Episode 80: Optimize & Control Your Brain Chemistry To Improve Health & Performance | Huberman Lab

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Key Takeaways

  • Adequate quality and duration of sleep and experiencing all the different stages of sleep (i.e., slow wave, REM) are important in optimizing metabolic circuits for health and performance
  • When done properly (i.e., sleeping and waking at roughly the same time, bright light exposure in the morning, dim lights in the evening, etc.) study participants experienced huge benefits in mood, stress, and grip strength (among other outcomes) when switching habits from “night owl” to “morning person”
  • Four main neuromodulators: (1) dopamine; (2) epinephrine/adrenaline; (3) serotonin; (4) acetylcholine
  • Different neuromodulators are naturally present at higher or lower levels in each phase of the day – leverage these natural fluctuations to optimize your focus and outcomes
  • “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
  • Tools optimize dopamine: sunlight, caffeine, tyrosine, mucuna pruriens, L-tyrosine, phenylehtylamine, cold exposure, B vitamins
  • Tools to optimize epinephrine: exercise, breathwork (cyclic hyperventilation), caffeine
  • Tools to optimize acetylcholine: foods rich in choline, nicotine (no, don’t smoke cigarettes), alpha-GPC, huperzine, narrow visual field
  • Tools to optimize serotonin: physical touch, gratitude, tryptophan, cissus quadrangularis, 5-HTP, myo-inositol
  • When trying any of the tools listed, start with the behavioral approach, then nutrition, then supplementation, then turn to the clinical/pharmaceutical approach if all else fails or there is a medical necessity


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)

New Research On Sleep & Metabolism

  • 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)

New Research On “Night Owls”

  • 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)

Fundamentals Of Neuroscience

  • 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

Phases Of The Day & Neuromodulators

  • 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

How Hormones Relate To Neuromodulators

  • 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

Tools To Optimize Dopamine Receptors And Levels

  • 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)

Tools To Optimize Epinephrine  

  • 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

Tools To Optimize Acetylcholine

  • 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

Tools To Optimize Serotonin

  • 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


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