Joe Rogan Experience #1842 - Andrew Huberman

1. 0:00 – 1:51

   Alcohol tolerance, genetics, and dopamine-driven “super drinkers”

   1. AHAndrew Huberman0:00

      (drumbeats) Joe Rogan podcast, check it out.

   2. NANarrator0:04

      The Joe Rogan Experience.

   3. AHAndrew Huberman0:06

      Train by day, Joe Rogan podcast by night. All day. (instrumental music plays)

   4. JRJoe Rogan0:12

      And we're up. All right, here we go. What's up, man?

   5. AHAndrew Huberman0:15

      Great to see you.

   6. JRJoe Rogan0:15

      Good to see you too. So, we were just talking about Ari blacking out trying to keep up with, uh, Shane Gillis, who is a, a superhuman drinker. Like it's, it's bizarre the volume he can put down. And you were, you were saying? You were about to say something?

   7. AHAndrew Huberman0:29

      Yeah. I mean, obviously there's a tolerance that's built up with drinking a lot, but I believe the number is approximately 8% of people have a mutation in a gene such that when they drink alcohol, it increases their dopamine levels very quickly and they get euphoric. They feel great. These are the people, like that character in Mad Men, the Don Draper character, like he would go out and just get plastered and the next day, you know, he's all fresh and, and ready. And pa- part of that is tolerance. But in certain Scandinavian countries, northern European countries, this gene tends to be more prevalent, and these people are the people that can just keep drinking and drinking. They feel great when they drink, whereas most people, they feel disinhibited at the beginning. You know, you have a couple drinks, your forebrain shuts down a little bit 'cause that's what it does. They start talking more, talking more. But if they keep drinking, they're blacking out. You know, they're stumbling, they're slurring their words. This 8% of people, by way of this genetic mutation, alcohol affects them very differently. It offsets all that sedative property and they can just go and go and go. This is the person who's doing a case a day or at the party and just shot for shot and just looking like they're improving in function.

   8. JRJoe Rogan1:36

      (laughs)

   9. AHAndrew Huberman1:36

      And obviously they're not, but you put one of those people against, uh, Ari Shaffir-

   10. JRJoe Rogan1:42

       Yeah. (laughs)

   11. AHAndrew Huberman1:44

       (laughs) ... and that's what you get.

   12. JRJoe Rogan1:45

       Yeah. So i- i- even for those people though, it still has a negative effect on your body, right?

2. 1:51 – 5:09

   ADHD stimulants and focus drugs: widespread non-prescribed use

   1. AHAndrew Huberman1:51

      Oh, yeah. I mean, the toxicity of the alcohol is universal, but in terms of how it impacts brain function. And you see this across all these different categories of drugs too, right? You know, uh, somebody takes, uh, Ritalin, Adderall, Modafinil, or Armodafinil, these are the common prescribed drugs now and people use them recreationally for ADHD. In fact, in researching an episode for our podcast on ADHD, turns out that more than 80, eight zero, percent of college students will rely on ADHD meds, quote unquote, "recreationally," not prescribed, they buy it from each other in order to study.

   2. JRJoe Rogan2:25

      80 percent?

   3. AHAndrew Huberman2:26

      Eighty percent.

   4. JRJoe Rogan2:26

      Wow.

   5. AHAndrew Huberman2:26

      And those drugs work mainly by increasing dopamine-

   6. JRJoe Rogan2:30

      Wow.

   7. AHAndrew Huberman2:30

      ... and increasing adrenaline, and they make your focus like this narrow and you're, you're in a trench and you can't-

   8. JRJoe Rogan2:36

      Yeah.

   9. AHAndrew Huberman2:36

      ... function. But a number of people take them and feel super distracted and lousy. But this is of course what they prescribe to kids with ADHD.

   10. JRJoe Rogan2:44

       Yeah. Now, when you, y- y- M- Modafinil, is that, that's Provigil? Is that what that is?

   11. AHAndrew Huberman2:49

       Yeah. Now there's some, it's very expensive. Um, it, it's like $1,000 a month in some cases.

   12. JRJoe Rogan2:55

       Really?

   13. AHAndrew Huberman2:55

       Yeah.

   14. JRJoe Rogan2:55

       That much?

   15. AHAndrew Huberman2:56

       It was originally for narcolepsy, so to offset daytime sleepiness. That was the original use of the drug. And then it also does work for enhancing focus, right? I mean, w- that has drawbacks. It's not perhaps as detrimental as, like, recreational drugs to, um, to increase focus. But most of the students out there and the tech workers and the, this is big in the finance world too, are relying on Ritalin, Adderall, and things like Vyvanse. And to be clear, they have legitimate clinical uses.

   16. JRJoe Rogan3:24

       Wait a minute, what is Vyvanse?

   17. AHAndrew Huberman3:25

       It's another one of these drugs for ADHD. H- here's the, the story around why these drugs, uh, initially came to be. If you look at kids or adults with ADHD, like true attention deficit disorder or hyperactivity disorder, you don't always have the hyperactivity. What you find is they can focus really well if it's on something they like. So a kid with ADD or ADHD that loves video games, that kid will play video games with laser focus for three hours.

   18. JRJoe Rogan3:50

       That sounds like me.

   19. AHAndrew Huberman3:51

       But then you put them in front of something they don't wanna do and they just can't anchor their discipline.

   20. JRJoe Rogan3:55

       Right.

   21. AHAndrew Huberman3:55

       They just don't have the discipline.

   22. JRJoe Rogan3:57

       That also sounds like me. (laughs)

   23. AHAndrew Huberman3:59

       (laughs) Although I doubt that. Oh, no. We, we, uh, maybe it'll come up later, but your discipline for fitness and ice baths and tr- training com-

   24. JRJoe Rogan4:05

       Yeah, but I like the, I like those things though.

