The guest
Andrew Huberman: Professor of Neurobiology and Ophthalmology at Stanford School of Medicine and host of the Huberman Lab Podcast, where he translates neuroscience into science-based tools for everyday life.
What this episode covers
In this solo episode, Andrew Huberman frames pain and pleasure as two ends of a single sensory continuum that begins in the skin's neurons and is interpreted by the brain. He explains how dopamine drives motivation and anticipation rather than the reward itself, and how intermittent reward schedules sustain motivation. He covers the highly subjective nature of pain, the homunculus body map, phantom limb treatment via mirror boxes, and factors like expectation, anxiety, sleep, circadian timing and genes that modulate perception. Finally he reviews concrete tools for managing pain and pleasure, including supplements, low-dose naltrexone, electroacupuncture, the gate theory of pain, self-hypnosis, and how dopamine and serotonin govern the pleasure system and addiction.
Recommended on this episode
ProductRecommended
Pilot V5 / V7 pens
Pilot
“My favorite pens”
“My favorite pens, these pilot, V5 or V7, which I love. If you were to close your eyes and I were to take these two pens”— Andrew Huberman
Also referenced (named, not recommended)
ProductReferenced
Naltrexone (low dose)
“The drug is called naltrexone. Naltrexone is actually used for the treatment of various opioid addictions”— Andrew Huberman
ProductReferenced
Acetyl-L-carnitine
“There is evidence that acetylcarnitine can reduce the symptoms of chronic whole body pain and other certain forms of acute pain”— Andrew Huberman
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Agmatine sulfate
“which are agmatine and S-adenosyl-L-methionine... Both of those have been shown to have some impact... on various forms of pain”— Andrew Huberman
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SAMe (S-adenosyl-L-methionine)
“SAMe in particular has been interesting because it's been shown head to head with drugs like Naproxen... to work at least as well”— Andrew Huberman
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Naproxen
“it's been shown head to head with drugs like Naproxen and other drugs of that sort, which are well established and sold over the counter”— Andrew Huberman
ProductReferenced
5-MTHF (5-methyltetrahydrofolate)
“what they think is a better or more bioavailable alternative, which is 5-methyltetrahydrofolate or 5-MTHF”— Andrew Huberman
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PEA (Phenethylamine)
“One in particular that's very interesting is something called PEA. PEA, it stands for Phenethylamine”— Andrew Huberman
ProductReferenced
Wellbutrin (Bupropion)
“certain drugs like antidepressants like Wellbutrin Bupropion as it's commonly called”— Andrew Huberman
ProductReferenced
Prozac
“the serotonin selective re-uptake inhibitors like Prozac, Zoloft and similar will increase dopamine and serotonin”— Andrew Huberman
ProductReferenced
Zoloft
“the serotonin selective re-uptake inhibitors like Prozac, Zoloft and similar will increase dopamine and serotonin”— Andrew Huberman
ProductReferenced
5-HTP
“Some people will take serotonin in precursor form like 5HTP or serotonin itself, or they'll take the amino acid precursor like tryptophan”— Andrew Huberman
Big reveals from this episode
- When a reward arrives, dopamine drops back to baseline; dopamine is the molecule of anticipation and motivation, not pleasure.
- Intermittent, random reward schedules can double or triple dopamine release, which is the basis of slot machines and gambling.
- Pain and tissue damage are not always correlated and can run in opposite directions.
- A construction worker had excruciating pain from a nail through his boot, but the nail had passed harmlessly between his toes and the pain vanished once he realized this.
- A patient with an amputated foot experienced orgasm in their phantom foot because the foot and genitalia lie adjacent on the brain's body map.
- Electroacupuncture of the legs activates a brain-to-adrenal circuit releasing anti-inflammatory catecholamines, while abdominal stimulation can either reduce or worsen inflammation.
- Obsessive new-relationship love raised pain tolerance in subjects, mechanistically via dopamine's effect on inflammation circuits.
- Every large dopamine peak triggers a mirror-symmetric activation of the pain system, which is the basis of addiction.
Worth remembering
- A single DRG sensory neuron can be a meter or more long, the largest cell of any kind in the body.
- On the brain's homunculus map the lips, face, fingertips, feet and genitals are massively enlarged due to dense innervation.
- Roughly 80 to 90 percent of people carry the herpes simplex 1 virus, which lives on the trigeminal nerve.
- Pain tolerance drops at night, with the lowest threshold between 2 and 5 AM on a standard circadian schedule.
- Cold receptors respond to relative temperature drops, so getting into cold water all at once and up to the neck is more comfortable than slowly.
- Sitting still in cold water you warm a thermal halo around your body; moving disrupts it and feels colder.
- The gate theory of pain explains why rubbing an injury helps: A-fibers inhibit pain-carrying C-fibers via GABA release.
- Redheads carry the MC1R gene variant that makes more beta-endorphin, raising their natural pain threshold.
- PEA, released by dark chocolate and aspartame, amplifies the perceived pleasure from a given amount of dopamine or serotonin.
- Specialized skin neurons respond to the direction of touch, which is why petting a cat with the grain of its fur feels good to it.
More from Andrew Huberman
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