Optimize & Control Your Brain Chemistry to Improve Health & Performance

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.260 | where we discuss science and science-based tools

00:00:04.880 | for everyday life.

00:00:05.900 | I'm Andrew Huberman,

00:00:10.360 | and I'm a professor of neurobiology and ophthalmology

00:00:13.360 | at Stanford School of Medicine.

00:00:15.300 | Today, we're going to discuss your brain chemistry

00:00:17.920 | and how to control and optimize your brain chemistry

00:00:20.800 | for all aspects of mental health,

00:00:22.840 | physical health, and performance.

00:00:25.120 | Many times before on the Huberman Lab Podcast,

00:00:27.560 | and frankly, every time I'm a guest on another podcast,

00:00:30.800 | I get questions about science and science-based tools

00:00:33.680 | for things like enhancing sleep, enhancing focus,

00:00:36.740 | enhancing creativity, improving relationships,

00:00:39.040 | getting over grief, and on and on,

00:00:41.500 | all of which are valid questions

00:00:43.220 | and for which there are protocols that are based in science

00:00:46.000 | and that work the first time and every time.

00:00:49.320 | However, far more important than knowing a protocol

00:00:52.300 | is understanding why a given protocol works.

00:00:55.000 | That's why I'm always hammering on mechanism

00:00:56.960 | and explaining the cells and circuits and chemicals,

00:00:59.480 | at least to some detail,

00:01:01.060 | so that people can understand not just what to do,

00:01:04.080 | but why it works and therefore how to change a protocol

00:01:07.720 | as their life circumstances change or as goals change.

00:01:11.280 | Now, today we are going to go even a layer deeper.

00:01:14.160 | We're going to explore the foundations of your biology

00:01:17.120 | in your brain and body that allow any protocol to work

00:01:21.360 | because as it turns out, all of the protocols out there,

00:01:24.460 | whether or not it's a breathing protocol or a supplement

00:01:27.100 | or a prescription drug or an exercise routine,

00:01:30.580 | they all tap into and leverage a core set

00:01:34.740 | of just a few biological mechanisms.

00:01:37.300 | That's right.

00:01:38.140 | Beneath everything you are able to do and feel,

00:01:41.420 | and indeed beneath every protocol

00:01:43.580 | that allows you to change for the better

00:01:45.660 | and optimize your mental health,

00:01:47.100 | physical health, and performance,

00:01:48.860 | there's just a small subset of chemicals

00:01:50.900 | that you're leveraging toward that change.

00:01:53.620 | So today we're going to talk about the four major pillars

00:01:56.420 | of neurochemistry that allow you to, for instance,

00:01:59.740 | be focused when you want to focus,

00:02:01.660 | that allow you to relax when you need to relax

00:02:03.820 | and de-stress, that allow you to optimize your sleep,

00:02:06.940 | that allow you to optimize your exercise routine

00:02:09.980 | or to work through a pain point in relationship

00:02:12.700 | or in career or in your relationship to yourself.

00:02:15.900 | So what I can say for sure is that by the end

00:02:17.940 | of this episode, you will have a much richer understanding

00:02:21.820 | about how your brain and nervous system

00:02:24.140 | and indeed your entire body work,

00:02:26.220 | and you will have a much firmer understanding

00:02:28.660 | as to which protocols and tools to reach for

00:02:31.740 | given your particular goals in the moment,

00:02:34.700 | in the day, across the week, across the month,

00:02:37.700 | across the year, and indeed across your entire lifespan.

00:02:40.720 | So what we're really going for today are principles,

00:02:43.400 | deeper understanding of why any given protocol works,

00:02:47.300 | and we are also going to discuss specific protocols.

00:02:50.460 | Some of those protocols I've discussed

00:02:52.340 | on previous episodes of the "Huberman Lab Podcast,"

00:02:55.080 | but I must say many of the protocols and tools

00:02:57.660 | that I will discuss are brand new and based on research

00:03:00.480 | that I have not discussed at all,

00:03:02.140 | simply because the research papers came out only recently,

00:03:05.480 | or these are papers that I only recently unearthed.

00:03:08.780 | In fact, I'm going to share with you two recent studies

00:03:11.300 | in a moment that are exceedingly important

00:03:14.140 | for optimizing your sleep, and these are studies that,

00:03:17.080 | again, I've never discussed in any episode on sleep

00:03:20.440 | or on any other podcast.

00:03:21.820 | So by the end of today's episode,

00:03:23.260 | you're going to have far more knowledge

00:03:24.620 | about your biology and psychology

00:03:26.260 | than you did at the start,

00:03:27.540 | and you'll be armed with many more tools

00:03:29.420 | and most importantly, principles so that you can navigate

00:03:32.680 | not just the tools presented on this podcast,

00:03:35.120 | but in the vast landscape of tools that are out there

00:03:37.760 | for mental health, physical health, and performance.

00:03:40.420 | The "Huberman Lab Podcast" is proud to announce

00:03:42.380 | that we've partnered with Momentus Supplements.

00:03:44.640 | We've done that for several reasons.

00:03:45.920 | First of all, the quality of their supplements

00:03:47.960 | is exceedingly high.

00:03:49.500 | Second of all, we wanted to have a location

00:03:51.600 | where you could find all of the supplements

00:03:53.200 | discussed on the "Huberman Lab Podcast"

00:03:54.880 | in one easy to find place.

00:03:56.860 | You can now find that place at livemomentus.com/huberman.

00:04:01.200 | In addition, Momentus Supplements ship internationally,

00:04:04.540 | something that a lot of other supplement companies

00:04:06.420 | simply do not do.

00:04:07.660 | So that's terrific whether or not you live in the US

00:04:09.560 | or you live abroad.

00:04:10.620 | Right now, not all of the supplements that we discuss

00:04:13.200 | on the "Huberman Lab Podcast" are listed,

00:04:15.260 | but that catalog of supplements

00:04:16.920 | is being expanded very rapidly,

00:04:18.620 | and a good number of them that we've talked about,

00:04:20.400 | some of the more prominent ones for sleep and focus

00:04:22.780 | and other aspects of mental and physical health

00:04:25.040 | are already there.

00:04:25.880 | Again, you can find them at livemomentus.com/huberman.

00:04:28.720 | Every so often, I come across a study or set of studies

00:04:32.480 | that I get so excited about

00:04:33.800 | that I start telling everybody in my immediate life,

00:04:36.380 | and I insist on also sharing it with you,

00:04:39.320 | the listeners of this podcast,

00:04:40.620 | because I find the information

00:04:42.520 | to be so incredibly interesting and actionable.

00:04:45.320 | The two studies that I'm going to discuss

00:04:47.120 | both relate to sleep and sleep states

00:04:49.620 | and how to access better sleep.

00:04:51.640 | The first one was published in the journal Cell Reports,

00:04:54.560 | Cell Press Journal, excellent journal,

00:04:56.320 | and the title of this paper

00:04:57.280 | is "Rapid and Reversible Control of Human Metabolism

00:05:00.360 | by Individual Sleep States."

00:05:01.860 | We will provide a link to the study in the show captions.

00:05:04.660 | The first author is Nora Nowak, N-O-W-A-K.

00:05:08.820 | And basically what they did is they measured

00:05:11.840 | the different forms of metabolism that occur

00:05:14.060 | while humans sleep.

00:05:15.660 | As far as I know, this is one of the first studies

00:05:17.860 | of this kind.

00:05:19.300 | There are many studies of metabolism.

00:05:21.080 | There are many studies of sleep.

00:05:22.620 | This study focused on how different states of sleep,

00:05:25.680 | such as rapid eye movement sleep,

00:05:27.420 | which is associated with dreaming

00:05:28.800 | and high emotional content dreams versus slow wave sleep,

00:05:32.220 | which tends to be more focused on physical repair

00:05:34.340 | of the body, more mundane dreams,

00:05:36.240 | how those different states of mind during sleep

00:05:38.860 | relate to different aspects of metabolism.

00:05:41.580 | And what they found was absolutely fascinating.

00:05:43.700 | First of all, they found that sleep states regulate

00:05:47.020 | more than 50%, half of all the metabolite features

00:05:51.260 | detected in human breath.

00:05:54.020 | What does that mean?

00:05:54.900 | Well, it turns out that you can figure out

00:05:56.420 | what humans are metabolizing in particular,

00:05:58.780 | more lipids or more carbohydrate,

00:06:00.500 | whether or not they're relying more on glucose metabolism

00:06:02.660 | based on the contents of their breath.

00:06:04.420 | This is true during waking and during sleep.

00:06:06.580 | And this is what allowed them to do

00:06:07.740 | these incredible measurements

00:06:08.780 | of what's being metabolized during sleep.

00:06:11.100 | They measured close to 2,000 metabolites in breath

00:06:14.380 | every 10 seconds across the entire night's sleep.

00:06:17.340 | And what they found was that there are major pathways

00:06:20.740 | related to lipid metabolism, fat metabolism,

00:06:23.620 | or to carbohydrate metabolism,

00:06:25.540 | or other forms of metabolism that are up or down regulated

00:06:29.340 | as human beings transition between slow wave sleep,

00:06:33.040 | rapid eye movement sleep, and waking.

00:06:35.260 | And you might say waking.

00:06:36.200 | Well, yes, they also looked as people fell asleep

00:06:38.040 | and as they emerged from sleep.

00:06:39.140 | And believe it or not, every so often during sleep,

00:06:41.240 | you wake up, you didn't know this,

00:06:42.860 | but you wake up in the middle of the night,

00:06:43.840 | you look around and you go back to sleep.

00:06:46.020 | You're not aware of it

00:06:46.860 | because you're still in a rather sleep-like state,

00:06:50.460 | although you are awake.

00:06:52.020 | What they found was that sleep

00:06:53.380 | and the various states of sleep

00:06:54.820 | regulated individual metabolic pathways.

00:06:57.820 | They found, for instance,

00:06:59.320 | that the switch from sleep to wakefulness

00:07:02.020 | reduces fatty acid oxidation.

00:07:04.180 | So that means while you're asleep,

00:07:05.460 | you're oxidating more fatty acids.

00:07:07.640 | And as you wake up, that becomes less the case.

00:07:11.020 | And there's a switch in slow wave sleep

00:07:12.940 | that increases fatty acid oxidation.

00:07:16.100 | And there's this transition from rapid eye movement sleep

00:07:19.040 | to other aspects of sleep

00:07:20.520 | that brings about things like the so-called TCA cycle.

00:07:23.460 | Some of you familiar with metabolism

00:07:24.960 | will be familiar with the TCA cycle,

00:07:26.560 | the so-called tricarbolic acid cycle,

00:07:28.760 | intermediates, that's fancy nerd speak

00:07:31.120 | for specific aspects of metabolism being regulated

00:07:35.020 | during this rapid eye movement sleep transition.

00:07:38.400 | What does all this mean and how is this actionable?

00:07:41.020 | Well, on many episodes of the Huberman Lab Podcast,

00:07:44.220 | such as the master sleep episode

00:07:46.580 | and the episode that we're going into in further depth today,

00:07:49.920 | we're going to talk about sleep and how to optimize sleep.

00:07:52.680 | It's been thought of, but not really tamped down,

00:07:57.100 | that quality and depth of sleep and duration of sleep

00:08:00.320 | is important for metabolism during the daytime.

00:08:02.820 | And indeed, that's the case.

00:08:03.940 | If people are sleep deprived or they're not sleeping enough,

00:08:06.760 | things like glucose metabolism, et cetera,

00:08:08.600 | get really disrupted during the daytime.

00:08:10.640 | But what this current study shows

00:08:12.720 | is that the metabolism that you experience during sleep,

00:08:15.960 | or to be more specific,

00:08:17.200 | the range of different types of metabolism

00:08:19.800 | that you experience during sleep may serve to tune up

00:08:23.320 | or to ensure that the specific aspects of metabolism

00:08:26.160 | that you require during wakefulness are working properly.

00:08:29.500 | In addition to that,

00:08:30.800 | this study clearly shows that getting enough sleep

00:08:33.820 | allows you to transition

00:08:35.120 | through all the various forms of metabolism

00:08:37.740 | and use all those different forms of metabolites

00:08:40.700 | during sleep in a way that's immensely beneficial

00:08:43.580 | for the systems of your brain and body.

00:08:45.780 | So the take-home message here is that, as the authors state,

00:08:49.940 | sleep and experiencing the different states of sleep,

00:08:53.640 | slow wave sleep early in the night predominantly,

00:08:55.860 | plus rapid eye movement sleep toward the end of the night,

00:08:59.100 | is extremely important for optimizing metabolic circuits

00:09:02.540 | for human performance and health.

00:09:04.520 | In other words, by not getting sufficient duration sleep,

00:09:07.160 | you're not allowing your body and brain to transition

00:09:09.800 | through all the different aspects of fuel utilization,

00:09:13.080 | and you're not teaching your brain and body

00:09:16.260 | how to use similar types of fuels during wakefulness.

00:09:19.060 | So again, all of this points to the fact

00:09:20.780 | that we need to be getting sufficient quality

00:09:23.100 | and duration of sleep.

00:09:24.240 | So if you're sleep deprived even by an hour or so,

00:09:27.160 | you're going to get far less rapid eye movement sleep,

00:09:29.420 | because rapid eye movement sleep

00:09:30.600 | is what occurs toward the end of a sleep night,

00:09:33.500 | during the early part of the night,

00:09:34.560 | far more slow wave sleep.

00:09:36.740 | In getting less rapid eye movement sleep,

00:09:39.440 | we know it makes you more emotionally labile,

00:09:41.260 | but now we know it's also going to alter certain forms

00:09:44.100 | of glucose metabolism during the night

00:09:47.720 | and during wakefulness.

00:09:49.720 | So that all underscores the need to get sleep.

00:09:52.760 | But then the question is how to get enough sleep

00:09:54.700 | and how to make sure you get

00:09:55.640 | into all these different sleep states.

00:09:57.400 | And this is particularly important

00:09:58.820 | for you so-called night owls.

00:10:01.080 | There's a lot of controversy out there

00:10:02.900 | as to whether or not different so-called chronotypes exist.

00:10:05.700 | That is people who just naturally

00:10:07.800 | or genetically want to be an early bird,

00:10:10.680 | wake up early and go to bed early.

00:10:12.040 | So these people that wake up at 4 a.m.

00:10:14.520 | and would be most comfortable going to bed

00:10:16.720 | by 7 or 8 p.m. or 9 p.m.

00:10:19.500 | Then there are so-called night owls,

00:10:21.400 | people that would feel best or tend to feel best

00:10:24.820 | when they go to sleep at 1 a.m., 2 a.m., even 3 a.m.

00:10:28.720 | and like to wake up later, 8, 9, 10,

00:10:31.000 | or even 11 a.m. or noon.

00:10:33.920 | And then of course, most people go to sleep somewhere

00:10:36.200 | between 10 p.m. and midnight

00:10:37.880 | and wake up somewhere between 5 a.m. and 7 a.m.

00:10:41.160 | Or I suppose more typically 6 a.m. and 8 a.m.

00:10:45.000 | Now, whether or not real chronotypes exist

00:10:47.120 | or whether or not people simply select schedules

00:10:50.080 | for sleep and wakefulness that they like

00:10:52.340 | because of their social schedules

00:10:53.700 | or the activities they enjoy.

00:10:55.000 | For instance, some people like to really go out.

00:10:57.120 | They like to go out dancing or hear music

00:10:59.220 | or spend time in venues that are only open late at night

00:11:02.080 | and don't even open until noon or after.

00:11:04.440 | Other people like myself rarely go out at night,

00:11:07.440 | but I like to get up early, I like to exercise,

00:11:09.560 | I like to see the sunrise, et cetera.

00:11:11.660 | So I don't know if I'm a morning person or an evening person,

00:11:14.280 | I just know the things I enjoy tend to happen

00:11:16.400 | in the early part of the day

00:11:17.500 | and the things that I don't enjoy quite as much

00:11:19.760 | tend to happen late at night.

00:11:21.660 | Regardless of whether or not

00:11:22.760 | there are real genetic propensities to be a night owl

00:11:26.120 | or an early bird

00:11:27.360 | or a sort of typical person right there in the middle,

00:11:30.880 | it's very important that people have some control

00:11:32.800 | over their sleep schedule.

00:11:33.840 | And even more important,

00:11:35.080 | that people are able to get sufficient amount of REM sleep

00:11:38.760 | and slow wave sleep for many reasons,

00:11:41.040 | but including the reasons I discussed

00:11:42.680 | in the previous study related to metabolism.

00:11:45.140 | I'm very excited therefore

00:11:47.480 | about a study that came out in sleep medicine.

00:11:49.560 | This was a few years ago, but somehow I missed this one.

00:11:51.800 | It was published in 2019.

00:11:53.360 | And the title of this article

00:11:54.800 | is resetting the late timing of night owls

00:11:57.040 | has a positive impact on mental health,

00:11:58.960 | physical health and performance.

00:12:01.000 | This is a study done in humans,

00:12:02.840 | focusing specifically on people

00:12:04.680 | that like to stay up late and sleep in,

00:12:07.480 | but who desire to be able to get up and feel alert

00:12:10.880 | in order to go to work or study,

00:12:12.520 | and they want to go to sleep a bit earlier.

00:12:14.460 | And so there are a lot of questions embedded in this study,

00:12:17.440 | in particular,

00:12:18.280 | whether or not people can actually shift their schedule

00:12:20.080 | by a few hours or more.

00:12:21.840 | Some people out there contend that if you're a night owl,

00:12:24.020 | that's just going to be impossible

00:12:25.640 | or very, very challenging to do.

00:12:27.640 | Turns out it's not impossible,

00:12:29.240 | and it's not even that challenging to do

00:12:30.680 | provided you do the right things.

00:12:32.120 | Just a brief overview of the study,

00:12:33.580 | and then I'll give you the key takeaways.

00:12:36.000 | It was a randomized control trial.

00:12:37.920 | It involved a number of different people,

00:12:39.600 | both male and female.

00:12:40.960 | And what they did was they used non-pharmacological,

00:12:44.160 | practical interventions in a real world setting.

00:12:47.160 | Here I'm paraphrasing.

00:12:48.460 | They used targeted light exposure.

00:12:50.840 | They used consistent sleep wake times.

00:12:53.620 | They used fixed meal times, caffeine intake, and exercise.

00:12:57.720 | And this is one of the reasons I love this study so much

00:12:59.560 | because I've done episodes where I've talked about

00:13:01.040 | temperature, exercise, feeding,

00:13:03.260 | and most importantly, light exposure as a way

00:13:05.880 | to control and shift your sleep wake cycles,

00:13:07.960 | your so-called circadian timing and entrainment.

00:13:11.560 | What did they find?

00:13:12.700 | Well, they found, quote,

00:13:14.440 | "Significant improvements in terms of mood,

00:13:17.240 | so far less depression and stress,

00:13:19.920 | subjectively measured,

00:13:20.980 | as well as improved cognitive performance

00:13:23.040 | that was objectively measured."

00:13:24.140 | So improved reaction times,

00:13:25.600 | improved physical grip strength,

00:13:27.720 | which is actually a measure, not just of strength per se,

00:13:30.540 | but also of nervous system function.

00:13:32.640 | And a number of things that people could do

00:13:35.460 | in order to optimize their morning hours,

00:13:37.520 | even though they were night owls previously.

00:13:40.040 | What do they have people do?

00:13:41.000 | Well, I'm just going to list this off

00:13:43.260 | in sort of a rapid fire succession.

00:13:45.440 | Then we'll provide a link to the study

00:13:46.840 | if you want to learn more.

00:13:47.880 | First of all, they told participants

00:13:50.040 | to try and wake up two to three hours

00:13:52.240 | before their typical wake-up time.

00:13:53.880 | Two to three hours.

00:13:54.720 | That seems brutal to me and probably seems brutal to you

00:13:57.640 | if you're somebody who typically wakes up at 10 a.m.

00:14:00.000 | to try and get up at eight or even seven a.m. consistently.

00:14:04.120 | But they were also asked to maximize

00:14:06.240 | at outdoor light exposure during the mornings

00:14:08.560 | for reasons that if you've listened to this podcast before,

00:14:10.920 | if you've heard me talk about before,

00:14:13.000 | that I'm constantly talking about,

00:14:14.360 | I'll probably go into the grave shouting,

00:14:15.840 | "Please get as much light exposure

00:14:18.600 | from sunlight early in the day as possible

00:14:20.600 | because it sets in motion a huge number of things

00:14:22.760 | that are beneficial for your mental health

00:14:24.300 | and physical health, including dopamine production,

00:14:26.840 | timing melatonin production correctly,

00:14:29.160 | reducing cortisol peaks late in the day, et cetera, et cetera."

00:14:32.780 | So they asked them to get a lot of outdoor light exposure.

00:14:35.520 | They didn't give them a specific amount,

00:14:37.120 | where they said maximize outdoor light exposure

00:14:39.360 | during the mornings, the time before noon.

00:14:41.520 | And again, they had them waking up two to three hours

00:14:43.360 | before their habitual wake-up time.

00:14:45.280 | They were also told, and this is very important

00:14:47.400 | if you're going to shift your schedule earlier,

00:14:49.200 | to try and keep sleep-wake times fixed

00:14:52.220 | between their workdays and their weekends.