   25. AHAndrew Huberman4:06

       Right. Well, y- well, and if you can arrange your life such that most of your stuff is around that, great. But, uh, these kids, if, prove that if you like something, you can focus. And-

   26. JRJoe Rogan4:18

       Right.

   27. AHAndrew Huberman4:18

       ... it comes as no surprise then that the drugs for ADHD universally increase dopamine, because dopamine is this incredible molecule that enhances focus, motivation, and drive, and literally narrows the aperture of your visual attention. And we've all experienced that. And of course, drugs like cocaine and amphetamine do that to a hyper extent, and then there's a crash. But with these drugs, if prescribed in the right way and the right situation, they're terrific. They teach the kid's brain how to focus. But nowadays, there is rampant adult ADHD and ADD. Part of that is probably due to the phone, part of, part of that is probably just due to all sorts of things, but there is also a lot of recreational use of these prescription drugs, not illicit drugs like cocaine and amphetamine, but prescription drugs that increase dopamine. And supplementation for increasing dopamine as well.

3. 5:09 – 7:00

   How drugs get marketed: patents, repurposing, and “failed” molecules

   1. JRJoe Rogan5:09

      I have read something about Modafinil, Nuvigil, Provigil, which- whichever one it was, that it, initially it was created as a performance enhancing drug, but they needed some sort of an ailment for it to, you know, to be prescribed. And that was when they decided to scr- prescribe it for narcolepsy. Had you heard anything like that?

   2. AHAndrew Huberman5:28

      I thought it was in the reverse, but I'm open to-

   3. JRJoe Rogan5:31

      Oh.

   4. AHAndrew Huberman5:31

      ... to hearing, um ... And listen, the, the course of a lot of these drugs and how they hit market is super interesting. I've been learning more and more about this, 'cause one of my colleagues who works on aggression and mating behavior, which fascinates me, has identified some peptides that can really reduce anxiety. They put these to the pharmaceutical industry, pharmaceutlentricet-... wasn't interested in them at all, even though the safety margins are huge. So you say, "Why, why wouldn't they want this?" Well, it turns out these same drugs failed in a schizophrenia trial a long time ago, so no one will go near it with a 10-foot pole. So what, the way the pharmaceutical industry generally approaches drugs is they love to re-market drugs for which there's already FDA approval-

   5. JRJoe Rogan6:10

      Mm-hmm.

   6. AHAndrew Huberman6:10

      ... 'cause then they don't have to go through all the safety stuff.

   7. JRJoe Rogan6:11

      Right.

   8. AHAndrew Huberman6:12

      And when they do that, they can renew the patent. This is crucial, right? 'Cause if you can get the generic version, now with things like GoodRx and these, like, little-

   9. JRJoe Rogan6:20

      Mm-hmm.

   10. AHAndrew Huberman6:20

       ... apps you can get, I mean, you can go into a pharmacy, you hit GoodRx and it'll say, "Oh yeah, we've got some stuff that's about to expire. This $300 a month drug is $10." I, I've had this happen. It's, uh, you know, amazing. If they can keep it out of the generic market, that's huge, and the way to do that is to find a new clinical use. So I don't know which one came first, narcolepsy or these, these focusing ADHD uses, but... Or as a performance enhancer. But if the pharmaceutical industry, the people that own the patent to that drug can find a new, legitimate use, they just bought themselves, I think, another 10 years on, on the, on the patent.

   11. JRJoe Rogan6:54

       So this was originally prescribed for schizophrenia, and then they were gonna use these peptides for mating, like...

4. 7:00 – 15:04

   Aggression and mating circuits in the hypothalamus: switches in the brain

   1. AHAndrew Huberman7:00

      Uh, yeah, so here... So in terms of the aggression, this is really interesting. This is the work of a guy at Caltech named David Anderson, and he works on mating and aggression and the relationship-

   2. JRJoe Rogan7:09

      In human beings?

   3. AHAndrew Huberman7:09

      In... Well, he has work related to humans and the neighboring lab works on humans, but in mice and in humans. But these areas of the brain are really conserved. This, this... Oh, we can talk about which brain area, but what he discovered is that-

   4. JRJoe Rogan7:19

      Conserved?

   5. AHAndrew Huberman7:20

      Meaning, um, sorry, that in mice and in humans these brain structures look identical-

   6. JRJoe Rogan7:24

      Okay.

   7. AHAndrew Huberman7:24

      ... and that the same classes of neurons exist that if you were to stimulate them, 'cause neurosurgeons have done this, people go into a rage. Or in animals, if you stimulate them, the animals g- go into a rage. In fact, there are these videos online, they're incredible, where... This is Dayu Lin's work when she was in David Anderson's lab. So you take two mice, a male mouse and a female mouse, and they're mating, right, as it were, and then they stimulate these neurons, 'cause they can do that now in a, you know, using light, believe it or not. And those ani- m- the male immediately tries to kill the female. You can even just put him in a cage alone with a glove filled with air. He's walking around, you stimulate these neurons, and he just goes into a rage, right?

   8. JRJoe Rogan8:04

      Wow.

   9. AHAndrew Huberman8:04

      Just, just trying to destroy this glove. But here's what's super interesting and no one understands. If you put this animal into a cage alone and stimulate, looks pretty normal. It doesn't do anything. So it's not like it attacks itself. And you know, and every time there's this, uh, you know, horrible news event like the school shooting thing or something like that, I always think, you know, like, "What's going on in the..." There's a certain brain area, it's called the ventromedial hypothalamus. This is a brain area that's really interesting because it has a population of neurons that control mating. You stimulate them and animals will just start trying to copulate with basically whatever's around. If you give them a choice of their usual preference of, you know, females if they're male, males if they're female, 'cause that's the way mice, mice go, one or the other, they will just try and start mating. You stimulate the other group of neurons, and they will try and kill the other mouse. A- so these are like switches in the hypothalamus.

