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Andrew Huberman: Peptides, Sleep Tech, and the End of Obesity

Daisy Wolf speaks with Dr. Andrew Huberman, professor of neurobiology and ophthalmology at Stanford University and host of the Huberman Lab podcast. They discuss how the pandemic sparked a consumer health revolution, the emerging peptide and GLP landscape, what the science actually says about focus drugs, and the neurotechnologies Huberman believes will let us write to our own biology within the next five years. Timestamps: 0:00—Introduction 1:15—The Health Awakening, Explained 7:02—MAHA's Role in the Health Movement 13:05—GLP-1: Nearly One in Seven Americans 18:37—The Non-GLP Peptide Craze 25:16—Rogue Experiments and Low-Dose GLP 31:40—Real-Time Cortisol Sensing 44:39—The Pet Octopus and AI Communication Resources: Follow Andrew Huberman on X: https://twitter.com/hubermanlab Follow Daisy on X https://twitter.com/daisydwolf Stay Updated: If you enjoyed this episode, be sure to like, subscribe, and share with your friends! Find a16z on X: https://twitter.com/a16z Find a16z on LinkedIn: https://www.linkedin.com/company/a16z Listen to the a16z Show on Spotify: https://open.spotify.com/show/5bC65RDvs3oxnLyqqvkUYX Listen to the a16z Show on Apple Podcasts: https://podcasts.apple.com/us/podcast/a16z-podcast/id842818711 Follow our host: https://x.com/eriktorenberg Please note that the content here is for informational purposes only; should NOT be taken as legal, business, tax, or investment advice or be used to evaluate any investment or security; and is not directed at any investors or potential investors in any a16z fund. a16z and its affiliates may maintain investments in the companies discussed. For more details please see http://a16z.com/disclosures.

Dr. Andrew HubermanguestDaisy Wolfhost
Mar 9, 202650mWatch on YouTube ↗

EVERY SPOKEN WORD

  1. 0:00 – 1:15

    Introduction

    1. AH

      You don't want to stimulate the sympathetic nervous system so much or so often. It can probably shorten your life. There's a whole category of what are called growth hormone secretagogues, which are very popular. When people hear erection, fat loss, energy, tan, like, "Oh, great." This isn't the kind of thing you do to like go on vacation. You gotta be real careful with these things.

    2. DW

      Nearly One in Seven Americans is Taking a GLP-1 Drug. 20% Have Tried Them. What do you think the future looks like?

    3. AH

      In theory, you could eradicate obesity. People can lose up to a third of their body weight. Melanotan, which makes people tan from the inside, raises energy and libido dramatically, fat loss dramatically. BPC-157, body protection compound, it's not legal, but it's not necessarily enforced. They list them as for research purposes only, not for human use. I mean, who's doing research on these peptides at home? Anytime you're stimulating cell growth, it could start going awry and maybe you get a tumor or something like that. If that's within your margins of risk, then that's up to you.

    4. DW

      I want to talk about what's happened over the last five years.

    5. AH

      Slowly, through the '80s, through the '90s, and then the early 2000s, everyone wanted to know what they could take to improve their immune system and their health. There's a very interesting drug that I think is gonna become far more popular soon, which is-

  2. 1:15 – 7:02

    The Health Awakening, Explained

    1. DW

      Dr. Huberman, welcome to the a16z show.

    2. AH

      Thank you. Delighted to be here.

    3. DW

      I want to talk about what's happened over the last five years. Like since you launched your podcast, there's been an extreme increase in consumer interest and focus on their own health. Like as an investor, we used to kind of think people were only willing to spend on what we'd like call sex or vanity drugs, like Propecia, Viagra, and that has totally changed in the last five years, and people are really interested in their health. I'm curious what you think the major drivers of that have been and what your role has been in it.

    4. AH

      So I think the major driver was there were a few breakthrough supplements that changed the way that people think about healthcare and decided they needed to be more self-directed in their healthcare. Return to that in a second. I think the other thing is that the, the health and fitness in- industry collided with mainstream medicine and just self-care in the following way. Um, when I was growing up, the only people that lifted weights were bodybuilders, football players, and, um, people going off to the military. I was told if you lift weights, the muscle will turn to fat if you stop, that everyone in gyms is on steroids. I think what happened is slowly, through the '80s, through the '90s, and then the early 2000s, the world started accepting, "Oh, there, there are modes of fitness that allow me to e-eat healthily and, and take care of myself." And yes, there's some extremes there, but there was-- that it was actually quite compatible with a, with a normal, healthy life. So what happened during the pandemic was everyone wanted to know, this was before and after the vaccines, wanted to know what they could take to m-improve their immune system and their health, and the first thing that sort of broke through was vitamin D.

    5. DW

      Mm-hmm.

