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