Huberman podcast – Notes on time perception by dopamine, serotonin, and hormones

Entrainment – how your internal bio / psychology is linked to external things

Circu-annual rhythms – our brain / body has a calendar system – via melatonin (regulates hormones, makes you sleepy at night)

Light is very powerful modulator of melatonin

When days are long = less melatonin release
Eg, winter = lower energy, lower mood

Longer days – make more testosterone and estrogen
Skin takes info about amount of light, turns into test & est – an endocrine organ, hormone influencing

Circadian rhythm – most powerful rhythm that we experience, none of us can overcome
Every cell in our body has a 24h timer
Influenced mainly of sunlight

Sleep broken into 90m cycles

Cannabis / serotonin – makes time slow down

Early in day – overestimate time passage – dopamine state
Late in day – underestimate time passage – serotonin state

Do hard things earlier in the day – dopaminergic circuits are more active – better able to parse that hard problem
You’re a more high resolution camera

Creative work – more serotonin helps / serotonin states – hence later in day

When sleep is disrupted – leads to dis-regulation of dopamine and serotonin states – they get mixed, we feel off, sense of passage of time is disrupted

People who experience trauma often OVERLOCK
Dopamine / epinephrine massively increased during event – frame rate increased – perceive things as happening in ultra slow motion
Good and bad – massive focus, but also much stronger memories of the incident – thus hard to forget the memory and its associations

Blinking = fine slicing time = shutter of life experience
Blink rate related to frame rate
Slow down = blink less
Speed up = blink more

Something fun = eg, kid’s day at amusement park = tons of dopamine = feel like the day goes by very fast, but in memory, will feel like it was very long, lots happened

In boring isolated environments, time dilates = time feels MUCH slower // but later, in retrospect, they seem like they passed very quickly (because we remember very little of it)

More novelty you experience with someone – feel like you know them more / better

How often and when you release dopamine — sets frame rate of time perception

Power of habits – specific, habitual routines – good way to incorporate dopamine system
Eg, morning habit that releases dopamine (eg, cold shower)
Helps us carve up our day’s experience

Book rec: Your Brain is a Time Machine

Huberman podcast: Notes from 2 eps on dopamine – “Universal currency of foraging and seeking”

The episodes – particularly the 2nd – helped me achieve some breakthroughs around motivation and understanding addiction, so I went back to take these notes

Added double asterisks (**) to points I particularly wanted to remember

Mistakes all mine

“Controlling dopamine for motivation, focus, and satisfaction”

Cold water submersion —> rise up to 250% increase in dopamine, sustained afterwards

There’s baseline level of dopamine
There are variations – called tonic (below baseline)) / phasic (above baseline)
**After peak (phasic), there is a trough (tonic), baseline level drops

Dopamine is primary determinant of how motivated, excited we are, pursue things

Parkinson’s – depletion / death of dopamine neurons which affects movement

Two dopamine circuits in brain
-mesocortico limbic pathway – one pathway really gets disrupted in drug addictions like coke, meth
-substantia nigra

Dopamine release can be very local or broad
Synaptic and Volumetric release

Pleasure / joy = dopamine peak relative to baseline, not just peak absolute

Neurons communicate in 2 modes:
1. Fast electronic synapses, sodium ions
2. Slow receptors (dopamine) – effects take awhile to occur

**Dopamine is really stimulating – sympathetic arousal – increases level of alertness, look outside and pursue things outside yourself

“Universal currency” in all mammals for moving us towards goals
It’s “how you track” pleasure and success

**When you do something you repeatedly enjoy, threshold for enjoyment goes up and up

Got giardia, went to hospital, was given thorazine which blocked his dopamine receptors – felt overwhelming sadness, most he’s ever felt, was a horrible experience

Everyone has baseline levels of dopamine

Epinephrine – wakes up neural circuits, gives us readiness, “energy” molecule
Dopamine and epinephrine (adrenaline) are closely related

What increases dopamine?
-chocolate – 1.5x – transient (few seconds to minutes)
-sex – pursuit and act – 2x
-nicotine (especially smoked) – 2.5x – but very short lived
-cocaine – 2.5x
-meth – 10x
-exercise – depends on perceived enjoyment – from 1-2x
-caffeine – only increases a little bit, but increases receptors uptake – more able to experience dopamine’s effects

