explanatory, but I
don't know what form it takes. Physiological size contrasted with other breathing methods
for stress reduction. Could you define what that is? Yeah. years ago when my laboratory got interested in studying
stress in humans we asked ourselves what are the patterns of breathing that allow for the most
rapid reduction in stress levels and more importantly what are the patterns of breathing
that can be done in real time so that people can adjust their stress while they're still engaging
in life, right?
Breathwork classes, running off to Esalen for a weekend is a magical experience, but life demands pressing on you.
That's typically when you feel stressed.
So it is still true that vacation, long meditation retreats and massages or a nice drink, if
you're of drinking age, still work, but they're slow and they take you offline.
The physiological sigh is a pattern of breathing
that was actually discovered by physiologists in the thirties. And that was essentially rediscovered
by professor Jack Feldman at UCLA, a world expert in the neurobiology of respiration.
And by my colleague, Mark Krasnow at Stanford, who studies lung function.
The physiological sigh is a pattern of breathing that we all engage in in deep sleep when levels of carbon dioxide in our bloodstream get too high
we or our dogs you can see your dog do this we'll do a double inhale followed by an extended exhale
children or or adults for that matter that are sobbing and lose their breath so to speak we'll
also do a double inhale, exhale.
That's the spontaneous execution
of what we call the physiological sigh.
The reason it works so well to relax us
is because it offloads a lot of carbon dioxide all at once.
And the way it works is the following.
Our lungs are not just two big bags of air.
We have all these little millions of sacks of air
that if we were to lay them out
flat, they would be as big as about a tennis court or so. The volume of air therefore,
and the volume of carbon dioxide that we can offload is tremendously high, except that we
get stressed as carbon dioxide builds up on our bloodstream and it's kind of a double whammy.
These little sacks deflate. Now, when we do a double inhale,
so I'll do this now twice through my nose, or you could do this, or you could do it through your mouth, but it works best through the nose. It's inhale. And then you sneak a little bit more
air in at the very end. When you do that, you reinflate those little sacks. And when you exhale,
then you discard all the carbon dioxide at once so the simple way to describe this protocol
is that unless you are underwater you do a double inhale followed by an extended exhale and you
offload the maximum amount of carbon dioxide and we found in our laboratory and other laboratories
have found that just one two or three of those physiological size brings your level of stress down very, very fast.
And it's a tool that you can use anytime.
I do hope that people will kind of watch other people
or dogs as they start to relax or go down to sleep.
You'll see this pattern of breathing,
but again, it can be consciously driven.
The other thing about breathing
and the reason why exhales are so vital
is the following. I know there's a lot of interest nowadays in heart rate variability. Well,
most people don't realize this, but your breathing is actually driving heart rate variability. So
when you inhale this dome shaped muscle beneath your lungs, your diaphragm actually moves down
because the lungs expand, it moves down. When you do that,
you create more space in the thoracic cavity and you actually, the heart gets a little bigger.
It actually expands. As a consequence, blood flows more slowly through that larger volume
and the brain quickly sends a signal down to the heart to speed the heart up. The short,
simple version of this is inhales speed the heart up. When you exhale,
the opposite is true. That dome-shaped muscle of the diaphragm moves up. The space in your
thoracic cavity gets a little bit smaller. The heart gets a little bit smaller. Blood moves more
quickly through that small volume, and the brain sends a signal to the heart to slow the heart
down. Physicians know this as respiratory sinus arrhythmia,
but this is the basis of what we call HRV, heart rate variability. And the simple way to remember
this is anytime you emphasize exhales, in other words, making them longer than your inhales,
you are slowing the heart rate down. You're calming your system. Anytime you emphasize
inhales, you make them more vigorous or longer than your exhales,
you're speeding up your heart.
I'd like to come back to hypnosis for a second.
I've never been hypnotized nor maybe I have self-hypnotized and just not realized that's what I was doing.
What characterizes hypnosis or how would we define that? And do the states induced by hypnosis have any
shared characteristics with some of the states induced by any psychedelics?
So hypnosis is a state of calm and high focus. So context is restricted. It's like looking at
something through a telephoto lens. You're eliminating the surround.
So it's a state of high focus, which normally, as we talked about earlier with the aperture,
the visual system would be associated with a high degree of excitement or stress.
But hypnosis is a unique state because you have a high degree of focus, but you're very
relaxed.
And just to remind people that neuroplasticity is triggered by
states of high focus followed by periods of relaxation later in deep sleep or in non-sleep
deep rest. In hypnosis, it brings both those states together at the same time. And this is
one of the reasons it's effective in accelerating neuroplasticity. I could probably do it right now
to see how hypnotizable you are.
There's actually a test, a clinical test called the Spiegel eye roll test. Spiegel's father was
a hypnotist and a psychiatrist. So these, I want to be clear, these are not stage hypnotists. These
are board certified MDs and PhDs who there's a lot of scientific research to support what we're
about to talk about. So typically when we get sleepy, when we're relaxed, our eyelids close and our eyes go down and the chin goes down. The induction to hypnosis involves doing the opposite,
looking up, which actually, believe it or not, creates a state of alertness, and then having
you close your eyes. So it creates a kind of conflict in the cranial nerves that innervate
the eye and eyelid muscles. Again, the eyes and your state of mind are so intricately wired back there in the brainstem. So if you could look up toward
the ceiling, Tim, with your eyes open, and then just while still maintaining upward gaze, if you
could just slowly close your eyelids. Oh boy, you're really hypnotizable. So what did you see that was deeply uncomfortable?
Yeah, I know. It's a little bit odd. So, so for those of you listening or watching,
you sort of look up towards what, you know, sometimes in yoga communities, they, or meditation
communities, they call the third eye center. You know, we don't actually have a third eye,
but if we did, it would probably be someone decided it would be between our two eyes and
our forehead. So by looking up, you're inducing alertness. And then you're creating this conflict
where I asked you to close your eyelids,
which is what you do when you're in a state of sleepiness.
And what Spiegel, both Spiegel Sr. and Spiegel Jr.
have figured out is that it's a very good predictor
of how hypnotizable people are.
You can look up the Spiegel eye roll test.
And what I was looking for is, let's say if somebody is not very hypnotizable people are. You can look up the Spiegel eye roll test. And what I was looking for is,
let's say if somebody is not very hypnotizable,
what'll happen is as they close their eyes,
they'll have a hard time closing them slowly.
They'll just kind of snap shut
and their eyes will roll forward.
In other words, I'll see their pupils again.
What happened when I saw you do this
is that your eyelids were closing very slowly
and I saw the whites of your eyes,
your eyes were starting to roll back into your head.
So you would have a score of probably about a four,
which is very hypnotizable.
I'm about a four.
Some people you'll just notice,
you say, look up and then slowly close your eyes
and their eyes will just kind of snap shut
and their eyes will roll forward right before it snaps shut.
So you can do this experiment of sorts
on people that you know,
and it predicts pretty well how quickly or easily you will go into
hypnosis. I should mention that no one will go into hypnosis if they don't want to. But if you're
interested in exploring hypnosis with the Reverie app or with a clinical hypnotist and your eyes
roll back the way that yours did, Tim, then you're home free. You're going to be long gone before.
Amazing. I could, maybe I'll start speaking in tongues too. It does have a good associated
look with it. How would you explain the utility of hypnosis? And then I do want to hear if there
are any sort of correlates to some of the known effects of psychedelics. And that's a wide spectrum of class. So we could choose a
given compound. But what are the clinical applications? Because in my hypnosis naive
mind, I think smoking cessation, isn't it good for quitting smoking? Isn't it good for
really just these anecdotal reports that I've read at one point or another, but what's the
clinical, what are some of the clinical applications or practical applications of hypnosis?
Yeah. So for smoking cessation, if people do the practice about a 60 to 80% success rate,
depending on the study you look at, these were all blinded controlled studies in terms of anxiety
relief. Those are tremendously strong effects. As many as 90% of
people are going to feel significant improvement in anxiety. For pain management, for chronic pain,
there's a high degree of success. So, you know, people will vary depending on how hypnotizable
they are and how regular they are about the practice. But anywhere from a 50 to 75% of people
will experience a significant reduction in chronic pain.
And if they are using pain meds, they tend to be able to take lower doses of pain medications in order to manage that pain.
So it's quite powerful.
Now for trauma and things of that sort, it needs to be done with a clinical, I would
hope, board-certified MD, clinical hypnotist.
And there, the success rates
are quite high as well. And if you want more research about this inside the Reverie app,
there's a long list of resources. You could also, I can send over a good review article
that David's written in. These are again, published in very fine quality peer review
journals of the new England journal, JAMA sort and things like that. Great. In terms of similarity to psychedelics, they are quite distinct, actually.
So hypnosis being a state of high degree of focus and relaxation is a bit similar to some
of the so-called psychedelics.
So MDMA, assisted psychotherapy, which it appears, thanks to the support and work of people like you and
the maps group and the group at Hopkins in particular, Matthew Johnson. And I realized
there are other people in that mix, but it's it, I have to just say as a, as a point, it's,
it's really exciting to see what's happening and the enthusiasm about safe building, safe protocols
that people can access after so many years of people having to do this kind of renegade or in unregulated environments.
MDMA creates in a very atypical state.
It's a state of high dopamine release.
Typically, dopamine is associated with a focus on things external to us.
Dopamine being a molecule associated with motivation and reward makes us want to do more of things that brought the dopamine, whether or not that's food, sex, online viewing of any kind, et cetera.
It's not always bad.
But online viewing.
Online viewing, whatever that is.
The best way to describe the effects of dopamine are that there's a book actually, quite good book called The Molecule of More. And that's a great way to describe it. I wish I had written that book. I read the book
and thought, I wish I'd written this book. It's because I love the neuromodulator systems and
it is the molecule of more. And actually anyone that thinks that dopamine is about pleasure,
not motivation or seeking more consider this. This is a, an anecdote I borrowed from my colleague,
Anna Lemke, who's in the Department of Psychiatry at Stanford.
The next time you eat a piece of chocolate or you engage in a behavior that feels particularly
delicious, notice the sensation and the thoughts in your mind.
It's rarely about complete presence and desire for staying present.
It's usually a desire for more.
It's this, I want more of this, please,
as opposed to really basking in the experience. And I should mention that Anna has a wonderful
book coming out in August called Dopamine Nation. She was in The Social Dilemma. She's an addiction
therapist and psychiatrist and talks a lot about the dopamine system. So dopamine makes us want
more of whatever feels really good.
And that tends to place us in an external focus.
Serotonin, another feel-good molecule, is the exact opposite.
It tends to make us feel good with what we already have.
It tends to be the incredible feelings of warmth that, you know,
holding a child or a loved one, or time with your dog.
I have this bulldog
Costello and there's times when I just sit with him and I feel immense pleasure just being there.