00:14:54.680 | So not sleeping in on the weekends

00:14:56.360 | or not having any sleep-in days,

00:14:58.120 | regardless of how well they slept the night before.

00:15:00.840 | How fixed?

00:15:01.760 | Within 15 to 30 minutes of their predesignated time.

00:15:06.420 | So if they were waking up at seven o'clock one day,

00:15:09.040 | they set their alarm and they made sure they got out of bed

00:15:12.000 | at seven o'clock every day, plus or minus 30 minutes,

00:15:15.360 | but never later than 7.30, never earlier than 6.30.

00:15:19.520 | Participants were also asked to try and go to sleep

00:15:23.200 | two to three hours before their habitual bedtime.

00:15:26.200 | So again, these are people that want to stay up late,

00:15:28.080 | like 11 p.m. perhaps, but even as late as 1 a.m. or 2 a.m.,

00:15:33.000 | and now they are asked to go to sleep two to three hours

00:15:35.960 | before their habitual bedtime

00:15:37.780 | and to wake up two to three hours earlier,

00:15:40.400 | as I mentioned earlier.

00:15:41.560 | They were also told, and I love this

00:15:44.280 | because it fits with many of the things we've talked about

00:15:46.200 | on this podcast before,

00:15:47.720 | to try and limit light exposure during the evenings.

00:15:50.820 | Dim the lights or limit altogether artificial lights.

00:15:54.800 | Lot of reasons for that.

00:15:55.860 | I covered that in the master sleep episode.

00:15:57.560 | I covered that in the optimize health using light episode.

00:16:00.720 | You can find those at hubermanlab.com.

00:16:02.840 | They're asking them to do that here.

00:16:04.520 | And they asked participants to keep a regular schedule

00:16:06.920 | for their daily meals, not eating on the hour consistently,

00:16:11.120 | you know, at 9 a.m., noon, 3 p.m. exactly,

00:16:14.120 | but within, again, about 15 to 30 minutes,

00:16:17.220 | they're always eating at the same times.

00:16:19.320 | That was also important.

00:16:20.560 | And again, that's because we have these so-called

00:16:22.680 | food-entrained circadian clocks.

00:16:24.480 | When you eat tells your body when to be alert

00:16:27.440 | and when you're not eating, when to be asleep.

00:16:30.240 | And they were told to not drink any caffeine

00:16:33.120 | after 3 p.m. in the afternoon,

00:16:35.200 | another theme that we've talked about on this podcast.

00:16:37.540 | They were also told not to take naps after 4 p.m.

00:16:41.840 | Naps are an interesting feature of the sleep-wake cycle.

00:16:45.140 | To be very brief about this and to pull from the episode

00:16:48.280 | that I did with world sleep expert

00:16:50.100 | from University of California, Berkeley, Matt Walker,

00:16:52.960 | naps are great for many people,

00:16:55.140 | but don't nap if it interferes with your nighttime sleep.

00:16:58.000 | And in this study, they told them don't nap after 4 p.m.

00:17:01.520 | And if you are a napper, don't nap for more than 90 minutes.

00:17:04.920 | 10 minute naps are fine, 20 minute naps are fine,

00:17:07.120 | zero minute naps are fine,

00:17:08.800 | but don't nap for more than 90 minutes

00:17:10.700 | and don't nap after 4 p.m.

00:17:12.140 | And to exercise during the morning.

00:17:15.820 | Now, this one can be a bit controversial

00:17:17.440 | because I know a lot of the PTs out there

00:17:19.260 | and a lot of the online gym rats and people who,

00:17:23.900 | and runners too, for that matter, will say,

00:17:26.080 | well, according to body temperature and research,

00:17:29.280 | it's best to exercise in the afternoon.

00:17:31.080 | Look, it's better to exercise sometime as opposed to no time,

00:17:34.160 | but if you're focused on how to shift your schedule earlier,

00:17:37.400 | meaning get up early and go to sleep earlier,

00:17:39.240 | this study had people exercise in the early part of the day,

00:17:42.760 | certainly before 2 p.m. and ideally before noon.

00:17:45.680 | So again, this is a really important study

00:17:48.220 | because it combines a lot of different variables

00:17:51.380 | to arrive at this very impressive shift

00:17:53.600 | where people can get up two to three hours earlier

00:17:55.860 | and then pretty consistently and reflexively

00:17:57.680 | start going to bed two to three hours earlier,

00:17:59.440 | feeling more alert during the day.

00:18:00.760 | Again, improvements in cognitive performance,

00:18:02.460 | mood and physical performance, grip strength, et cetera.

00:18:06.040 | Very few studies are able to or willing to tackle

00:18:09.600 | so many variables and combine them in one study.

00:18:12.920 | This paper, I think, does a marvelous job of doing this

00:18:15.540 | and is incorporating things that individually

00:18:17.960 | each have some support for them in animal studies

00:18:20.580 | and previous human studies.

00:18:22.000 | But as far as I know, this is one of the few studies

00:18:24.240 | that really combines all these different features

00:18:27.080 | in one place, eating times, keeping those consistent,

00:18:31.220 | getting maximal sunlight exposure earlier in the day,

00:18:35.200 | getting up at a consistent time,

00:18:36.640 | going to sleep at a consistent time and on and on.

00:18:40.180 | It's a really marvelous study for that reason.

00:18:41.880 | And I think for any of you that are night owls

00:18:44.280 | and any of you that want to reinforce your early waking

00:18:47.720 | and early to bedtimes, and I think for most all of you

00:18:51.320 | who fall into that general middle category

00:18:53.520 | of tend to go to sleep somewhere between 10 p.m.

00:18:55.720 | and midnight, 'cause that's most people,

00:18:57.080 | and tend to wake up sometime between 6 a.m. and 8 a.m.,

00:19:00.600 | well, maybe you want to become more of an early riser

00:19:02.520 | or maybe you're going to travel

00:19:04.160 | or the seasons are changing and you want to shift your time

00:19:07.140 | or you have a new job, et cetera,

00:19:08.920 | or something that's actually very common

00:19:10.760 | in terms of relationship struggle.

00:19:12.000 | You want to match your awake sleep times

00:19:14.560 | or maybe you want to offset your awake sleep times

00:19:17.000 | from a significant other.

00:19:19.100 | These sorts of approaches that I described here

00:19:21.260 | and that are supported by the data in this paper

00:19:23.900 | are absolutely powerful and science supported.

00:19:26.700 | And I'm certain that if you were to apply them

00:19:28.180 | that you would see essentially the same effects

00:19:30.240 | that were observed here.

00:19:31.180 | Before we begin, I'd like to emphasize

00:19:32.880 | that this podcast is separate from my teaching

00:19:34.760 | and research roles at Stanford.

00:19:36.280 | It is, however, part of my desire and effort

00:19:38.360 | to bring zero cost to consumer information about science

00:19:40.920 | and science-related tools to the general public.

00:19:43.500 | In keeping with that theme,

00:19:44.560 | I'd like to thank the sponsors of today's podcast.

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00:21:12.400 | Today's episode is also brought to us by Thesis.

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00:21:30.020 | in the brain or chemicals in the brain for being smart.

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00:24:03.680 | Let's talk about how to optimize

00:24:05.280 | and indeed how to control your brain chemistry

00:24:08.360 | for sake of health and performance.

00:24:10.800 | Now, in order to do that,

00:24:12.600 | we all need to be on the same page about some basic facts.

00:24:16.040 | Some of those basic facts involve learning some basic biology

00:24:19.640 | and I promise that even if you don't have a biology

00:24:21.920 | or chemistry background, everything I'm about to say

00:24:24.460 | should be accessible and clear to you.

00:24:26.620 | The important thing to know is that your brain

00:24:30.000 | and your spinal cord

00:24:31.800 | and the rest of your so-called nervous system

00:24:35.120 | control all the organs of your body

00:24:37.180 | and that all the organs of your body feed back,

00:24:40.120 | meaning they communicate through chemicals

00:24:42.160 | and other means to your nervous system.

00:24:44.880 | Now, your nervous system plays a particularly important role

00:24:48.120 | in generating everything from sleep to wakefulness,

00:24:50.740 | creativity, stress, calm, et cetera,

00:24:54.640 | by way of a particular type of cell-cell interaction

00:24:59.400 | and that's called synaptic communication.

00:25:02.860 | What is synaptic communication?

00:25:04.560 | Well, in order to understand that,

00:25:06.780 | let's dial back a little bit further

00:25:08.620 | and try and understand for a moment

00:25:10.800 | what makes up your nervous system.

00:25:13.240 | In its simplest form, your nervous system

00:25:14.840 | is made of nerve cells that we call neurons.

00:25:18.540 | Neurons communicate with one another through chemicals.

00:25:21.800 | They release certain chemicals that make other neurons

00:25:25.240 | more or less likely to be electrically active.

00:25:28.480 | What do we mean by electrically active?

00:25:30.240 | We mean, as it sounds,

00:25:32.840 | electricity passing down through cells

00:25:36.280 | and then literally causing electricity in other cells.

00:25:40.280 | The simplest way to think about this

00:25:41.800 | is maybe when you were a kid or maybe even still now,

00:25:44.320 | you would wear socks and you'd shuffle along the floor

00:25:46.800 | to generate some static electricity

00:25:48.500 | and then you touch someone

00:25:49.720 | and you'd shock them with your finger.

00:25:51.800 | I'm a younger brother,

00:25:52.640 | so I'd occasionally do that to my sister.

00:25:54.680 | I had friends, we would do that to one another.

00:25:56.360 | I know it's kind of silly and childish,

00:25:58.560 | yet it illustrates the principle

00:26:00.220 | that we can generate electricity

00:26:02.280 | and pass electricity to other beings

00:26:05.240 | or in the case of neurons, from one neuron to the next.

00:26:08.080 | The way neurons do that is that in between the neurons,

00:26:11.520 | they're little spaces.

00:26:12.400 | Those little spaces are called synapses

00:26:15.000 | and neurons literally vomit.

00:26:18.040 | Well, they don't literally vomit,

00:26:19.340 | but they release little packets

00:26:21.600 | of so-called transmitter chemical

00:26:24.600 | into that space we call a synapse.

00:26:26.660 | It travels across the synapse.

00:26:28.680 | It attaches to the cell on the other side, the other neuron.

00:26:32.080 | And then depending on what that chemical is,

00:26:34.320 | it either makes that next neuron more electrically active

00:26:37.800 | or less electrically active, so-called excitation.

00:26:40.740 | It either excites the next neuron

00:26:42.640 | to be electrically active also,

00:26:44.800 | or it inhibits, it prevents the next neuron

00:26:48.200 | from being electrically active.

00:26:50.400 | So again, very simply, we have nerve cells

00:26:52.220 | that communicate with one another

00:26:53.440 | through electricity and chemicals

00:26:55.600 | that inspire that electricity.

00:26:57.540 | And the little gaps between neurons are called synapses.

00:27:01.580 | If you can understand that,

00:27:02.760 | I'm certain you can make it through the rest of the episode

00:27:04.720 | and that you will get all the depth

00:27:06.920 | and important detail that you need to know.

00:27:09.480 | But I want to go just a little bit further

00:27:11.540 | and explain that neurons don't just talk one-to-one.

00:27:15.160 | There are trillions of neurons in your nervous system

00:27:17.900 | that allow you to be happy, to be in love, to be sad,

00:27:20.920 | to be in grief, to remember things, and so on.

00:27:24.880 | And what you do at any moment,

00:27:27.740 | what you feel and what you think,

00:27:30.140 | relates to which so-called neural circuits are active.

00:27:34.860 | So a lot of times we think about brain areas,

00:27:36.760 | and we've all seen these pictures of the brain

00:27:38.240 | where someone was in a fMRI scanner,

00:27:42.080 | or they were in a brain scanner of some sort,

00:27:44.420 | and they saw a picture of something

00:27:46.320 | and a certain area of the brain lights up, as it's called.

00:27:49.600 | That lighting up of the brain really reflects the activity

00:27:52.120 | of hundreds, if not thousands,

00:27:53.520 | maybe even millions of neurons in that region.

00:27:55.920 | Those images of brain areas lighting up,

00:27:59.400 | and indeed talking about brain areas lighting up,

00:28:01.700 | can be a little bit or a lot misleading,

00:28:03.500 | because in fact, no single brain area

00:28:05.800 | controls any one single perception

00:28:08.540 | or behavior or feeling state.

00:28:10.520 | Rather, we have so-called neural circuits,

00:28:13.000 | chains of neurons, chains of specific neurons, that is,

00:28:17.720 | that create different states of mind

00:28:20.160 | that lead to specific behaviors,

00:28:22.360 | that lead to specific emotional states.

00:28:25.180 | And those neural circuits are made up

00:28:26.940 | of lots of different brain areas

00:28:28.440 | that light up in particular sequences.

00:28:30.360 | And when I say light up, excuse me,

00:28:32.760 | what I mean is that particular brain areas

00:28:35.240 | either excite or prevent the excitation,

00:28:38.760 | that is, they inhibit other brain areas

00:28:40.900 | in a particular sequence.

00:28:42.520 | Much like keys on a piano played in a particular sequence

00:28:46.200 | makes up a particular song,

00:28:48.120 | particular brain areas activated or made silent

00:28:52.040 | in a particular sequence leads to a particular behavior,

00:28:55.940 | like getting up out of a chair,

00:28:57.640 | or a particular feeling state,

00:28:59.500 | like being particularly happy one day when you wake up,

00:29:02.200 | or particularly depressed,

00:29:03.940 | whether or not that depression is caused by a life event

00:29:07.040 | or whether or not it arises spontaneously.

00:29:09.580 | So we have neurons, we have synapses,

00:29:11.500 | and we have neural circuits.

00:29:14.100 | And vitally important is the fact

00:29:16.680 | that which neural circuits are active

00:29:19.900 | and which neural circuits are likely to be less active

00:29:23.160 | at any given moment

00:29:24.880 | depends on two major categories of chemicals.

00:29:28.680 | It depends on hormones

00:29:30.680 | and it depends on so-called neuromodulators.

00:29:34.400 | Now, we're mainly going to focus on neuromodulators today

00:29:36.820 | because those are the things

00:29:38.280 | that if you can learn to control them,

00:29:40.140 | and indeed there are tools to control them,

00:29:42.480 | then you can control which neural circuits

00:29:45.920 | are more likely or less likely to be active in you

00:29:48.960 | at any given moment.

00:29:50.100 | And in doing so, you can control

00:29:52.780 | whether or not you are going to be alert and focused

00:29:55.560 | or deeply asleep.

00:29:57.040 | You can control whether or not

00:29:58.440 | you are going to be in a creative state

00:30:00.240 | or whether or not you're going to be in a state of mind,

00:30:02.560 | more fit, more capable that is of doing focused work

00:30:07.200 | or math or more so-called linear types of work

00:30:09.720 | where there's a correct answer.

00:30:10.920 | There's a specific thing to follow

00:30:13.100 | and you're simply going to plug and chug as it were

00:30:15.800 | through a particular set of steps

00:30:18.140 | in order to accomplish something.

00:30:19.400 | Or for instance, whether or not

00:30:21.000 | you're going to be in a more relaxed and creative state

00:30:23.620 | where you're thinking about new ideas

00:30:25.700 | or new ideas are just seem to be

00:30:27.560 | spontaneously coming to mind.

00:30:29.760 | All of that can be controlled to a considerable extent

00:30:34.760 | by leveraging these so-called neuromodulators.

00:30:38.100 | What are neuromodulators?

00:30:39.800 | Neuromodulators are particular chemicals

00:30:44.040 | that make it likely that certain neural circuits

00:30:46.840 | will be active and not others.

00:30:48.760 | And the four neuromodulators

00:30:50.480 | that we're going to talk about today

00:30:51.800 | that are of the utmost importance for your goals

00:30:55.520 | are dopamine, epinephrine, also called adrenaline,

00:31:00.360 | serotonin, and acetylcholine.

00:31:03.320 | That's dopamine, epinephrine, serotonin, and acetylcholine.

00:31:07.180 | Today, I'm going to teach you

00:31:09.220 | how each of those different categories

00:31:11.140 | of neuromodulators work and the things that you can do

00:31:15.280 | to control those neuromodulators,

00:31:18.200 | that is increase them or decrease them

00:31:21.360 | through behavioral tools and supplementation

00:31:24.600 | in ways that allow you to access the brain and body states

00:31:28.120 | that you want at the times that you want.

00:31:30.700 | Just very quickly,

00:31:31.680 | I want to talk about how neuromodulators are able to work

00:31:35.040 | regardless of whether or not it's dopamine or serotonin

00:31:37.720 | or epinephrine, et cetera.

00:31:39.440 | There are many features of how neuromodulators work,

00:31:43.340 | but for sake of today's discussion,

00:31:45.560 | we only need to focus on two of those features.

00:31:48.040 | And those are fast acting features

00:31:50.480 | and longer slower features

00:31:52.360 | or what we call baseline features.

00:31:54.980 | What am I talking about when I say faster or baseline?

00:31:58.680 | Well, consider that at any given moment,

00:32:01.760 | whether or not you're asleep or awake,

00:32:03.380 | whether or not it's morning or afternoon or night,

00:32:05.880 | you have some amount of dopamine being released

00:32:09.200 | in your brain and body, some amount of serotonin,

00:32:12.040 | some amount of epinephrine,

00:32:13.680 | and some amount of acetylcholine.

00:32:16.560 | It is rarely, if ever the case,

00:32:19.260 | that you have zero dopamine or zero serotonin.

00:32:22.840 | So often we hear about someone being dopamine depleted,

00:32:25.420 | or these days you hear a lot about that anyways,

00:32:27.680 | or you'll hear that people's serotonin is bottomed out.

00:32:31.640 | In reality, none of these neuromodulators

00:32:33.840 | ever disappear completely,

00:32:36.200 | but they tend to be present at different levels

00:32:39.060 | or different relative levels.

00:32:40.920 | Another important thing to point out

00:32:42.620 | is that they don't work alone.

00:32:45.060 | In fact, as you'll soon learn,

00:32:46.680 | dopamine and epinephrine are close cousins that collaborate

00:32:51.340 | in terms of creating states of focus and motivation,

00:32:54.540 | for instance, or in creating states of energy

00:32:58.060 | and the pursuit of particular goals.

00:33:00.280 | When I say they're close cousins,

00:33:01.340 | what I mean is that they tend to impact

00:33:04.800 | some of the same neural circuits.

00:33:07.120 | And believe it or not,

00:33:08.260 | dopamine and epinephrine are chemically related too.

00:33:11.760 | I'll just tell you right now that epinephrine

00:33:13.780 | is actually derived from dopamine chemically.

00:33:16.980 | Epinephrine, that is adrenaline,

00:33:19.860 | is made from the molecule dopamine.

00:33:22.700 | Now, dopamine and serotonin can also work together

00:33:26.260 | to impact certain circuits in the brain,

00:33:28.260 | but in large part, they operate on separate circuits.

00:33:32.060 | And acetylcholine, which you'll soon learn

00:33:35.240 | is involved in states of focus and can actually open up.

00:33:38.380 | It can literally create states in the mind

00:33:41.480 | in which your brain is more plastic

00:33:43.700 | and able to change and learn more quickly.

00:33:46.320 | Well, acetylcholine can do that on its own,

00:33:48.740 | but rarely does it do it on its own.

00:33:51.180 | More typically, it gets assistance

00:33:53.380 | from some of the other neuromodulators.

00:33:55.260 | Now, that might seem like it complicates the picture,

00:33:57.020 | but it actually makes the picture far simpler

00:33:59.320 | because what we can say for sure

00:34:01.380 | is that the fast actions of dopamine

00:34:04.820 | or the fast actions of epinephrine,

00:34:06.580 | serotonin or acetylcholine are actions that occur

00:34:09.860 | on the order of seconds or minutes

00:34:11.940 | or up to about an hour or so.

00:34:13.980 | Whereas the slower actions of those neuromodulators

00:34:17.220 | tend to occur on the order of hours, days or even weeks.

00:34:21.300 | Now, perhaps surprisingly,

00:34:22.620 | I'd like to focus on the slow actions

00:34:24.460 | of the neuromodulators first,

00:34:26.380 | because those slow actions of the neuromodulators

00:34:29.260 | are happening in you and in me and in everyone right now.

00:34:33.200 | And they set the backdrop, the context

00:34:36.020 | in which the various tools to manipulate dopamine,

00:34:39.040 | epinephrine, serotonin or acetylcholine will work.

00:34:43.660 | What do I mean by the context or the backdrop

00:34:45.900 | or the baseline?

00:34:47.020 | Well, it's fair to say that most people

00:34:50.500 | are awake during the daytime and asleep at night.

00:34:52.660 | I do realize that there are people

00:34:54.300 | who are going to be doing shift work

00:34:57.340 | or they're raising young children,

00:34:59.200 | or that might have a sick person at home

00:35:01.880 | that they're tending to, et cetera,

00:35:03.180 | or even have insomnia, they're tending to them.