**Dopamine is actually LOWERED if you hate doing X, but force yourself to do it afterward in anticipation of reward – it makes the “doing” worse

Alcohol + smoking
Caffeine + smoking
Can synergies and give bigger dopamine increases, but can cause troughs

“Universal currency of foraging and seeking”

The higher the peak, the lower the trough later (eg, 1-2 days)

Pleasure / pain balance
Pain comes from lack of dopamine – when the readily releasable pool gets depleted

Addiction = baseline gets lower over time, gets progressively less pleasure over time (eg, video game addiction, drug addiction)

Work hard / play hard can lead to burnout, because both the work and play are both spiking dopamine – it’s just one currency for motivation + pleasure

To replenish the dopamine POOL, stop engaging in those behaviors (!) – eg, 30d of no video games

If you layer on things to try to get max dopamine – eg, gym + fave music + coffee = makes it hard to get the same dopamine in future
**Remove multiple sources of dopamine release from activities that you like / want to enjoy
Eg, stimulants + studying, fave music + gym, phone + anything

Make sure high peaks don’t occur too often
eg, intermittent rewards

Phone can bring you out of context / focus – and is a source of constant little dopamine hits
eg, Huberman doesn’t allow phone into workouts

**Caffeine is bit of an exception since it increases density / effectiveness of dopamine receptors
Yerba mate is particularly good

Cocaine / amphetamine reduces ability to learn (in addition to lowering baseline dopamine) afterwards for a period of time

How do we increase / sustain baseline dopamine?
-**cold exposure (eg, Wim Hof) – dopamine can reach 2.5x baseline (comparable to cocaine) – not a rise and crash but a sustained rise for 2-3 hours after

**If children intrinsically enjoy drawing, but we add a reward to it, then a lot of kids will actually draw less once the reward is tied to it (vs intrinsic motivation)

David Goggins is great example – turning effort into the reward

**“Ability to access pleasure from effort” – most beautiful thing about dopamine

“Learn to spike dopamine from effort itself”

Cultivating growth mindset = learning to access rewards from effort and doing itself
Find dopamine from friction and challenge you’re currently in

“The effort part is the good part”

Intermittent fasting is a good example
When we eat, we get dopamine release – especially when we’re hungry
Perception of dopamine is heightened when you haven’t seen much of it – eg, not eating for a long time

Dopamine isn’t just attached to primitive behaviors, but also to prefrontal cortex and other higher activities

If we hear something that validates a belief we have, can increase dopamine (!)

Big dopamine release = harder for future big dopamine release

Porn – big dopamine release – can lead to challenges

Macuna pruriens – OTC, is a precursor to dopamine, can lead to large surge in dopamine, increases sperm concentration + quality

L-Tyrosine – potent stimulus for increasing dopamine

Dopamine conditions / disfunction can occur when taking certain dopamine medications – and can also be innate eg, anxiety, schizophrenia

**Huberman not fan of melatonin for enhancing sleep – also Matt Walker – only for jet lag
Decreases dopamine 60m after melatonin

Phenylethylamine (PEA) – chocolate enriched in it – increases synaptic levels of dopamine
Huberman takes supplements
Sharp transient increase that lasts 30-45m

**Oxytocin and social connection and pair bonding triggers dopamine release

“Leverage Dopamine to Overcome Procrastination & Optimize Effort”

Dopamine is neuromodulator

Brain circuits
-Substantia nigra – contains neurons that are full of dopamine
-Mesolimbic pathway
-Mesocortical pathway
-several other pathways but I didn’t take notes

Prefrontal cortex – behind forehead – much larger in humans
Involved in long term planning, understanding context, making decisions
“Area of brain that says ‘shhh’ or ‘no, not now’”

**Eyes are part of brain, got extruded during development (!)

Addiction = progressive narrowing of things that bring us pleasure

Dopamine peaks & troughs
**Analogy of the “wave pool” – Dr. Kyle Gillett
Large waves – many peaks – water can slosh out, baseline drops