I don't think I want four bulldogs. In fact, I definitely don't want four bulldogs. The snoring
is loud enough already, but it's about experiencing the here and now in a full and complete way.
MDMA is unique because it creates huge increases in dopamine and serotonin
at the same time. And we don't ordinarily see that in natural experience. And it has this unique
property of making people feel very excited and positive about their relationship to their
internal state. And so it has a kind of looping back of a mechanism
that normally would place us in the viewing of the exterior. What's out there? What can I get
more of? Who can I interact with more of? What drug can I take more of that's going to make me
feel this way? So MDMA is very unique. And I mentioned it because it has certain correlates
with hypnosis in that it's a very focused state. In fact, so much so that let's
just say, I could imagine that if you're hearing music and you focus on that music, you can really
kind of start to merge with the music. Whereas if you focus on your internal state, you can merge
with your internal state. And that's why I do think it's important that some of that, if people
are doing it in a clinical setting, be guided because otherwise the experience can be sort of lost on whatever is external.
Other psychedelics of the sort like psilocybin, LSD, they have a very sleep-like state. They
tend to be more serotonergic in nature, and they are very similar to sleep in the sense that space
and time become very fluid. Whatever top-down governing mechanisms exist in the brain, so-called executive function,
some of that seems to be dysregulated enough so that inside of those psychedelic states,
and certainly inside of dreams, anything can really happen and you can essentially see and
appreciate novel associations that normally wouldn't occur in waking states. We should remember that the two extremes of human experience are stress and or excitement.
So highly contracted visual window,
highly contracted time domain,
everything sliced very finely.
What's happening next?
What's going to happen next?
Think you're in the line at the airport
and the person in front of you is moving slowly
and you got a plane to catch.
Everything constricted to right there,
both in space and time. And then sleep, where in sleep, space and time are extremely fluid.
Anything can happen and you are essentially out of control mentally. It's just whatever is going
to happen is going to happen. Psychedelics are very much like that, except that in LSD and
psilocybin-assisted states, you're alert. So I would say that psilocybin and LSD-like states
are similar to hypnosis in that way,
but hypnosis has a little bit more of a rigidity to it.
It's set toward a particular focus,
like let's work on your control over stress
or smoking or pain.
And so I would say the three of them
occupy neighboring spaces,
but none of them overlap
completely.
Yeah, I'd be so curious to see some type of multimodal study, and perhaps they've been
done, but just looking at pharmacological interventions combined with hypnosis, right?
So if we made hypnosis the default sort of control state, and then you had an arm that was comparing
hypnosis plus fill in the blank, not necessarily psychedelics, certainly.
I mean, it could be an intactogen or an empathogen like MDMA.
It could be a tryptamine like psilocybin, or it could be like a phenethylamine like
mescaline, which has very different effects.
Certainly, I think Michael Pollan does a good job of describing this in his new book,
Your Mind on Plants. He has an entire section discussing the mescaline experience, which is
really, in a sense, an amplification of the real in high resolution, certainly dose dependent versus transportation,
a la the tryptamines like LSD or psilocybin. That'd be very, very interesting to see.
It would. And I have to say, as usual, you're five years or more ahead of everybody else,
Tim. And I don't say that for sake of flattery. I mean, you have a way of spotting the horizon.
And I think we are so caught up as a culture now
in asking what should we do?
What should we take?
What device should I use?
I would say you've got behavioral tools.
We all have to eat sooner or later.
Nutrition, supplementation, prescription drugs,
off-label and on-label.
And then you got brain machine interface devices
for reading and writing to the nervous system and body
for measuring things and changing things.
And we always think of those as separate bins.
But as you're pointing out, I think the most interesting bin is to consider, well, maybe
at some point a learning bout is going to be 300 milligrams of alpha GPC and a particular
breathing protocol that will have a synergistic effect.
I think that's where the real immediate future of beneficial brain change lies.
And I think even the folks at Neuralink,
you know, a guy that came up through my lab,
he's a neurosurgeon, Matt McDougall,
is at Neuralink now.
And they have other excellent neuroscientists there.
And you can be sure
that they're thinking clinical issues first.
And they're thinking obviously brain machine interface
and chips and robotics and things of that sort.
But you can bet just given who makes up that company roster that they're probably also thinking about ways to accelerate plasticity using a combination of brain machine interface and pharmacology. And if they're not thinking about that, they definitely should. who's not going to plant a chip beneath their skull, I think you're hitting the nail on the head, which is that we need to think about what works independently and combining those for sake
of synergy. That's what's going to get us where we need to go much faster. I also think, just to
build on what you said, and thanks for the kind words, that when you look at these possible
synergistic combinations, you could also end up, and this is not a certainty, but it's a possibility,
having a much more appealing risk-benefit calculus in the sense that if you can lower the required
dose of a pharmacological intervention, if you can lower the exposure necessary with some type of neurofeedback or neuro stim, like a TMS or a TDCS or any
of these other tools, if you're able to lower the required doses of several things when they're
used in combination and get a similar or better outcome, it just has such incredible ramifications
for the clinical use of these things. Let's take a step back here.
So now we've covered a bunch of the research. We've covered a bunch of the tactical, practical
implementations of some of the research findings. Now I want to paint a picture for people who
don't know you at all. So we've already covered Costello. We have not discussed the fact that you have, looks like full sleeve tattoos on both arms.
I think you're the, I think you outed me. Yeah. There's a, you're the first, this is the first.
Yep. It's true. All right. Birthmark. They're all birthmarks. Of course.
They're all birthmarks.
Kids don't start because they're like potato chips. Can't get just one.
And we may get to aquascaping. That's a whole separate conversation. So we may get to that.
But I want to rewind the clock for a second because I read your bio, obviously a very
impressive bio. You've received numerous awards. You've produced a lot of incredible work with your colleagues and your lab.
Let's go back to what happened to you in July of 1994.
So in July of 1994, I was living in a little town called Isla Vista, which is near Santa
Barbara.
It's the home of UC Santa Barbara, University of California, Santa Barbara.
Just as a little bit of background, I was not a good high school student.
I had a very disrupted high school experience despite growing up in a good area.
Just a lot of tension and stuff at home.
So I barely finished high school, but I followed a high school girlfriend off to college.
Somehow I got in.
At the time, I wanted to be a firefighter,
took fire science courses at Mission College in the South Bay.
And I thought I'd be a firefighter.
And I put that in my entrance exam and somehow they let me in.
But by the end of my freshman year of college, I had terrible marks.
I had been thrown out of the dormitory living for getting in fights, something I'm
certainly not proud of. And I was basically doing nothing. That summer, I was living in a,
I was squatting. I was living in an empty house because a lot of the houses were empty. I figured,
why pay rent? You know, living in an empty house with my pet ferret. And to sort of set the context right, I think I was still grappling with
a lot of anger and resentment and confusion based on having a rather confusing teenage years and a
lot of disruption. Fortunately, I'd formed a lot of friendships and formed a community in the
skateboarding and punk rock culture. I was fortunate enough to get to know a lot of guys
that have gone on to do great. Like my friend, Carl Watson is Adidas skateboarding. I,
I spent some time and got to know, although we weren't close friends with the great Danny way,
probably the great, one of the greatest skateboarders of all time jumped the great
wall of China, but I wasn't a very good skateboarder. I was not a musician. I knew
how to do essentially nothing well. And July 4th, 1994, I went to a barbecue with some friends
and some guys were robbing the house that we were having this party at. We came back from the store
and we saw these guys essentially taking a bunch of possessions out of the house. And the thing
erupted into this big fight, this huge melee. I definitely went in excited to fight. I've been involved in
fights before and I had an adrenaline seeking thing. I felt like it was justified. I'm certainly
not encouraging anybody else to do this, but essentially what happened was my friends took off,
my so-called friends took off, and I ended up in a fight with four or five guys.
Knives came out, bottles. It's the sort of thing where quickly you realize
that things could go badly wrong.
Fortunately, I stayed on two feet
and nobody got badly hurt or killed.
The police showed up.
And actually because of the fact that they were robbing us,
they actually congratulated me.
I'll never forget.
This is actually what made me feel worst of all.
One of the police officers said, you know, like nice work or something like that. And I, and I
just realized that I was in serious trouble. You know, I'm 19. I barely finished high school. I
barely scraped through my first year of college. I'm living in a squat with my ferret. My girlfriend
had left me. I didn't do anything. Well, I didn't know how to do anything well.
And so that day, and I still have this letter. I actually sat down and I wrote a letter to myself
and to my parents saying that I was going to turn things around. I don't know why I wrote to them
because at the time I was kind of avoiding contact with them entirely. I've since formed a really good relationship with both my parents. But I decided that day that I would use the one power that I seem to have, which is to
remember facts and information. And what I did was I left Santa Barbara. I took a leave of absence,
went to a local community college in the Bay Area. I did two quarters there and I just started studying
like a maniac. First psychology, then biology. I eventually fell in love with neuroscience and
related themes of endocrinology and the rest is sort of history in terms of eventually going to
graduate school and getting a PhD and becoming a professor, tenured and all that stuff. But it was one of those moments where I realized
I am no longer going to be a young screw up.
I'm going to be a 20 year old screw up.
And with time, people are going to be less and less forgiving.
And whatever had happened prior, no one's going to care.
It doesn't even really matter.
And if I do want people to care,
and it's not like I have a need to talk about
the challenges early on,
but I need to get my act together.
I need to do something.
I need to get good at something.
And so I became a kind of a maniac.
Actually, when I read your book,
The 4-Hour Workweek and The 4-Hour Body,
which I read and loved and own, I should say,
again, not for sake of flattery,
but they really helped me.
There are a lot of useful tools in there.
There were certain things that resonated. I figured out that if, not for sake of flattery, but they really helped me. There are a lot of useful tools in there. There were certain things that resonated.
I figured out that if I drank a lot of coffee and took certain supplements, I could focus
for many hours.
And then if I worked out, I built another capacity.
And if I ran, I built another capacity for endurance.
And I started to explore the crossovers between weightlifting is one thing.
It's not about building muscles
or necessarily maybe it's about that.
It's about really moving against a physical force
in real time and really learning how to do that.
Endurance work is about learning how to push
through a different kind of barrier
and learning the carryover and crossover points.
So I was the guy that would sit down at my desk.
I decided to live alone in a studio apartment
and I would set a timer for several hours and I wouldn't allow myself to get up. I was allowed to listen to
rancid best band ever for me on repeat and Bob Dylan. That's all. I wouldn't even allow myself
to change music. And then I would just sit there and I would read my textbooks, underline my
textbooks, write my textbooks. And I just decided I'm going to get straight a marks. I'm going to go to graduate school. I'm going to get a PhD. I should mention
there were people that came along at various times and helped me, role models, mentors, people that
spotted that. But it started with a switch that flipped on July 4th, 1994 and getting in a bad
fight. And here I am. Deciding to choose a different path. So I want to underscore or explore a few
things. And I really appreciate you sharing this because I think it's very easy for people
listening to folks with a bio like yours to sort of assume a certain trajectory, to assume that
it has always come easy and that you've always,
since you were two years old, known exactly which direction you were heading, which is not the case.