   10. JRJoe Rogan8:53

       I mean, are these, like, very distinct? Like when you, we talk about, like, neurons and switches, like how, how do you distinguish between the w- can you see them? Like, what is the difference?

   11. AHAndrew Huberman9:02

       Great question. So for many decades, it was known that if you stimulate this brain area, you could get aggression. This is actually Nobel Prize-winning work of a guy named, whose last name is Hess, and what they found was if you stimulate this brain area, cats would go into either two kinds of, of aggression. It was either defensive aggression, kind of with, with, you know, hair up-

   12. JRJoe Rogan9:22

       Back up, right?

   13. AHAndrew Huberman9:22

       ... or you would stimulate a little bit more and they would do the, the, you know, predatory aggression, right? I'm probably doing this wrong, but you know, like ears forward and you know-

   14. JRJoe Rogan9:30

       (laughs)

   15. AHAndrew Huberman9:30

       ... "You're, you're the hunter." Last time... I'm still learning about, you know, animal behavior in this way. But what's really interesting is that for years no one could understand why if you also stimulated this brain area and you used a different pattern of stimulation, you'd get mating behavior. And it turns out that the neurons are mixed in there like salt and pepper. David Anderson's lab figured out that these are molecularly distinct neurons, and what makes them distinct is really interesting. If they stimulate only the neurons that have the estrogen receptor, they become aggressive. And this again goes back to this thing that we talked about a while ago, which is that testosterone con- aromatized, converted into estrogen, has these incredible effects on aggression and masculinization of the brain. And a lot of people think... In fact, people heard me say that last time and said, "Oh, you're trying to say that it, estrogen is doing everything testosterone's doing." No. It's that things like testosterone and estrogen control gene expression, and so the fact that it's estrogen or testosterone, it doesn't really matter. It's the fact that these are molecularly distinct neurons, they can trigger these neurons, and they can get very distinct outputs in behavior. But what's crazy is you stop stimulating, the animal just goes back to doing whatever and then it goes, "Oh, man, I think I'll try and mate again." Now eventually the female's like, "Hey, this is getting confusing," but this... It's clear that these sorts of things are also happening in humans, but normally we have kind of a weighting of aggression versus mating behavior, right? Some people choose to combine those, right? There's kind of ex- extremes with that. R- rape, there's, uh, rough sex, there's all sorts of... You know, it's a, it's uncomfortable for people to think about th- but there's a continuum between ag- aggressive versus approach-type behaviors. And for whatever reason, this drove me to start looking at different mating behaviors of animals online. Like if you watch ferrets mating, it's, like, he's biting the back of her neck, she's squealing all over the place, like this is uncomfortable for some people to see, but some people probably like watching this stuff. But you look at animals mating and there's a, kind of a, a balancing act between, you know, what looks... It's not... You wouldn't call it lovemaking, let's put it at that.

   16. JRJoe Rogan11:29

       Right.

   17. AHAndrew Huberman11:29

       You'd call it mating that's pretty aggressive, and that's very common in, in the animal kingdom, so...

   18. JRJoe Rogan11:35

       Is it common in the animal kingdom because f- in order to have strong genes that pass on, you need a strong animal and so they express themselves in this aggressive way to prove to the female that they're strong enough to mate and, and procreate? Like what is the reason f- for that sort of aggressive... D- is there a reason?

   19. AHAndrew Huberman11:55

       Well, it's a, it's a great question. So th- there's this theory called hydraulic pressure theory. This was developed by Konrad Lorenz, which is another Nobel Prize winner who studied animal behavior, and here's the idea, is that all of these dis- different populations of neurons are in the hypothalamus. This is a little, tiny, tiny thing. I mean, it's the size of like a-... like, a little gobstopper candy, like a little gumball.

   20. JRJoe Rogan12:14

       Mm-hmm.

   21. AHAndrew Huberman12:14

       And you've got neurons for aggression, neurons for mating, neurons that turn on to make sure that you- that animals don't try and mate with the wrong species. Right? We take this for granted. Like-

   22. JRJoe Rogan12:23

       Hm.

   23. AHAndrew Huberman12:23

       ... How come a cat doesn't try and mate with a dog? Now, the dog might hump, but that's a different thing all together. So, it's all harbored in there, and th- this hydraulic theory is that all of these things are kind of weighted probabilities. So, there's never zero probability that any of this will happen unless they're in sleep. But maybe it's 10% aggression, 80% mating while they're mating. Maybe another male enters the arena, and now there's sort of like a confusion, like, "Am I gonna have to fight or can I keep mating?"

   24. JRJoe Rogan12:50

       Mm-hmm.

   25. AHAndrew Huberman12:50

       These kinds of things 'cause oftentimes, these animals are communal in some way. And so, the way that Anderson explained this to me, when we had a conversation about this recently, is that the brain might actually get confused in certain moments. That, you know... And there's also a kind of opioid pain relief thing that gets released during sexual activity. Pain threshold goes way up. Right? And we were talking about this in the context of fetishes because, you know, if you look at fetishes, they're not random. True fetishes are, like... Can be pathologies where people actually require the presence of something in order to become aroused. And those things almost always, if you look at true fetishes, are things like feet, dead bodies, feces, animals. Things that are all very infec- infectious. Exactly. Your facial expression illustrates it perfectly.

   26. JRJoe Rogan13:39

       My facial expression, for those listening, is yuck. (laughs)

   27. AHAndrew Huberman13:41

       Exactly. So, you know, that's disgust, and you have circuits in your brain that are for disgust that are about getting you away from that thing because it's infectious, putrid, disgusting, and out of context. And then you think about sex and food appetite and all that, and it's, it's all appetitive, as they call it. It's moving towards it. It's bringing in more of those molecules as opposed to trying to get away from, like, vomit or something.