00:35:05.780 | So schedules of sleep and wakefulness will vary,

00:35:09.080 | but in general, everybody,

00:35:11.100 | regardless of whether or not you're nocturnal

00:35:13.240 | or you're so-called diurnal, you're awake during the day,

00:35:16.500 | pretty much everybody follows a schedule

00:35:18.460 | in which from zero to nine hours after waking,

00:35:23.460 | that is from the time you wake up

00:35:25.060 | until about nine hours later,

00:35:28.260 | the neuromodulators dopamine and epinephrine

00:35:32.380 | tend to be at their highest levels

00:35:34.340 | that they will be at any point in the 24 hour period,

00:35:39.060 | in any period of the day.

00:35:41.060 | So we can call this zero to nine hour period phase one

00:35:45.260 | of the day, just for simplicity.

00:35:46.580 | And I've referred to this before in a previous episode,

00:35:49.780 | but not in this exact context.

00:35:52.220 | From nine to about 16 hours is what we will call phase two.

00:35:57.020 | And that's when dopamine and epinephrine levels

00:36:00.260 | tend to subside a bit compared to the earlier phase one

00:36:04.220 | part of the day, and serotonin levels start to increase.

00:36:08.860 | And then phase three of the 24 hour cycle,

00:36:11.900 | which is from about, and again,

00:36:13.680 | about the zero approximates,

00:36:15.380 | from about 17 hours after waking

00:36:17.380 | until about 24 hours after waking is phase three of the day.

00:36:22.380 | And during that time, there is chaos

00:36:26.580 | in terms of which neuromodulators

00:36:28.740 | are most present in the brain.

00:36:30.300 | And why chaos, what I mean is that during sleep,

00:36:33.540 | you have incredible peaks in acetylcholine

00:36:35.840 | and drops in acetylcholine.

00:36:37.900 | You have incredible peaks in dopamine and drops in dopamine.

00:36:41.520 | You have incredible peaks in serotonin

00:36:43.260 | and drops in serotonin.

00:36:45.120 | Most often, you are not going to see much,

00:36:48.140 | if any, release of epinephrine, adrenaline.

00:36:51.380 | And that's because epinephrine, also called adrenaline,

00:36:54.840 | tends to wake us up and put us into action mode behaviors.

00:36:59.060 | And that's simply not happening during sleep.

00:37:01.160 | But for the other three neuromodulators,

00:37:03.460 | across the night, it's sort of chaos.

00:37:06.620 | You've got peaks and drops and peaks and drops

00:37:08.580 | in different combinations

00:37:09.700 | than you would ever see in wakefulness.

00:37:11.360 | And this plays important roles in dreaming,

00:37:13.260 | important roles in some of the reparative functions of sleep.

00:37:16.780 | The point is that during that phase three,

00:37:20.160 | the levels of neuromodulators are all over the place,

00:37:22.560 | but it's not random, right?

00:37:24.780 | I say it's chaos,

00:37:25.860 | but it's organized according

00:37:27.340 | to the specific reparative goals of sleep,

00:37:29.620 | the specific metabolic roles of sleep, et cetera.

00:37:32.580 | We're not going to focus too much on phase three today,

00:37:35.500 | because phase three of the 24 hour cycle,

00:37:38.620 | that 17 to 24 hour period,

00:37:40.480 | is one in which you ought to be deeply asleep,

00:37:42.860 | whether or not you're nocturnal or diurnal, right?

00:37:44.860 | 17 hours after waking, you ought to be asleep.

00:37:47.900 | And there are a lot of episodes of this podcast,

00:37:50.380 | and indeed today I started talking

00:37:52.260 | about two particular studies related to sleep.

00:37:54.880 | There are a lot of tools to enhance sleep, et cetera.

00:37:57.760 | And of course, there are things that you can do

00:37:59.300 | in the late portion of phase two of the day

00:38:03.000 | in order to enhance your transition time

00:38:05.680 | into and depth of sleep.

00:38:07.420 | But you can't really do much during sleep, right?

00:38:10.040 | You're not taking supplements,

00:38:11.200 | you're not doing breathing practices.

00:38:13.220 | There are things to fall back asleep,

00:38:14.540 | but you're not really doing much during sleep.

00:38:15.900 | So we're mainly going to focus

00:38:17.540 | on what we're calling phase one and phase two.

00:38:20.580 | Phase one being this dopamine epinephrine dominated phase

00:38:24.020 | of our day, and phase two being this more serotonergic

00:38:27.700 | or serotonin dominated portion of the day.

00:38:30.020 | And then you might say, well, what about acetylcholine?

00:38:32.980 | Forgot about acetylcholine.

00:38:34.100 | Well, we didn't forget about acetylcholine.

00:38:35.700 | Acetylcholine is under control more in terms

00:38:39.620 | of what we happen to be doing at any given moment,

00:38:42.900 | whether or not we're focusing or not focusing,

00:38:44.720 | whether or not we're learning or not learning.

00:38:47.180 | And here I'm referring to acetylcholine specifically

00:38:49.260 | in the context of the brain and thinking,

00:38:51.700 | because as some of you are probably shouting out there,

00:38:54.700 | right, if you're exercise physiologists

00:38:56.580 | or you know anything about how the brain controls movement,

00:39:00.260 | acetylcholine is used at the nerve to muscle synapse, right?

00:39:03.840 | So neurons don't just control other neurons electrically.

00:39:07.360 | The way you're able to move in fact is

00:39:09.100 | because neurons are controlling the electric activity

00:39:11.620 | of muscles, literally the contraction of muscle fibers,

00:39:15.460 | and that control is exerted

00:39:18.320 | through the release of acetylcholine.

00:39:19.660 | So acetylcholine is working at muscles as well,

00:39:21.660 | but we're not focused on that today.

00:39:23.460 | We're focused on what we can do during phase one of the day

00:39:27.780 | and what we can do during phase two of the day

00:39:30.060 | to control the specific neuromodulators,

00:39:33.220 | dopamine, epinephrine, serotonin, and acetylcholine

00:39:36.000 | toward particular end goals.

00:39:37.920 | And as I've been harping on for the last five

00:39:40.900 | or 10 minutes or so, it is important to understand

00:39:44.180 | that in the early phase one part of the day,

00:39:46.400 | again, zero to nine hours,

00:39:48.440 | dopamine and epinephrine already dominate

00:39:52.700 | the neuromodulator landscape.

00:39:54.740 | That is, they are already elevated

00:39:56.740 | and then they will taper off in phase two.

00:39:58.700 | Whereas in phase two of the day,

00:40:00.340 | serotonin tends to dominate more than dopamine

00:40:04.520 | and epinephrine.

00:40:05.580 | And so if you think about that,

00:40:08.000 | what it means is that if your goal is to increase serotonin

00:40:11.620 | in order to get some particular effect

00:40:14.460 | on your mental performance or physical performance or health,

00:40:19.060 | or if your goal is to increase your dopamine

00:40:21.900 | or epinephrine to get some particular effect

00:40:24.240 | on your mental health, physical performance, et cetera,

00:40:28.580 | well, then you need to consider what the background level

00:40:32.220 | of dopamine or epinephrine or serotonin happens to be.

00:40:35.980 | Because in doing so, you will know which tool to select

00:40:39.860 | and how hard you need to push on that tool, right?

00:40:43.980 | If your levels of dopamine are already riding pretty high

00:40:47.140 | because it's the early part of the day,

00:40:49.040 | well, then it doesn't take a whole lot more

00:40:51.960 | to get dopamine to a level in which it can, for instance,

00:40:55.300 | change your level of motivation.

00:40:57.080 | Whereas if you are in the late part of the day,

00:40:59.320 | let's say eight or 9 p.m.

00:41:01.480 | and you have a lot of serotonin swimming around

00:41:04.300 | in your system and you really need to be focused and alert,

00:41:08.300 | well, you can do that by leveraging the dopamine

00:41:11.800 | and epinephrine system

00:41:12.780 | and indeed the acetylcholine system too,

00:41:15.020 | but you're going to have to resort to tools

00:41:17.800 | that can do that far more potently

00:41:20.220 | and that can do that in a much more sustained way

00:41:23.500 | if you're going to access the state that you want.

00:41:26.060 | So again, it's really important to understand

00:41:29.340 | what the backdrop of these neuromodulators is,

00:41:32.820 | the so-called baseline, and that they vary across the day

00:41:36.460 | if you're going to be able to leverage tools

00:41:38.740 | to optimize your brain chemistry.

00:41:40.620 | Anyone that tells you do this protocol

00:41:42.900 | in order to increase your dopamine,

00:41:44.460 | do this protocol or take this supplement

00:41:46.660 | to increase your serotonin,

00:41:48.580 | they can be telling you the absolute truth,

00:41:50.920 | but if you don't consider the backdrop

00:41:53.140 | over which that supplement or behavior

00:41:55.480 | is going to have its effect,

00:41:57.240 | well, then you can't really predict the effect it will have,

00:41:59.800 | but if you can understand these backdrop baseline elements

00:42:03.560 | to how neuromodulators work,

00:42:05.240 | well, then you're in a terrific position

00:42:06.900 | to leverage the best tools in the immediate and short-term

00:42:10.120 | and that is on the order of seconds, minutes, and hours.

00:42:12.940 | Before we dive into the more pointed,

00:42:15.160 | directed effects of specific tools on neuromodulators,

00:42:19.080 | I'd like to just briefly mention hormones

00:42:21.180 | because they are also important for understanding

00:42:23.780 | the background and the context

00:42:26.460 | and these baseline levels of neuromodulators.

00:42:29.540 | Now, here I'm going to paint with a bit of a broad brush,

00:42:32.460 | but what I will say is accurate,

00:42:34.040 | even though it might not be exhaustive.

00:42:36.060 | What I mean by that is everything I'm about to say is true,

00:42:38.920 | but it doesn't cover every example in detail

00:42:41.280 | and nuanced possibility out there.

00:42:43.760 | Hormones have many different effects on the brain and body

00:42:48.000 | and not unlike neuromodulators,

00:42:49.520 | some of those effects are very fast,

00:42:51.600 | some of them are very slow.

00:42:53.080 | In fact, certain hormones, for instance,

00:42:55.980 | the steroid hormones like estrogen

00:42:59.240 | and like testosterone and corticosterones,

00:43:02.940 | and here, of course,

00:43:04.740 | I'm referring to the steroid hormones for what they are,

00:43:07.120 | they are indeed steroid hormones,

00:43:08.880 | but I'm not talking about steroids that people inject

00:43:11.880 | for sports performance or for physical augmentation,

00:43:14.280 | I'm talking about the steroid hormones

00:43:16.020 | that you make naturally

00:43:17.040 | because indeed you make these naturally.

00:43:19.400 | Well, the steroid hormones

00:43:21.420 | can actually control gene expression,

00:43:23.520 | they can change the identity of cells

00:43:25.360 | and the genes and proteins that cells express.

00:43:28.240 | This is why during puberty, for instance,

00:43:30.520 | testosterone and estrogen are released into the body,

00:43:33.120 | growth hormone is released into the body

00:43:34.900 | and bodies and voices and personalities and brains

00:43:38.600 | change tremendously because literally

00:43:41.160 | there is a transformation of the breast tissue,

00:43:44.760 | of the testicular tissue, of the ovarian tissue,

00:43:47.760 | of the bones, of the muscles,

00:43:49.880 | of the tissues and cells that control hair growth.

00:43:54.500 | Gene expression changes in all those cell types

00:43:57.720 | and the child becomes an adolescent,

00:44:00.240 | becomes a young adult, right?

00:44:02.120 | That's what puberty really is.

00:44:03.740 | In fact, puberty is perhaps the most dramatic transformation

00:44:07.600 | that we go through in our entire lifespan

00:44:10.400 | in terms of our aging,

00:44:11.920 | 'cause indeed it reflects a very rapid,

00:44:15.180 | I should mention, period of aging

00:44:16.960 | and transformation of the identity of cells.

00:44:19.780 | So steroid hormones and other hormones

00:44:21.440 | can have very slow, long lasting actions in that way.

00:44:26.100 | They can also have very fast actions.

00:44:28.240 | So for instance, adrenaline epinephrine

00:44:30.880 | released from the adrenal glands

00:44:32.480 | can immediately make your heart beat faster,

00:44:34.680 | can immediately change the circumference

00:44:37.620 | of your blood vessels and arteries

00:44:40.000 | and capillaries and change the way blood flows.

00:44:42.540 | It can change the way you see the world, literally.

00:44:44.980 | It does change the way you see the world

00:44:46.620 | through your visual system.

00:44:47.840 | And that all happens on the order

00:44:49.400 | of hundreds of milliseconds or seconds.

00:44:52.120 | These are extremely fast actions.

00:44:54.440 | Corticosteroid also can have fast actions and slow actions.

00:44:58.440 | But since this isn't a discussion about hormones per se,

00:45:02.960 | and we've done entire episodes

00:45:04.220 | like the optimized testosterone and estrogen episode,

00:45:06.960 | you can find that at hubermanlab.com

00:45:08.680 | where the interview with the incredibly knowledgeable

00:45:12.040 | and clear and really wonderful tutor

00:45:17.040 | of actionable information, Dr. Kyle Gillette,

00:45:19.400 | who is also on this podcast.

00:45:20.440 | You can learn a lot about hormones there.

00:45:22.280 | Today, we want to think about hormones

00:45:23.640 | as they relate to these neuromodulators,

00:45:25.480 | the dopamine, serotonin, epinephrine, and acetylcholine.

00:45:29.160 | And in general, testosterone tends to collaborate

00:45:33.600 | with and increase the action of dopamine.

00:45:37.200 | That's not always the case, but in general,

00:45:39.560 | when testosterone goes up, dopamine goes up.

00:45:42.680 | And sometimes even vice versa,

00:45:44.460 | when dopamine goes up, testosterone go up.

00:45:46.520 | And this is true for both males and for females.

00:45:50.760 | In general, when corticosterones like cortisol

00:45:55.440 | and some related steroid hormones increase,

00:45:58.440 | epinephrine levels go up.

00:46:00.380 | And in general, when hormones like oxytocin

00:46:03.480 | or prolactin are increased, levels of serotonin go up.

00:46:08.480 | We can't draw a direct link

00:46:10.400 | between any one hormone system and acetylcholine.

00:46:13.040 | Acetylcholine kind of sits off

00:46:14.280 | in a category of its own in that way.

00:46:16.460 | But again, in general, testosterone and dopamine

00:46:18.900 | tend to collaborate in the same direction.

00:46:21.600 | Cortisol and epinephrine tend to collaborate

00:46:24.640 | in the same direction.

00:46:25.720 | Oxytocin and prolactin, which are hormones,

00:46:30.240 | and serotonin tend to collaborate in the same direction.

00:46:33.680 | And then we have poor old lonely acetylcholine

00:46:37.020 | off on its own, but it's not poor and lonely.

00:46:38.720 | It actually has incredibly potent effects on its own.

00:46:40.760 | So it's really that it just doesn't need much help

00:46:42.920 | from the hormone systems,

00:46:45.000 | or at least not the steroid hormone systems

00:46:46.720 | in order to have its tremendous effects.

00:46:49.160 | Now, a lot of what people think about and will do

00:46:51.400 | when trying to improve mental health and physical health

00:46:54.400 | is they will try and increase or decrease

00:46:57.200 | certain categories of hormones

00:46:58.920 | of the sort that I mentioned, testosterone, estrogen,

00:47:00.960 | oxytocin, prolactin, and so on.

00:47:02.900 | But oftentimes the effects of those manipulations in hormones

00:47:08.760 | that are going to be most salient

00:47:11.080 | are not going to be due to the direct effects

00:47:13.000 | of those hormones.

00:47:14.060 | Sometimes it could be,

00:47:15.420 | but oftentimes it's going to be due to their effects

00:47:18.140 | on the brain and nervous system

00:47:19.880 | by way of how those hormones impact neuromodulators.

00:47:24.060 | So for instance, there are various things

00:47:26.660 | that people can do, both men and women,

00:47:28.240 | to increase their testosterone and estrogen

00:47:30.700 | in the appropriate ratios.

00:47:32.480 | I talked about one such approach in a previous episode,

00:47:36.460 | and that is to get sunlight onto a large portion

00:47:41.060 | of one's skin each day.

00:47:43.720 | Believe it or not, this actually works,

00:47:45.800 | and it works because your skin

00:47:48.120 | is actually an endocrine organ, a hormone secreting organ.

00:47:51.880 | It's a beautiful study.

00:47:52.720 | I've covered it on this podcast before.

00:47:54.320 | We will provide a link to this study again,

00:47:56.040 | but it had people spend at least 20 minutes or so

00:48:01.040 | closer to 30 minutes each day

00:48:02.560 | trying to maximize sunlight exposure

00:48:04.500 | to as much of their skin as they could

00:48:06.120 | in terms of still maintaining decent exposure,

00:48:09.400 | meaning not overexposing themselves in a cultural way,

00:48:11.940 | meaning wearing enough clothes that they were decent,

00:48:14.040 | but still getting a lot of sun exposure

00:48:16.560 | a couple of times per week or more.

00:48:18.360 | What they found was that people's testosterone

00:48:21.240 | and estrogen levels went up,

00:48:22.640 | feelings of wellbeing went up,

00:48:24.160 | feelings of well, or I should say increases in libido

00:48:27.640 | were observed as well.

00:48:29.440 | They subjectively reported more passion, et cetera.

00:48:32.300 | Testosterone and estrogen did indeed both go up.

00:48:35.380 | And again, I want to highlight that increases in estrogen,

00:48:38.420 | not just testosterone,

00:48:39.440 | are related to increases in libido in both men and women.

00:48:43.200 | This is why you never want to crush your estrogen

00:48:45.040 | down to zero, whether or not you're male or female,

00:48:47.400 | if you want to maintain some sort of healthy libido

00:48:50.880 | and general feelings of wellbeing unrelated to libido.

00:48:53.960 | Well, many of those effects we know

00:48:57.340 | are not due to direct effects of testosterone and estrogen,

00:49:00.640 | but rather are due to the effects of testosterone

00:49:03.080 | and estrogen on the neuromodulators, dopamine and serotonin,

00:49:07.140 | because much of libido and feelings of wellbeing

00:49:10.480 | and feelings of relaxation,

00:49:12.740 | but also desire, motivation, et cetera,

00:49:15.400 | originate because of the activation of neural circuits

00:49:19.520 | that dopamine controls and promotes,

00:49:22.200 | and that serotonin promote and control.

00:49:25.560 | So this is very important to understand

00:49:28.560 | as we move toward more specific discussion of the chemicals

00:49:32.440 | that we call neuromodulators,

00:49:34.380 | because hormones are controlling those neuromodulators

00:49:38.280 | in a very slow modulatory way.

00:49:41.040 | So yes, I said it, hormones modulate neuromodulators.

00:49:45.560 | I sort of said it twice on purpose.

00:49:49.100 | And this is a dramatic and potent effect.

00:49:52.220 | So I'll just give you one more example.

00:49:53.840 | The hormone prolactin tends to be antagonistic.

00:49:57.060 | It tends to reduce amounts of dopamine

00:49:59.300 | or at least when prolactin levels are high,

00:50:02.140 | dopamine levels tend to be lower.

00:50:04.520 | You observe this after the birth of a new child,

00:50:07.140 | you observe this postcoitally after mating

00:50:09.900 | in all species, humans and animals.

00:50:12.580 | When prolactin is elevated, serotonin tends to be elevated.

00:50:17.740 | And when prolactin is elevated, levels of dopamine

00:50:21.300 | and the effects of dopamine tend to subside.

00:50:26.060 | Now, as I move toward explaining

00:50:27.940 | what each of the four categories of neuromodulators do,

00:50:31.120 | this will start to make more and more sense

00:50:32.660 | as to why this would be.

00:50:34.320 | I always say I wasn't consulted at the design phase,

00:50:37.260 | meaning I didn't design these circuits.

00:50:39.500 | And if anyone tells you that they did,

00:50:40.880 | you should back away quickly

00:50:42.280 | because none of us designed these circuits.

00:50:44.180 | This is the way that evolution and nature

00:50:46.500 | created these systems.

00:50:48.800 | And they tend to work in a bit of a seesaw fashion,

00:50:51.120 | prolactin up, dopamine down, right?

00:50:53.980 | Dopamine up, prolactin down.

00:50:55.640 | In general, that is the way they work.

00:50:58.180 | So if we are to take a look at how each of these

00:51:01.260 | neuromodulator systems functions on its own,

00:51:05.060 | while understanding that they never truly function

00:51:07.480 | on their own, we can start to really make sense

00:51:10.340 | of the landscape of tools that are available to us

00:51:12.620 | and which tools are going to be most powerful to select

00:51:15.720 | if our goal is, for instance, to be focused,

00:51:18.320 | or if our goal is to be less stressed,

00:51:20.980 | or if our goal is to be highly motivated

00:51:24.720 | and highly focused for sake of learning.

00:51:26.680 | All of that is indeed possible

00:51:28.680 | if you understand these four neuromodulators

00:51:31.680 | and you understand that while there are many tools

00:51:34.320 | ranging from pharmacologic to behavioral

00:51:36.220 | that can tap into these neuromodulator systems

00:51:38.180 | that can kind of press on the gas of dopamine,

00:51:40.620 | pull back on serotonin and so on,

00:51:44.340 | but that there are particular tools,

00:51:46.700 | both behavioral and supplementation-based,

00:51:48.660 | and to some extent, prescription drug-based too,

00:51:51.440 | and we'll touch on a few of those.