One clarification with UC Santa Barbara, this might be an important point, it might not.
You did not drop out, you took a leave of absence. Is that right? Is that material to the story?
Because I know in a lot of cases, there are folks who are kind of painted as dropouts, but in fact, they kept sick, that allows you to leave and come back. And it's distinctly different from
dropping out. Although I was pretty close to dropping out of being forced to drop out for
reasons related to poor grades and poor behavior. Fortunately, that didn't happen.
I think it's a really important point because we hear that Bill Gates dropped out of college.
Steve Jobs dropped out of college. that Bill Gates dropped out of college. Steve Jobs dropped out of college.
Mark Zuckerberg dropped out of college.
I think maybe it was Ryan Holiday, who I don't know, who said something like that.
The people who are doing poorly in college, they're the ones that should stay in college
because it's that one environment where everything's scripted out for you, what you need to do
in order to hit the next metric of success.
And a leave of absence is very different.
None of those people dropped out of college.
They took leave of absences that gave them an insurance policy that they could go back
if they wanted to.
And it's very hard to make it back into a system of any kind, but it certainly is much
harder if you completely divorce yourself from that system.
I am a believer in formal, rigorous
coursework. I am a university professor. I know that college isn't perfect for everybody. It might
even be the wrong decision for certain people. But if you're still uncertain about what you want
to do, I think if it can be arranged financially and it's in the scope of things that somebody
might want to do, I think learning how to sit down in a chair and force yourself to learn and then compete with others in terms of how well
you learn that information, I think is a great way to evaluate oneself early in life and it sets the
stage right. I agree with that. If you're open to it, and certainly you can say no, or we can talk
about it and then you can elect to have it edited out of the conversation.
But you mentioned tension and stuff at home, disruption.
Are you open to sharing a bit more detail about what you mean when you say those things?
Sure.
So I had a pretty magical childhood, really.
My dad's a scientist.
My mom wrote children's books and was a teacher.
We ate dinner as a family, everybody together.
In the early part of my life, I acknowledged that I had great privilege in having that
experience and growing up where I did.
Good schools, good public schools.
I completely acknowledged the benefits of that, especially early in life.
Around 13, when I was 13,
my parents split up. And either because of the time in which it happened or because they weren't equipped with the right tools, there was a complete fracture of that picture.
My dad was very much out of the picture at that time. My mom hit, I think, a series of challenges
adjusting. I think it was what could only be described as a major depression. I think a series of challenges adjusting. I think it was a, what could only be described as a
major depression. I think her view of family was one in which everyone stuck together,
no matter what she's from the East coast. She's from New Jersey. Like you stick together.
That's why we had an argument the other day. I don't think she'll mind me selling this. And like
we got on and we were like ready to scrap and we haven't had one of those in years,
but I just remembered that at the end of this conversation, we're going to be okay. And at the
end we were, we were closer. So we both have that. And I think for her, the fact that there was a
complete disintegration of the picture, my sister out of the house, my dad out of the house and me
there, she really hit the skids and home became a very empty, very quickly became a very empty and depressing place.
It was really, it was just really sad.
And I found care and love and community in the world of skateboarding.
This was the early 90s.
And there was this collection of mostly young guys at that time who would aggregate at Embarcadero
Plaza, Justin Herman Plaza in San Francisco.
I started going up there and hanging out at the,
it's now the famed EMB for it's kind of got a golden era reputation now.
And that's where I learned that you don't have to go to school.
There are a lot of guys not going to school.
There was a lot of drinking,
a lot of drug use,
a lot of wild behavior, but also I should say a
lot of amazing skateboarding and amazing characters and personalities and fights and everything.
It was true street life.
And so I started staying there.
I'd stay at people's houses or sometimes we'd even sleep there.
And I learned a lot about how people outside the cozy suburbs of the South Bay, how they lived. I'm grateful for
that because it exposed me to the fact that many of these kids had no parental oversight from any
age that they had to scrap for everything. But quickly I realized that I wasn't very good at
skateboarding. I didn't have a future in it and I wasn't going to school. My home life was really disrupted and I lapsed into a pretty serious depression. I just remember,
and anyone who's experienced depression, I hope this will resonate with, although I'm sorry that
it exists, but there's this weird thing about depression, which is that it changes your actual
view of the world. I remember leaving Embarcadero sometimes
and looking up at the sky.
Back then they had the Embarcadero Freeway
and thinking the sky is so sad.
Like not the sky as a third, as a separate object,
but that this scene of this sunset is so sad.
And actually yesterday I was thinking about this
because there's this beautiful sunset where I live.
And I thought, gosh, I haven't felt sad at the view of the natural world in so long.
And so it's clearly a shift in my internal state.
And fast forward, what happened was eventually the school picked up on the fact, my high
school picked up on the fact that I wasn't going.
They called me in at some point.
I was sitting down with a school counselor and they had this guy in the room with me sitting there. And pretty soon I realized that I was in a different kind of situation. And I realized they were going to probably try and take me away because I was completely truant. I an attempt to run away, I was taken to a place up the peninsula,
which was neither a juvenile hall nor a psychiatric hospital, but we were under lock and key.
And I was in there with kids that had dealt with everything from sexual abuse to hardcore
substance abuse issues.
I'll never forget this. They said, the kids in the ward next door,
they're crazy because they're really young. And the adults in the ward on the other side,
they're crazy. But you guys, you're not crazy. And I thought, well, that's ridiculous because
they're probably saying the same thing to the ones on the other side. But I had no one to call.
I called my skateboard team manager out of
sympathy, not because I was any good. I'd got put on a, on a wheel company and a truck company
for skateboarding. And I called the guy and I said, I don't know what to do. I'm in this place.
And, and he I'll never forget. He said, look, I can barely take care of myself. And you're the
most normal guy I know. And I realized at that point,
I'm like, I'm really alone here. So the long and short of it was I did the work. I put my trust in
the counselors that were there. They seemed like good people. And, you know, I did the work, but
it's part of an agreement for getting let back into school. Actually, it's part of an agreement
for being let out. I had to do weekly therapy. And I was fortunate enough that I got placed working with somebody who understood my
particular needs, worked with adolescents, and really encouraged me to start exploring my mind.
Certainly the situation I was in, but encouraged me to start meditating. He gave me Jon Kabat-Zinn's
book, Wherever You Go, There You Are. He saw how much physical energy I had,, but encouraged me to start meditating. He gave me Jon Kabat-Zinn's book, Wherever You Go, There You Are.
He saw how much physical energy I had
and he encouraged me to start running.
I was always hurting myself skateboarding.
And he said, well, maybe running or swimming
and running and swimming are amazing
because unless you really do it wrong,
you can go and go and go.
It's just an, I could burn off all that anger
and energy over time.
And then I started getting into weightlifting
and weightlifting is kind of a double-edged sword. I should mention, I think it's one of
those things that is great, but you know, if you exceed a certain size, it can actually make people
kind of scared of you. Sort of like the tattoos thing. A lot of like a lot of the reason why I
cover up tattoos is because then people just see the, see your tattoos. But I, it's true. I started
getting tattooed pretty young. The wrong way.
Don't do it this way with India ink and a needle.
This was before.
This was autoclaves.
Bad.
Don't do it.
But I decided at that age that the therapy and this one person who seemed to really care
about my mental and physical well-being and would spend the time was really worth investing
in.
And I hid it from everybody because no one did therapy then.
No one talked about it.
It's like late 80s, early 90s.
Nobody did that.
And I will confess,
I don't think I've ever said this publicly,
but I've found a way,
either through insurance or through my own income,
I've continued therapy with that same individual now
for 32 years.
And so I do, I confess, I do three sessions a week of psychoanalysis
remote or in person. And I know people have a lot of, they do the other kind of eye roll,
not the Spiegel eye roll test, but the other kind of eye roll. When you say psychoanalysis,
I think an exploration of the mind is extremely powerful. It has to be done with the right person.
And there's only one person I know who's done this
kind of extended work for so many years. And that's the late Oliver Sacks, who's a kind of a
hero of mine, also worked with a psychoanalyst for many, many years. And so psychoanalysis,
a fight on July 4th, 1994, a lot of attempt to both stabilize my mind and also organize my behavior.
Those things go hand in hand, of course, but also biology to leverage.
I guess you could call it biohacking or you call it, I just call it biology.
I mean, when I learned, for instance, that taking a thousand milligrams per day of EPA,
essential fatty acids, not just fish oil, but getting above that threshold
is as effective as antidepressants in double blind placebo controlled studies. You know,
when I saw those papers, I realized, well, I probably have a bit of a leaning toward depression.
I'm going to do that. Now, did I do that and drop therapy? No, I do that and therapy and I train and
I try and work on my sleep. It's a constant process. But biology and the information contained in books like yours and hopefully in the information
that I'm trying to put out into the world now, that stuff helps in a major way too.
So it was a multi-pronged support system and many incredible mentors along the way.
But I was definitely at the edge.
I know you've talked about this publicly too. I mean, there were times when I just thought like, why continue?
And I'm fortunate nowadays, I feel very far from that. There's a saying in the world of addiction
and addiction treatment, which is that no matter how far you drive, you're always the same distance
from the ditch. That I would say is true of addiction. Fortunately, at least in my own experience,
that is not true of depression. I have vowed to never go back to a place where living seems
meaningless. And anyone who's been close to that place, all I can say is the work works,
whether or not it's therapy, biology, et cetera, you have to do it. And there are things that can
accelerate that process, but it's an ongoing battle, to be honest. Well, you're fighting the good fight,
man. I'm certainly right in there with you. How does it feel to talk about this stuff?
It's interesting. I always get a little quaky on this. I would say there are only two things that
will always consistently make me cry. And those are the thought of, I don't even want to talk
about for too long because I prefer not to cry. But one would be when my bulldog Costello goes, we're very bonded and
he's close, unfortunately. So he's in his final years. And the other is when I think about my
mentors in particular, one passing away, talking about this gets me in a mode where it's
uncomfortable. I'm definitely uncomfortable this moment. I'm okay to talk about it because I think these issues are important. And I wholeheartedly believe that
many people struggle with them. You know, I'm always conscious of protecting the people in my
life who were doing the best they could with what they had. So, you know, my parents are good people
that generation didn't have the tools that I had access to. And I do hope the next generation and
we'll have access to more tools. So I want to
protect them. They are, you know, I'm blessed. I acknowledge my privilege. And I don't say that
for political reasons, by the way. I just want to say I acknowledge that I was born into a pretty
fortunate or very fortunate situation that provided buffers. And I only know my own experience,
but I acknowledge it as real. Thanks for sharing all that.
And a mutual friend has prompted me to ask about the Hoffman process.