Say you’re hungry and thinking about food
Dopamine starts rising in anticipation
Relates to our propensity / desire to move (dopamine helps motivate it)
Eat sandwich – if it’s good – dopamine has another peak

“Reward prediction error” – dopamine released is relative to what you expected to get
Higher the expectation, lower the reality = less dopamine

Craving:
1. Desire for something (eg, a delicious sandwich)
4. 4. 4. Desire to relieve pain of not having that thing

Most findings came in the last 5 years

As we strive for something, always looking for cues if we’re on the right path
Why some people are so motivated, but others are the opposite
Why is goal seeking so context dependent?
All these cues adjust your baseline dopamine constantly – “reward prediction error”

Dopamine is propeller driving us in direction we wish to pursue

The system basically learns from everything you do, to better understand and adjust and influence how and what you pursue in the future

2 alcoholic drinks a week is fine, after that starts to create problems
But 0 is better

**Duration between desire and effect matters – if very short gap, then system expects that in future (eg, cocaine instantly boosts dopamine)

**Higher the peak, and faster the rise to peak, the further the fall below baseline

Drop below baseline triggers desire for more, starts vicious loop especially for easy dopamine hits (eg, drugs)

**Subsequent hits = lower peaks, and deeper troughs below baseline

Cocaine = 10x (1000%)
Meth = 10-100x
Sex = 4-5x (but some individuals double)
Coffee = 2x

Reset of addiction = 30 days of abstinence = dopamine trough makes you feel bad (among other things)

“Binding behaviors” (reminds me of Anna Lembke) – self-limits / setting boundaries – space & time
Binding engages pre-frontal cortex

We need enough water in the wave pool – a healthy baseline of dopamine
-sufficient sleep – restores dopamine reserves
-non sleep deep rest – not meditation (which is a focusing exercise, not a “rest”) – but yoga nidra (relaxation, guided meditation)
-nutrition (tyrosine levels) – cheese, nuts, meats
-morning sunlight (!!)
-regular movement – circuits that generate movement interact with dopamine generating circuits

Some people have gene adaptations for higher dopamine, lower activation energy – that “go” drive

Increase in baseline = any dopamine increase > 1hr

Cold water = 3-5 hours sustained dopamine increase
Or warm water (eg, 60F) for up to 1 hour (!)

Compounds to increase dopamine
-Macuna purins – increases peak, kinda spike-y
-L-tyrosine – can increase baseline dopamine, cognitive improvements

Postpartum depression – concept can apply to peak dopamine experiences
Important to remember
-that baseline takes several days to replenish

Holy grail of motivation:
-Stanford study – observing kids with free time, kids chose to draw pictures, experimenters introduced rewards to those kids, this increases dopamine, but once rewards were removed, the kids spent less time drawing (!) – repeated in variety of contexts and cultures – bigger peak, then bigger trough, but eventually it can reset to normal
-if you enjoy an activity a lot, guard and protect it – don’t layer and add rewards to create a higher peak, because it can lead to bigger trough later

He fell into habit of creating excess peaks in the activities he enjoyed doing (eg, running, or science lab experiments) by stacking supplements, caffeine, etc – but increasingly it led to troughs / burnout

Better to hold onto intrinsic motivation / pleasure of doing an activity and not stacking other things to seek more peaks

MAKE EFFORT THE REWARD

Reward-prediction error – difference between our desire / expected outcome, and the actual received outcome – the higher the positive gap, the more motivation we have in the future, and vice-versa

“Growth mindset” is important – it’s not “you’re not good at X”, it’s “you’re not good at X YET”

Dopamine trough is experienced as craving, wanting, pain

**If deep trough – best way is sharp accelerated rate to get out – WAIT will take too long – to rebound faster, do something more painful / harder than waiting (eg, cold shower, go for a workout, clean the house)

“What would be worse than this state?” – something that really sucks and yet is safe
This steepens the trough, so then you bounce back faster

Does meditation increase dopamine?
If it’s effortful, it can increase dopamine

Not about achieving outcome, but rather forcing yourself into a deeper state of discomfort