00:51:53.480 | If you understand that and why they work,

00:51:56.040 | well, then you can create a sort of kit,

00:51:59.860 | a grab bag of things that you can use in any context,

00:52:02.980 | or I should say that you can look to,

00:52:05.540 | depending on the context you're in,

00:52:07.640 | and create the states of body and mind that you want.

00:52:10.320 | Now, once again, painting with a somewhat broad brush,

00:52:13.360 | but nonetheless, an accurate brush,

00:52:15.760 | we can say that dopamine, when elevated above baseline,

00:52:20.760 | tends to increase states of motivation,

00:52:25.080 | both mental and physical motivation,

00:52:28.080 | drive, and to some extent, focus.

00:52:30.820 | I've said it many times before, and I'll say it again,

00:52:34.160 | there's a lot of misconception about dopamine.

00:52:36.840 | Many people out there think that dopamine

00:52:39.000 | is all about pleasure.

00:52:40.280 | You hear about dopamine hits or people chasing dopamine

00:52:43.440 | or the need to have a dopamine fast, et cetera.

00:52:46.520 | Dopamine is not about pleasure.

00:52:47.860 | Dopamine is about motivation, craving, and pursuit for goals

00:52:52.860 | or for things that are outside our immediate possession

00:52:56.940 | and experience.

00:52:58.340 | The motivation and pursuit of a mate,

00:53:00.900 | the motivation and pursuit to mate,

00:53:03.320 | the motivation and pursuit of food,

00:53:05.160 | the motivation and pursuit of a career goal,

00:53:07.520 | et cetera, et cetera.

00:53:08.920 | Things we do not yet have, but that we want,

00:53:12.780 | and we get into sort of a forward center of mass

00:53:15.960 | and a pursuit of, and that pursuit can be physical,

00:53:18.080 | that pursuit can be cognitive,

00:53:19.560 | it can be both cognitive and physical,

00:53:22.460 | and it can involve talking about something, right?

00:53:25.200 | Because in some professions,

00:53:26.280 | pursuit of things involves talking.

00:53:27.800 | I think about lawyers, they talk a lot

00:53:29.760 | in pursuit of winning cases and money, et cetera,

00:53:33.260 | putting people in jail or keeping people out of jail,

00:53:35.280 | et cetera, that's done with their mouths,

00:53:36.780 | not with their bodies.

00:53:38.160 | Athletes in a state of motivated training

00:53:40.940 | or in motivated competition use their bodies,

00:53:43.500 | which all this is obvious, of course,

00:53:45.440 | but perhaps what is not so obvious is that one molecule,

00:53:49.600 | not working alone, but predominantly one molecule, dopamine,

00:53:53.440 | is responsible for all of those motivated states,

00:53:55.940 | which again underscores the power of these neuromodulators.

00:53:59.760 | So dopamine, we can think of,

00:54:01.640 | at least in the context of today's discussion,

00:54:03.360 | as controlling and indeed promoting motivation, drive,

00:54:08.160 | and pursuit, and to some extent, focus.

00:54:10.940 | Epinephrine and a closely related molecule

00:54:15.000 | called norepinephrine, and again,

00:54:17.880 | I want to emphasize that epinephrine is adrenaline

00:54:20.820 | and adrenaline is epinephrine.

00:54:22.920 | Norepinephrine is noradrenaline

00:54:25.080 | and noradrenaline is norepinephrine,

00:54:27.080 | but today we're going to just simply talk about epinephrine

00:54:29.560 | and norepinephrine.

00:54:31.840 | That category of neuromodulator is mainly responsible

00:54:36.000 | for generating our energy, our level of fuel

00:54:41.000 | and baseline level of forward center of mass,

00:54:45.160 | as I like to call it.

00:54:46.320 | You can also think of it as how high your RPM are.

00:54:49.400 | Now we're not a car and the car analogy sort of falls apart

00:54:53.160 | as we go further into the biology,

00:54:55.480 | but it's a decent one for now.

00:54:57.400 | When epinephrine levels are high, we tend to feel agitated,

00:55:00.360 | we tend to feel like we want to move,

00:55:01.820 | we tend to feel like we can't shut down our thinking

00:55:04.560 | and our anticipation of what's going to happen next.

00:55:07.080 | And when epinephrine levels are very, very low,

00:55:09.600 | we actually have less physical energy,

00:55:11.620 | we tend to have less mental energy

00:55:13.960 | in terms of generating thoughts very quickly

00:55:16.800 | and so on and so forth.

00:55:17.840 | And as I mentioned before, dopamine and epinephrine

00:55:20.760 | are closely related, so much so that we know for a fact

00:55:25.200 | that epinephrine is actually manufactured

00:55:27.680 | from the molecule dopamine.

00:55:29.320 | So that's why I'm talking about these two neuromodulators

00:55:31.200 | in very close juxtaposition,

00:55:32.840 | because they do indeed collaborate with one another.

00:55:35.760 | But for sake of today's discussion,

00:55:38.000 | we can just think of epinephrine as increasing energy.

00:55:41.180 | Adrenaline increases energy and our state of readiness.

00:55:44.320 | It also, I should mention, activates our immune system.

00:55:48.060 | Contrary to popular belief

00:55:49.800 | that stress inhibits our immune system,

00:55:52.000 | epinephrine is deployed, it's released at great levels

00:55:55.280 | in our brain and body when we are stressed,

00:55:57.160 | and that actually protects us against infections

00:56:00.400 | of multiple kinds, at least in the short term.

00:56:03.280 | That and all the details of that and tools related to that

00:56:08.240 | were covered in our episode on the immune system,

00:56:10.520 | if you want to check that out.

00:56:12.240 | Now, the neuromodulator serotonin

00:56:14.960 | creates a number of different states in the brain and body,

00:56:17.800 | but for sake of today's discussion,

00:56:19.940 | we're going to think about the predominant states

00:56:22.440 | that it creates, and those are states of contentedness,

00:56:26.360 | being happy, feeling fairly relaxed, feeling soothed,

00:56:30.400 | and to some extent, even some relief from pain

00:56:33.820 | or lack of pain.

00:56:35.240 | Serotonin is associated with a feeling of satiety,

00:56:39.200 | of having enough of what we already have.

00:56:42.640 | Now, when serotonin is very, very high,

00:56:46.720 | people can even be sedate.

00:56:48.760 | They can be completely amotivated,

00:56:51.620 | no motivation to seek out things like food or sex or work

00:56:55.160 | or et cetera, whereas when serotonin levels are very low,

00:56:59.280 | people can actually exhibit agitation

00:57:01.440 | and high levels of stress.

00:57:03.440 | So the levels matter here, but again,

00:57:06.200 | for sake of today's conversation,

00:57:07.880 | when we leverage serotonin,

00:57:10.200 | where you are really leveraging a neuromodulator

00:57:12.760 | that tends to increase the activity of neural circuits

00:57:15.520 | in the brain and body that make us feel relaxed and happy,

00:57:19.220 | and it tends to decrease the activity of neural circuits

00:57:23.080 | that make us rabidly in pursuit of things

00:57:25.240 | that we don't have, right?

00:57:27.160 | The opposite of content and sated is motivation, desire,

00:57:32.160 | and hunger and thirst for things that we don't have.

00:57:35.020 | So serotonin is the molecule of peace.

00:57:39.000 | It is the molecule of contentness.

00:57:40.900 | It is the molecule of having enough,

00:57:43.740 | at least for the time being,

00:57:45.560 | or the feeling that we have enough for the time being.

00:57:48.040 | Now, acetylcholine is a fourth category of neuromodulator

00:57:51.160 | that, as I mentioned earlier, is somewhat,

00:57:52.920 | not totally, but somewhat distinct from any direct control

00:57:56.020 | by the major hormone systems of the body,

00:57:58.180 | or at least the major steroid hormone systems.

00:58:01.200 | And acetylcholine, we can say,

00:58:03.320 | is mainly associated with states of focus.

00:58:08.320 | And we can go a step further

00:58:10.160 | and say that it's mainly associated with steps of focus

00:58:13.120 | as they relate to learning and encoding new information,

00:58:16.240 | so-called neuroplasticity.

00:58:18.580 | Now, neuroplasticity, or the brain and nervous system's

00:58:21.720 | ability to change in response to experience,

00:58:23.520 | can be impacted by an enormous number of different chemicals,

00:58:26.440 | not just acetylcholine.

00:58:28.180 | But acetylcholine has a particularly potent ability

00:58:32.500 | to open up the thing that we call neuroplasticity

00:58:36.560 | to allow plasticity to happen in one moment,

00:58:38.860 | whereas in a previous moment, it could not occur

00:58:41.700 | because acetylcholine had not been released in the brain

00:58:45.600 | or in the spinal cord.

00:58:47.800 | So acetylcholine is involved in focus and in learning.

00:58:51.380 | But it is not necessarily always associated

00:58:55.100 | with learning in the context of highly motivated,

00:58:58.560 | really ramped up states.

00:59:00.400 | It can be, but acetylcholine can also be released

00:59:04.760 | and can encourage the learning

00:59:06.480 | and neuroplasticity associated with calm states.

00:59:09.500 | For instance, if somebody has a newborn child,

00:59:14.000 | we know that they are flooded with oxytocin,

00:59:18.460 | which has actually even been called the love hormone,

00:59:20.480 | although it does many things in addition to control feelings

00:59:23.680 | of romantic attachment and attachment to children, et cetera.

00:59:27.520 | It does all of that, but it does a lot more as well.

00:59:30.120 | But when people have a new child,

00:59:32.640 | they also tend to be hyper-focused on that child,

00:59:34.960 | not just its wellbeing, but they narrow all their thinking,

00:59:38.420 | all their vision, all their hearing to that child

00:59:41.600 | and their obvious adaptive reasons for wanting to do that.

00:59:45.440 | I recall a family dinner we had,

00:59:47.600 | gosh, this was over 10 years ago,

00:59:49.500 | we had a couple over, they were,

00:59:51.600 | my mom was in the habit of inviting people over

00:59:53.860 | who didn't have places to go on the holidays,

00:59:55.720 | 'cause that's just who she is,

00:59:56.920 | and I think it's quite nice.

00:59:58.760 | So she brought over this couple, they had a newborn,

01:00:01.180 | I think this baby had been born

01:00:02.080 | maybe two or three weeks before,

01:00:03.400 | and it was seated, not seated, it was lying down,

01:00:07.700 | it couldn't see, it was like a potato bug,

01:00:09.080 | it barely holds head up,

01:00:10.280 | but it was lying in a little bassinet on the floor

01:00:13.260 | as we ate dinner, and it was almost hilarious,

01:00:16.400 | it actually was hilarious, we laughed a lot about this,

01:00:18.580 | that the entire meal,

01:00:20.220 | they were basically staring at this baby,

01:00:22.480 | they were so clearly in love with the baby

01:00:25.000 | and so flooded with oxytocin and also prolactin,

01:00:28.800 | that they couldn't take their focus off this baby,

01:00:31.320 | it was actually really wonderful and endearing to see,

01:00:34.040 | but in addition to that, I'd be willing to bet,

01:00:37.320 | had I been able to do a little bit of micro dialysis,

01:00:39.600 | which is the ability to measure the amounts

01:00:42.640 | of neuromodulator at a given location in the brain,

01:00:45.760 | had I been able to do that experiment on them,

01:00:49.020 | in that moment, I would have found

01:00:50.340 | that levels of acetylcholine were exceedingly high

01:00:52.880 | because they were so hyper-focused on this child,

01:00:56.140 | not just in love with, but focused on that child,

01:00:59.260 | and without a doubt, the neural circuits

01:01:02.180 | related to focus and plasticity were heavily engaged,

01:01:05.220 | again, for obvious adaptive reasons

01:01:07.340 | related to child rearing and learning the coos and cries

01:01:11.420 | and pain signals and pleasure signals of one's offspring.

01:01:14.540 | So we have dopamine associated with motivation,

01:01:17.220 | drive, and pursuit, and to some extent, focus.

01:01:20.280 | We have epinephrine and norepinephrine associated

01:01:22.480 | with energy of having a forward center of mass,

01:01:26.140 | mentally and/or physically.

01:01:27.920 | We have serotonin, which is associated

01:01:29.840 | with a peaceful, content, sated state of being.

01:01:34.500 | And we have acetylcholine, which is associated with focus,

01:01:38.940 | and in particular, focus as it relates

01:01:40.540 | to learning and encoding new information.

01:01:43.480 | So let's say you want to be more motivated.

01:01:45.160 | You want to be more in pursuit of goals,

01:01:47.780 | and you want to have more energy and to be more focused.

01:01:50.760 | There are many ways to go about that.

01:01:52.360 | In fact, there's a near infinite cloud of opportunities,

01:01:56.040 | everything from prescription drugs to illicit drugs,

01:01:59.080 | which I certainly do not recommend, supplements, nutrition.

01:02:03.940 | You can listen to particular music.

01:02:05.760 | You can do all sorts of cognitive, behavioral,

01:02:08.600 | nutritional supplementation tricks,

01:02:10.680 | or you can just understand that what you're really after

01:02:15.320 | are increases in dopamine above baseline that you control.

01:02:19.720 | And there are ways to control them that are quite potent.

01:02:22.800 | And science tells us which tools are going to be

01:02:26.160 | the most potent and the most versatile for you.

01:02:29.780 | So I'm going to share those tools with you now

01:02:31.740 | with the caveat that each one of those tools

01:02:35.240 | could be its own entire podcast episode,

01:02:37.680 | and that we've done near entire episodes on each

01:02:41.120 | of these tools or small collections of these tools.

01:02:43.240 | So I'm going to cover these in somewhat superficial manner.

01:02:45.920 | We can provide links to previous episodes

01:02:48.120 | that relate to each of these tools in detail,

01:02:50.440 | but I'll give you enough detail about them

01:02:52.760 | that would allow you to incorporate them

01:02:54.120 | into your routine should you choose.

01:02:56.160 | Let's say you want to increase dopamine

01:02:57.600 | for sake of increasing motivation.

01:02:59.460 | The first thing to do is to understand

01:03:03.200 | what the natural behavioral tools are for increasing dopamine

01:03:06.200 | and to do those as consistently as possible.

01:03:09.140 | Again, these are tools that you'll want to do

01:03:11.120 | nearly every day, if not every day.

01:03:14.480 | And I know I'm sounding like a broken record on this one,

01:03:17.400 | but here again, we come to sunlight,

01:03:20.980 | and I should say not just the desire to,

01:03:25.060 | but really the need for viewing the maximum amount

01:03:28.520 | of sunlight that one can reasonably get given schedules

01:03:31.680 | and locations in the world, time of year, et cetera,

01:03:34.080 | in the early part of the day.

01:03:36.440 | Within the first hour of waking, ideally,

01:03:39.660 | but certainly in the first three hours of your day,

01:03:42.040 | you're going to want to maximize sunlight exposure

01:03:44.580 | to your eyes.

01:03:45.420 | Never look at the sun or any other light so bright

01:03:48.440 | that it's painful to look at.

01:03:49.520 | And yes, of course, blinking is fine, but no,

01:03:51.280 | take sunglasses off, go outside once the sun is out

01:03:53.940 | and get some natural light in your eyes.

01:03:55.560 | And if it's appropriate, or I should say in a way

01:03:59.060 | that's appropriate, maximize the amount of sunlight exposure

01:04:01.880 | to your skin, but please don't get burned.

01:04:04.720 | Please do wear sunscreen if you're prone to getting burned.

01:04:07.800 | Typically, early day sunlight is not going to burn you,

01:04:10.360 | at least not most people,

01:04:11.720 | unless you're extremely fair-skinned.

01:04:14.040 | So don't get burned.

01:04:14.880 | Do what you need to in order to protect yourself from burn.

01:04:17.320 | There's some emerging controversy about sunscreen

01:04:20.120 | and which ones are safe and which ones aren't safe.

01:04:21.780 | We have not done an episode on that yet,

01:04:23.460 | but I find it to be an important and interesting topic.

01:04:26.320 | Daria Rose, Dr. Daria Rose, I should say,

01:04:28.760 | has a podcast called the Daria Rose Podcast

01:04:31.200 | and did an episode all about sunscreens which are safe,

01:04:34.120 | which are not safe by interviewing an expert on that.

01:04:36.780 | So I refer you to that podcast as it relates to sunscreen,

01:04:39.240 | but get some natural light exposure in your eyes.

01:04:42.080 | And if you wake up before the sun comes out,

01:04:44.480 | turn on as many bright lights inside

01:04:46.080 | as you can turn on reasonably,

01:04:48.560 | given your electric bill, et cetera.

01:04:49.920 | Get a lot of bright sunlight exposure early in the day

01:04:52.620 | and get a lot of sunlight exposure to your skin

01:04:55.360 | in the early part of the day in a way that doesn't burn you,

01:04:59.280 | meaning burn your skin or blind you.

01:05:00.880 | Please, please don't do anything that harms your vision,

01:05:03.640 | like stare into bright light that's painful.

01:05:05.840 | What does that do?

01:05:07.840 | Well, it sets in motion

01:05:09.600 | a number of different biological cascades.

01:05:11.440 | Some are very fast.

01:05:12.920 | There are fast actions of sunlight that will trigger,

01:05:15.060 | for instance, dopamine release

01:05:16.800 | from different parts of your brain

01:05:18.040 | and your endocrine system.

01:05:19.660 | And we now know that it increases levels

01:05:22.760 | of genes related to thyroid hormone

01:05:25.200 | and actually increases certain dopamine receptors.

01:05:28.700 | So there's a wonderful paper.

01:05:29.760 | We will provide a link to this paper

01:05:31.680 | that shows that sunlight exposure can actually increase

01:05:34.760 | the amount of so-called DRD4.

01:05:36.960 | This is a particular type of dopamine receptor,

01:05:38.840 | the dopamine receptor 4.

01:05:41.020 | The genes for dopamine receptor 4

01:05:42.640 | are actually under photic control.

01:05:44.480 | So if you get sunlight exposure to your eyes,

01:05:46.280 | and it does have to be to your eyes

01:05:47.580 | in the early part of the day,

01:05:48.760 | you increase the amount of dopamine receptor that you have,

01:05:51.400 | which allows whatever circulating dopamine happens

01:05:54.000 | to be there to have a greater effect on motivation

01:05:57.280 | and I should say also on mood and feelings

01:05:59.480 | of being in pursuit and generally in craving

01:06:03.560 | and pursuit of things in life.

01:06:05.240 | Now there's another way to increase the effect

01:06:07.520 | of whatever dopamine happens to be circulating

01:06:09.720 | in your brain and body.

01:06:11.360 | And this again relates to increasing the number

01:06:14.520 | or the efficacy of the receptors for dopamine.

01:06:18.360 | Now here we're not talking about the dopamine receptor 4,

01:06:21.040 | but a different category of dopamine receptors,

01:06:23.240 | the D2 and D3 receptors,

01:06:25.220 | which are expressed multiple places in your brain and body

01:06:28.120 | and bind dopamine,

01:06:29.540 | meaning dopamine parks in them like a parking spot

01:06:32.000 | and allows dopamine to generally increase the activity

01:06:36.440 | of the neurons and cells

01:06:37.880 | that express those dopamine receptors.

01:06:39.880 | How do you do that?

01:06:41.060 | Well, it turns out that regular ingestion of caffeine

01:06:45.240 | at safe and appropriate levels of about 100 to 250 milligrams

01:06:50.040 | is going to increase the number

01:06:51.640 | of D2 and D3 dopamine receptors.

01:06:54.040 | I talked a little bit about this on a previous episode.

01:06:57.000 | Again, we'll provide links to these studies,

01:06:58.940 | but this is an important finding, I believe,

01:07:00.640 | because this is not about the acute,

01:07:03.240 | the immediate effects of caffeine on alertness,

01:07:05.420 | although those occur too.

01:07:06.800 | When you drink caffeine,

01:07:08.160 | it's going to increase your levels of adrenaline

01:07:10.960 | and so-called epinephrine,

01:07:12.320 | which will increase your energy levels.

01:07:13.680 | It's going to decrease levels of something called adenosine,

01:07:16.480 | which builds up while you're sleepy.

01:07:17.820 | It's going to make you feel less sleepy,

01:07:19.160 | more alert, more energetic.

01:07:20.800 | That's sort of obvious.

01:07:22.180 | But what's less obvious is that it's increasing the number

01:07:24.760 | and efficacy of dopamine receptors

01:07:26.800 | so that whatever dopamine happens to be around in your system

01:07:29.440 | is going to have more of a potent effect.

01:07:32.760 | So how much caffeine should you drink?

01:07:34.440 | That's going to vary from person to person.

01:07:35.920 | Some people are very sensitive to caffeine, others are not.

01:07:39.160 | I tend to be fairly insensitive to caffeine

01:07:42.080 | 'cause I've been drinking it for a long period of time.

01:07:44.280 | But after one or two cups of espresso or coffee,

01:07:47.720 | I feel like I've had enough.

01:07:48.900 | I tend to drink my caffeine early in the day,

01:07:50.600 | which is what I'm going to recommend that you do,

01:07:52.180 | not drinking caffeine past two and certainly not 4 p.m.