Oh yeah, the Hoffman process.
So the Hoffman process is a personal development process.
It's a full immersion week long process.
I think it used to be two weeks.
I don't want to give away too much about it because if one were to go, you want to have the experience for the first time without expecting
or knowing what's coming. It involves a lot of both physical and a kind of emotional purging.
And what's interesting is it's generally between 20 and 40 people go. You don't publicly share
any of the issues that you're grappling with. There is a teacher there that you communicate with and who knows a lot about your situation.
There's a lot of work that you do beforehand and paperwork.
So they really know closely what you're grappling with.
And you do get to know people there, but there are strict rules, no romantic relationships,
no discussion of politics, no discussion of work, no discussion of sports.
And you quickly find that you realize that you spend a lot of time thinking about and
talking about those things in the outside world. And B, that there are other ways to connect with
people that are very authentic that don't involve those things. Hoffman process was one of several
things for me that was transformative. For me, it was most transformative in the realm of forgiveness.
I felt completely resolved of my challenges with, you know, inability to focus, complete work,
structure, et cetera. I'd solved all that. I learned how to work hard, perform well by time
I went to Hoffman, which was in my early forties. I'm 45 now. I learned how to control my physical landscape
as best as one could or should. I went there thinking like, why would I go here? What's the
purpose in going? And yet I realized that I harbored a lot of resentment, mostly toward
family members, but also toward experiences and people outside my family. And I almost got kicked
out of Hoffman the first day, not for misbehavior, but because I slept through the first day I'd been
working so hard. They kept saying, you're trying to escape by sleeping. And I'm like, I'm just
tired. Like they take really good care. They take really good care of you there. I've actually never
felt so nurtured. I'm not somebody who accepts nurturing very easily. I like to think I'm more of a caretaker and a more of a kind of caretaker
loner type than being taken care of. And Hoffman, I felt comfortable to be taken care of in certain
ways. And I discovered in doing the work that there were all these resentments. And I was able to purge those resentments. And I have to say, it completely
erased all feelings that I was wronged by anybody or anything. And that's powerful. And it's
completely behavioral nature. There's no pharmacology there. I would say Hoffman is among
the two or three things that were maybe four or five things that were really transformative for me.
And there is a price point, but they do have a scholarship program that's been established thanks to the generosity of various folks.
So for people that can't afford the price point, they do have a fairly simple scholarship program where you write something out.
People who are practitioners, you know, therapists and in the wellness community, I think also get a break of some sort.
I have no business relationship to Hoffman, but i've recommended that several people go and it is
powerful and it does last in fact the reason i decided to go to hoffman was because somebody
actually a mutual friend of ours tim who i don't think went wendy yalom who i know from way back
when we haven't been in touch in years, but I think she
said something about Hoffman and she said she knew somebody who went and I contacted that person.
And that person said, I went to Hoffman and 10 years later, it still has a profound positive
effect on my life. And I found it to be more useful than any other therapy or training of any kind.
That's my Hoffman story, and it's powerful.
And for people who want to hear more about Hoffman, I talk about it at length also with Blake Mycoskie in the last conversation I had with him, so people can find that episode.
You mentioned one of four or five things.
What are some of the other things that have had a
disproportionate positive impact? This is a broad category, but get your biology right.
Start with sleep, figure it out, figure out how to get your sleep right, because it's the
fundamental layer of mental health. So get that one right. Other things in the biological category
are learn how to focus, learn how to defocus, learn how to flip the switch on, learn how to flip the switch off, get good at sleeping. Of course, exercise of various kinds is going to be, psychotherapy, journaling, or some sort of
internal reflection that's somewhat unregulated, but obviously not damaging to you or anyone else.
So don't punch concrete walls, but have the ability to sit down and data dump and reflect.
If you can't afford therapy, reflect on what you're seeing and reading and feeling,
have the ability to experience what's internal. So that would be the second one.
The third one is, and I realize there's some issues around legality and things. And right
now everything's in transition. I was part of a clinical trial, so I can safely say this,
I do think that there are certain
aspects to, let's just call it what it is, either plant medicine or I was part of MDMA-assisted
psychotherapy trial that was extremely valuable. There's no question to me that that's a powerful
mover of one's ability to feel comfortable in internal state. The way I would just briefly
describe that experience for me is that I could feel and perfectly fine from here to here and
from the belly button down, but I had this feeling always that I couldn't kind of experience things
in mind and body at the same time. I know this is going to sound really wacko to people who maybe
haven't experienced this, but somehow in that brief experience,
I was able to resolve that. And I now experienced my nervous system as a complete entity.
And I do not think people should cowboy this stuff and do it on their own or try and do therapy for
their friends or do this on their own. I don't think this is something that people should play
around with. These are very powerful tools. You should do this with a board certified MD, sign up for a clinical trial. Hopefully this will be done in these sorts of
medical settings soon, legally, and you don't have to be part of a clinical trial. But if you
struggle ongoing in some way, I do think there's utility there. So that's another bin. And then
there's another bin, which for me has been very powerful, which is stay on the adventure, continue to have fun. It's so easy to forget to have fun when you're doing all these other things like stay in the adventure and don't get killed doing it. These dopamine systems are positively reinforced by novelty and exploration.
We know that.
And by venturing into new territories.
And that requires getting certain things wrong.
It means going to a retreat that sucks.
It means taking a class that is not that interesting.
It means finding out that, you know, a particular relationship is not right for you.
But it's important to stay in a
mode of adventure because that's fundamental to the human experience and it's fundamental to these
neurochemical systems as well. A couple of points I'd love to underscore here. So the biological
piece you've discussed in other places, this principle, it's a quote of sorts, a maxim that I think is really
worth remembering. And I'm saying that to myself as much to anyone listening, that is, you cannot
control the mind with the mind. And whether or not there might be exceptions to that, I think,
is a general rule using the bidirectionality, as you've mentioned, of body, mind, mind, body, and when in doubt,
working through your fuller biology is incredibly powerful.
I mean, for me, to get out of my head, I need to get into my body.
There's just no metacognitive way generally for me to otherwise do that.
Or if there is, it's just much more difficult.
I've even told
my girlfriend, I'm like, if I'm trying to figure out what is bothering me and I spend more than
like a half hour on it, just tell me to go to the gym and lift heavy things for at least 30 minutes.
Best remedy in the world.
And then I come out, I'm like, yeah, that bullshit's fine. It doesn't matter.
And that's what was necessary. On the adventure side, actually, before I get to the adventure side, just a quick note
on Costello, because I think a lot about my dog, Molly, and mortality.
And it's just, it's like so easy to get sad.
And-
How old is she?
She's seven, but she's had some health issues.
She's had two spinal surgeries.
And if you haven't looked into the canine research with rapamycin, I would look into that.
It's very, very compelling.
So that might be-
Thank you.
I'll do that.
I listened to your podcast with Peter Attia and a lot of discussion about rapamycin.
I'll definitely check it out.
Yeah, it's check it out. Yeah.
It's,
it's worth checking out.
There's also a separate episode with David Sabatini of MIT who is a genius
and,
and it's sort of mTOR wizard.
That family,
his,
he has a brother,
Bernardo Sabatini,
who's a famous neurobiologist at Harvard, who I know quite
well.
And their dad, there's another Sabatini who was at NYU Med.
So those Sabatinis, they're kind of like the Kornbergs.
Kornberg discovered RNA.
His son discovered the structure of RNA.
They both got Nobels.
And I think their brother is an immunologist, something like that.
So if you're thinking about changing your last name, Sabatini or Kornberg is a good
one to select.
Yeah, not bad.
Yeah, they come from the secretariat stock of the scientific gene pool.
That's right, exactly.
On the adventure side, so you said don't die or don't let something kill you,
which I think is a perfect segue to, as I'm reading it from a paragraph from Outside Magazine,
Huberman was about 40 miles off the coast of Mexico and 40 feet below the periwinkle
surface of the ocean.
What does this refer to?
Oh my, yeah.
So before I went to Hoffman, I was still working out some things.
The quick backstory of this is in 2016, I decided I was going to shift a lot of my laboratory
work toward humans.
I understand
the issues of animal research and why it's important. My lab still does work on mice
because there are certain things you can only do on mice, but I want to work on humans.
And I want to use virtual reality to induce fear in the laboratory and study stress and fear and
other brain states. And we realized that VR as it stood at the time was just pretty lame. It was computer
generated images. It didn't have 360 video or sound. And so I got linked up with a guy named
Michael Muller, M-U-L-L-E-R, who's a very, very famous photographer in Hollywood mostly. Does
all the Marvel stuff. He's shot everybody that you just can go to his website.
It's just,
it's kind of a,
just a constant scroll of iconic images.
Muller and I got to be friends.
And the reason I was excited about getting to know him is because a hobby of
his is that he takes photos of great white sharks underwater.
He brings these giant strobe lights underwater and Muller is,
you know,
you hear about the character,
the Wolverine Hugh Jackman, right right? Mueller is a Wolverine. He's kind of hunched over and he's
the nicest guy in the world, but it was like, it was immediate friendship, but he loves adventure.
He's got, he's got a family, kids, everything, but he loves adventure. And he said, and this is
my best Mueller impersonation. He's like, bro, you got to come down to Guadalupe. The sharks are there. And I was like, well, what are we going to do? And he's
like, well, we'll just film them with 360 cameras. So in 2016, we went down there and we filmed great
white sharks as a stimulus for this fear laboratory that we were building and got 360 video. And the
way we did that was that Mueller and a couple other guys, these expert great white
shark divers would leave the cage.
You lower the cage about 40 feet below and they leave the cage to come back in.
So-called cage exiting.
Definitely illegal to do.
We got permits from the Mexican government because this was for a scientific study.
I would have loved to see that permitting process.
Anyway, continue.
That was something else.
So we got the footage, brought it back, built this thing up.
And then what happened was in the subsequent year, the technology for VR really improved.
So we decided we were going to go back.
And I decided for whatever reason that I was going to cage exit also.
I actually learned how to scuba dive for the first trip, but I had stayed in the cage.
And so the second trip, we went out there and I brought a good friend of mine. He was actually a mutual friend through Blake Mycoskie.
Pat Dossett is a former, former seal team guy. I brought Brian McKenzie because Brian learned,
Brian McKenzie learned how to scuba dive in a lake in Oregon. And his first ocean dive was
cage exit with great whites. Now, of course the guy has unscared tattooed on his
knuckles. I know he was featured in a number of your, your books. So it was Brian, Pat,
me and some other guys, we went out there with the intention of getting better footage
to create a very realistic VR experience of great white sharks. So what happened was on the first
day I decided I'm not going to cage exit today. Let Pat go. He's the SEAL team guy.
He'll do it.
He did it, of course, masterfully the first time, went a few meters beyond everybody because
those guys aren't competitive or anything.
Anyway, it all worked out.