    6. AH

      Maybe because it can be increased by sunlight and everyone gets some exposure to sunlight. Doctors weren't saying, "Don't take it." The studies on it were kind of mixed. But they were like, "Okay, you know, ta- everyone start having some vitamin D around." Then, you know, the melatonin craze had already kind of come and gone. Um, but that, that's a hormone. And then as time went on and people started getting more interested in physical fitness, not just jogging or doing cardio, but as resistance training came in-

    7. DW

      Mm-hmm

    8. AH

      ... it inevitably brought with it an interest in protein needs. So are you gonna take supplements that increase your daily protein? You know, we could argue about whether or not you need more or less protein. I don't necessarily think everyone needs one gram per pound of body weight. Some people feel kind of poisoned, like overwhelmed when they eat that much.

    9. DW

      Yeah.

    10. AH

      I think you have to sense for yourself what, what you want and what you need. Um, but in any event, people started realizing, "Oh, th-this is interesting. If I'm gonna work out, then, you know, uh, caffeine before that seems to help." And then gradually, now the creatine craze. It's funny, c-creatine was something that was popular in gyms in the-- it-- when I was like 16 years old, 17 years old. And then, oh, there are all these cognitive benefits, et cetera. So it came in with the fitness.

    11. DW

      Mm-hmm.

    12. AH

      Vitamin D came in with COVID. Um, and then with COVID, pe-people were very actively debating whether or not you could trust the government to give you what you needed to make you healthy. And I think whether you were pro-vaccine, vaccine skeptical, or anti-vax, what became very clear is everyone realized, some bell went off, we are all responsible for our own health.

    13. DW

      Totally. I think-

    14. AH

      It-

    15. DW

      ... COVID reminded people of their own mortality.

    16. AH

      Mm-hmm.

    17. DW

      And they realized just because like they go to a doctor for an annual physical does not mean they're healthy or protected or safe.

    18. AH

      Mm-hmm. Mm-hmm. A lot of the mental health issues that we saw during the lockdowns were disruption in circadian biology. I know people were indoors more. There was more drinking. There was a bunch of other issues, but I'll just say there's a really beautiful study with more th- more than 80,000 subjects out of the UK that shows, and this is a recent study, that shows that the brighter people's days are and the darker their nights, the healthier they are mentally. And this is especially true for people with OCD, anxiety, um, mania, schizophrenia, major depression. I mean, basically every psychiatric challenge is made worse by dim days and bright nights. And so what we saw during COVID was people were just drifting in a circadian sense. It, it was as if we had put people into a cave and done the cave experiment, and then there was COVID, right? And then there's all the vaccine stuff, which, you know, frankly isn't my domain. But it-It was so important to me to give people tools to be able to control their circadian biology, um, momentary anxiety with things like long exhale breathing, which just simply, uh, reduces heart rate. We know through something called respiratory sinus arrhythmia, involves the vagus nerve. You know, the vagus is s- is sending a bunch of sensory information about the body to the brain, but then a percentage of the vagus is descending. It's motor. It controls the heart rate. So when you exhale deliberately, you slow your heart rate down. So this is the-- You don't need to do breathwork. You just, if you wanna calm down, you, you do a long exhale. And so these little simple things for which there's mechanistic science to support them, that w- was really what we started putting out into the world. So I think that's what happened, and then, you know, there we were, you know, in my... I was literally in a closet with my bulldog and my producer and a microphone and just like talking out to the world and things just-- So people became really strong advocates for themselves, and they're like, "Oh, shit, I need to go figure out how, how to take care of

  3. 7:02 – 13:05

    MAHA's Role in the Health Movement

    1. AH

      myself."

    2. DW

      What do you make of kind of MAHA's role in this broader health awakening? What do you think the effects will be-

    3. AH

      Mm-hmm

    4. DW

      ...on our health?

    5. AH

      Well, I very deliberately not join a MAHA panel to maintain the flexibility that I want to say what I believe. Um, a good example would be, I think that some of the things they're doing are directionally right, trying to improve the food supply, um, get people embracing healthy behaviors. Or these, these are very much like Huber- Huberman Lab things, right?

    6. DW

      Mm-hmm.

    7. AH

      At the same time, I, for instance, think that the mRNA vaccines for cancer are a transformative, incredible life-saving technology.

    8. DW

      And a lot of funding has been cut.

    9. AH

      Yeah, I think that-- Well, it's interesting. So, um, the, the funding for, um, mRNA vaccines for respiratory illnesses has been cut. I was told, and I don't know if this is true, that the funding for mRNA vaccines for cancers was not cut, but there was some very tricky messaging around that at that time. So much so that, you know, 'cause I'd gone on Bill Maher, and I said, "It's foolish to cut this funding for the, the cancer research." But, um, I got a call from Washington and said, "We didn't cut the, the money for that. We cut the money for the other thing." And I said, "Okay." So it's like it's-- But the messaging has been deliberately broad on both sides.