01:07:55.220 | if you're on a typical schedule and you want to be able

01:07:56.940 | to sleep that night, even if you can fall asleep.

01:07:59.840 | Having too much caffeine in your system is not good

01:08:01.740 | because it disrupts the architecture of sleep.

01:08:03.620 | And now knowing about all the metabolic variability

01:08:06.700 | across the night, according to different stages of sleep,

01:08:09.380 | it should be even more obvious as to why disrupting

01:08:12.660 | the architecture of sleep will be bad for you.

01:08:14.620 | So limit that caffeine intake to early in the day

01:08:16.660 | and don't go ballistic if you're not,

01:08:18.680 | certainly don't go ballistic in any case.

01:08:20.120 | But for most people, anywhere from 100 to 400 milligrams

01:08:23.140 | of caffeine is going to have this effect.

01:08:25.860 | And this effect, again, is a slow accumulating effect

01:08:29.200 | by drinking caffeine consistently day to day.

01:08:31.100 | I get my caffeine mainly from Yerba Mate tea.

01:08:33.660 | I want to emphasize that it's probably a good idea

01:08:35.140 | to stay away from the smoked Mates.

01:08:36.880 | There's some evidence those can be carcinogenic,

01:08:38.980 | but I brew my own Yerba Mate tea,

01:08:41.140 | or sometimes I'll drink coffee or espresso

01:08:43.060 | or sometimes both, frankly.

01:08:44.280 | As long as I'm hydrating enough and I'm getting enough salt,

01:08:46.380 | then I tend to feel fine with that much caffeine.

01:08:48.820 | The other way to increase dopamine and to make sure

01:08:51.340 | that your baseline levels of dopamine are high enough

01:08:53.360 | is to make sure that you're eating sufficient numbers

01:08:55.140 | of tyrosine-rich foods.

01:08:56.820 | You can look up which foods include tyrosine.

01:08:59.360 | Tyrosine is a precursor to dopamine.

01:09:01.620 | It's an amino acid that is a direct pathway

01:09:04.760 | to dopamine synthesis.

01:09:06.380 | And tyrosine foods include things like certain meats,

01:09:10.660 | Parmesan cheese, very high in tyrosine, for instance.

01:09:13.800 | In fact, there's something called the cheese effect,

01:09:15.760 | believe it or not.

01:09:16.600 | I don't want to go too far off topic,

01:09:17.780 | but the cheese effect is kind of interesting

01:09:19.320 | because certain people will take antidepressants

01:09:22.980 | that are so-called MAO inhibitors,

01:09:25.600 | monoamine oxidase inhibitors.

01:09:28.000 | Anytime you hear ASE, that's an enzyme,

01:09:30.020 | they will take these inhibitors that prevent the breakdown

01:09:34.500 | of dopamine and other so-called catecholamines,

01:09:37.300 | which allow more dopamine to be in circulation.

01:09:39.840 | But if these people eat certain cheeses,

01:09:42.440 | including Parmesan cheese, and there are other foods,

01:09:45.040 | of course, that include not just tyrosine,

01:09:47.140 | but one of the derivatives of tyrosine, called terramine,

01:09:51.700 | that generates what's called the cheese effect,

01:09:54.620 | which is people get potent migraines, headaches,

01:09:57.100 | blood pressure goes up, why?

01:09:58.780 | Well, because they've got a lot of tyrosine in their system

01:10:01.200 | and dopamine in their system,

01:10:02.560 | and they've got less of the enzyme that removes that dopamine

01:10:06.680 | or limits its action, and so they have an excess of dopamine

01:10:09.780 | and dopamine has effects on blood pressure, et cetera.

01:10:12.980 | So the cheese effect is something to avoid.

01:10:14.740 | If you are somebody who's taking drugs that tap into

01:10:18.300 | or manipulate the dopamine pathway,

01:10:20.140 | either for Parkinson's or depressions,

01:10:21.720 | obviously you're going to want to be careful

01:10:23.000 | about adjusting up or down levels of dopamine too potently.

01:10:27.780 | So mind the cheese effect if you're taking an MAO inhibitor.

01:10:31.260 | There's a lot of information about this online.

01:10:33.020 | For most people, eating foods like Parmesan cheese,

01:10:35.780 | eating foods like certain meats and certain vegetables

01:10:39.500 | also can increase tyrosine levels,

01:10:41.420 | which will increase dopamine synthesis.

01:10:43.780 | So these are ways of modulating

01:10:45.580 | more or less the baseline of dopamine

01:10:47.620 | that you are able to produce

01:10:48.900 | and the ways that dopamine can have its action

01:10:51.820 | by way of binding to receptors more potently.

01:10:54.720 | Now, there are other ways to increase dopamine

01:10:58.260 | in a more acute or directed way,

01:11:00.500 | ways to spike your dopamine

01:11:02.740 | to enhance your state of motivation, mood, focus, and so on.

01:11:07.740 | And in thinking about the vast landscape of tools

01:11:11.700 | that can do that, we have one category of tools,

01:11:14.400 | which are the really, really bad things

01:11:15.820 | that I don't recommend anybody do.

01:11:17.200 | In fact, I recommend nobody do ever,

01:11:19.560 | which are things like cocaine, methamphetamine, et cetera.

01:11:22.840 | They are incredibly destructive for lives

01:11:25.820 | because of the way that they so potently increase dopamine

01:11:28.480 | and then the crash in dopamine that occurs later.

01:11:30.940 | I mean, they can indeed and often do ruin lives,

01:11:33.480 | so we're leaving those off the table.

01:11:35.680 | There are, of course, prescription drugs

01:11:37.900 | that many people, especially people

01:11:40.180 | who have clinically diagnosed ADHD,

01:11:43.220 | attention deficit hyperactivity disorder,

01:11:45.180 | rely on and in fact benefit from in many cases,

01:11:48.460 | things like Ritalin, Adderall, Vyvanse.

01:11:52.040 | Nowadays, there's also a lot of interest

01:11:53.900 | in use of things like modafinil, R-modafinil.

01:11:56.760 | I covered all of those in the episode on ADHD,

01:11:59.620 | and you can find that at hubermanlab.com

01:12:01.380 | and the other places this podcast is found.

01:12:04.480 | Prescription drugs aside,

01:12:05.760 | because they require a prescription and a discussion

01:12:08.140 | that's in-depth and appropriate with your physician,

01:12:10.800 | healthcare provider, there are supplements

01:12:14.260 | that can very potently increase dopamine as well,

01:12:17.120 | perhaps not to the extent

01:12:18.300 | that some of those other prescription drugs can,

01:12:20.820 | but certainly to a degree that will impact

01:12:22.920 | and increase dopamine and motivation

01:12:24.940 | and the other states dopamine is associated with.

01:12:26.760 | And the two main categories of supplements

01:12:29.680 | that are very effective in raising dopamine,

01:12:31.780 | and here I should provide the caveat

01:12:33.300 | that anytime you're going to add or remove anything

01:12:35.180 | from your supplementation protocols,

01:12:38.000 | please talk to a physician who is knowledgeable

01:12:40.420 | on these topics.

01:12:41.320 | If you're somebody who has,

01:12:43.280 | or is taking drugs for depression or mania,

01:12:46.320 | please be very cautious

01:12:47.440 | about manipulating your dopamine in any case.

01:12:50.000 | I don't just say that to protect us,

01:12:51.400 | I say that to protect you.

01:12:52.780 | But if we were to look at the supplement landscape

01:12:56.140 | and ask which supplements increase dopamine,

01:12:58.080 | there are a vast number of them,

01:13:00.240 | but the three main ones,

01:13:02.720 | the most effective ones that are readily available out there

01:13:05.160 | without a prescription are macuna prurines.

01:13:07.640 | This is actually the outside of a velvety bean

01:13:10.280 | that has been extracted and put into a supplement.

01:13:12.920 | Macuna prurines is actual L-DOPA.

01:13:15.480 | It's 99% L-DOPA, which is a prescription drug

01:13:18.960 | that is given for Parkinson's and for other purposes

01:13:22.180 | where increasing dopamine is important.

01:13:25.680 | I don't recommend macuna prurines.

01:13:27.680 | I'm not saying that no one should take it,

01:13:29.220 | but I don't take it and I don't recommend it

01:13:31.340 | because it tends to so potently

01:13:33.740 | and acutely increase dopamine

01:13:35.200 | that there's a pretty substantial crash afterwards.

01:13:38.000 | So I avoid it and I don't generally suggest

01:13:40.640 | that anyone take it unless there's really a clinical need

01:13:44.400 | or they're working very closely with somebody

01:13:46.240 | that can really monitor that.

01:13:48.440 | The other two supplements that can increase dopamine

01:13:52.040 | in a short-term way but in a significant way are L-tyrosine.

01:13:57.040 | So you can buy that as a supplement amino acid.

01:13:59.680 | I sometimes take this.

01:14:00.720 | I would say I probably take it about once a week maximum

01:14:04.340 | for workouts or workouts.

01:14:07.120 | I'll take it in dosages of anywhere

01:14:08.920 | from 500 milligrams to 1,000 milligrams.

01:14:11.200 | People vary tremendously in their sensitivity

01:14:13.720 | to supplementing L-tyrosine.

01:14:15.200 | I know people that can take two grams.

01:14:17.200 | I know people that can barely take 100 milligrams.

01:14:20.080 | I know people that the best dose for them is zero milligrams.

01:14:22.820 | So there's a lot of variation there depending on sensitivity

01:14:25.360 | and their natural baseline levels of dopamine

01:14:28.560 | and whether or not they're doing a lot of other things

01:14:30.040 | to support dopamine.

01:14:31.800 | But nonetheless, taking L-tyrosine

01:14:33.280 | will lead to fairly substantial increases in dopamine

01:14:36.560 | within about 15 to 45 minutes.

01:14:38.640 | And it lasts for about 30 minutes to two hours.

01:14:41.900 | And then there's kind of a tapering off.

01:14:43.680 | Some people experience a little bit of an emotional

01:14:45.820 | or, and or I should say energetic crash.

01:14:48.480 | Some people don't.

01:14:49.320 | And then the other supplement that I certainly use

01:14:52.360 | and that I know a number of other people use

01:14:53.760 | is more fast acting but more potent,

01:14:55.320 | which is phenylethylamine.

01:14:57.160 | This relates to the so-called PEA molecule, P, P-E-A.

01:15:02.320 | And phenylethylamine increases dopamine

01:15:05.640 | and some metabolites related to dopamine

01:15:07.640 | in ways that really increase energy

01:15:09.360 | and feelings of wellbeing and motivation.

01:15:11.040 | And again, it's fast acting.

01:15:12.700 | So my particular protocol, the one I use,

01:15:14.720 | is I'll take phenylethylamine

01:15:17.160 | at dosages of about 300 to 600 milligrams

01:15:19.800 | along with some L-tyrosine.

01:15:22.580 | Or I'll take it on its own with a molecule,

01:15:25.640 | or I should say a compound

01:15:26.640 | that we'll talk about a little bit later

01:15:27.720 | as it relates to acetylcholine alpha-GPC.

01:15:30.280 | But tyrosine and phenylethylamine taken alone or together

01:15:33.240 | will make you feel more motivated and more alert,

01:15:35.840 | more willing and able to lean

01:15:38.120 | into particular motivated behaviors,

01:15:40.240 | whether or not they're physical or cognitive.

01:15:42.400 | If you'd like to learn more about these compounds

01:15:44.760 | and their supplementation and their effects,

01:15:46.840 | I encourage you to check out the ever valuable website,

01:15:50.000 | examine.com.

01:15:51.240 | It's zero cost to access and they provide references

01:15:54.120 | and some more details about these sorts of compounds

01:15:57.040 | and other related compounds.

01:15:58.720 | Now, if we were going to look at behavioral tools

01:16:00.820 | for potently increasing dopamine,

01:16:03.080 | that too is a vast landscape.

01:16:05.400 | And we know based on hundreds, if not thousands of studies,

01:16:09.660 | that things like winning at some sort of competition

01:16:13.600 | or succeeding in reaching a goal

01:16:15.800 | can certainly increase dopamine.

01:16:17.360 | We talk a lot about this in the episode

01:16:19.000 | on dopamine motivation and drive.

01:16:21.480 | But leaving that aside,

01:16:23.200 | there are certain behavioral protocols

01:16:25.400 | that are unrelated to your overall goals and motivations

01:16:29.400 | that can increase dopamine in a very sustained way.

01:16:32.160 | And without question,

01:16:33.740 | the most potent behavioral tool for doing that

01:16:36.340 | is going to be deliberate cold exposure.

01:16:39.520 | Deliberate cold exposure has been talked about a lot here

01:16:43.180 | and elsewhere in terms of its ability to do things

01:16:47.660 | like reduce inflammation as a way to test

01:16:51.240 | and improve resilience because uncomfortable cold

01:16:54.800 | provided it's applied safely

01:16:56.520 | is a great way to learn to be more resilient

01:16:58.680 | because you're essentially staying

01:17:00.320 | or forcing yourself to stay in a circumstance

01:17:02.400 | where your system is flooded with adrenaline.

01:17:04.980 | But one lesser known aspect of deliberate cold exposure

01:17:09.980 | is one that's been demonstrated quite convincingly in humans.

01:17:13.040 | It comes from a study published in the year 2000.

01:17:15.040 | I'll link to this study.

01:17:16.080 | I love this study, by the way.

01:17:18.560 | I covered it many times on this podcast

01:17:20.120 | because I love it so much and I think it's truly important.

01:17:23.400 | And that's the study from Sramak et al.

01:17:26.440 | entitled Human Physiological Responses to Immersion

01:17:28.820 | into Water of Different Temperatures.

01:17:30.400 | I'm not going to go into this into a ton of detail

01:17:32.200 | for sake of time,

01:17:33.400 | but basically what they show is that

01:17:35.500 | putting people into cold water,

01:17:36.680 | and I should mention the water that they used in this study

01:17:39.160 | wasn't that cold.

01:17:40.160 | They had a bunch of different conditions,

01:17:41.360 | but they had people that got into, for instance,

01:17:43.480 | 60 degree Fahrenheit water for up to two hours.

01:17:46.440 | I had them sitting there

01:17:47.800 | in a lawn chair up to their neck,

01:17:49.440 | had very long sustained increases in dopamine transmission

01:17:54.400 | and dopamine circulation in their brain and body.

01:17:57.920 | And also some of the other catecholamines.

01:18:00.800 | As I mentioned before, dopamine tends to collaborate

01:18:02.840 | with epinephrine and vice versa.

01:18:05.220 | Now you don't need to put yourself

01:18:07.080 | into 60 degree Fahrenheit water

01:18:08.900 | to get these kinds of sustained increases.

01:18:11.080 | And you certainly don't need to do it for two hours.

01:18:13.640 | We have strong reason to believe

01:18:16.120 | based on subsequent studies,

01:18:17.760 | in fact, published just this last year,

01:18:19.760 | that getting into much colder water

01:18:22.760 | of say 50 degrees or 55 degrees

01:18:24.760 | or even 45 degrees Fahrenheit

01:18:27.400 | can potently increase dopamine and epinephrine as well.

01:18:30.560 | And that you don't need to expose yourself

01:18:32.120 | to that cold water for nearly as long.

01:18:34.560 | So perhaps even as short as one minute

01:18:37.480 | or even 30 seconds exposure to really cold water

01:18:40.640 | can lead to these potent long lasting increases in dopamine.

01:18:44.480 | Many people will ask which protocols to follow.

01:18:46.980 | For instance, will a cold shower suffice?

01:18:49.320 | Very likely yes, if your shower gets cold enough.

01:18:51.560 | Do you need ice floating in the bath?

01:18:53.440 | No, it's all about the temperature and not

01:18:55.260 | whether or not there's ice present or not.

01:18:57.120 | How long to stay in there?

01:18:58.300 | There are a lot of details

01:18:59.660 | that we don't have time to go into this episode.

01:19:01.520 | Please see the episode on the use of deliberate cold

01:19:05.040 | for health and performance.

01:19:06.320 | You'll find that at Hubermanlab.com.

01:19:08.060 | We have a newsletter related to this.

01:19:09.640 | It gets into a lot of detailed protocols.

01:19:11.820 | But in general, we can say

01:19:14.400 | that the way to evoke dopamine and epinephrine release

01:19:17.580 | using cold water is to,

01:19:20.000 | ideally you would do cold water immersion.

01:19:22.000 | If you can't, you'd use cold shower.

01:19:24.100 | But you want to use a temperature that is safe,

01:19:26.840 | meaning you're not going to have a heart attack,

01:19:28.480 | but that is uncomfortable,

01:19:29.660 | such that you really want to get out

01:19:31.140 | and then staying in for anywhere from one minute

01:19:33.940 | to 10 minutes depending on how cold adapted you are.

01:19:36.580 | And then getting out and drying off

01:19:38.940 | and going about your day

01:19:39.780 | unless you have some other protocol

01:19:40.980 | that you're trying to extract from the cold.

01:19:42.780 | So this is a cold exposure protocol

01:19:45.140 | specifically aimed at increasing dopamine.

01:19:48.520 | For some people out there, you might think,

01:19:50.440 | this is kind of silly using cold water to increase dopamine.

01:19:53.360 | But when you look at the data in humans

01:19:56.100 | on the effect of cold water exposure

01:19:58.040 | to stimulate long lasting,

01:19:59.780 | very significant increases in dopamine and epinephrine,

01:20:02.840 | I think you'll agree that this is a really potent tool

01:20:06.280 | that provided it's given safely and gone about safely

01:20:09.820 | is giving you the kinds of increases in dopamine

01:20:12.060 | that you would seek using prescription pharmacology.

01:20:14.900 | Now it shouldn't be used as a replacement

01:20:16.720 | for prescription pharmacology,

01:20:18.500 | although people have done that to success.

01:20:20.740 | One of the previous guests on the Huberman Lab Podcast

01:20:23.620 | was Dr. Anna Lemke,

01:20:24.740 | our director of the Dual Diagnosis Addiction Clinic

01:20:26.820 | at Stanford.

01:20:27.660 | She has an amazing book called "Dopamine Nation,"

01:20:29.660 | all about dopamine and both its uses,

01:20:32.380 | healthy and its perils in things like addiction.

01:20:35.380 | And she describes a patient of hers

01:20:38.020 | that used deliberate cold exposure

01:20:39.740 | to try and maintain dopamine levels

01:20:41.660 | while coming off of drugs

01:20:43.300 | that were increasing dopamine so potently

01:20:45.940 | that they were putting him down the path of addiction.

01:20:48.060 | So the use of cold water for increasing dopamine

01:20:51.580 | is a real tool.

01:20:52.820 | It's, I would say, a power tool.

01:20:54.860 | In fact, it's the kind of thing

01:20:56.380 | that if you want to increase dopamine

01:20:57.860 | for sake of motivation,

01:20:59.660 | it might be your first go-to,

01:21:01.180 | provided you're also doing the things

01:21:02.680 | to maintain dopamine baseline,

01:21:04.380 | like sunlight exposure in particular,

01:21:06.460 | making sure you're getting sufficient amounts of tyrosine

01:21:08.880 | containing foods and so on.

01:21:10.580 | And now just very briefly,

01:21:11.740 | I want to point to a few quick tools

01:21:14.060 | that good peer-reviewed data tell us can be leveraged

01:21:19.060 | in order to make sure that you have sufficient dopamine

01:21:21.620 | when you want it,

01:21:22.540 | or that it's available for it to be released

01:21:24.900 | by any number of the tools I provided thus far.

01:21:27.900 | And those are sufficient number of B vitamins.

01:21:31.240 | So it turns out that B vitamins,

01:21:34.100 | in particular B6 or vitamin B6,

01:21:37.120 | can potently reduce prolactin levels.

01:21:40.020 | And again, prolactin and dopamine tend to work

01:21:42.360 | in kind of push-pull fashion.

01:21:44.040 | That said, you should be cautious

01:21:45.960 | about taking excessive levels of B6.

01:21:48.900 | It is a vitamin that if you take too much,

01:21:50.940 | you'll likely excrete it through your urine,

01:21:52.780 | but there is evidence

01:21:54.180 | that having excessively high levels of B6

01:21:56.860 | or supplementing with excessively high levels of B6

01:21:59.420 | can cause some peripheral neuropathy,

01:22:01.300 | some death of nerves in the periphery.

01:22:03.580 | If you want to know what dosage levels are relevant there,

01:22:05.540 | just simply look it up online.

01:22:06.680 | There's a lot of information about this,

01:22:08.220 | but you do want to make sure that you're getting enough

01:22:10.420 | B6, B12, et cetera,

01:22:12.340 | such that you can keep prolactin levels in check.

01:22:15.420 | And if you suspect that you have a dopamine deficiency,

01:22:18.880 | please talk to your doctor and talk to them

01:22:20.460 | about ways you might adjust that prolactin down

01:22:23.020 | and thereby dopamine up.

01:22:25.180 | The other way to ensure that dopamine levels stay high

01:22:28.700 | or put differently that you don't quash

01:22:31.500 | whatever dopamine you have in your system

01:22:33.760 | is to really avoid bright light exposure to your eyes

01:22:36.620 | between the hours of 10 p.m. and 4 a.m.