But the first day I was in the cage, so I went down.
I'd been in the cage before and you're breathing off a hookah line, which is up to the surface.
You're not on scuba.
And the reason you don't bring scuba is because you don't want to take up too much space in the cage. So the other divers, Muller
and a couple other guys had left the cage and I was there just watching the sharks and really
enjoying it. I'd been down there the previous year and these great white sharks, their girth
is incredible. And they come at you on like a Volkswagen and they'll stop right in front of you
and hover. They'll eyeball you and then disappear into the darkness. So it's really amazing. And I realized as I was down there,
I'm like, I'm alone in the cage this time. I've never been alone in the cage.
We had a lot of sharks that day. So I was moving around and swiveling around a lot.
And then all of a sudden I had no air, nothing, just nothing coming through the mouthpiece. And I looked up and the hookah line got all boa constrictored up.
So I popped up to it thinking, oh, I'll just untangle this thing.
And it's like hard as concrete.
It's like, oh, good.
So I took another suck of air and nothing.
And I looked down, there's safety tanks in the two corners.
So I spit out the mouthpiece.
I dropped down to the safety tanks, open them up and the needle doesn't move.
They're empty.
This is like the biggest nightmare.
And it's interesting.
We were talking about Costello.
I had one thought at that moment, a totally inefficient use of mental space.
But the one thought was, I'm going to go home alive.
I'm going to see Costello.
He just popped into my head.
So this stuff really does happen apparently.
So nothing off the safety tanks.
So I decided I got to get out of here when there's sharks everywhere, but I've got to
get to the surface and you're just desperate for air.
So I pop up to the top of the tank and I've got a weight vest on and I've got to take
that weight vest off if I want to get up to the top of the tank and I've got a weight vest on and I've got to take that weight vest off if I want to get up to the surface. Now the sharks actually don't eat you when you're
outside the cage. If you're swimming toward them, they actually, if you loom on them,
they steer away. That's the way that these cage exit divers are able to avoid getting eaten.
Or if you're ocean Ramsey, you just kind of understand them and you swim next to them.
But I was genuinely frightened and stressed.
And so I thought, okay, I'm going to shoot for the surface. I could see the silhouette of the
boat. I'm going to shoot for the surface. I'll either get eaten or I'll drown, but
I'm certain I'll drown if I stay here. And then what happened was one of the divers,
his name's Brock, saw me and started kicking back toward me. And he's carrying this big vacuum cleaner size VR
thing. And that felt like an eternity. He's coming back to me, back to me slowly. So I'm just hoping
if I pass out, I want to fall into the cage. If I float, I want to make sure I float up. But
it was a good 20 or 30 more seconds, which doesn't sound like very long, but it's not like-
That sounds like an eternity.
It was an eternity. So he made it back.
We did the share air thing,
but then we had a whole other problem,
which was that we're sharing air.
Those guys are out there.
We're now on one tank and the safeties are empty.
So now there's a chance that we both might have to shoot for the surface.
So fortunately, everybody made it back in time
and we got up to the surface,
but I will never forget that experience.
I do feel like I'm on borrowed time.
And I did feel quite traumatized by it.
And I will say that that night I did one thing.
And the next day I did something else was that night I was able to sleep.
I did yoga nidra.
And I was able to calm my mind and my nerves. And the next day, because I,
I understand a bit about the relationship between trauma and exposure. I did go back down the very
next day and I cage exited. And some people might think that's foolish. I certainly didn't do it to
be tough or to seem like I'm tough. I did it because facing the trauma is the best way to purge the trauma. We know this.
And cage exiting for me allowed me, I believe, to report the experience. I feel nothing in my body,
no tension, no stress, no quaking or anything related to that. So I do think it's been
completely purged. I want to dig into what I read as a definition of fear from you and just to hear more about
your fascination with fear and where it comes from.
So here's what I have, and you can fact check this, please.
Quote, fear, it's the anxiety that you feel when you don't know what behavior can remove
a feeling of helplessness in the face of a threat,
end quote. Does that sound right to you? You can't have stress without anxiety.
You can't have trauma without stress, but you can have stress or anxiety without trauma.
I think that the key variables are anxiety is a state of heightened alertness. It's contracting in the visual field,
quickening of the heart rate, breathing,
all the kind of standard stuff that we hear of sympathetic nervous system activation.
But the mental component is one in which
time is being sliced very finely.
So you're constantly anticipating
and evaluating your environment and your internal state.
Because oftentimes people are aware
of their so-called interoception. They're
keenly aware of how nervous they are or upset they are. And this element of uncertainty of being
unable to predict when it's going to pass. And this creates a kind of meta stress. It's sort of
like when people have trouble sleeping, then they create this kind of meta anxiety and insomnia.
Now they're stressed about not sleeping. And so then it makes it even harder to sleep. The same thing with stress.
The more we stress, the more we want the stress to pass. And I think that resolving the uncertainty
element is powerful. And I think it starts by taking control of the mind through the route
of the body. When our mind is not stable, whatever that means, but we're not able to control our mental
state or it's not where we'd like it to be, we need to look to the powers of respiration,
of vision, of movement, of weight training, of running to reorient the mind.
I think it is futile to try and rescue thinking with thinking.
That's not to say that thinking and an exploration of the mind,
like with psychoanalysis or journaling,
is not powerful,
but for restabilizing our system,
these brain states of mind and body,
I think the body is the more powerful entry point.
And have you always been fascinated by fear?
Or why did that become a focal point?
Probably because I was the kid that was last to drop in on the ramp. Probably because I
have lived and existed with a fair amount of fear. This seems to have gotten better over the years.
For instance, I can remember skateboarding home. There's this bike path that used to connect the
school that I went to the back of some houses and I would push back through there at night. And I would start to imagine that
terrible things were going to happen to me. I think that fear was, it was a strong default
and I can't assign that to any earlier experience. I think I just had a lot of baseline anxiety and
fear. And so resolving that and figuring out tools that people could use, that I could use also to resolve those things really fast has been a major, a major effort
in my life, including my laboratory. I'd like to, if it's okay with you,
shift gears a little bit and just pepper you with a bunch of random questions that have
absolutely no continuity with anything we just talked about. Great. That's okay. Sure thing.
All right. Because I have this sort of scratch pad full of these various things that I want to
ask about often without a whole lot of context, just from various reading and so on. So turmeric's
effects on DHT. Could you elaborate on this? So DHT, dihydrotestosterone i'm guessing what should we
know about dht and turmeric's effects on dht and i ask in part because it's something that i use
all the time in cooking there seems to be some research to suggest that products like theracumin
i believe it's called as the brand name might attenuate some risk relatedrelated, say, neurodegenerative disease or Alzheimer's.
So I'd love to know more about this.
Yeah, so brief endocrinology lesson on testosterone. DHT testosterone is the androgen,
of course, that's responsible for muscle growth, deepening the voice, aggression, sex drive, etc.
But DHT, dihydrotestosterone, is made from testosterone through an enzyme called
5-alpha reductase. DHT is the more powerful androgen, anywhere from 300 to 600 times the
affinity for the androgen receptor. DHT and its affinity for the androgen receptor,
not so incidentally, is the basis of nandrolone, DECA, known in gym circles. Actually, a female runner that was a good pick for the 1500 just got a four-year ban.
Oops.
For a Nandrolone positive test.
She claims and her coach claims that it came from a burrito containing pork with Nandrolone.
I actually would love somebody to go explore.
We're going to see more of this in the years to come.
I'd like somebody to actually analyze meat for clembuterol and nandrolone to just see.
And I'm not happy that this happened. It's a sad situation, but we could fairly say that
there's been a dark shadow cast by a burrito over the Olympic qualifications.
It's kind of like when all the sprinters were diagnosed as narcoleptics you remember that with
oh really yeah they're all on the daffodil on various stimulants and so they had these scripts
from their doctors and letters saying they were all narcoleptics it's just amazing the venn diagram
to get them quick out the blocks that's where the race is won hear that gun and get out the blocks
that's so nandrolone is deca the the reason people take it, whether or not she took it or not, I don't know, but the reason people take it is because DHT, as the more powerful androgen with this higher affinity, is the one that's mainly responsible for libido and many of the cognitive effects of testosterone is that because of the fact that there are androgen receptors in the
amygdala, that it has a fear suppressing component to it. And DHT, testosterone, but really DHT
has a property of making effort feel good. That's probably the main psychological effect
of testosterone aside from its effects on libido and the body
periphery.
So some people are very DHT sensitive.
If you're somebody, for instance, that takes creatine and experiences hair loss very quickly,
you're probably DHT sensitive.
That's because creatine increases DHT.
DHT will promote hair loss on the scalp, like my hairline's retreating quite nicely now
because of DHT receptors here, and it promotes beard growth.
So it has these inverse effects on the face and on the scalp.
But turmeric is a fairly potent DHT antagonist.
Now, whether or not it does that by occupation of the androgen receptor or some other mechanism,
I don't know.
People will vary in their sensitivity.
I am very sensitive to turmeric. of the androgen receptor or some other mechanism, I don't know. People will vary in their sensitivity.
I am very sensitive to turmeric. If I take turmeric, my DHT levels plummet and I'm not taking nandrolone, nor am I eating pork burritos. But the sensitivity will vary and you can kind of
predict that sensitivity by how you react to creatine. If you're somebody that takes low
doses of creatine, which many people do, and experience hair loss, chances are when you take turmeric,
you're going to see a reduction in DHT. It means that your 5-alpha reductase system and or this
interaction between turmeric and the androgen receptor are, for whatever reason, more sensitive
in you. Some people take turmeric and feel perfectly fine. I noticed an immediate blunting of all the good stuff, let's say,
that DHT and testosterone do when I take even a minimum of turmeric. Now, that doesn't mean I
can't have a little bit of turmeric in a drink, like a juice drink or something, but dosing
turmeric is not something that I do or that I recommend for people. Now, women do make a little
bit of DHT. It might be a whole different story with them.
But I think for men, you probably just want to do the experiment.
It's quickly reversible if you stop taking turmeric.
So you could evaluate this.
Some people will be fine.
You could do a blood test.
You could do it subjectively. Is finasteride, propesia, that is often used for mitigating hair loss, that is, I think
it's a 5-alpha reductase inhibitor. Would that also have
the effect of decreasing DHT levels? I want to say there are anecdotal reports, and people,
please do your own homework. Go to PubMed and do some research. But I want to say that at least
among strength athletes that I've heard anecdotal reports of propitia use correlating to decreases
in strength gains for male athletes. Yeah, absolutely. And it certainly can
reduce DHT levels, certainly more for those that are sensitive to it. Just to underscore how
powerful DHT is, we have what are called primary and secondary sex characteristics. Secondary sex
characteristics are like body hair, deepening the voice, et cetera. But the primary characteristics,
like the presence of a penis or not, and this is independent of gender. This is just biological
sex. It's encoded by the Y chromosome. That's entirely controlled by DHT during development.