   28. JRJoe Rogan14:03

       Right, but the feet thing, isn't it, like, guys like pretty feet?

   29. AHAndrew Huberman14:07

       It... You know, we're very visual animals, and so it may cross over into visual perception, and what arouses people differs obviously. People have their different proclivities. But true fetishes are a kind of a confusion of this circuitry, right? Where people confuse or learn arousal associated with something that's actually quite dangerous. I mean, take the extreme one like dead body. It's, like, incredibly-

   30. JRJoe Rogan14:27

       Is that normal?
5. 15:04 – 26:28

   From animal studies to humans: surgical stimulation, rage “hotspots,” and isolation peptides

   1. JRJoe Rogan15:04

      Now, when you... Talking about studies in animals, and they're doing this, i- it's ki-... The- there- there's these ethical questions if you're gonna do a study on humans. If you wanted to stimulate those same neurons and try to incite aggression or hostility or even arousal, but has anybody done it?

   2. AHAndrew Huberman15:22

      They have.

   3. JRJoe Rogan15:22

      They have.

   4. AHAndrew Huberman15:23

      They have. So, a good friend of mine, Eddie Chang, he's the chair of neurosurgery at UCSF. He's spends his life and he makes his living probing around in the brain of people who have epilepsy, looking for the site where if they stimulate, the person will have a seizure, so that they can burn that area out or make some other manipulation. And he's told me that he's been poking... You can't poke around at random. Right? You can't... You know, every scientist would love to just do that experiment, just go in and kinda search. But there are sites where they'll s- stimulate thinking they might evoke a feeling of pleasantness or no feeling at all, and the person will go into a rage in the, in the OR, in the operating room.

   5. JRJoe Rogan16:00

      Really?

   6. AHAndrew Huberman16:00

      Because they're wide awake. Yeah, you've probably seen these things of people with neurosurgery, and they're playing the violin-

   7. JRJoe Rogan16:04

      Mm-hmm. Yeah.

   8. AHAndrew Huberman16:05

      ... or things of that sort. Occasionally, they'll hit an area where the person will say, "I'm feeling super angry right now," and they'll say, "Let's back off a little bit from there," and they'll chart where they were in the brain.

   9. JRJoe Rogan16:14

      That is wild. So there's just, like, a spot?

   10. AHAndrew Huberman16:17

       Yeah. There is. And we have switches, right? I mean, we have switches for rage, switches for all these things. I mean, that's like the psychologist Carl Jung, you know, this idea that we have all things inside of us. I mean, people vary in their propensity for rage or for love or for anything, but at some level, we do have all things inside of us. We have the circuitry within us.

   11. JRJoe Rogan16:38

       And do you feel like that variation is n- neurochemical? That there's-

   12. AHAndrew Huberman16:42

       I think it is neurochemical, and I think it is learned as well. Th- this peptide that we were talking about earlier becomes relevant in the... In this context. So, David's lab discovered there's a peptide called tachykinin. It's related to another molecule that's involved in pain relief called substance P that we all make. Tachykinin has a bunch of different forms, but in humans, there's tachykinin I and tachykinin II. In mice or humans that are socially isolated for a period of time, tachykinin levels go through the roof. This is very relevant to the recent past of... Around the pandemic, in my opinion. It goes through the roof, and what happens? It creates anxiety, anger, and in particular, aggression. And so, there are drugs that are tachykinin inhibitors, and I asked David, I said, "Well, why aren't we giving tachykinin inhibitors to people that are feeling anxious and, and aggressive, and, you know, kinda tamp that down?" And we just had yet another school shooting, and we could talk about what that's about but... Or not, but... And he said, "This drug is actually approved. It's very safe."

   13. JRJoe Rogan17:46

       When you... Wait, stop. What are you s- what are you saying? What are you saying?

   14. AHAndrew Huberman17:48

       There's a drug that can block-

   15. JRJoe Rogan17:49

       No, no. B- b- but you're saying what, what that's about but we're not?

   16. AHAndrew Huberman17:52

       Oh, sorry. The, the...The tachykinin, I mean, is- was it elevated in, for instance, the kid that went in and shot all those kids and, and-

   17. JRJoe Rogan18:01

       How could they find that out post-mortem?

   18. AHAndrew Huberman18:02

       I think they could do what's called mRNA in situ hybridization. They could see how much of the gene for tachykinin was being made. I think they should do post-mortem. I don't know how h- he was killed, if his brain is still intact. Um, I think like most people, there's very little concern about him and more concern about-

   19. JRJoe Rogan18:17

       Yeah.

   20. AHAndrew Huberman18:17

       ... the victims, as it should be. But y- just like with CT in football players, you- you wanna know where the damage was, and also, whether or not there was a brain thing there. And if that brain thing was there, it doesn't mean necessarily that he was born with a bad brain, he might have been born with a dysfunctional brain, but social isolation increases anxiety and aggression, there's no question. And actually, I was in New-

   21. JRJoe Rogan18:38

       Social isolation increases aggression?

   22. AHAndrew Huberman18:40

       Absolutely.

   23. JRJoe Rogan18:41

       Really?

   24. AHAndrew Huberman18:41

       Absolutely.

   25. JRJoe Rogan18:42

       Like-

   26. AHAndrew Huberman18:42

       Feelings of aggression and kind of friction with the world, us/them kind of thinking, this is-

   27. JRJoe Rogan18:46

       Oh, okay.

   28. AHAndrew Huberman18:47

       I was in New York, uh, this was a few months back, and it was l- it was the most eerie experience, 'cause we were there recording some podcasts and something came over the news that, you know, there was literally killer loose, and it was that guy in Brooklyn went into a subway, released some smoke bombs and shot people, right?