01:22:38.780 | Or another way of putting this,

01:22:40.020 | because I realize people sleep at different times, et cetera,

01:22:42.500 | is to avoid bright light exposure to your eyes,

01:22:45.060 | not just blue light, but all colors of light,

01:22:47.660 | in phase three, that is 17 to 24 hours after waking up

01:22:52.620 | because that's really when you should be asleep

01:22:54.420 | or trying to get asleep if you're having trouble sleeping.

01:22:57.640 | Work from Samir Hatar's lab,

01:22:59.360 | the director of the Chronobiology Unit

01:23:00.860 | at the National Institutes of Mental Health,

01:23:02.960 | again, a previous Huberman Lab podcast guest,

01:23:06.980 | tell us that bright light exposure in phase three

01:23:11.520 | of your circadian cycle, 17 to 24 hours after waking,

01:23:15.520 | can have dramatic effects in reducing dopamine levels

01:23:18.480 | by way of activating a neural circuit

01:23:20.360 | involving something called the habenula.

01:23:22.280 | Want to get into too many details right now,

01:23:24.260 | but really try and keep the lights dim

01:23:26.060 | in the middle of the night or off if you can do that safely.

01:23:29.120 | It's really going to help

01:23:30.440 | if you're turning on your phone brightly,

01:23:32.800 | if you're turning on bright lights,

01:23:34.720 | it's not just going to negatively impact melatonin,

01:23:37.320 | the hormone that helps you fall and stay asleep,

01:23:39.040 | it's also going to negatively impact dopamine levels,

01:23:43.160 | not just that night, but the subsequent day.

01:23:46.400 | So that more or less summarizes our coverage

01:23:49.000 | of ways to use behavior and supplementation and nutrition

01:23:52.640 | to increase dopamine and dopamine receptor efficacy

01:23:55.440 | and number and to keep sufficient amounts of dopamine

01:23:58.560 | in your system day to day for motivation, mood, and focus.

01:24:02.800 | And of course, keep in mind those things

01:24:04.440 | that can suppress dopamine, the bright light exposure,

01:24:07.920 | elevated prolactin, and so on.

01:24:10.080 | My hope is that by understanding those tools

01:24:11.940 | and how they work and understanding

01:24:13.640 | that dopamine does certain things and not others,

01:24:16.520 | that you can assemble a versatile kit of behaviors

01:24:20.300 | and other things that you can do

01:24:21.680 | in order to adjust your dopamine levels

01:24:23.800 | according to your particular goals.

01:24:26.380 | I want to just briefly return to the fact, however,

01:24:29.860 | that all of that is riding on that phase one,

01:24:33.180 | phase two background,

01:24:34.540 | meaning it's probably going to take less cold water exposure,

01:24:38.300 | or I should say less time doing cold water exposure

01:24:41.100 | early in the day to get a big increase in dopamine

01:24:43.860 | than it would later in the day,

01:24:45.580 | because later in the day,

01:24:46.500 | your baseline levels of dopamine are lower

01:24:48.900 | and you've got more serotonin circulating.

01:24:51.620 | That should make sense to you now as to why that's the case.

01:24:54.460 | And does that mean that you should really modify

01:24:56.940 | your protocols dramatically?

01:24:58.420 | Probably not, but you might keep that in mind

01:25:01.220 | that if, for instance,

01:25:02.280 | you need to be in a highly motivated focused state

01:25:04.380 | in the late part of the day for whatever reason,

01:25:06.520 | it might take a few or more of these tools in combination

01:25:10.040 | in order to accomplish that.

01:25:11.460 | Whereas if you're somebody

01:25:12.300 | who feels pretty good during the day,

01:25:13.420 | but you're kind of lacking motivation

01:25:15.100 | and you want to increase dopamine levels

01:25:16.500 | and you don't yet need to

01:25:18.240 | or want to resort to prescription drugs or supplementation,

01:25:20.940 | well, then you might layer in

01:25:21.900 | a couple of behavioral protocols,

01:25:23.260 | paying attention to, of course,

01:25:24.700 | the things that you might be doing

01:25:25.760 | that would also potentially suppress dopamine.

01:25:28.580 | So again, that kit of tools is designed for you to play with

01:25:32.780 | if you choose, if it's safe for you to apply them,

01:25:35.640 | then do that.

01:25:37.000 | Consider doing them individually,

01:25:38.780 | not trying to hit all the tools all at once, right?

01:25:42.220 | I mean, why throw all those tools

01:25:44.380 | at your dopamine system at once?

01:25:46.380 | Better would be to have those tools in your kit

01:25:48.680 | and be able to deploy them

01:25:49.860 | depending on whether or not you're on travel,

01:25:51.420 | whether or not you're eating well or less well,

01:25:53.880 | whether or not you're sleeping well or less well,

01:25:56.060 | that's highly individual.

01:25:57.300 | And I like to think that in having those tools in hand,

01:26:00.040 | you'll be able to adjust them and apply them

01:26:01.980 | in the ways that allow you to access

01:26:04.140 | the dopamine increases that you're after.

01:26:06.820 | So next I'd like to talk about epinephrine,

01:26:08.820 | also called adrenaline.

01:26:10.700 | I want to point out that epinephrine is released

01:26:13.420 | both in the brain and the body.

01:26:15.560 | In fact, there's a barrier between brain and body

01:26:17.680 | that prevents the epinephrine

01:26:19.140 | that's released from your adrenal glands,

01:26:21.360 | crossing the blood brain barrier.

01:26:23.320 | So your brain has a separate site called the locus coeruleus.

01:26:27.120 | This is a collection of neurons in the back of the brain

01:26:29.240 | that kind of sprinkler the rest of the brain

01:26:30.760 | with epinephrine and essentially wakes up

01:26:35.000 | whatever neural circuits happen to see,

01:26:37.560 | or I should say wake up any circuits

01:26:40.460 | where that epinephrine happens to arrive, right?

01:26:43.900 | And generally increase the excitability of those networks.

01:26:46.560 | That's why we say epinephrine increases energy.

01:26:50.020 | I'm not talking about caloric energy,

01:26:51.660 | although that's distantly related to this,

01:26:53.700 | but really energy and the desire to move,

01:26:57.140 | the feeling that we can think,

01:26:58.840 | the feeling that we can be alert.

01:27:00.500 | In fact, if you look at somebody

01:27:02.140 | and their eyelids are wide open, in large part,

01:27:04.860 | that's because of a lot of adrenaline in their system.

01:27:07.100 | If their pupils are really big

01:27:08.620 | and their eyes are really wide open, in general,

01:27:11.060 | that means they have a lot of epinephrine circulating there.

01:27:13.380 | Whereas when we're tired and we're kind of hood-eyed

01:27:15.460 | and we're sort of sleepy or our pupils are really small,

01:27:18.240 | in general, that's because levels of epinephrine

01:27:20.940 | and also dopamine, remember they work together,

01:27:23.340 | levels of epinephrine and dopamine tend to be lower.

01:27:26.300 | This is also why when people take any drug,

01:27:28.540 | like again, not recommending this amphetamine or cocaine

01:27:31.640 | or any stimulant, their pupils tend to be huge,

01:27:34.340 | their eyes tend to be wide open,

01:27:36.740 | they don't blink very often,

01:27:38.720 | and the opposite is true when people take sedatives.

01:27:42.260 | So it all starts to make sense

01:27:43.660 | when you think about the basic actions of these things.

01:27:46.660 | For many people, increasing adrenaline or epinephrine

01:27:51.240 | might seem like a crazy idea.

01:27:52.520 | Most people probably associate this molecule with stress

01:27:55.280 | and they would like to be less stressed.

01:27:56.860 | And we've done entire episodes about stress,

01:27:58.740 | how to master stress, how to leverage stress,

01:28:00.800 | how to conquer stress, there are a lot of great tools

01:28:02.800 | to do that that are behavioral, supplementation-based.

01:28:05.560 | Please see the episode on mastering stress for those tools.

01:28:08.760 | But there are people, including me,

01:28:11.840 | that want to increase our levels of epinephrine

01:28:14.400 | at least early in the day.

01:28:16.160 | I'm somebody who wakes up rather slowly.

01:28:17.900 | In fact, right after waking up,

01:28:19.160 | I rarely want to bounce out of bed.

01:28:21.060 | I try and push myself to do that.

01:28:22.660 | I'm always impressed by these chock-a-willing types

01:28:25.220 | that are up at 430 or up at five and already into action.

01:28:29.000 | I tend to be kind of thinking about thinking about

01:28:32.200 | maybe being in action early in the day,

01:28:34.680 | but I try and push myself to get into action,

01:28:37.880 | which itself can increase epinephrine.

01:28:40.400 | I should mention that any physical activity,

01:28:42.980 | any physical activity, walking, running, weightlifting,

01:28:46.220 | swimming, even talking for that matter,

01:28:48.900 | is going to increase levels of epinephrine.

01:28:51.220 | Locus coeruleus is a brain structure

01:28:54.180 | that is tightly coupled with behaviors

01:28:56.920 | in a bi-directional way.

01:28:58.460 | That is, when you are in action,

01:29:01.140 | you increase the amount of epinephrine released

01:29:03.300 | from locus coeruleus, you wake up the brain.

01:29:06.340 | And conversely, when locus coeruleus is active,

01:29:09.680 | the brain wakes up.

01:29:10.560 | So it's reciprocal, it goes both directions.

01:29:13.260 | So I saw a funny tweet actually earlier today.

01:29:16.240 | It was something like going to the gym gives you energy,

01:29:20.220 | but you need energy to go to the gym,

01:29:21.960 | sounds like a pyramid scheme to me,

01:29:24.120 | which made me chuckle, but of course,

01:29:26.800 | overlooks the fact that indeed, if you have energy,

01:29:29.860 | you are more likely to be willing

01:29:31.520 | to get into physical movement or cognitive movement

01:29:34.380 | and thinking hard or thinking a lot about something.

01:29:37.880 | But also it is absolutely scientifically proven

01:29:42.160 | that being in action increases levels of epinephrine.

01:29:46.200 | This is why exercising early in the day

01:29:49.000 | gives you more energy for rest of day.

01:29:51.660 | You still might experience a little bit of a crash

01:29:53.540 | in the afternoon,

01:29:54.580 | especially if you're getting up extra early,

01:29:56.820 | or if you're drinking caffeine too close to waking.

01:29:59.120 | I've talked about this before.

01:30:00.300 | If you drink too much caffeine close to waking,

01:30:03.220 | you're going to have an afternoon crash.

01:30:04.740 | Better to push that caffeine intake out

01:30:06.860 | about 90 to 120 minutes after waking.

01:30:09.120 | I know this is really painful for certain people,

01:30:11.300 | but caffeine does increase epinephrine.

01:30:15.140 | Caffeine does other things to limit sleepiness.

01:30:17.760 | And by pushing it out 90 to 120 minutes after waking,

01:30:20.960 | you will avoid the afternoon crash to a large degree.

01:30:25.420 | And if you get up and you exercise

01:30:27.820 | or even do any movement of any kind,

01:30:29.680 | 100 jumping jacks or a walk if you can't do that,

01:30:32.820 | anything like that will increase the total amount

01:30:35.700 | of epinephrine that you secrete into your bloodstream

01:30:38.280 | and in your brain and will get you more energy,

01:30:41.980 | not just in that moment, but throughout the day.

01:30:43.760 | So keep that in mind.

01:30:44.700 | Exercise does indeed give you energy.

01:30:47.580 | It burns caloric energy, but it gives you neural energy

01:30:50.760 | by way of increasing epinephrine transmission

01:30:53.180 | from locus coeruleus.

01:30:54.680 | And presumably if the exercise is intense enough,

01:30:58.420 | adrenaline epinephrine release from the adrenals

01:31:01.220 | within your body as well.

01:31:02.860 | So we have exercise and we have caffeine as potent tools

01:31:05.960 | for increasing epinephrine and thereby energy.

01:31:09.100 | Another potent tool that's purely behavioral,

01:31:11.540 | but is known to work based on excellent studies in humans.

01:31:14.820 | And actually my laboratory has been doing similar types

01:31:17.260 | of studies that are soon to be published, we hope,

01:31:20.040 | is so-called cyclic hyperventilation.

01:31:22.820 | Some of you may be familiar with Wim Hof breathing.

01:31:25.300 | There's also Tummo breathing, which is very similar,

01:31:28.140 | Kundalini breathing.

01:31:29.900 | All of those styles of breathing involve cyclic

01:31:32.780 | hyperventilation, deep inhales and either passive exhales

01:31:37.100 | or active exhales, but repeating inhale, exhale, inhale,

01:31:39.940 | exhale in a very deep and repetitive way.

01:31:42.660 | If you were to do that right now,

01:31:44.620 | it doesn't matter if you do it through your nose or mouth,

01:31:46.540 | although ideally you would do the inhale through your nose

01:31:48.860 | and the exhale through your mouth.

01:31:49.820 | If you did that for 25 repetitions,

01:31:52.900 | 25 inhales and exhales, you would feel more alert.

01:31:55.980 | You'd also feel more warm, why?

01:31:57.660 | Because you increased epinephrine adrenaline release

01:32:00.920 | in the brain and body.

01:32:02.020 | It works the first time and it works every time

01:32:04.520 | to increase epinephrine and thereby energy.

01:32:07.380 | And in fact, there are protocols and great scientific

01:32:10.900 | studies of using cyclic hyperventilation for periods

01:32:15.300 | of minutes, if not longer, where for instance,

01:32:17.860 | you would do 25 big inhales and exhales,

01:32:20.560 | followed by a brief breath hold with your lungs empty,

01:32:22.940 | then repeat 25, then brief breath hold, excuse me, exhale,

01:32:27.180 | hold your lungs empty, and then repeat again

01:32:29.100 | for a third round if you like.

01:32:30.740 | If you do that over and over, you're going to be very alert.

01:32:33.200 | You're going to have more energy.

01:32:34.260 | You're going to feel like you want to move around

01:32:36.060 | a lot more.

01:32:36.900 | In fact, you might even feel agitated.

01:32:38.260 | So people with a lot of anxiety or prone to panic attack

01:32:41.220 | might want to be cautious in how they train

01:32:43.500 | and embark on that type of breathing,

01:32:45.220 | might want to approach it a little more carefully

01:32:46.780 | or avoid it altogether.

01:32:48.020 | But for most people, cyclic hyperventilation

01:32:50.100 | is simply going to get you more energized

01:32:51.660 | and feeling like you want to move,

01:32:53.660 | feeling like you can think more clearly

01:32:55.380 | and you will be more wide-eyed and alert

01:32:57.100 | because you are releasing adrenaline.

01:32:59.820 | And the cold water exposure protocol

01:33:01.380 | that I talked about earlier,

01:33:02.380 | and that's covered in our episode on cold

01:33:04.540 | and in the newsletter on cold.

01:33:06.620 | Well, that, as I mentioned earlier,

01:33:08.560 | potently increases dopamine, but also epinephrine.

01:33:11.900 | So that's another terrific tool,

01:33:13.220 | whether or not it's applied by cold shower or cold immersion

01:33:16.720 | or some other thing like cryo,

01:33:19.060 | that is going to make you more alert

01:33:20.820 | because it releases adrenaline.

01:33:23.060 | Now, we can't really say that there are foods

01:33:25.500 | to increase epinephrine.

01:33:27.240 | Rather, there are foods that include a lot of tyrosine

01:33:30.780 | that will increase dopamine.

01:33:32.660 | And remember, dopamine is the molecule

01:33:34.480 | from which epinephrine is synthesized.

01:33:37.200 | So we can't really point to a particular food

01:33:40.060 | or categories of food for increasing epinephrine.

01:33:42.080 | I think caffeine and things like it

01:33:44.480 | will increase epinephrine.

01:33:46.220 | There are, of course, prescription drugs

01:33:48.220 | that will increase epinephrine.

01:33:50.220 | And of course, there are all sorts of so-called beta blockers

01:33:53.540 | that will block the receptors for epinephrine

01:33:55.920 | to make you feel calm for public speaking

01:33:58.260 | or for various heart conditions, et cetera.

01:34:00.300 | That's really the domain of physicians

01:34:02.240 | and should really be worked out with your cardiologist,

01:34:05.460 | with a physician, et cetera.

01:34:06.860 | I think the tools of exercise

01:34:09.680 | and should you want very potent increases in adrenaline,

01:34:13.940 | high-intensity exercise, as well as the tools of caffeine,

01:34:17.860 | cyclic hyperventilation, and deliberate cold exposure

01:34:20.780 | really combined to give you a nice little kit.

01:34:24.580 | I would say a versatile kit of ways to increase epinephrine

01:34:28.100 | for sake of having more physical and mental energy.

01:34:30.780 | So next is the neuromodulator acetylcholine.

01:34:33.540 | And as I mentioned earlier,

01:34:35.180 | acetylcholine is associated with states of focus.

01:34:38.900 | And those states of focus

01:34:40.140 | can be high-energy states of focus.

01:34:42.460 | So the ones that are accompanied

01:34:45.280 | by high levels of dopamine and epinephrine

01:34:47.860 | and where we're really excited about

01:34:49.920 | and really lasered in on something,

01:34:51.940 | or they can be the calmer, more relaxed states of focus,

01:34:56.020 | like reading a book or practicing music

01:34:58.820 | or listening very carefully to somebody

01:35:01.120 | in a way that's relaxed and calm.

01:35:03.340 | And yet nonetheless, where we have a narrow cognitive

01:35:06.980 | and typically a narrow visual aperture

01:35:10.140 | and typically also a narrow auditory aperture,

01:35:12.860 | that is our auditory system and our visual system

01:35:15.680 | and our thinking can be very broad,

01:35:17.860 | it can be all over the place,

01:35:19.560 | or it can be very narrow and it can be very focused.

01:35:23.740 | Acetylcholine is released from two major sites in the brain,

01:35:26.980 | nucleus basalis, which is in the forebrain

01:35:29.540 | and extends connections out to many different brain areas

01:35:32.500 | to offer the opportunity to release acetylcholine locally

01:35:36.660 | and more or less in a chemical way,

01:35:39.140 | highlight those particular neurons and synapses

01:35:42.660 | for strengthening for plasticity later.

01:35:45.660 | And it is released from sites in the back of the brain

01:35:48.940 | in a way that can increase the so-called fidelity

01:35:52.660 | of information coming in through our eyes,

01:35:56.020 | our ears, our nose, et cetera.

01:35:57.120 | What do I mean by fidelity?

01:35:58.220 | Well, we are constantly being bombarded

01:35:59.920 | with sensory information through all of our various senses

01:36:03.380 | and acetylcholine released from this area

01:36:05.720 | in the back of the brain has the ability

01:36:08.100 | to increase the extent to which say visual information

01:36:12.460 | or just visual and auditory information

01:36:15.280 | would make it through to our consciousness,

01:36:17.320 | whereas all the other types of sensory information

01:36:19.640 | that are coming in are filtered out.

01:36:22.660 | So your brain, because it's taking in all this information,

01:36:25.880 | needs to decide what to pay attention to.

01:36:27.820 | And in this way, we can say that acetylcholine

01:36:29.740 | has a lot to do, not just with focus in air quotes,

01:36:32.720 | but literally attention,

01:36:34.360 | which neural signals become relevant to our consciousness.

01:36:38.420 | There's a whole discussion to be had there

01:36:40.060 | and we don't have time for that.

01:36:41.420 | Rather, I'd like to focus on what are the tools

01:36:43.800 | that one can use to maintain healthy baselines

01:36:47.680 | of acetylcholine and increase acetylcholine

01:36:50.980 | for sake of learning any type of information,

01:36:53.660 | physical, cognitive, or otherwise.

01:36:55.540 | Now, it turns out there've been a lot of studies,

01:36:57.300 | including many quality peer-reviewed studies

01:36:59.100 | carried out in humans looking at what happens

01:37:01.620 | when you increase acetylcholine levels in the brain

01:37:05.380 | and you accompany that with the attempt to learn.

01:37:07.980 | And what you find almost always

01:37:10.400 | is that people experience increased focus

01:37:13.640 | that when measured,

01:37:15.020 | the neuronal responses become more specific,

01:37:18.220 | so less broad scale activity in the brain

01:37:20.260 | and more specific neural circuit activity,

01:37:23.140 | and that this triggers immediate and long-lasting changes

01:37:27.500 | in the way those circuits work,

01:37:28.900 | even when acetylcholine is not being deployed,

01:37:31.180 | so-called neuroplasticity, the circuits literally change.

01:37:34.340 | So this is great.

01:37:35.340 | The work of Michael Silver at Berkeley,

01:37:37.740 | the work of Mike Merzenich at UCSF,

01:37:40.360 | the work of Michael Kilgard down in Texas,

01:37:42.380 | all of those laboratories see this again and again and again.

01:37:44.860 | Increase acetylcholine before and during learning,

01:37:47.500 | and there's a much higher probability

01:37:49.480 | that the learning will quote unquote sink in,

01:37:51.500 | that the information will be retained

01:37:53.100 | because those neural circuits change.

01:37:55.380 | Now, ways to increase acetylcholine in a potent way

01:37:59.060 | include, again, nutrition and supplementation.