And masculinization of the brain is a separate pathway. But there's this phenomenon that I think
is in the Dominican Republic, a genetic disruption
in some of these pathways.
And people can look this up, the so-called huevidosis.
This is a famous story in endocrinology of children that look female at birth by genitalia.
And then because of a surge in DHT later, they literally sprout a penis at about, and
testicles descend at about age 12. Wow.
Wow. And there's a whole story there. It actually was part of the story that helped
neuroendocrinologists and developmental biologists understand the role of 5-alpha reductase in
testosterone's conversion to DHT. Fascinating biology there. Much too much to go into now in
detail, but people can look it up online. DHT is powerful in development and it's powerful throughout the
lifespan. So you want to keep levels of DHT appropriately high, but don't take nandrolone
if you're sprinting in the Olympics. So that's not the way to get your, nandrolone is not the
way to get your DHT. Yeah. Even if you do get it through anabolic piggies, it's just like there's
so many more cost-effective ways to make pigs grow. DECA, Durabilin injections is probably
not high on the list. They need natty menus, right? They need menus that are like, if you're
an Olympic athlete, please just prepare your own food. Yeah. Yeah, yeah, exactly. So, so many directions to go here.
It makes me wonder also if anyone has looked at turmeric or curcumin or whatever the actual
compound is responsible for this DHT inhibition, whether it's via 5-alpha reductase or otherwise,
on pregnancy and birth gender.
I'm wondering if that would have any effect, if DHT is suppressed in a woman
who is pregnant, if that would have any effect on birth gender. Yeah, that's a topic that I don't
think the experiment's ever been done, but my postdoc advisor, Ben Barris, was transgendered.
And it's an interesting story. Briefly, he was an identical twin. He, From a very early age, he felt entirely uncomfortable in a female body.
He knew he wanted to be male from a very young age, long before puberty.
His sister, who I've interacted with as well, is perfectly happy being a woman, enjoys being
a woman.
And they're identical twins.
And their mother was actually treated with an androgenic drug during pregnancy.
Ben unfortunately passed away of pancreatic cancer a few years ago.
He was an incredibly accomplished neuroscientist and physician.
His name is Barris, B-A-R-R-E-S.
There are a number of obituaries.
I wrote one for Nature that describes his life and his transition and some of the biology.
But nonetheless, Ben and I spent about a year before he died.
I recorded a lot of conversations with Ben that I haven't released yet,
talking about what it was like to be a girl, what it was like to be a woman,
what it was like to be a man later in life.
Just as he's a close friend of mine, I want to understand that.
And he described that this was an immediate effect.
As soon as he knew there was a difference between boys and girls, he knew that he was
in the wrong body.
He likened it to if you woke up tomorrow and you were in a gorilla's body, that's how
uncomfortable it was, knowing that that's how he described it.
And he thought that perhaps this early androgenic drug treatment might have shaped his brain
differently than his
sister somehow. Raises so many interesting questions about phytoestrogens or sort of these
xenoestrogens and the environmental inputs that could affect that entire biochemical cocktail
to different outputs. Testosterone. So we've talked a little
bit about DHT. There's a Goldilocks range, depending on your gender and your objectives
for testosterone. Are there any particular supplements that you use to, I hesitate to
use this word because it's so goal dependent, but optimize your testosterone or DHT levels or reduce sex
hormone binding globulin or whatever. If you're sort of toying with your androgens, how do you
like to do it? Optimizing and or understanding testosterone, I think is vital for men and women
because it's so powerful. Obviously get your sleep right. That's an important one. And you do that through. So that's an indirect effect. Stress, keep stress,
chronic stress to a minimum. That's an indirect effect. Train hard, but not too long. That's an
indirect effect. Mostly in the supplementation space, there are two things that have worked
very well for me and that I've recommended to a number of people that have worked well for them. And
those two things are Tongat Ali, which at 400 milligrams per day is thought to reduce sex
hormone binding globulin because of, for those that don't know, testosterone can exist in a
free bound form. People hear binding globulins and they bind up testosterone and prevent free
testosterone. They think this is terrible, but actually albumin and sex hormone binding globulins and they bind up testosterone and prevent free testosterone, they think this is terrible. But actually, albumin and sex hormone binding globulin are wonderful because they ensure
that whatever testosterone you make will be delivered to your tissues over a long period of
time. And different tissues need different amounts of testosterone. And so you don't want to plummet
sex hormone binding globulin, but Tonga Ali, either through reducing sex hormone binding globulin or through direct
effects on increasing androgen release, will increase your testosterone. Now, the way to
explore this, and I'm not saying anyone should do this, you definitely want to work with your
physician, but the way to explore this is 400 milligrams per day taken once per day early in
the day, because it can have a little bit of
a stimulant effect and make you more alert. That works well. It does need to be taken chronically.
It tends to work better as you get into the second and third month of use. And I don't see any reason
to cycle it unless somehow something spikes on your liver enzymes or something. The other
supplement that is quite useful
is Fidogia agrestis.
Fidogia agrestis is one of these plant alkaloids
that I think it comes from a Nigerian shrub.
I might have that wrong,
but Fidogia agrestis acts as a luteinizing hormone mimic.
So it actually stimulates the testes
to produce more testosterone.
So it's like HCG. It's like bit like HCG, but for whatever reason, it doesn't seem to increase estrogen,
which is unique because HCG will increase estrogen. Now, just anecdotally, I started
using those in combination. So it's 400 milligrams of Tonga Ali. I have no relationship to the
company,
so I can mention where I get it from, although I hope they don't sell out as a,
they will sell out as a consequence. A Solarae makes a good version of this. Sometimes these
things are packaged in with other things, but Solarae has a pure form. And then Fidojia
Agrestis, I think it's herbal elixirs makes a Fidojia Agrestis. And some people make the
mistake of taking far too much Fidogeo Agrestis.
I think on the bottle,
they recommend two to three times a day.
One 425 milligram capsule,
I believe is more than sufficient.
And anecdotally for me,
what this did is it increased my total testosterone
by about 200 points.
So I fell kind of in the middle of the range.
I was neither high nor low. I was at about 600, hovering somewhere around 600. These two supplements consistently
bring it up into the high sevens or low eights, which is in the direction that I wanted to go.
Do you think Fidogea agrestis, if it is luteinizing hormone similar, meaning it's a mimic of sorts, do you think that would have any,
I guess it probably would have a sort of down-regulating effect on endogenous production
of LH? Well, what's interesting is when I've done my blood work twice a year, at least for me,
it did not down-regulate LH, which is nice because things like HCG definitely would downregulate LH.
People who take testosterone cypionate, so-called TRT or similar, will see a downregulation in
luteinizing hormone. So Fidocia and Tonga Ali, I mentioned because they're sort of an intermediate
between doing nothing with respect to supplements or taking things that don't really work.
There are a lot of those out there. Or taking the full plunge into TRT. And I'll just mention,
if I may, about TRT. There's a lot of interest and excitement in TRT. They now even have what's
called sports TRT, which is not... And just for people who don't have the context,
I'm not sure if you already kind of named it out, but testosterone replacement therapy, TRT.
So what's sports TRT?
Is this like med spa type stuff?
Yeah.
So people are probably wondering, wait, you're a neurobiologist.
Why do you know so much about this stuff?
Well, I have the good fortune of doing work with various high-performing communities, and there's just a lot of discussion around hormone and neural augmentation. And so I'm not making recommendations.
What I generally do with those communities and what I'm doing now is point people to the fact
that there are things that lie somewhere between doing nothing and going the prescription drug
route. Eating pork burritos. Yeah, exactly, exactly.
In the realm of TRT, testosterone replacement therapy,
the typical dosages that people use
are 160 to 200 milligrams a week,
but the way it's administered doesn't match the biology.
I think this is a serious problem
that needs to be dealt with.
Typically, if you get a prescription,
you'll go in, they'll give you one injection
of anywhere from 160 to 200 milligrams.
And then you go back two weeks later
and you get another injection.
The testes normally make anywhere
from about five to 10 milligrams of testosterone a day.
So if you're taking 160 milligrams of testosterone
on one day, you're going to set in motion
all sorts of cascades of aromatization into estrogen,
conversion into DHT that you might feel terrible then, great four days later, and then so-so
two weeks later.
The way people are doing this now more intelligently is to do their injections at home, either
into subcutaneously or into muscle, and every third or fourth day to take a low dose of maybe 40 milligrams and to dose
it more evenly because these long lasting forms like cipionate do release over time.
But sports TRT is this intermediate that's been created on the internet where people are neither
doing testosterone replacement therapy to get levels up to normal or high normal, nor are they
doing what the gym rats call blasting.
They're not taking three, four, 500.
They're taking 200 a week or 300 a week.
And the amount of self-directed pharmacology
that's happening out there is pretty incredible.
And like, I don't pass judgment.
Everybody, it's your life to live,
but there are a lot of horror stories too.
You can really mess
yourself up by getting androgen levels too high. I'm a fan of gently moving into the supplementation
space for this, seeing how it works, doing a blood test. And then if people want to do TRT
over time, that's certainly their right. That's not my place to judge. And you need a prescription
anyway. You have to talk to a doctor. Yeah. And just a couple of additional thoughts on all of this stuff. Well, first, the lower
dose, higher frequency regimen can also be applied to many things, right? Growth hormone would be
another example from the same sort of portfolio of interventions slash augmentations that a lot
of folks would use. And separately, I would say,
and please feel free to correct me or fact check on this, but whether you're eating pork burritos,
injecting yourself with anabolics of different types, or eating deer antler velvet, or whatever
the latest fad is that people claim increases testosterone, if you dramatically
increase your testosterone levels, if you are not taking an anti-aromatase, you are also going to
increase your estrogen levels, even though it depends on the anabolic. Obviously, anandrolone
is very different from different types of testosterone and so on, which some are more
anabolic, some are more androgenic. But if you suddenly wallop yourself
with much higher levels of testosterone, you are also going to, a portion of that will be
converted to estrogen. And so it's just something to be aware of. It's very hard to get a biological
free lunch. And if you're feeding yourself a bunch of stuff and your testes like the Siberian, what were they? Albino rats?
Siberian hamsters. therapy, PCT, various drugs to successfully off-ramp from these types of interventions.
Unless, like some powerlifters, you're just going to be loaded all year round, 365, 24-7, which
is obviously your choice if you want to do something like that. But suffice to say,
good idea to get medical supervision for all these things.
Definitely. And along those lines, I should just mention, well, I will say that Fidojia tends to have
the opposite effect on the testicles.
It actually will cause a fairly, not pronounced, but it increases testicle size.
That's a pretty strong effect or media effect of Fidojia.
The other thing is that right now there's a lot of excitement about peptides.
People are like, oh, the so-called secretagogues.