   29. JRJoe Rogan19:03

       Right.

   30. AHAndrew Huberman19:03

       They found him in the Lower East Side walking around, someone found him. So like, killer on the loose in New York became a real thing for the time we were there, and it was super weird because we're staying down near the Lower East Side. And they get the guy, and what do they say? They say the same thing they always say about these guys. "He was a loner-"
6. 26:28 – 29:22

   Creativity timing, neuromodulators, and why late-night work can feel different

   1. AHAndrew Huberman26:28

      Yeah, you know, there's a really cool phenomenon wherein early in the day, or after, uh, we should say after someone's been asleep for a while, for that first zero to nine hours of the day, I call this phase one, just 'cause gotta label everything with a name-

   2. JRJoe Rogan26:42

      Mm-hmm.

   3. AHAndrew Huberman26:42

      ... to make it clear. During that time, we know that dopamine, adrenaline, and cortisol, healthy levels of cortisol, are highest in your system r- in those first nine hours. You might not wake up quickly, but they're highest. And then those start to taper off, and molecules like serotonin start to predominate. And the way these molecules like dopamine, serotonin, they do a lot of different things, they're involved in tons of things, but we can generally say that they modulate, they're called neuromodulators. They bias the probability that certain brain circuits and areas will be active and certain ones won't. So when dopamine and epinephrine are really churning around in your brain, you're really good at linear types of things, like math, organization, working out, sets and reps, this does this, this does this, we're going here, itineraries, where there's a right answer and you're just trying to plug and chug. As serotonin and other molecules kick in, which is later in the day and at night, the brain becomes much better at these, I call this phase two of the day. They become... So it's like seven to 16 hours aft- uh, uh, sorry, 10 to 17 hours after waking, so zero to nine for phase one and 10 to 17 for phase two. Your brain is much better at non-linear thinking, creative thinking, brainstorming. Um, y- I don't know what the writing process, comedy process is for you, but, you know, i- you're doing anything creative, you're organizing existing things into new ways, you're kind of playing with ideas, and it, it actually can be beneficial to be slightly sedated.

   4. JRJoe Rogan28:05

      Yeah.

   5. AHAndrew Huberman28:05

      This is actually why so many, um, great writers and musicians and maybe comics have used a little bit of alcohol, a little bit of cannabis to put their brain into that kind of liminal state where you're not, you're not super lasered in. You're not looking for the right answer. The, the right answer just kinda comes to you.

   6. JRJoe Rogan28:19

      Yeah.

   7. AHAndrew Huberman28:20

      And for some people, they have a hard time accessing that when they're in this hyperdrive mode. And jazz musicians, right, famous for abusing a lot of substances because jazz is all about the spontaneous incorporation of, of notes and et cetera. So I think that late-night creativity makes a lot of sense.

   8. JRJoe Rogan28:39

      Yeah. Tim Dillon and I were just having this conversation 'cause Tim is sober. And, you know, Tim used to have a l- like, a real problem with substances, and he says he does his podcast really late at night. Like, they don't even start filming till, like, after midnight.

   9. AHAndrew Huberman28:54

      Is that why he's got the aviators on?

   10. JRJoe Rogan28:55

       Yeah, that's pro-... But, but it's also, like, that's sort of his drug, you know. Like, he's sleepy, and he's kind of just, like, half out of it. And, you know, when he puts the sunglasses on, he just... It's almost like he's in an altered state of consciousness, but without having to snort ketamine or whatever the fuck he was doing.

   11. AHAndrew Huberman29:13

       Oh, goodness.

   12. JRJoe Rogan29:13

       You know? He's just-

   13. AHAndrew Huberman29:14

       Definitely a healthier (laughs) approach.

   14. JRJoe Rogan29:16

       (laughs)

   15. AHAndrew Huberman29:16

       That guy used to snort ketamine?

   16. JRJoe Rogan29:17

       I don't know. I don't think he did ketamine.

   17. AHAndrew Huberman29:18

       Ketamine's now legal, but please, uh, I can't imagine snorting ketamine is good for him.

   18. JRJoe Rogan29:21

       Well, ketamine is legal though.

   19. AHAndrew Huberman29:22

       Yeah.

7. 29:22 – 32:22

   Ketamine for depression: dissociation, memory/plasticity, and perspective shifts

   1. JRJoe Rogan29:22

      You can get, you can do ketamine therapies, which are really weird. Like, a lot of people are doing them for depression.

   2. AHAndrew Huberman29:28

      Why a-... So here... I've got colleagues who study ketamine. I've been spending a lot of time trying to understand how this drug works. It's a dissociative anesthetic. So it is, it's like PCP.

   3. JRJoe Rogan29:39

      Mm-hmm.

   4. AHAndrew Huberman29:39

      It works by blocking something called the NMDA, N-methyl-D-aspartate receptor, if people wanna look that up. This-

   5. JRJoe Rogan29:44

      It's very similar, right? Carl Hart was telling me that it's almost the same thing as PCP.

   6. AHAndrew Huberman29:48

      Absolutely. This receptor is a receptor that becomes active only when you're hyperfocused on something and it ch- and it has the capacity to create brain change in a very dramatic way. Sort of, 'cause your brain can't... They say, "Oh, your brain is different five minutes after this conversation than it was before." That's, that's bullshit. Basically, your brain doesn't change unless it needs to. And that signal of need to comes from something being really intense, really stressful, really exciting, really novel, right? Makes sense, right?

   7. JRJoe Rogan30:16

      Right.