01:38:03.440 | It is important to have baseline levels of acetylcholine

01:38:06.980 | be sufficiently high as well.

01:38:08.620 | And for that, really the ideal situation

01:38:10.620 | is to regularly ingest foods

01:38:12.440 | that provide enough of the precursors

01:38:14.420 | for acetylcholine to be made.

01:38:16.380 | If you go online and you were to do a search

01:38:18.900 | of which foods contain a lot of choline,

01:38:21.860 | which is related to the synthesis of acetylcholine,

01:38:25.200 | you would get some interesting information back.

01:38:27.180 | For instance, beef liver is the most potent source of choline.

01:38:31.780 | I know nowadays there's kind of a growing micro trend,

01:38:34.600 | if you will, of ingesting beef liver, even raw liver,

01:38:37.380 | which to be honest, the thought of ingesting raw liver

01:38:39.940 | of any kind activates my area of postrema,

01:38:42.420 | which is the area of the brain that triggers nausea.

01:38:44.620 | In fact, I'm starting to salivate a bit,

01:38:46.220 | not because I'm hungry,

01:38:47.060 | but I think the whole concept makes me ill.

01:38:49.960 | Nonetheless, cooked liver or raw liver for that matter,

01:38:54.540 | or liver of any kind seems to contain a lot of choline.

01:38:57.940 | I realize most people,

01:38:59.880 | most people are not going to be running out

01:39:02.220 | and ingesting large amounts of beef liver.

01:39:04.780 | Eggs contain a lot of choline, beef contains choline,

01:39:07.540 | soybeans contain choline.

01:39:08.740 | So there are vegan or non-meat sources.

01:39:11.260 | Chicken, fish, mushrooms, kidney beans,

01:39:13.860 | these sorts of things contain a lot of choline.

01:39:16.100 | And there are other vegetables that contain choline.

01:39:17.800 | So depending on your dietary preferences and needs,

01:39:20.180 | you can select certain foods to ingest

01:39:23.300 | to get enough choline to synthesize

01:39:24.740 | enough baseline acetylcholine.

01:39:27.420 | In the realm of supplementation,

01:39:29.900 | there are some excellent tools for increasing acetylcholine

01:39:33.980 | in the acute short term,

01:39:35.680 | meaning over the course of about 30 minutes out

01:39:38.780 | to about two hours or maybe even four hours.

01:39:40.960 | And the number of different molecules that can do that,

01:39:44.040 | that are available without a prescription,

01:39:45.620 | at least in the US, is pretty vast.

01:39:48.320 | The most common of those molecules is actually nicotine.

01:39:51.080 | Nicotinic acetylcholine receptors are abundant

01:39:54.340 | throughout the body and brain.

01:39:55.780 | They're in various brain circuits.

01:39:57.780 | They are on muscle.

01:39:59.600 | And yes, smoking nicotine either by vaping or cigarette

01:40:03.720 | will activate those nicotinic receptors.

01:40:07.700 | But of course, smoking is a terrible thing.

01:40:10.180 | It will also activate things like lung cancer.

01:40:12.740 | So I definitely don't recommend that.

01:40:14.140 | It also activates addiction because of the ways

01:40:16.980 | that it triggers activation of the dopamine circuit.

01:40:20.060 | So I think that triggering activation

01:40:24.100 | of acetylcholine related pathways

01:40:25.860 | by ingesting nicotine by way of inhalants

01:40:28.660 | is generally a bad idea.

01:40:31.300 | However, some people will chew Nicorette

01:40:34.740 | or other nicotine type gums.

01:40:37.760 | I've never done that,

01:40:38.600 | but I have friends who actually rely on that.

01:40:40.480 | These are typically former smokers

01:40:42.740 | that are trying not to smoke,

01:40:44.160 | but still want to get some of the focus enhancement

01:40:47.460 | that they experience from nicotine.

01:40:49.320 | Some people are very sensitive to nicotine,

01:40:51.320 | and this is important.

01:40:52.280 | Some people are very sensitive to ingested nicotine.

01:40:54.940 | So nowadays there are nicotine dipped toothpicks.

01:40:58.320 | There of course is nicotine gum

01:40:59.720 | and other sources of nicotine.

01:41:00.960 | Some people can take that and feel fine.

01:41:02.740 | Some people take it and feel absolutely terrible.

01:41:05.700 | I confess I've never actually tried nicotine

01:41:08.740 | in any of those forms.

01:41:10.560 | So I don't know how they work for me,

01:41:12.020 | but some people do use them as cognitive enhancers.

01:41:14.500 | In fact, I know one Nobel prize winning neuroscientist

01:41:17.880 | who's quite well known in our field

01:41:19.560 | for chewing Nicorette all day long.

01:41:21.560 | He insists that it really helps him with his focus

01:41:23.660 | and he is exceedingly smart and productive.

01:41:25.860 | Although I'm sure there are other reasons for that.

01:41:28.060 | Supplements that I have used and do use

01:41:31.100 | for increasing acetylcholine

01:41:33.420 | are things like Alpha-GPC or Hooperzine.

01:41:37.980 | Alpha-GPC is in the choline pathway

01:41:42.260 | such that more acetylcholine is synthesized

01:41:44.980 | after you ingest it.

01:41:46.140 | That's the general logic or framework of how it works.

01:41:48.840 | Whereas Hooperzine is mainly in the enzymatic pathway.

01:41:52.420 | It tends to adjust how much acetylcholine is broken down

01:41:55.720 | and lead to net increases in acetylcholine.

01:41:59.580 | I will often take 300 milligrams of Alpha-GPC

01:42:02.680 | prior to workouts or prior to cognitive work bouts.

01:42:06.380 | But when I say often,

01:42:07.560 | I tend to do this anywhere from three to four times a week,

01:42:11.780 | typically not every day.

01:42:13.480 | Although there are people,

01:42:14.640 | including people who are trying to offset

01:42:16.460 | age-related cognitive decline

01:42:17.800 | that will take 300 milligrams of Alpha-GPC

01:42:20.700 | three times a day every day,

01:42:22.640 | which closely mimics some of the studies

01:42:24.640 | that have been done on humans,

01:42:25.840 | looking at offsetting age-related cognitive decline

01:42:28.780 | using things like Alpha-GPC.

01:42:31.420 | I should point out that there have been a few studies,

01:42:34.200 | a few, not many,

01:42:35.600 | but these studies emphasize that people

01:42:38.440 | who take a lot of Alpha-GPC chronically over time

01:42:41.480 | may be at increased risk for stroke.

01:42:44.040 | I think the data are still out on that

01:42:46.380 | and we need more data.

01:42:47.960 | But for me,

01:42:48.800 | in terms of thinking about the risk benefit profiles,

01:42:51.400 | taking 300 milligrams of Alpha-GPC

01:42:53.880 | most certainly does increase my ability of focus.

01:42:56.000 | I've noticed that I tend to take it

01:42:57.280 | alongside caffeine and phenylethylamine.

01:43:00.120 | So I take that in combination

01:43:01.760 | either before workouts or work bouts,

01:43:03.440 | really sharpens my focus.

01:43:04.800 | And again, I'm doing that three, maybe four times per week.

01:43:07.440 | And I'm careful to do that in the early part of the day

01:43:10.000 | so that it does not disrupt my sleep.

01:43:12.280 | Although I have taken Alpha-GPC

01:43:13.840 | in the second half of the day

01:43:15.240 | and I had no trouble sleeping at all.

01:43:17.320 | I don't know what the exact half-life is

01:43:19.600 | of the given form that's typically in supplementation.

01:43:22.460 | It's actually hard to get that information.

01:43:24.500 | But typically the focus effects wear off

01:43:27.640 | after about two, maybe four hours maximum.

01:43:30.360 | Now, one thing that I don't think

01:43:31.640 | has ever been discussed before,

01:43:33.140 | certainly not on this podcast,

01:43:34.800 | is that if you take Alpha-GPC even semi-regularly,

01:43:39.540 | you may notice that a particular feature

01:43:42.520 | of your blood work will increase.

01:43:44.180 | And that's TMAO,

01:43:45.640 | which is sometimes associated

01:43:47.480 | with increased cardiovascular risk.

01:43:50.240 | This may, again,

01:43:51.440 | may relate to some of the potential risk

01:43:53.900 | of very high levels of Alpha-GPC ingestion

01:43:56.820 | over many years, increasing stroke risk.

01:43:59.700 | Again, those studies looked at people

01:44:00.820 | who've been taking it for up to a decade.

01:44:03.040 | But in any case, one way to prevent the increase in TMAO,

01:44:07.740 | if you're taking Alpha-GPC at all,

01:44:10.420 | is to take 600 milligrams of garlic

01:44:13.320 | because it contains something called allicin.

01:44:15.840 | This was a trick that was handed off to me

01:44:18.300 | by Dr. Kyle Gillette,

01:44:19.780 | who, again, was a guest on this podcast some time ago,

01:44:21.960 | talking about hormones and hormone health.

01:44:23.860 | Turns out that ingestion of 600 milligrams of allicin

01:44:27.180 | alongside or even just same day as Alpha-GPC

01:44:30.280 | can really clamp those TMAO levels

01:44:33.000 | that would otherwise increase if you're taking Alpha-GPC.

01:44:35.480 | And indeed, I've done the blood work,

01:44:37.140 | and that turns out to be the case.

01:44:38.940 | I saw a spike in TMAO.

01:44:40.300 | I started taking 600 milligrams of garlic,

01:44:43.180 | and those TMAO levels came down.

01:44:45.180 | And last, as it relates to acetylcholine,

01:44:47.100 | but certainly not least,

01:44:49.060 | just as acetylcholine can increase focus,

01:44:51.740 | focus can increase acetylcholine.

01:44:54.380 | I talked a lot about this in the episode on focus,

01:44:57.400 | but there are behavioral tools

01:44:58.820 | that you can use to enhance focus.

01:45:00.540 | Things like staring at a particular visual target

01:45:03.580 | at the same distance at which

01:45:05.180 | you're going to perform some work

01:45:06.540 | and doing that for 30 to 60 seconds,

01:45:09.460 | narrowing in a very deliberate way your visual field,

01:45:11.880 | and then moving into a focused work bout.

01:45:14.760 | That behavioral practice of narrowing your visual aperture

01:45:19.760 | will increase the amount of acetylcholine transmission

01:45:22.400 | in particular neural circuits

01:45:24.160 | that will then make it easier to focus.

01:45:25.920 | How do we know that?

01:45:26.800 | Well, I covered in that episode

01:45:29.120 | some of the peer-reviewed studies

01:45:30.600 | that relate to protocols that are now actively

01:45:32.840 | being deployed in schools in China and elsewhere,

01:45:36.340 | where kids are doing deliberate visual focus exercises

01:45:40.080 | in order to increase their mental focus.

01:45:41.880 | And while they're not doing micro dialysis

01:45:43.640 | or brain imaging on those kids in real time,

01:45:46.120 | the cognitive effects and indeed the performance effects

01:45:49.880 | in terms of academic ability and output

01:45:52.320 | are pretty impressive.

01:45:53.480 | So acetylcholine increases focus.

01:45:55.700 | We talked about some dietary

01:45:58.160 | and some supplementation based ways to improve acetylcholine

01:46:02.040 | or I should say increase acetylcholine.

01:46:04.000 | And that does in fact lead to increases

01:46:06.960 | in one's ability to focus.

01:46:08.880 | This is why a lot of the prescription drugs

01:46:11.240 | for the treatment of Alzheimer's,

01:46:12.440 | age-related cognitive decline,

01:46:14.400 | and indeed even some of the drugs

01:46:15.820 | that tap into treatments for ADHD

01:46:19.160 | also involve the acetylcholine system.

01:46:21.560 | So there's nothing surprising or heretical here,

01:46:25.040 | but it is important to point out

01:46:26.380 | that your behavioral ability to focus

01:46:28.560 | is also related to your ability to access

01:46:30.960 | and deploy acetylcholine.

01:46:32.480 | So never do we want purely pharmacologic treatments

01:46:37.060 | to be the only way that people are increasing

01:46:40.200 | a given neuromodulator.

01:46:41.400 | I always say behaviors first, then nutrition,

01:46:45.400 | then supplementation, and then if there's a need,

01:46:48.200 | certainly a clinical need, then prescription drugs, et cetera,

01:46:51.240 | of course administered through a physician.

01:46:53.780 | So let's discuss serotonin.

01:46:55.680 | Serotonin, as I mentioned earlier,

01:46:57.200 | is associated with brain and body states

01:46:59.640 | of wellbeing, of comfort, of satiety,

01:47:03.040 | and therefore it should come as no surprise

01:47:04.800 | that a lot of the prescription drug treatments

01:47:06.560 | for things like depression

01:47:08.000 | involve increasing levels of serotonin

01:47:10.540 | in the brain and body.

01:47:12.340 | That said, anytime you talk about prescription drugs

01:47:15.040 | for serotonin, we also want to acknowledge

01:47:17.760 | that there are often side effects associated

01:47:19.960 | with increasing serotonin.

01:47:21.240 | In particular, if serotonin levels go too high,

01:47:23.760 | that is if the dosages of those treatments go too high,

01:47:26.560 | people will, for instance, feel reduced appetite,

01:47:29.620 | reduced libido, increased lethargy, et cetera,

01:47:32.520 | and there's a so-called serotonergic syndrome.

01:47:35.040 | All of that can and should be considered

01:47:37.820 | with a well-trained physician.

01:47:40.240 | So because they're prescription drugs controlling the dosage,

01:47:43.720 | deciding what dosage to take, deciding which SSRI to take,

01:47:48.520 | and whether or not to come off those drugs,

01:47:50.160 | how to come off those drugs, again,

01:47:51.480 | all of that should be handled with a licensed physician.

01:47:55.200 | That said, there are behavioral tools, nutritional tools,

01:47:59.640 | and supplementation tools that can tap

01:48:01.680 | into the serotonin system,

01:48:03.120 | not to the same degree in potency, but nonetheless,

01:48:05.940 | in ways that can still impact our feelings of wellbeing

01:48:09.320 | in positive ways.

01:48:11.160 | So let's focus first on the behavioral tools,

01:48:14.160 | and some of these might make people chuckle a little bit,

01:48:16.640 | but I want to point out that a lot of these tools

01:48:19.200 | are quite potent.

01:48:20.300 | In fact, they are power tools for modulating serotonin,

01:48:24.040 | and we know that based on human neuroimaging studies,

01:48:27.000 | human and animal micro-dialysis studies,

01:48:30.240 | and other studies that really have evaluated circulating

01:48:33.240 | levels of serotonin and the particular brain circuits

01:48:36.080 | that release serotonin when people do certain things.

01:48:39.120 | What sorts of things?

01:48:40.360 | Well, for instance, physical contact,

01:48:43.340 | in particular with loved ones, this can be romantic love,

01:48:45.800 | this can be children, so your own children,

01:48:49.600 | or your spouse, even if it's not sexual contact,

01:48:53.400 | friend to friend contact, even friend to animal contact.

01:48:58.280 | As a former dog owner, I hope to have another dog soon,

01:49:01.580 | 'cause unfortunately Costello passed away,

01:49:03.360 | but there is something really comforting and wonderful

01:49:05.600 | about petting your dog.

01:49:06.680 | And certainly given that many of the studies on serotonin

01:49:10.580 | and these other neuromodulators were done on animal models,

01:49:14.280 | we also know that serotonin is being evoked in the dog,

01:49:17.600 | and of course, in the child,

01:49:19.000 | and in the significant other, et cetera.

01:49:20.860 | So things like holding hands, believe it or not,

01:49:23.440 | hugs, cuddling, et cetera,

01:49:26.240 | can increase serotonin transmission,

01:49:28.360 | and they make people feel good.

01:49:30.240 | This shouldn't really come as a surprise.

01:49:32.160 | There's also gratitude,

01:49:33.400 | and we did an entire episode about gratitude.

01:49:35.640 | There's a lot of misunderstanding about gratitude.

01:49:38.060 | Oftentimes when people hear gratitude, they think,

01:49:40.300 | oh, gratitude, this is just being thankful

01:49:42.040 | for what you have, and it's kind of a weak sauce effect,

01:49:44.900 | meaning it's kind of like maybe a little serotonin goes up,

01:49:48.760 | or maybe there's a little bit

01:49:49.600 | of increased feelings of wellbeing.

01:49:51.920 | Nothing could be further from the truth.

01:49:53.400 | It turns out, first of all,

01:49:55.160 | that receiving, not giving gratitude,

01:49:57.960 | is what has the most potent effects

01:49:59.600 | on increasing serotonin and activity of the brain circuits

01:50:02.760 | that involve serotonin and that lead to increases

01:50:05.240 | in feelings of wellbeing.

01:50:06.720 | So this is interesting.

01:50:08.120 | Receiving much more than giving gratitude

01:50:12.280 | is what activates those serotonergic pathways.

01:50:14.800 | So the takeaway from that is both give and receive gratitude

01:50:18.740 | and of course do it in an authentic way.

01:50:20.720 | The other thing about gratitude

01:50:21.840 | that's somewhat counterintuitive

01:50:23.120 | is that observing others giving and receiving gratitude

01:50:27.240 | is immensely powerful for evoking serotonin

01:50:30.460 | and the activity of serotonergic circuits

01:50:32.800 | in you, the observer.

01:50:34.480 | So receiving and observing gratitude

01:50:36.920 | turns out to be the most potent way

01:50:38.800 | to increase serotonin in the brain and body.

01:50:41.680 | And these, again, are dramatic effects

01:50:43.400 | that are quite long lasting and not the sorts of effects

01:50:46.240 | that are going to lead to side effects,

01:50:47.480 | at least there's no reason to think they would.

01:50:49.840 | Now, what about nutritional approaches

01:50:52.720 | to increasing serotonin?

01:50:54.080 | Well, just as we have tyrosine as an amino acid precursor

01:50:57.600 | upstream of dopamine synthesis,

01:50:59.820 | we have the amino acid tryptophan,

01:51:04.340 | which is upstream of serotonin synthesis.

01:51:07.280 | And one simply has to go online

01:51:09.580 | and put in tryptophan containing foods

01:51:12.000 | and you will discover that there are a lot of foods

01:51:13.720 | that are enriched in tryptophan

01:51:15.360 | that can lead to net increases in the amount of serotonin

01:51:18.960 | available in the brain and body.

01:51:20.560 | The most kind of famous or infamous of these

01:51:23.020 | is white meat turkey, the so-called tryptophan effect,

01:51:25.920 | where people get very sleepy after eating white meat turkey

01:51:28.340 | and it is indeed highly enriched in tryptophan.

01:51:31.400 | Although typically the getting sleepy after eating turkey

01:51:33.660 | is most often associated with the Thanksgiving meal

01:51:36.740 | and the Thanksgiving meal, at least in the US,

01:51:38.500 | is often associated with people vastly overeating.

01:51:40.880 | And so I do want to point out

01:51:42.200 | that if you fill your gut with food,

01:51:44.200 | no matter what that food is,

01:51:46.120 | there's going to be a diversion of blood to your gut

01:51:47.900 | that's going to make you feel sleepy

01:51:49.080 | because there's a diversion of blood away from other tissues.

01:51:51.840 | So if you eat a lot, you're going to get sleepy, period,

01:51:53.720 | whether or not you eat turkey or some other substance.

01:51:56.160 | Nonetheless, there are a number of foods

01:51:57.920 | that contain a lot of tryptophan

01:52:00.200 | and that some people will leverage

01:52:02.720 | in order to try and increase

01:52:04.700 | the total amount of circulating serotonin available to them

01:52:07.520 | in order to have a modest increase

01:52:10.480 | in overall mood and wellbeing.

01:52:12.220 | So what are some of these foods?

01:52:13.540 | These are things like milk, in particular, whole milk,

01:52:16.720 | so full fat milk.

01:52:18.240 | I know a number of people choose not to drink milk

01:52:20.660 | 'cause they're lactose intolerant.

01:52:22.500 | I'm raising my hand 'cause I'm one such person.

01:52:24.460 | Although when I was a kid, I did enjoy milk.

01:52:28.260 | Canned tuna, turkey, as we mentioned before,

01:52:31.220 | high in tryptophan, oats.

01:52:32.940 | I am a consumer of oatmeal, so that resonates with me.

01:52:35.980 | Cheese, and here I read,

01:52:38.000 | although not as high in tryptophan

01:52:39.400 | as meat and other dairy sources,

01:52:42.100 | certain cheeses like cheddar cheeses

01:52:43.500 | can be rich in tryptophan.

01:52:45.180 | Certain nuts and seeds, certain breads.

01:52:48.240 | Chocolate, I know a number of people

01:52:50.060 | will be relieved to hear that.

01:52:51.440 | I know chocolate lovers are always looking

01:52:53.500 | for an excuse to eat chocolate.

01:52:55.020 | I confess I've never really liked chocolate

01:52:56.660 | except, dare I say, I like the smooth 100% chocolates.

01:53:00.340 | I know many people gag when they hear 100%.

01:53:02.500 | I actually really like them.

01:53:03.500 | And some fruits can be highly enriched in tryptophan.