It sounds like synagogue, but it's secretagogue, which these are like not taking
growth hormone, but taking peptides that promote growth hormone release. And then people are
taking, you know, gastric peptide this, and here's the deal. Things that make us feel more vital,
like testosterone, DHT, growth hormone, generally will shorten your life.
I know that's a bit of a controversial statement, but if you step back and you just ask yourself,
what is the most vital energetic phase of your life? It's puberty, when all these hormones are
really high. And puberty is the most rapid period of aging that any of us go through.
I was talking about this recently with a longevity researcher, the most rapid period of aging that any of us go through. I was talking
about this recently with a longevity researcher and I, and it's kind of interesting that all the
longevity, the attempts at increasing lifespan are like starving yourself, which is catabolic,
reducing blood sugar, which is catabolic. And that's on the opposite side of all these things
like testosterone, which is anabolic insulin, which is anabolic, insulin, which is anabolic, growth hormone, which is anabolic. And so anabolism sounds like a great thing,
although it does sound remarkably similar to cannibalism, but growth and vitality, libido,
strength, et cetera, that all sounds wonderful and in its proper form and context is wonderful.
But the reason why I think we see people dying early who do a lot of growth hormone
and testosterone is because they've effectively created a third and fourth round of puberty.
You're accelerating aging. And so I think vitality and longevity always have to be
balanced with one another. Totally. And we could go for hours just on this one topic.
One other cautionary note, well, two actually.
Number one, unless you're type one diabetic, don't inject insulin.
There are athletes who do this, but you can very easily kill yourself.
The second is if you're taking a lot of growth agents, some of them are not selective to
skeletal muscle tissue.
And you may, as a male, end up looking like you're in your second trimester
from enlarged organs. And guess what? When you get off of those drugs, your organs don't
automatically resume their smaller size. This is also why certain baseball players and so on have
gone up multiple helmet sizes. It's not from pork burritos. Those effects are durable. You can't
just hit undo on those things.
Very good points.
Pays to be cautious. All right. So to a few other things, cognitive enhancement or cognitive boosting supplements, much like the testosterone playing field, there's a clown car full of
ridiculous propositions. There are, of course, then the prescription and medical
route where there are certain things that'll help. Some things like nicotine can be tremendously
effective but come with some possible downsides associated. Do you have any particular thoughts
on cognitive enhancement or how you think about that specifically on the pharmacological
supplement side? I know there are many other things that we could also talk about.
Yeah, I'm glad you mentioned many other things. I won't list them out again, but I do believe that
the most powerful nootropic and cognitive support is going to come from quality sleep.
Yeah, 100%. Agreed. in capsule form of 300 milligrams or so. I think taken occasionally or more than occasionally,
provide it's fairly early in the day,
it does increase focus without increasing
the kind of sympathetic arm of the nervous system.
In other words, without increasing arousal
and alertness too much.
So I do think alpha-GPC is a useful supplement
and I use it from time to time.
If I've slept well, I don't take it.
If I really want to push a workout hard or a work session, a writing session or data analysis
session hard, I'll take 300 milligrams of that and drink a couple espresso or drink some mate
and some water, stay hydrated. Hydration is a big one for cognitive function, and it's one that people often overlook.
But the simple rule is that
this is what I call the Galpin equation,
because Andy Galpin, who's a great exercise physiologist,
came up with this for physical work,
but it turns out to work for cognitive work too,
which is that basically your body weight in pounds
divided by 30 will give you the number of ounces of water
that you should drink about every 20 minutes
when exercising
or doing mental work. Might seem like a lot. There might be an extra trip to the bathroom or two,
but it's worth it. Dehydration is a subtle but very pernicious creep where you start having
a hard time focusing your eyes. You just feel like you want to go to sleep. That hydration
factor is real. So drink plenty of fluids, especially if you're ingesting caffeine, which of course is a diuretic.
My personal favorite vehicle for caffeine remains yerba mate. I just absolutely adore
the effects of yerba mate. I'm not saying it's for everyone, but you have the caffeine,
and I might be getting the pronunciation off. You also have, I believe, theophylline, which you would find in green tea and theobromine,
which you would also find in say dark chocolate. Side note, trivia for folks, theobromine from
Theo as in theosophy, theobroma, food of the gods. So that's kind of fun.
Oh, I didn't know that.
Yeah. But the pharmacokinetics of those are all different.
So unlike coffee, which I have a love-hate relationship with because I metabolize it
so quickly that I get this sort of Snickers bar sugar high of caffeine for a very short time,
20 or 30 minutes. And then my baseline of sort of subjective perceived energy is lower than when I started.
So what happens then?
I become a crackhead who drinks eight cups of coffee a day.
Not so with yerba mate, especially when you're kind of titrating it in, in the way that they
would consume it in a place like Argentina or Uruguay, where you're just kind of sipping
it slowly.
It's great stuff.
I found a brand that, and I don't have any relation to them,
but I found one that I particularly like. It has a weird name, but it's Anna Park.
It's an organic yerba mate. I don't know who Anna is or her park, or maybe her name is Anna Park,
but it's nice. It has the right amount of that tobacco flavor, but it's not burnt to the point
of feeling kind of overwhelming. The other thing about caffeine that's kind of
interesting is that most people would benefit from waiting 90 minutes to two hours after waking
to ingest their caffeine. The way caffeine interacts with the adenosine receptor. Remember,
you get sleepy because of time of day with that whole circadian clock mechanism, but also because
of the buildup of adenosine in your system. That's the sleepiness factor really.
And when you wake up in the morning,
if you immediately compete out any residual adenosine,
you lose the benefit of that cortisol pulse
essentially clearing out the rest of the adenosine.
And so a lot of people,
despite the pain of having to do this the first day or two,
feel much better throughout the day,
less of that cracked out kind of rise and crash feeling on caffeine if they delay their coffee
or mate for about 90 minutes to two hours after waking.
Oh, that's great to know. Side note for people who may want to do some further research and
reading into caffeine, the name Roland Griffiths has come up multiple times
on this podcast.
He is an incredible scientist and researcher
based at Johns Hopkins.
He is one of the most, I would say, esteemed researchers
alongside, say, Matt Johnson.
Roland has just been at it for longer
with respect to psilocybin and psychedelics.
So he's associated with that, but prior to psychedelics,
he was one of the world's foremost experts
in caffeine metabolism.
And so he has published and performed studies
related to caffeine that are intensely interesting.
So for people who wanna dig deeper into that,
Roland Griffiths is a great resource. One thing I've been wondering,
because there are drugs that you can use
to counteract other drugs, right?
So if you go to Bellevue and you're at the psych ER
and someone comes in just high out of their mind
on cocaine, right?
There are medications that could be given
to try to take them down a notch or two or three or ten, like Halidol. I'm not sure if that's used any longer, but there are many different drugs that could be used. for sake of argument, is working on his laptop at a restaurant and said restaurant has excellent
service, which means they also have the never-ending cup of coffee. And so before he
knows it, he's had five cups of coffee, even though he only ordered one coffee.
Is there a way to reverse or counteract the effects of caffeine on adenosine such that
you can actually get to sleep? So if you hit the golf ball and you're like, oh, fuck, looking at the half-life of caffeine,
there's no way I'm getting to sleep until like three in the morning.
Is there any way to address that?
Or is it just fait accompli and you're more or less screwed?
Yeah, one direct and two indirect.
The direct way to do that is increase your glucose.
You know,
the whole notion that you can soak it up by eating some bread, you will see a blunting of the stimulant effect. Now, whether or not that's also due to some, I don't know, increase in
serotonin or something from the carbohydrate isn't clear, but yeah, you could have a bagel or two or
whatever it is that you're the compatible carbohydrate. These days, carbohydrates are
such a complicated thing
for most people.
I like carbohydrates, especially late in the day.
I do the, I either fast and go low carb,
no carb during the day,
because that lets me focus.
And that's a meat and salad during the day
or not eating for portions a day.
And then at night I eat pasta and rice
and I eat very little protein, sleep like a baby.
That's what works.
But the other way is to take theanine.
So before we were to take theanine. So before we were
talking about theanine in reference to pre-sleep supplementation, 30 or 60 minutes before sleep,
but a hundred to 200 milligrams of theanine will take the jitters out of a caffeine experience.
And in fact, so much so that a lot of energy drinks now are starting to include theanine
as an attempt to get you to ingest more of those energy drinks because they understand that at some
point people hit threshold and they feel so wide eyed and wired that they're not going
to consume more.
So they, they're tricking you this way and it does indeed work.
The other thing is if you ever really need to sleep, I mean, again, be cautious, do what's
compatible with your physician's advice, but GABA, you know, you can buy GABA and glycine in capsule form.
So a gram of GABA, a gram of glycine in combination, that's more of a heavy hit over the head.
But if you're having a hard time getting to sleep, that can help.
I don't recommend people take those chronically because GABA of course is a neurotransmitter. And I don't believe really in taking things that are very close to the actual
thing that you're trying to manipulate. For instance, I'm not a fan of taking L-DOPA.
Why would I do that? I don't have Parkinson's, but people will take mucunipurines, which is
essentially 99% L-DOPA and you'll get really, really elevated, but then you'll really crash for a day or two.
So I think that pulling on the marionette strings a little bit from a distance is better than taking
the specific compound that you're trying to replace, unless there's a clinical need, of course.
One more topic. And since we're at about two hours and 30, we'll wrap up in just a little bit.
But the vagus nerve, what is the vagus nerve?
What is the latest and greatest?
Why is it of interest?
Yeah, so the vagus nerve is a nerve network.
It's many nerves.
It could even be thought of as its own major branch
of the peripheral nervous system.
It comes out of the brain, basically,
and connects to all the organs of the body.
And this is the pathway by which a mental state can influence our digestion, our heart
rate, our breathing.
We talked earlier about HRV, heart rate variability.
The vagus is an important component to the slowing down of the heart rate when we exhale.
It's a very important pathway and it's bidirectional.
So the organs of the body that I just mentioned,
the lungs, the gut, the heart, et cetera, the spleen,
they also send nerve connections back to the brain.
And there's been a lot of interest in the vagus as a purely calming system.
And that's simply not true.
The medical textbooks call it appropriately cranial nerve 10.
It's in the parasympathetic arm of the nervous system,
which suggests that it's all calming, but actually it's not. It has branches of it that are kind of stimulating as well.
So in the kind of wellness and self-help community, you hear, oh, you know, you should do
this thing of rubbing in front of your ears. That's a branch of the vagus that calms you down
or stimulate the vagus to calm down. Now in neuroscience laboratories, and even in some
human neurosurgery laboratories, the way that you get people more Now in neuroscience laboratories, and even in some human neurosurgery
laboratories, the way that you get people more alert, in fact, a form of depression treatment
is to stimulate the vagus and it makes people more alert and more positive and excited.
So vagal stimulation can easily cause increases in alertness.
How do they do the stimulation?