   8. AHAndrew Huberman30:16

      Why reprogram the machine unless there's a need? And so you have a chemical signal. Ketamine basically is, was initially used to block memory formation after trauma. So people would come into the...... into the emergency room, let's just imagine, like, horrible scenario, right? And someone was just in the passenger seat and watched their closest loved one get impaled on a steering column. That person is in a state of shock, and they're never gonna forget what they see. So what do you do? You give them ketamine, you try and dampen the plasticity, the brain change, that would c- occur to remember that incredibly traumatic event.

   9. JRJoe Rogan30:50

      Mm.

   10. AHAndrew Huberman30:51

       Now it's being used as a way to bring people into the clinic, or it seems like it is pretty rampant use now, and put people into this dissociative state so that they see themselves having an experience. In fact, I've talked to people who've gone through ketamine trials, and they describe it as watching themselves get out of their own car. They're like third personing themselves.

   11. JRJoe Rogan31:10

       Mm.

   12. AHAndrew Huberman31:11

       This, to me, sounds like a horrible state to be in. But a lot-

   13. JRJoe Rogan31:14

       Why? Why is that?

   14. AHAndrew Huberman31:15

       I mean, I've been working my whole life to just be comfortable with the body I'm in, and I'd like to stay in it, not because it's always comfortable to be there, but because, you know, getting good at that seems to be the key to having a good life, being able to tolerate discomfort. This is about-

   15. JRJoe Rogan31:27

       But isn't the point-

   16. AHAndrew Huberman31:28

       ... getting out of yourself.

   17. JRJoe Rogan31:30

       Yeah, but isn't the point for these people to try to figure out what they're doing wrong with their life, so they can look at it objectively as a third party?

   18. AHAndrew Huberman31:35

       Yeah, that makes sense to me that they would look at, like, for instance, their suicidal depression and say-

   19. JRJoe Rogan31:39

       Yeah.

   20. AHAndrew Huberman31:40

       ... you know, that like, this, this, the new age-y kind of thing is like, "You are not your feelings." And so that's a tough one for people to incorporate because when I have really strong feelings, it certainly feels like it's happening inside me. So this is allowing them to get next to their feelings and see their feelings as a experience, not them.

   21. JRJoe Rogan31:57

       Yeah, I mean, but even when you know that you're, you're, it's definitely happening to you, you know that you are also sometimes not burdened by those feelings.

   22. AHAndrew Huberman32:05

       That's right.

   23. JRJoe Rogan32:05

       So it's some sort of an external factor.

   24. AHAndrew Huberman32:07

       Right.

   25. JRJoe Rogan32:08

       Or even if it's an internal factor.

   26. AHAndrew Huberman32:09

       Right.

   27. JRJoe Rogan32:09

       It's a thing other than the core of what you are.

   28. AHAndrew Huberman32:12

       Right.

   29. JRJoe Rogan32:12

       Right?

   30. AHAndrew Huberman32:12

       It doesn't define you.
8. 32:22 – 42:26

   Psilocybin research: macro-dosing, “letting go,” and unknown mechanisms

   1. AHAndrew Huberman32:22

      Yeah, and it seems to work quite well for intractable depression, as it's called. What's really odd about the fact that it works, at least to me, is that if you look at the other new emerging very effective treatment for severe depression, it's the exact opposite. It's this incredible work that Matthew Johnson and colleagues are doing out at Johns Hopkins, giving people macro doses of psilocybin.

   2. JRJoe Rogan32:42

      Mm-hmm.

   3. AHAndrew Huberman32:43

      Uh, I talked to him, we had him on the podcast, and he... And I asked him, I'm like, "What are your thoughts on micro dosing?" And he was like, "Pfft, macro dose." And I thought like, "Whoa, this is an academic saying this."

   4. JRJoe Rogan32:54

      Right.

   5. AHAndrew Huberman32:54

      This isn't like some guy who's, you know, trying to push psychedelics for his own agenda. This is a guy who's studying these in a, like purely through the lens of science. Like, what are you talking about? What's critical about the macro dose of psilocybin?

   6. JRJoe Rogan33:04

      When you say macro, what kind of dose are you talking about?

   7. AHAndrew Huberman33:06

      I don't know how they dose these, but this would be like in the gram d- range.

   8. JRJoe Rogan33:09

      How many grams? One gram?

   9. AHAndrew Huberman33:10

      Uh, I'm g- I need to check with-

   10. JRJoe Rogan33:12

       Okay.

   11. AHAndrew Huberman33:12

       We should l- check with Matt before people run off and start (laughs) taking...

   12. JRJoe Rogan33:15

       Yeah.

   13. AHAndrew Huberman33:15

       But certainly not micro, right? They're hallucinating, they're feeling a lot.

   14. JRJoe Rogan33:19

       Mm-hmm.

   15. AHAndrew Huberman33:19

       And I said, "What's the key thing? You're seeing success after success after su- eating disorders, depression, la-"

   16. JRJoe Rogan33:24

       Yeah.

   17. AHAndrew Huberman33:24

       You know. And he said, "It seems to be, quote, unquote, 'letting go'." And I'm like, "Well, that's not science, right? What is letting go? Are you talking about heart rate 50% above baseline? Are you talking about breathing?" You know, and he said, "There does seem to be something crucial about the people in these trials experiencing what would normally give them a complete panic attack, and being able to just let go and go into the experience without trying to control it, without trying to tamp it down or ramp it up, just be in it."

   18. JRJoe Rogan33:57

       But what kind of experience that would give them a panic attack?

   19. AHAndrew Huberman33:59

       For some people, it's, um, you know, he said there was one woman in, who came in, I believe it was a woman who, there was a painting on the wall and she thought she could jump through it. And so that, you know, they're holding her back.

   20. JRJoe Rogan34:10

       Oh, Jesus. (laughs)

   21. AHAndrew Huberman34:10

       You know. Yeah, they're holding her back.