01:53:06.040 | Things like bananas and apples and things of that sort,

01:53:09.340 | although not nearly to the degree of things

01:53:12.300 | like turkey, canned tuna, and milk.

01:53:14.800 | I'm sure there are other excellent sources of tryptophan

01:53:17.640 | from the diet, including vegan sources.

01:53:20.220 | So please peruse the internet to try and find the sources

01:53:23.020 | that are compatible with your nutritional program

01:53:25.760 | if indeed your goal is to increase tryptophan.

01:53:28.700 | Now, there are supplements that can increase tryptophan

01:53:31.040 | and can do so quite potently.

01:53:33.580 | One of the ones that has received increasing attention

01:53:36.980 | as of lately is Sissus quadrangularis, complicated name.

01:53:41.900 | When taken in dosages of about 300 to 600 milligrams

01:53:45.680 | can pretty dramatically increase serotonin levels.

01:53:49.540 | In fact, anywhere from 30% to 39% increases

01:53:53.780 | in circulating serotonin.

01:53:55.640 | That's a big increase.

01:53:57.780 | And I can provide a link to that study.

01:53:59.780 | The study was focused not so much on serotonin,

01:54:02.700 | but was focused mainly on treatment of obesity

01:54:06.060 | and appetite and weight loss.

01:54:07.900 | And it should come as no surprise that serotonin,

01:54:11.340 | if increased, might lead to decreases in appetite.

01:54:15.060 | A cautionary note, Sissus quadrangularis

01:54:18.700 | may need to be cycled.

01:54:20.020 | How quickly to cycle it, meaning do you do two weeks on,

01:54:23.620 | two weeks off, whether or not you need to do

01:54:26.460 | more rapid cycling, like two days on, two days off,

01:54:29.220 | is a matter of debate.

01:54:30.420 | There are not a lot of data on this just yet.

01:54:33.220 | There are a lot of opinions about this on the internet,

01:54:35.240 | but again, not a lot of quality peer review data.

01:54:37.880 | Nonetheless, Sissus quadrangularis has been showed

01:54:40.260 | to potently increase serotonin in humans.

01:54:42.820 | And for people that are seeking to increase serotonin,

01:54:45.560 | maybe in particular, for sake of appetite and weight control,

01:54:49.180 | that might be a useful compound.

01:54:51.080 | I know many people also take 5-HTP,

01:54:53.500 | one of the precursors to serotonin in dosages

01:54:56.700 | of anywhere from 300 to 500 milligrams.

01:54:58.980 | Typically, people are doing this in anticipation of sleep,

01:55:02.240 | meaning in the final hour of wakefulness

01:55:04.380 | before going to sleep.

01:55:06.220 | I, myself, have tried 5-HTP prior to sleep,

01:55:08.940 | and all I can tell you is that it led to very deep sleep

01:55:11.520 | for about one to three hours,

01:55:12.740 | and then I woke up and I could not fall back asleep.

01:55:15.100 | I ran that experiment twice before I decided

01:55:17.600 | to abandon 5-HTP as a sleep aid,

01:55:19.680 | and that's why I've never put it into our sleep kit,

01:55:22.700 | or at least my sleep kit.

01:55:24.860 | And when I refer to the sleep kit,

01:55:26.740 | that's something you can find at hubermanlab.com.

01:55:28.740 | This is a zero-cost resource where you can see

01:55:30.900 | behavioral tools and also supplementation tools

01:55:34.560 | that can improve the transition time into

01:55:36.940 | and the depth of sleep,

01:55:38.020 | and none of those rely on 5-HTP supplementation.

01:55:41.580 | That said, I know a number of people

01:55:43.220 | use 5-HTP supplementation outside of sleep,

01:55:47.180 | or I should say during the daytime,

01:55:48.460 | to try and increase serotonin,

01:55:50.020 | and it will indeed increase circulating serotonin.

01:55:52.940 | But again, people vary in their sensitivity

01:55:55.500 | to these sorts of things.

01:55:57.040 | Some people might find, for instance,

01:55:58.420 | that 300 milligrams of 5-HTP is just far too much.

01:56:01.780 | It blunts their appetite, might even reduce libido.

01:56:04.800 | There aren't a lot of very well-controlled studies

01:56:06.760 | looking at this, and so it has to be figured out

01:56:08.940 | on an individual basis if you decide to approach it at all.

01:56:12.360 | Now, one molecule that I've found

01:56:13.860 | to be particularly interesting and useful,

01:56:16.180 | and this is one that I haven't talked about yet

01:56:18.220 | on this podcast, is inositol, in particular, myoinositol.

01:56:23.100 | Myoinositol can have the effect of increasing serotonin

01:56:27.180 | and other neurochemicals, but primarily,

01:56:30.980 | at least in terms of the neuromodulators discussed today,

01:56:33.440 | serotonin.

01:56:34.620 | I've been taking 900 milligrams of myoinositol

01:56:37.980 | every third night or so as a test of its ability

01:56:40.620 | to improve sleep, and I have to say,

01:56:42.900 | the depth and quality of sleep that I've been obtaining

01:56:46.100 | on myoinositol is pretty remarkable.

01:56:49.260 | In fact, I've used it alone and in combination

01:56:52.080 | with the magnesium threonate apigenin/theanine sleep kit

01:56:55.360 | that I've talked about and that's included in that,

01:56:57.780 | again, zero-cost kit that's available as a PDF

01:57:00.340 | on our website.

01:57:01.340 | So myoinositol is known to increase circulating levels

01:57:04.200 | of serotonin.

01:57:05.380 | It has been explored extensively in both animal models

01:57:09.140 | and in humans for its daytime use for treating anxiety.

01:57:13.300 | It does seem to reduce anxiety,

01:57:15.380 | and for all sorts of things.

01:57:17.260 | It's been explored for bipolar disorder.

01:57:19.460 | We're going to do an episode

01:57:20.420 | about bipolar disorder coming up.

01:57:22.900 | It's been explored for the treatment of migraine.

01:57:25.080 | It's been explored for ADHD.

01:57:27.000 | It's been explored for a huge number

01:57:29.060 | of different conditions of brain and body.

01:57:31.300 | Again, I've been using the 900 milligrams of myoinositol

01:57:34.980 | in the 30 to 60 minutes before sleep to improve my sleep,

01:57:38.100 | and it has been doing that very dramatically,

01:57:40.180 | especially when I take it alongside the rest

01:57:43.140 | of those sleep kit supplements.

01:57:45.260 | A quick note about myoinositol

01:57:47.020 | for sake of increasing serotonin.

01:57:49.360 | If you look at the human studies on myoinositol

01:57:52.020 | that are out there,

01:57:53.060 | and in particular focus on the human studies,

01:57:55.420 | what you'll find is that the dosages that are often used

01:57:58.100 | are tremendously high, things like five grams, eight grams,

01:58:01.480 | 18 grams of myoinositol taken throughout the day.

01:58:05.300 | I don't know how people stomach that.

01:58:06.900 | And in fact, many people drop out of those studies

01:58:09.100 | because of gastric discomfort.

01:58:10.860 | And yet I also wonder how people tolerate it

01:58:14.440 | because it has somewhat of a sedative effect

01:58:16.420 | and it's kind of anti-anxiety effect.

01:58:18.520 | And I can't even imagine,

01:58:20.280 | given my experience with 900 milligrams,

01:58:22.420 | what one would experience taking multiple

01:58:25.260 | or many more grams per day.

01:58:27.540 | So I certainly am not encouraging that.

01:58:30.460 | And the only reason I mentioned myoinositol

01:58:32.820 | is that it has a known effect of increasing serotonin.

01:58:35.520 | At least in my experience,

01:58:38.020 | it does not lead to this falling deeply asleep

01:58:40.360 | and waking back up.

01:58:41.380 | Actually to the contrary,

01:58:42.380 | if I wake up in the middle of the night

01:58:43.540 | to use the bathroom or I wake up in the middle of the night

01:58:45.500 | for whatever other reason,

01:58:47.000 | I find it far easier to fall back asleep

01:58:49.760 | if I've taken 900 milligrams inositol prior to sleep.

01:58:53.940 | So for me, it's proving to be a quite useful compound.

01:58:56.960 | I'm not aware of having any serotonergic deficiency overall.

01:59:00.700 | I don't consider myself depressed.

01:59:02.560 | And of course, I should mention that no supplement,

01:59:05.540 | either added or withdrawn from your protocol,

01:59:08.220 | should ever be used as a direct replacement

01:59:11.300 | for prescription drug treatments

01:59:12.620 | that your physician has given you.

01:59:13.660 | You should always talk to your physician

01:59:15.000 | anytime you remove or add something to your drug protocol

01:59:18.780 | or prescription protocol, of course.

01:59:20.680 | So we've got behavioral protocols

01:59:22.780 | that as silly as it feels to say,

01:59:25.740 | have been shown to potently increase serotonin,

01:59:27.820 | things like physical contact, cuddling, holding hands

01:59:30.540 | with people that you love, of course, right?

01:59:32.860 | I think if they were people that you despised,

01:59:35.380 | it would have the opposite effect for obvious reasons.

01:59:38.380 | But also receiving gratitude and observing gratitude,

01:59:42.100 | very potent increases in serotonin.

01:59:44.240 | And things like cystis quadrangularis,

01:59:47.180 | things like 5-HTP may have their uses, right?

01:59:50.060 | They're very potent at increasing serotonin,

01:59:53.220 | but they do seem to have the need to cycle them

01:59:56.140 | and they are nuanced.

01:59:57.580 | Some people respond well to them, others like myself don't.

02:00:00.860 | And of course, always be on the lookout for dramatic

02:00:03.860 | or even subtle decreases in appetite or libido

02:00:06.260 | or things that you might not want

02:00:08.260 | if you are going to be tinkering

02:00:10.060 | with your serotonergic levels and pathways.

02:00:13.260 | And then myoinositol actually is proving

02:00:15.640 | to be quite useful to me.

02:00:17.660 | And whether or not that's because of its effects

02:00:20.300 | on serotonin or through some of its other effects

02:00:22.820 | on maybe reducing anxiety, which certainly I experience

02:00:25.820 | if I wake up in the middle of the night,

02:00:26.780 | I don't like waking up in the middle of the night,

02:00:28.340 | but on myoinositol, I sort of seem to not really care

02:00:30.780 | that I woke up and I fall right back asleep.

02:00:32.480 | So the direct source of the positive effects

02:00:34.660 | that I'm getting aren't clear,

02:00:36.060 | but nonetheless, I thought I'd pass it along

02:00:37.780 | as a useful tool because it is out there

02:00:40.500 | and it is available over the counter.

02:00:42.740 | And provided you're taking the appropriate safety steps

02:00:45.180 | in considering whether or not to use it or not,

02:00:47.820 | I think it might be a useful tool.

02:00:49.880 | And of course, as with all the other neuromodulators

02:00:52.660 | we discussed, you have both a baseline of serotonin

02:00:56.740 | and the ability to give or provide yourself peaks

02:00:59.820 | of serotonin through these various protocols.

02:01:02.180 | The dietary interventions of the sort that I mentioned,

02:01:05.580 | meaning eating foods that are enriched in tryptophan,

02:01:08.460 | those are mainly going to adjust

02:01:10.420 | your baseline levels of tryptophan.

02:01:12.780 | For instance, if you really want to be sleepy,

02:01:15.180 | sure, you could eat some white meat turkey

02:01:17.140 | in hopes that that tryptophan will convert to serotonin

02:01:20.140 | and make you sleepy, et cetera.

02:01:21.800 | But in general,

02:01:22.640 | those are going to be pretty long lasting effects,

02:01:24.900 | especially given the fact that not all of the tryptophan

02:01:27.260 | you will ingest is going to be converted into serotonin

02:01:30.300 | in your brain.

02:01:31.540 | It's going to have other effects on other tissues

02:01:33.520 | and organs of your body.

02:01:35.020 | Nonetheless, if you want to increase serotonin,

02:01:37.460 | providing the appropriate baseline context

02:01:40.300 | is going to be useful.

02:01:41.500 | And again, this is a general theme

02:01:43.260 | of all four of these neuromodulators,

02:01:45.500 | dopamine, epinephrine, acetylcholine, and serotonin.

02:01:48.340 | You want to make sure that you have sufficient baseline

02:01:51.900 | levels of those things through things like diet,

02:01:54.460 | regular behaviors,

02:01:55.940 | and then you have the opportunity to use supplementation.

02:01:59.400 | And if it's appropriate for you,

02:02:00.500 | prescription drugs and certain behavioral protocols

02:02:03.320 | to try and get these potent increases,

02:02:05.120 | these acute increases in whichever the neuromodulators

02:02:08.420 | you happen to want to leverage for your particular goals.

02:02:11.880 | So that brings us to the end of at least this exploration

02:02:14.880 | of the neuromodulators, dopamine, epinephrine,

02:02:18.280 | acetylcholine, and serotonin.

02:02:20.120 | Some of you who are regular listeners of this podcast

02:02:22.320 | might be saying, well, we've heard all this before, right?

02:02:24.560 | You had an episode on dopamine.

02:02:25.800 | You had an episode on anxiety.

02:02:27.160 | You had an episode on sleep.

02:02:28.480 | And indeed that's true.

02:02:30.440 | But what I've tried to provide today is a framework

02:02:33.720 | that cuts through all those episodes.

02:02:36.280 | And at the same time builds out a new

02:02:38.680 | and what I believe to be a really important theme

02:02:41.080 | and principle, which is that whether or not

02:02:44.040 | you're using nutritional tools or supplementation

02:02:47.420 | or prescription drugs or any other sort of protocol

02:02:51.360 | to try and create a desired effect of focus

02:02:54.680 | or energy, motivation, relaxation,

02:02:57.640 | you're playing with the same neurochemical ingredients.

02:03:01.920 | Just as in the realm of nutrition, you have macronutrients,

02:03:05.540 | you have proteins, carbohydrates, and fats

02:03:08.040 | that can be adjusted in different ratios

02:03:09.840 | and arranged at different times

02:03:11.900 | in order to achieve certain desired effects.

02:03:14.680 | Well, when it comes to your neurochemistry

02:03:17.140 | and your ability to perform mentally,

02:03:19.120 | to perform physically, and your overall wellbeing,

02:03:22.960 | you are dealing with a small handful

02:03:26.300 | of especially potent molecules.

02:03:28.460 | And I acknowledge that there are many neuromodulators,

02:03:31.900 | there are indeed many neurotransmitters,

02:03:33.780 | glutamine, glycine, GABA, et cetera.

02:03:36.260 | But today we focused on the main four,

02:03:38.600 | meaning the most potent and most widespread neuromodulators

02:03:43.400 | in the brain and body that give you access

02:03:46.680 | to particular brain states and body states

02:03:49.660 | of the sort that most people desire.

02:03:51.900 | So what I'm hoping is that rather than decide

02:03:54.940 | that any one tool is the most useful

02:03:56.980 | or that any one neurochemical is most useful

02:04:00.140 | for that matter, that the information

02:04:02.260 | that I've provided today allows you a kit of versatile tools

02:04:07.140 | that allows you to figure out what levels of dopamine

02:04:11.100 | and augmentation of dopamine are appropriate

02:04:13.660 | and necessary for you.

02:04:14.980 | What levels of acetylcholine and tools

02:04:18.620 | for manipulating acetylcholine are going to be most useful

02:04:21.220 | for you and so on and so forth.

02:04:23.160 | Because at least at this stage in time,

02:04:26.700 | that is June, 2022, there is no simple at-home test.

02:04:31.700 | In fact, there is no simple laboratory test

02:04:34.820 | that allows us to know whether or not our dopamine levels

02:04:37.220 | are high and our serotonin levels are low.

02:04:39.240 | We can look at somebody and their behavior,

02:04:41.180 | we can look at ourselves and our own mood and behavior,

02:04:44.020 | and we can infer what those levels may or may not be.

02:04:48.720 | But unfortunately we don't have a really good test

02:04:53.020 | of dopamine levels or serotonin levels

02:04:55.180 | that would allow us to say, okay, this person

02:04:58.460 | or I need to increase dopamine twofold

02:05:01.860 | in order to achieve the kind of motivation that we want.

02:05:04.840 | Unfortunately, that doesn't exist.

02:05:06.160 | Rather, we are confronted with a situation

02:05:09.000 | where we understand generally

02:05:11.400 | what these different neuromodulators do,

02:05:12.960 | the different mental states and physical states

02:05:14.920 | that they tend to put us into, and we reviewed those.

02:05:17.840 | And we know that there are really potent tools

02:05:21.720 | to adjust those neuromodulators, if not alone,

02:05:25.100 | but in certain combinations.

02:05:26.880 | That is ingestion of caffeine will tap into

02:05:30.320 | and support dopamine and epinephrine.

02:05:33.720 | Increasing dopamine and epinephrine

02:05:36.160 | alongside increasing acetylcholine

02:05:39.360 | will allow us to access certain brain states,

02:05:41.480 | that is focused, alert, energized brain states,

02:05:44.680 | great for learning and plasticity of all kinds.

02:05:47.780 | Whereas augmenting serotonin is going to put us

02:05:50.560 | into a more relaxed state and so on and so forth.

02:05:53.080 | And I'd like you to keep in mind

02:05:54.640 | that there is no negotiating the fact

02:05:57.800 | that we all have different phases of our 24 hour cycle

02:06:01.000 | during which those very same neuromodulators

02:06:03.240 | tend to be naturally higher or naturally lower.

02:06:05.840 | And I reviewed that at the beginning of the episode.

02:06:08.160 | So my wish for you is that you will take this information,

02:06:11.060 | experiment with it as you see fit for you and in a safe way.

02:06:15.400 | And as you go forward to really try and gain intuition

02:06:19.600 | and understanding as to not just how these protocols work,

02:06:23.400 | but how any protocol that you might encounter,

02:06:26.120 | supplement-based, drug-based, behavioral-based,

02:06:29.660 | how those might tap into these different

02:06:31.280 | major neuromodulator systems.

02:06:32.840 | And from that, to be able to better predict and evaluate

02:06:36.200 | whether or not they're going to be useful to you,

02:06:37.920 | detrimental to you, or whether or not they should be used

02:06:40.160 | in combinations that would be more useful to you.

02:06:42.800 | If you're learning from and/or enjoying this podcast,

02:06:45.120 | please subscribe to our YouTube channel.

02:06:46.780 | That's a terrific zero cost way to support us.

02:06:49.200 | In addition, please subscribe to the podcast

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02:06:54.880 | you can leave us up to a five-star review.

02:06:57.420 | If you have feedback for us, or you have topics or guests

02:07:00.640 | that you'd like us to cover on the Huberman Lab Podcast,

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02:07:07.140 | and that's the best place to give us that sort of feedback.

02:07:10.540 | In addition, please check out the sponsors mentioned

02:07:12.660 | at the beginning of today's episode.

02:07:14.120 | That's the best way to support this podcast.

02:07:17.060 | During today's episode, we talked a lot about supplements.

02:07:19.740 | While supplements aren't necessary for everybody,

02:07:22.000 | many people derive tremendous benefit from them.

02:07:24.460 | As mentioned at the beginning of today's episode,

02:07:26.300 | we partnered with Momentous Supplements

02:07:28.400 | because they're extremely high quality,

02:07:29.920 | they ship internationally, they are available in the dosages

02:07:33.580 | and single ingredient formulations that are ideal

02:07:36.520 | for building a supplementation protocol.

02:07:38.220 | You can find all those at livemomentous.com/huberman.

02:07:41.820 | If you're not already following us on social media,

02:07:44.060 | we are @hubermanlab on Twitter and @hubermanlab on Instagram.

02:07:48.460 | There I cover science and science-based tools,

02:07:50.820 | some of which overlap with the content

02:07:52.460 | of the Huberman Lab Podcast,

02:07:54.100 | but much of which is distinct from the content

02:07:56.100 | of the Huberman Lab Podcast.

02:07:57.820 | And if you're not already subscribing to our newsletter,

02:07:59.980 | we have a neural network newsletter, as it's called,

02:08:02.500 | that comes out about once a month.

02:08:04.580 | We provide summaries, we provide protocols

02:08:07.620 | based on podcast episodes.

02:08:09.420 | All of that is zero cost to access.

02:08:11.140 | You just go to hubermanlab.com, go to the menu,

02:08:13.860 | click on newsletter, and you can sign up.

02:08:15.580 | We do not share your email with anybody,

02:08:17.620 | and our privacy policy is there.

02:08:19.740 | In fact, if you want to see previous newsletters,

02:08:22.060 | they are available without having to sign up in PDF form,

02:08:25.620 | also at hubermanlab.com under the newsletter tabs,

02:08:28.560 | things like a toolkit for sleep

02:08:30.260 | and a neuroplasticity super protocol,

02:08:32.300 | all available as immediately downloadable PDFs.

02:08:35.180 | So I'd like to thank you once again for joining me today

02:08:38.020 | in our discussion about these incredibly powerful molecules

02:08:41.020 | we call neuromodulators and the things we can do and take

02:08:46.020 | in order to control them so that we can enhance

02:08:49.040 | our mental health, physical health, and performance.

02:08:51.480 | And last, but certainly not least,

02:08:53.920 | thank you for your interest in science.

02:08:55.740 | [upbeat music]

02:08:58.320 | (guitar music)

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

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