Huberman Lab – notes on Chris Palmer (ketogenic diet) and Kyle Gillett (hormones)

Took notes on parts of both podcasts

Started notes 1 hour+ in

Mitophagy – subset of autophagy
Autophagy is stimulated by fasting states
When body doesn’t have enough food, it hunkers down and recycles dead old parts
Can stimulate through fasting, calorie restriction
Becoming lean and conservative

Mitochondrial dysfunction – associated with many ailments

David Sinclair – Cell journal – mitochondria are unified link in everything we know about aging

Mitophagy – how to get rid of old / defective mitochondria
Most powerful signal is diet – calorie restriction, fasting

Glucose levels in brain need to be reduced
Neurons love glucose – but why is too much glucose bad?

High glucose levels may be a symptom of metabolic dysfunction, possibly mitochondrial dysfunction

Infants – breast milk is most beneficial / healthy food source
If infants have seizures – ketogenic diet can help

Even experts don’t know what causes obesity epidemic
Believes mitochondria is the answer
Maybe epigenetic factors in womb environment

Mitochondrial DNA comes exclusively from moms DNA?
“Unequivocally no”
Mitochondria encoded in 36 genes – but majority of proteins that comprise mitochondria are encoded in nuclear DNA which is inherited from both parents

Diet, drug, alcohol use (including THC), lack of sleep – all impair mitochondrial function

Alcohol disrupts how brain uses all kinds of fuel – including glucose metabolism
If alcoholics switch to ketogenic diet – less alcohol craving, better brain metabolism, reduced brain inflammation

Rats on ketogenic diet – much more responsive to alcohol (“cheap dates”)
5x higher BAC levels!

Hypothalamus – involved in motivation and craving

Brain metabolism deficits can be corrected in short term with ketone supplements (eg, liquid ketone esters / ketone salts)

Ketogenic diet isn’t just about ketones themselves – also lowering glucose levels, ramping mitochondrial biogenesis

If metabolically healthy, ketones themselves *could* have benefit

Started 1:08 in

L-carnitine – oral only absorbs 10%
Increases androgen receptor density

Vitamin D – optimizes testosterone if deficient

Free testosterone should be ~2% of total testosterone – reference range is 1-4%

Longjack – up regulates several enzymes

Tongkat – helps synthesize testosterone; 300-1200mg/day; be careful with standardization
Andrew takes it early in day, has stimulant effect – increases free testosterone for him
No reason to cycle it
Can increase DHEA

Fadogia – increases LH (luteinizing hormone), stimulates production of sperm / testosterone
300mg / day as a safe dose or 600mg / every other day

1st trimester pregnant ladies have high HCG levels in urine

Growth hormone / IGF-1 – usually don’t need to optimize it, but sometimes in diabetics it can be dysregulated
Amino acids before bed can help with growth hormone release
Some weight training regimens can increase growth hormone

Helpful to avoid eating 2 hours before bed as general health protocol
While fasting increases growth hormone release, downstream effects are mitigated so not significant net effect

Podcast notes: Stanford prof Andrew Huberman on all things cannabis and weed (1000x more powerful than your body’s natural cannabinoids)

Contains # of psychoactive compounds, main one is THC, also CBD (cannabidiol), also CBN (cannabinol)

THC = largely responsible for psychoactive fx of cannabis
CBD / CBN = profound effects, but not same altered perceptions / moods

“High” = number of changes in brain and body, some of which are actually result of CBD but this is not widely known

Cannabis plant has 400+ biologically active compounds

1 Sativa
2 Indica
3 Ruderalis – not often consumed; not widely known
4 hybrids of all three

Sativa taller longer plant, Indica is shorter stouter, different morphologies

Sativa = more stimulant, invigorated and alert, not as sedative, reported heightened focus / creativity, less susceptible to pain / noxious stimuli, “head biased effect”

Indica = more full body effect, full body relaxation, sedative effect, state of sleep, relieve anxiety, less stimulant
**Indica = “in the couch”

Many hybrid strains
Growers are growing strains with very nuanced effects on brain and body

**Now there’s type 1, type 2, type 3 for any given eg indica, sativa, hybrid – differing THC/CBD ratios
Type 1 = THC>CBD
Type 2 = more balanced THC:CBD
Type 3 = CBD>THC

Why is there any effect (of weed) at all?