   22. JRJoe Rogan34:11

       (laughs) .

   23. AHAndrew Huberman34:11

       And, um, and they do give them tools to control their anxiety. So my lab works on a lot of breathing tools for real-time rapid control of anxiety, and we handed some of those off to Matt. So they give these to people as tools. They also have defibrillators in there. They have everything 'cause it's a cl- you know, it's a university setting-

   24. JRJoe Rogan34:26

       Right.

   25. AHAndrew Huberman34:26

       ... just in case. And he said that the key thing is that they kind of feel overwhelmed, but then they feel supported enough by the therapist to lean into whatever's happening and they stop trying to regulate it, and that's where apparently he thinks the breakthrough is.

   26. JRJoe Rogan34:43

       Mm.

   27. AHAndrew Huberman34:43

       And so that reveals something very fundamental. It says that there's something powerful in terms of dep- long-term depression relief that can be learned in those states that has to do with not regulating one's self or one's need to run for safety.

   28. JRJoe Rogan34:58

       Mm.

   29. AHAndrew Huberman34:58

       And I find that fascinating because, you know, it raises all these questions. For instance, do you need to hallucinate? M- maybe not. Maybe it has nothing to do with hallucinations. Maybe it just has to do with getting the person into a state of, like, real fear and then allowing them to lean into it. I don't know. That's a speculation. But I think that what's interesting about all this work on psychedelics is, it's clearly working in these clinical trials. I mean, overwhelmingly, the data are more positive than negative, and yet no one knows exactly (laughs) why it's working.

   30. JRJoe Rogan35:25

       Right.
9. 42:26 – 48:18

   Cannabis, interoception, training focus, and mind–muscle connection

   1. AHAndrew Huberman42:26

      But then I asked about cannabis. Now this isn't something he does in his own clinic. He does talk therapy, not drug -not drug therapy. Although he's a psychiatrist, so he can prescribe things. But and he said, you know, cannabis is interesting and it may actually have some therapeutic potential, but the main effect of cannabis is to narrow attention and focus. It actually can increase attention and focus. Now the problem is, it's not a very good filter, so people can narrowly attend to just video games or just to their anxiety if they're already anxious. That's a problem. But when it comes to psilocybin, psilocybin seems to increase creative thinking, new -kinda new rules and algorithms about what could be an answer. So I'm not aware of how it might directly impact visual perception unless it narrows focus, but most of the drugs that impact serotonin are going to increase focus at -to some degree or another. And that can be good if what you're focusing on is pleasant. It can be really bad if what you're focusing on is really unpleasant. I knew people, I'm sure you've known them, who just smoke weed and they have a panic attack.

   2. JRJoe Rogan43:26

      Yeah. The- the- the smoke weed thing is a weird one, because it just- it- it's- it's like many things. It's completely dependent upon the individual. Like the- their individual genetics, their biology, whatever it is that they've had in their past. I know people that smoke marijuana and they're high functioning, and I know people that smoke marijuana and they don't get anything done, and I don't know if they're relate -those two things are related. I think people who generally have, um, drive and discipline, marijuana gives them a break. It gives them a nice little- just a little rest stop, and I think that's probably beneficial. And I also think it makes you a little kinder, a little more compassionate, a little more sensitive, which is probably very beneficial to someone who's hyper-focused. Like people that are like type A personalities who're trying to get things done all the time, you smoke a little pot and you're like, "What am I doing? What? Let's fucking relax a little."

   3. AHAndrew Huberman44:20

      That's a good-

   4. JRJoe Rogan44:20

      And then you get back to it. You're all right. I think it's- it's- that's- there's a great benefit to that. But I should also say that it's very popular in the jujitsu world.

   5. AHAndrew Huberman44:30

      Oh yeah.

   6. JRJoe Rogan44:30

      Yeah.

   7. AHAndrew Huberman44:30

      I always thought that had something to do with, um, uh, the kinda creativity part of it.

   8. JRJoe Rogan44:35

      Yes.

   9. AHAndrew Huberman44:35

      Like that you- you can't plan jujitsu.

   10. JRJoe Rogan44:38

       Right.

   11. AHAndrew Huberman44:38

       You have to improvise.

   12. JRJoe Rogan44:39

       Yeah there's-

   13. AHAndrew Huberman44:39

       Like jazz.

   14. JRJoe Rogan44:40

       ... in a lot of ways. There's definitely that, but it's also the focus thing, that you're only thinking about that. Like while you're rolling, you're really only thinking about rolling. While you're smoking cannabis and then rolling, you're hyper-focused on it.

   15. AHAndrew Huberman44:55

       And physical strength, you feel fine? You don't feel lethargic or anything like that?

   16. JRJoe Rogan44:58

       No, not at all. I actually enjoy it. I actually enjoy it when I lift weights too.

   17. AHAndrew Huberman45:02

       Oh. Haven't tried that one.

   18. JRJoe Rogan45:03

       Yeah, I feel it. Like I feel it in the fibers. It's almost like I'm more aware-

   19. AHAndrew Huberman45:07

       Hmm.

   20. JRJoe Rogan45:08

       ... of like what's going on instead of like this uh, blunt sort of um, you know, uh, you know, d- d- almost like distance from uh, each individual muscle fiber, which I am normally. Normally I'm just trying to warm up and then I warm up and then I start getting going, then I, you know, lift light first, and then I work my way up to what- what I normally use. But when I'm high, it's like I could feel like where it connects to the bone. Like just I feel everything. It just makes you more sensitive about what you're actually doing and for um, martial arts techniques, particularly for striking, I feel like I incorporate leverage better into things, I'm- I- I'm- I have better balance in terms of like not trying to execute a technique when I'm off position, you know? And it just makes me uh, just more aware of like what's going on with my body.