This is a beautiful story. A colleague of mine, perhaps in least to my mind,
the most impressive neurobiologist I know, a guy by the name of Carl Deisseroth, he invented,
discovered and invented channel rhodopsins, which are these from algae essentially that are light
sensitive, clone the genes. You can put those genes into neurons. You have to do this by viral
injection. And then you have a little blue light diode that will allow you to stimulate just those
neurons locally. Carl's a psychiatrist, a bioengineer, and a neurobiologist operating at the very highest
level.
Actually, there's a book that he just published that I'm listening to now that is, it's just
can only be described as beautiful.
It's a description of the landscape of psychiatry and his attempts to build tools that are better
than drugs to manipulate the nervous system.
It's called Projections.
And it's a beautiful read.
You'll learn a ton of neuroscience.
Carl is well on his way to win every big prize in science.
He's got all of them right now except the last one.
And I'm not on the committee that votes for those.
But he's remarkable.
Also has five children, happily married.
I mean, he's like one of these.
His wife is a phenomenal scientist and physician.
These people are,
one of the reasons I like being at Stanford
is because the mean is so very high,
but Carl shifts the mean.
Like he's that dot way out there.
In any event, Carl, there's a beautiful article
that I can reference,
send you the link to in the New Yorker,
where Carl is sitting there talking with his patient
and she has suicidal
depression. And she's describing her lack of desire to live. And then he cranks up the intensity on
this stimulation of the vagus. And in real time, she starts describing how she actually would be
interested in applying for a couple of jobs this year. This is happening in the order of seconds
by stimulation of the vagus.
What is the machine?
What is it actually, how does it connect to her?
That one is an implanted electrical stimulation device
that's placed probably on,
there are many branches of the vagus,
and so on a branch that isn't going to impact breathing.
Sometimes people have challenges with swallowing.
So there are problems with doing that.
Carl, a big part of his mission
is to create very
small light diodes that can stimulate nerves without the need to inject viruses and things
of that sort. So that I think at a time not too far from now, thanks to his work and the work of
other bioengineers, we are going to be able to stimulate, for instance, just the serotonin
neurons in the RAFE that lead to active coping.
This is a well-known phenomenon. Whereas when you take Prozac or Zoloft or one of these other drugs,
it will stimulate those neurons, but will also stimulate the serotonin receptors on the spinal neurons that control the sexual response. And that's why they have sexual side
effects. So more precision is coming. So as it relates to vagus, the other way in which the vagus is stimulating
is something that we do quite often.
We have neurons in our gut
that we all hear about the gut brain axis
and people say, oh, it's your second brain,
but very seldom does anyone actually describe
how the second brain actually impacts the other brain.
And the simple way to put this is
we have these neurons that live
in the mucosal lining of our gut.
And those
neurons sense three things. They sense fatty acids. So they like fat. They sense amino acids.
They love that umami flavor and they love amino acids because that's vital to protein repair,
metabolism, et cetera, protein synthesis, excuse me. And they like sugar. And when you eat something
that has fatty acids, amino acids, or sugar, these neurons
send a signal.
They're part of the vagus nerve up to a little cluster of neurons in your neck called the
nodose ganglia, N-O-D-O-S-E.
And the nodose ganglia then stimulates your deep brain centers to release dopamine.
And the amazing thing about this, these are data from a guy named Diego Borges at Duke
University. The amazing thing about this system is that even if you numb the mouth, even if you
just gavage a person or an animal and put these substances into the stomach, you will seek more
of these foods. And so you're actually seeking sugar, amino acids, and fat more when you ingest
those foods independent of how they taste.
And so this has a whole set of implications for hidden sugars and the fact that so many of the
foods we eat, we just find ourselves eating more of them. We think this doesn't even taste,
I don't even know why I'm eating this. It's because these neurons in your gut are stimulating
dopamine release. And as we talked about before, dopamine isn't a molecule of pleasure. It's a molecule of
making you want to do whatever led to dopamine release. Yeah. The molecule of more. The molecule
of more. So the Vegas is multifaceted and we will soon hopefully subdivide it into some more
meaningful pathways. I don't like to knock on anyone else's work, but I do think that most of
what you read out there about the Vegas and what it does and various theories about it are partial truths to total nonsense.
But they are partial truths to total nonsense that were grounded in the biology as we understood it at the time.
And just a lot more has been understood in the last 10 years or so.
So no disrespect to those people, but it's time for a revision.
Maybe two or three more questions
then we'll we'll go get some food uh something along those lines the first is what books have
you gifted the most to other people or are there any books that come to mind that you've gifted
often to other people i love poetry and it's almost cliche now to say this because so many people
like his work, but I think David White's work is just beautiful and is a wonderful kind of
entry point to, to poetry. I'm also a big Wendell Berry fan has written a lot about farming and the
natural world and I've never met him, but I'm a huge Wendell Berry fan. Some I'll sometimes give
Wendell Berry books as gifts.
The book that I think is perhaps, at least to me, the most beautiful book of all
is Longitude by Dava Sobel about the history of the discovery of timekeeping at ocean,
which is not a trivial problem to solve. And it's just a beautiful story of how scientists, or in this case,
a particular scientist merged the quest for a technology with a scientific problem with adventure
and going out on boats and risking one's life for the sake of science is something that
resonates with me a bit. It's a beautiful short book and it's very accessible to anybody,
whether or not you have a background in science or not.
And she's an absolutely wonderful writer.
And so that's the one I gift most often.
Is there a particular David White book or starting point that you might recommend?
You know, I own several of his books, but I confess that I'm forgetting the titles now.
You know, what's interesting about David White is that his poetry is best consumed
by listening to him read it
because he does this thing of repeating things twice
and his cadence is so impressive.
And so I would, even though I loathe
to kind of push people toward online,
do buy his books, but I would suggest
just going online and listening to a YouTube video
or watching a YouTube
video of David reading one of his poems. He's onto something. The thing about poetry that's
so fascinating to me, it's the same reason why I love anything sung by Bob Dylan or Joe Strummer,
is that the words don't necessarily make sense in the pure cognitive landscape. They're tapping
into some sort of deeper layer of the nervous system that defies the normal structure of sentences and thoughts. And so I think good
poets are accessing the subconscious. And it has nothing to do with rhyming. It has to do with
accessing some layer of neurobiology that we just don't have a name for.
Andrew, this question is sometimes a complete dead end, and I'll take the blame for that if it is. But just to go fishing and see what we catch here, if you could put anything on a gigantic billboard, metaphorically speaking, to get a message out, a quote, an image, a word, could be anything, a quote from someone else, anything at all, two billions of people, what might you put on that billboard?
Well, assuming this is a big billboard, I could probably squeeze two things on there,
but I would diminish the impact of either one.
So it's so simple, but it's the most use, at least has been the most useful thing in
life to me, which is credit goes to the Oracle, which is know thyself.
If there's one thing that's a really useful pursuit is to
take a really good stock of what you've come into the world with and where you happen to be at
present, get really honest about that with yourself. And in doing that, it illuminates the
path to filling in the gaps and improving oneself. And knowing thyself is a dynamic process.
And the answers to knowing thyself
and what that is will change over time.
But that is the question that I think everybody,
as soon as we are able to,
should be asking ourselves and constantly updating.
Know thyself.
What was second pick?
You can put it on the other side of the billboard.
Yeah, the other one was far weaker as the one I think, but use the body to control the mind.
I really worry about this current state of the world where people are so unable to regulate
their autonomic nervous system.
They're stressed, they're angry, they're pissed.
And look, I suffer from this too.
Someone, sometimes I comment on whatever, I'm mostly on Instagram, but sometimes
on Twitter. And I noticed all this anger and stuff, and you start getting pulled into it from
time to time. I regulate my behavior, but I don't respond, but we're all subject to this, but almost
all harm, almost all self-harm and unfortunate things in life are the consequence of a poorly
regulated autonomic nervous system. We say the wrong thing. We do the wrong thing. We're impulsive, et cetera. And I think controlling
the autonomic nervous system is simple in one sense and challenging in the other. Simple in
the sense that the tools exist. I do believe that respiration and vision are the two ways to control
the autonomic nervous system in real time, the best
ones. And at the same time, it's very hard to do. So we have to remind ourselves, that's why I'd
want to put it on the billboard, that when your mind isn't where you want it to be, use your body
to control your mind. I love that. Going to use that on a long hike with the pooch a little later today. And we'll also include,
for everybody listening, show notes with links to various resources, all the resources that we've
discussed. So the yoga nidra, the various types of breath work. I'll also add a name, which is
Dr. Leah Lagos has done a lot of really good work
looking at resonance training using breathwork for improving HRV, although improved HRV is really
just a proxy for all of these other desirable outputs and effects in the world and in life.
So we'll include all of that in the show notes. Andrew, we've covered a lot of ground. Is there anything else that you would like to mention or say or point people to in your
request of the audience?
Anything at all that you'd like to add before we wrap up for today?
We mentioned some of the things at the beginning.
I teach neuroscience on Instagram at Huberman Lab.
Those are resources, brief snippets, anywhere from one to three minutes
about neuroscience, exciting papers.
I see a lot of tools.
Be wonderful if people want to check out the podcast.
We cover a lot of topics, not just neuroscience,
and we batch those by month
so that we do four or five episodes
in one thing like hormones
and then move on to something else.
And I suppose one request would be,
we have this saying in a
laboratory, it's certainly not unique to laboratories, which is watch one, do one,
teach one. And what would be most gratifying for me would be if people find tools that they find
useful and that they learn about them, that's the watch one part, that they do them, they apply them
in their own life and modify them if you like. And then I think the way the world works best, at least in my view, is when people go on to teach those tools and
attribution isn't required. I didn't, as I always say, you know, I wasn't consulted at the design
phase and I don't know anyone else that was either. So, you know, mother nature and deserves
and biology deserve credit for all this. And so if people would like to learn, practice and teach,
I like to think that the world
can improve by virtue of sharing of tools. I love it. I dig it, man. And there are a number
of places people can follow you and should check you out. As you mentioned, the Huberman Lab
podcast, hubermanlab.com and hubermanlab, at hubermanlab on Instagram and Twitter.
This has been so fun and I really appreciate all the time.
It's been a real pleasure spending time with you, Andrew.
And I look forward to many more conversations.
I have a feeling that people will want a round two.
So until then, thanks to you and thanks to everyone for tuning in.
Hey guys, this is Tim again.
Just a few more things before you take off.
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A lot of runner friends of mine use them on their IT bands after long runs. There are a million ways to use it. And the Gen 4 Theraguns start at just $199. I said I have two. I have the Prime,
and I also have the Pro, which is like the super Cadillac version. My girlfriend loves
the soft attachments on that. So check it out. Go to theragun.com slash Tim.
One more time, theragun.com slash Tim.
This podcast episode is brought to you by Helix Sleep.
Sleep is super important to me.
In the last few years, I've come to conclude
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