**Top 3 most used drugs – #1 alcohol, #2 nicotine (1-2B users), #3 cannabis
Caffeine would be above all 3 if it were considered a drug

**From early conception (still in womb), you have cannabinoid receptors – because body has endogenous cannabinoids (EC) which you make from conception to death
Cannabis has compounds that bind to those same cannabinoid receptors —> biological fx
**THC / CBD bind to those receptors with greater affinity, have greater fx than our endogenous (naturally made) chemicals – 1000x greater potencyyour endogenous cannabinoids are out-competed
This is why dependence starts to emerge
This is also why you can experience worse mood, anxiety, etc when not consuming – because your own body’s compounds stop working as well

Similar to how our body makes its own testosterone, but you can take synthetic (artificial) testosterone that gives “super physiological effects” – much stronger than our own body-made testosterone
Same with nicotine + nicotinic receptors

Just because it’s from a plant / naturally occurring does not mean it’s safe or healthy for the human body – depends highly on the plant, compound, person, genetics, etc

Two main kinds of EC (endo cannabinoids)
Released from neurons (nerve cells) – pre-synaptic > post-synaptic – excitation and inhibition
ECs are post-synaptic – they’re a brake on system, adjusting levels
**While marijuana can disrupt short-term memory, these natural ECs can actually strengthen the neuronal connections
ECs work in number of ways, not straight-forward fx

Two kinds of EC receptors – CB1 is highly enriched in brain (found everywhere) / nervous system, CB2 is immune system / liver / genitals
ECs interact with both CB1 and CB2

Cannabis has THC / CBD that potently bind CB1 receptor – 1000x stronger than ECs – “essentially leave ECs dysfunctional”

**Cannabis is fast entering bloodstream = 30 seconds
Faster than alcohol and nicotine
After 30-60 min will have peak concentrations and biological fx
**Effects last 3-4 hours – can depend on familiarity / frequency of use

Lypophilic – affinity for fatty cells, can remain in those cells for long time
**After consumption, typically stay in those cells and can be detected for 80 days (!)

CB1 receptors present in many nerve cells / brain
Sativa acts on those receptors in pre-frontal cortex (PFC)
PFC = brake on amygdala (which detects threats)
**Sativa compounds eg, calm down the amygdala, and ramp up the PFC – seesaw effect – enables states of flow / focus / creativity / elevated mood
Except in some individuals – fx are opposite and can experience intense anxiety / paranoia
THC / CBD simply increase fx (“potentiate”) of your existing systems – thus likely to experience similar effect every time

**No good predictors of how an individual will respond to a given strain – lots of street lore but no scientific proof

**Indica also suppresses amygdala, but also shuts down hippocampus (memory) – indica can harm short and even long-term memory

Brain / body areas impacted
-deficits in memory (reductions in hippocampus activity)
-PFC – activated by sativa, indica turns off (=relaxation, promoting sleep)
-suppression of basal ganglia and cerebellum (action planning, balancing, motor planning and sequencing) – less physically mobile, reddening of eyes, drier mouth, etc
-increase in appetite – high density of CB1 receptors in hypothalamus – narrow focus to food, hypothalamus signaling to gut that regulate blood sugar leading to increases in appetite
-CB1 receptors in spinal cord – can provide some pain relief – big component of this is a perceptive shift of pain (qualitative)

Most studies detail THC amount, but don’t distinguish sativa vs indica strains

Does cannabis increase creativity?
“Depends”
Convergent (synthesis, analysis) vs divergent (brainstorming, exploration) thinking
**When dopamine is high, divergent thinking more likely = throw out lots of disconnected ideas
From review of scientific literature: in professions where creativity is required, find more manic depression (manic = elevated dopamine) and schizophrenia (also elevated dopamine)
**Creativity involves both – first divergent (high dopamine), then convergent (lower dopamine)
Creativity = process, not an event

Note: only 1/2 finished – will add more notes if I finish the rest