Dr. Andrew Huberman, Ph.D. is a Professor of Neurobiology and Ophthalmology at Stanford University School of Medicine. His lab focuses on neural regeneration, neuroplasticity, and brain states such as stress, focus, fear, and optimal performance.
In this episode of the Huberman Lab podcast, Andrew Huberman goes back to fundamentals. He breaks down the biology and practical importance of the body’s four major neuromodulators: dopamine, epinephrine, serotonin, and acetylcholine. He also provides actionable behavior and tools to enhance levels of brain chemicals and improve mental health, physical health, and performance.
Host: Andrew Huberman (@hubermanlab)
Different states of sleep (rapid eye movement (REM) versus slow wave (deep sleep)) relate to different aspects of metabolism
The sleep state regulates more than 50% of metabolite features detected in human breath
You can figure out what humans are metabolizing most (e.g., more lipids vs more carbs vs more glucose) based on breath
Major metabolic pathways are up-regulated or down-regulated as we transition between slow wave sleep, REM, and waking
Sleep regulates individual metabolic pathways: transitioning from sleep to wakefulness reduces fatty acid oxidation, transition to slow wave sleep increases fatty acid oxidation, and transition out of REM kicks off a tricarboxylic acid cycle
The different types of metabolism experienced during sleep assists in supporting the metabolism needed during wakefulness
Getting enough sleep allows your body to transition through all the different forms of metabolism and use metabolites properly for the brain and body
Full study: Rapid and reversible control of human metabolism by individual sleep states (Cell Reports)
Study design to shift schedule: participants woke up 2-3 hours before habitual (late) waking time, were exposed to outdoor light exposure in the morning, and told to keep sleep times fixed (+/- 30 minutes) even on weekends, dim lights in the evening, regular schedule for daily meals (+/- 30 minutes), no caffeine after 3 pm, no naps after 4 pm, exercise in the morning
Benefits of switching from “night owl” to “morning person”: improvement in overall mood & less depression, lower stress, improved reaction times, improved grip strength
Full study: Resetting the late timing of ‘night owls’ has a positive impact on mental health and performance (Sleep Medicine)
Neurons: the nerve cells that make up the nervous system
Synaptic communication: cell to cell interaction by generating and passing electricity to either excite or inhibit cells
The brain, spinal cord, and overall nervous system control the organs of the body – and the organs send signals to the nervous system
The nervous system generates everything from sleep, stress, desire, etc.
What you do, how you feel, how you think, etc. depends on which neural circuits are active
No single brain area completely controls a state – neural circuits (chains of neurons) work together in a particular sequence to inhibit or activate certain states
The activity of neural circuits depends on (1) hormones (Check Out Dr. Kyle Gillett: How To Optimize Your Hormones For Health & Vitality) & (2) neuromodulators
Neuromodulators: chemicals that make it likely certain substances will be active or inhibited
Four main neuromodulators: (1) dopamine; (2) epinephrine/adrenaline; (3) serotonin; (4) acetylcholine (in the context of the brain & thinking, not nerve-muscle synapse for this discussion)
Neuromodulators can be fast-acting (signal response within seconds, minutes, or hours) or slow-acting/baseline (signal response within hours, days, or weeks)
Features of all neuromodulators: they don’t disappear but are present at different levels at different times & don’t work alone
Phase I (0-9 hours after waking): dopamine and epinephrine are at their highest levels
Phase II (9-16 hours after waking): dopamine and epinephrine subside; serotonin starts to increase
Phase III (17-24 hours after waking): “organized chaos” – peaks and valleys in dopamine, acetylcholine, serotonin – but unlikely to see epinephrine since that puts us into action mode which isn’t happening during sleep
We can leverage phases of the day and neuromodulators most present to help us achieve specific goals & productivity
Like neuromodulators, some hormones act fast while others act slow
Testosterone and dopamine are related (in males and females) – when testosterone goes up, dopamine goes up, and vice versa
Corticosteroids like cortisol are related to epinephrine – when cortisol goes up, epinephrine goes up
When oxytocin or prolactin go up – levels of serotonin go up
Getting sunlight on the skin (as much skin as possible/appropriate) each day increases testosterone, estrogen, libido, and feelings of well-being via dopamine & serotonin
“Dopamine is not about pleasure, it’s about motivation, craving, and pursuit for goals or things outside our immediate experience or possession.” – Dr. Andrew Huberman
When elevated above baseline, dopamine increases mental & physical motivation, drive, and focus
For a full dive on dopamine, check out Huberman’s previous episode: Dopamine, Mindset & Drive
Epinephrine is released in the brain & body and is responsible for generating energy
When epinephrine is high we can’t shut down thinking, or want to move; when epinephrine is low, energy is low
Epinephrine is manufactured from dopamine
Epinephrine activates our immune system, contrary to popular belief that stress inhibits our immune system
Serotonin creates states of content, satiety, relaxation, soothing, and relief from pain
When serotonin is high: people experience reduced appetite, libido, drive
When serotonin is low: people exhibit agitation and high levels of stress
When we leverage serotonin, we’re increasing circuits that make us relaxed and happy and decreasing neural circuits that put us in pursuit of things we don’t have