   21. AHAndrew Huberman46:00

       And that's super powerful. We had- uh, the- the nerd in me wants to say in neuroscience they call that interoception. Like people-

   22. JRJoe Rogan46:06

       Mm-hmm.

   23. AHAndrew Huberman46:06

       ... vary tremendously in their awareness of their internal state. You can know if you have a high or low degree of interoception by trying to count your heartbeats without taking your pulse. Some people can just do that. It's a skill you can build up over time. This is great for some people, but some people who are highly anxious, it sucks to have a lot of interoception. But we know, of course, that the mind-muscle connection is really powerful and it's not just mind-muscle connection as a whatever they call bro science thing. The reality is that from peer reviewed studies that if people focus on the contraction of a muscle during resistance training as opposed to moving the weight, right, something that's hard to measure if they're actually doing it, the strength and hypertrophy gains are much greater.

   24. JRJoe Rogan46:48

       Mm-hmm.

   25. AHAndrew Huberman46:48

       I think it's like a 15%. We need- I had Andy Galpin on the podcast and he would know the exact number. Um, but I always uh, wonder about this like in gyms where there are mirrors and people are watching themselves lift in the mirror.

   26. JRJoe Rogan47:00

       Mm-hmm.

   27. AHAndrew Huberman47:00

       I mean you're exterocepting, you're not focused as much as you could on the actual feeling. So, you know, there's always a weighting between exteroception to the out- everything beyond the confines of your skin and interoception, and if cannabis allows more interoception, you could imagine that those workouts would be more effective in that way.

   28. JRJoe Rogan47:17

       But isn't there benefit to observing yourself in a mirror because you make sure that you use the proper technique?

   29. AHAndrew Huberman47:22

       Absolutely. I mean it- right, I mean, you always see those people-

   30. JRJoe Rogan47:25

       Right.
10. 48:18 – 1:11:21

    Testosterone, doping gray zones, and the hidden cost of sleep deprivation

    1. JRJoe Rogan48:18

       No, but what do you think about a person like, I bring him up all the time because he's so odd, Jon Jones. Like Jon Jones has the smallest calves of any man I've ever seen who is an elite athlete and obviously he's an elite athlete. He's one of the greatest fighters-

    2. AHAndrew Huberman48:33

       Mm-hmm.

    3. JRJoe Rogan48:34

       ... of all time and even now while he's worked his way up to heavyweight, so he's-... he hasn't fought in two years because over that time, he's been building himself up. And now, he's like a legit 255 pounds, he's fucking huge, tiny calves.

    4. AHAndrew Huberman48:47

       Well-

    5. JRJoe Rogan48:48

       What's going on there?

    6. AHAndrew Huberman48:48

       What's really interesting is if you look at elite sprinters-

    7. JRJoe Rogan48:51

       Like look at this. Is that real?

    8. AHAndrew Huberman48:52

       Yeah. So, look how short the, the muscle bellies are on his calves.

    9. JRJoe Rogan48:56

       Mm-hmm.

    10. AHAndrew Huberman48:56

        But if you look at elite sprinters, like y- Olympic sprinters, they'll have big legs, but if you look at ... And sometimes they'll have big, bulging calves, but their calves are very short. That's actually gonna lend itself to sprinting. You don't see Manny Pacquiao calves on sprinters.

    11. JRJoe Rogan49:11

        Interesting.

    12. AHAndrew Huberman49:11

        Not good ones, anyway.

    13. JRJoe Rogan49:12

        But he's not a sprinter.

    14. AHAndrew Huberman49:14

        No, but he's got a lot of explosive power, from what I understand.

    15. JRJoe Rogan49:17

        Oh, yeah, definitely.

    16. AHAndrew Huberman49:17

        I mean, I'm not a, I'm not a knowledgeable about MMA. Pretty much everything I know about MMA, I've learned from you and from Lex.

    17. JRJoe Rogan49:22

        So, look at him there. Even at 255 pounds, I mean, he's-

    18. AHAndrew Huberman49:26

        Yeah, he's got tweezers down there.

    19. JRJoe Rogan49:28

        These very small calves. Which is, it's really unusual for someone who's built the way he is.

    20. AHAndrew Huberman49:33

        Mm-hmm. But his explosiveness out of those calves is probably, uh, met by that short muscle belly.

    21. JRJoe Rogan49:40

        Well, he's not th- the fastest guy, you know? And his whole thing is he's the best at, uh, controlling distance, 'cause he's very tall, especially for light heavyweight, not going to be as tall for a heavyweight. But he's fantastic at controlling distance. And if you're a person who wants to maximize your, y- like, you have a certain amount of weight you can be. You can be 205 pounds and that's it, if you wanna be championship weight. At 205 pounds, he's got the perfect physique. See, 'cause he's really long for 205.

    22. AHAndrew Huberman50:09

        Long arms and legs.

    23. JRJoe Rogan50:10

        Long arms and legs.

    24. AHAndrew Huberman50:12

        Ugh.

    25. JRJoe Rogan50:12

        So, you can't get close to him. And he's a fantastic striker. And he uses those arms and long legs in a great way with his wrestling and his submissions 'cause he has fantastic leverage. He's really like the perfect build for fighting.

    26. AHAndrew Huberman50:26

        How tall did he say he was? Is it six plus?

    27. JRJoe Rogan50:27

        I think ... Yeah, Jon is 6'3", 6'4".

    28. AHAndrew Huberman50:31

        Is he back in it? I know he had a steroid pop, but is he back?

    29. JRJoe Rogan50:34

        Oh yeah, no, he's back. That was a long time ago. That, that's ... The steroid pop is a weird one, man. You know, he, he kept ... 6'4".

    30. AHAndrew Huberman50:41

        That's-

Episode duration: 3:01:20