A lot of treatments for depression and other mental health disorders involve increasing serotonin
Acetylcholine is powerful on its own and largely unsupported by the hormone system
Mainly associated with focus, particularly neuroplasticity (learning and processing new information) in calm states
When you increase acetylcholine in conjunction with attempts to learn, you will experience increased focus, more specific neural activity, and immediate and long-lasting changes in neural circuitry
The ability to focus relies on the ability to tap into and activate acetylcholine
Incorporate the natural tools to increase dopamine every day or almost every day
Tip #1 – sunlight: view the maximum amount of sunlight you can safely do to your eyes and skin within the first hour of waking (choose a safe sunscreen if needed, check out this podcast for helpful info); if you wake up before the sun or in a climate there is no morning sun, turn on as many bright lights overhead as you can
Sunlight exposure increases dopamine receptors which enhances the effect of circulating dopamine
Avoid bright light in Phase III (17-24 hours after waking)! Exposure will impact melatonin and negatively impact dopamine levels that night and the next day
Tip #2 – caffeine: regular ingestion of safe levels of caffeine (150g-400g) increases the number of dopamine receptors – but don’t drink caffeine past 2-3 pm
Try to push caffeine 90-120 minutes after waking to avoid an afternoon crash
Tip #3 – tyrosine: consume tyrosine-rich foods (meat, parmesan cheese, certain vegetables) to increase dopamine receptors
Tip #4 – supplements: (1) mucuna pruriens (it’s actually L-dopa) – not recommended because of the potency in increase and substantial crash after; (2) L-tyrosine (500mg-1000mg); (3) phenylethylamine (300-600mg)
Tip #6 – cold: deliberate cold exposure (45-50 degrees F) can increase dopamine even after 1 minute; cold water immersion or shower if no other option for 1-3 minutes (for full benefits of cold & protocols, check out Huberman’s episode: Ice Bath & Cold Benefits)
Tip #7 – B vitamins, particularly vitamin B6 increase prolactin which increases dopamine (but be careful with dose)
There are benefits to increasing stress early in the day to get up and into action
Tip #1 – exercise: any – ANY physical activity (walking, running, swimming, etc.) increases epinephrine release and “wakes up” the brain – this is why exercising early in the day gives you energy for the rest of the day
Tip #2 – breathwork: cyclic hyperventilation (deep inhales and passive exhales) such as Wim Hof breathing; try short bursts of fast inhales and exhales for one minute, then hold breath for about 15 seconds & repeat 25 reps
Tip #3 – caffeine: regular ingestion of safe levels of caffeine (150g-400g) increases the number of dopamine receptors – but don’t drink caffeine past 2-3pm
There are no foods to point to which will increase epinephrine
Tip #1 – food: eggs, beef (particularly beef liver), soybeans, chicken, fish, and mushrooms, all contain a lot of choline
Tip #2 – nicotine: nicotine increases choline by activating nicotinic receptors – but don’t start smoking cigarettes! You can chew Nicorette or try nicotine-dipped toothpicks
Tip #3 – alpha-GPC: more acetylcholine is synthesized after ingesting; a dose of 300mg prior to workouts or work bouts
Note, there are some studies that show that people who chronically take alpha-GPC may be at increased risk of stroke – but the risk-benefit profile is still worth it; TMAO will also increase with chronic use and have adverse effects on the heart (offset with 600mg of garlic)
Tip #5 – huperzine: leads to net increases in acetylcholine via enzymatic pathway, adjusting how much is broken down
Tip #6 – visual field: narrow visual field then move into what you’re working on or focusing on
Tip #1 – physical contact: romantic, platonic, or embracing a pet can increase serotonin
Tip #2 – gratitude: observing & receiving, not giving gratitude has potent effects on stimulating brain activity and activating serotonergic pathways
Tip #3 – tryptophan: foods high in tryptophan increases circulating serotonin (e.g., whole milk, turkey, oats, cheese, chocolate, some nuts & seeds)
Tip #4 – cissus quadrangularis: does need to be cycled but there is not a lot of data about the timing of cycle (e.g., two days on-two days off or two weeks on two weeks off)
Tip #5 – 5-HTP: can help with deep sleep in some if taken before bed
Tip #6 – myo-inositol: can improve depth and quality of sleep, increase serotonin levels, and curb anxiety among many other conditions (900mg every few days)
Note, doses of myo-inositol in studies are extremely high – tinker with the dose and start low
Articles Mentioned
Rapid and reversible control of human metabolism by individual sleep states (Cell Reports)
Resetting the late timing of ‘night owls’ has a positive impact on mental health and performance (Sleep Medicine)
Skin exposure to UVB light induces a skin-brain-gonad axis and sexual behavior (Cell Reports)
The Role of Gene Encoding Variation of DRD4 in the Relationship between Inattention and Seasonal Daylight (bioRxiv)
Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain (Translational Psychiatry)
Human physiological responses to immersion into water of different temperatures (European Journal of Applied Psychology)
The effect of Cissus quadrangularis (CQR-300) and a Cissus formulation (CORE) on obesity and obesity-induced oxidative stress (Lipids in Health and Disease)
Additional Resources Discussed
The Darya Rose Show: Sunscreen & Sun protection with Dr. Brian Diffey
Huberman Lab: Controlling Your Dopamine for Motivation, Focus & Satisfaction
Huberman Lab: ADHD & How Anyone Can Improve Their Focus
Huberman Lab: Using Deliberate Cold Exposure for Health and Performance