    10. DW

      Mm-hmm.

    11. AH

      So, um, the challenge has been that because we now, let's just call a duck a duck, we've got right-wing media, and we've got left-wing media, and then we've got a few people in the middle like Bill Maher who are kinda like, you know, just calling shots.

    12. DW

      I see you went on Bill Maher.

    13. AH

      Yeah.

    14. DW

      It was a really good episode.

    15. AH

      Yeah. So thank you. Um, but for the most part, the, the way that clicks and ad revenue, et cetera, is, is working for these news outlets is, is don't say anything positive about the other side-

    16. DW

      Mm-hmm

    17. AH

      ...even if there's something that they're do- that's favorable, and really paint with a broad brush, and both sides are really guilty of that. The left has been, um, not supportive of the, the moves that I think are directionally correct, uh, which are improving the food supply, getting people more active, et cetera, because th-their criticism is, um, that's rearranging deck chairs on the Titanic. That's their, their criticism. My stance is anything that gets people moving in the direction of their own health, uh, doing things that are proactive for their own health, circadian health, reducing anxiety, improving sleep, eating cleaner food, more movement, is fantastic. Is it the only thing I'd like to see done? No. Um, but it certainly is important, and so I'll be supportive of the things I think are, are good, and I'm gon- going to criticize the, the things that I, I think are, are not good, and I'm just gonna continue to do that. It means I have fewer friends and more enemies.

    18. DW

      [chuckles]

    19. AH

      But I'm kinda used to that by now. Um, I've had-

    20. DW

      You're a personality on the internet.

    21. AH

      I often get, get referred to as a, as a influencer or a health podcaster. They seem to have forgotten the, the, my science training, but I, but I get it. I understand why... I unders- Now after five years, I really understand w- how media works.

    22. DW

      Yeah.

    23. AH

      In part because podcast channels have become bigger than a lot of the, at least in the health domain, than the more traditional, uh, houses. So I think, um, w- I've been called a MAHA podcaster. I don't know how they got to that because I, I don't ever recall, um-

    24. DW

      You also predate MAHA.

    25. AH

      Yeah. Yeah. They took it from me. No, I'm kidding. The, uh, [chuckles] the, um... Yeah, thank you. Um, the, I did make a comment about the food guidelines. I said that I thought it was directionally right but that I would've liked to see more, uh, vegetables and fiber, some, you know, low sugar fermented foods, and it's so interesting to see how that w- would get attacked. If w- if I see something like that that I said getting attacked, then I think, wow, like they must be so poorly paid or just so desperate to write something for whatever, 500 bucks or 1,000 bucks to make rent, that like, that to spend that, to spend time on that. I, I do think that there's been a real, um, just like a, a real drop in standards of what we consider news.

    26. DW

      Okay.

    27. AH

      And, and that makes me sad, frankly. It's kind of, it, it saddens me because it, it cheapens the entire health space. And so it's very easy to point at how, you know, health influencers and biohackers have, have contaminated the space. But I think, I actually think that traditional media is, is more to blame because are we really arguing about whether or not the food guidelines are, are, are perfect? They, they were cast as, oh, you know, now they're promoting a lot of meat.

    28. DW

      Mm.

    29. AH

      No, that's not what it was. If you looked, if you act- if you actually read it, the servings of grains and fruits and vegetables wereAt least as high as what they were recommending for me. So it's, it's just silly. It's just silly. It's, it's like red shirts... It's like red shirts, blue shirts, kind of, um, like a playground-

    30. DW

      Totally. Partisanship plays-

  4. 13:05 – 18:37

    GLP-1: Nearly One in Seven Americans

    1. DW

      Let's talk about peptides.

    2. AH

      Yeah.

    3. DW

      Um, nearly one in seven Americans is taking a GLP-1 drug. 20% have tried them. These numbers continue to rise. You've talked about, um, retatrutide, um, a GLP in Lilly's pipeline. What do you think the future looks like as it regards to kind of GLPs? And then let's talk about other peptides after that.

    4. AH

      Yeah. Um, I'm hoping this analogy works. You know, when I was growing up, if you could afford a nice car, you had a nice car. Otherwise, there were a lot of kinda junky cars on the road.

    5. DW

      Mm-hmm.

    6. AH

      Um, and then this thing called credit came along, where everyone could have a nice car or at least a nice car. So you don't really see the, like, run-down cars in a lot... You know, you do some places, but you really don't. Um, I, I see the GLPs the same way. It used to be that being really fit at a certain age, um, reflected the fact that you did a lot of exercise, and I think that the GLPs make it such that people can, um, be a healthy weight without having to exercise. We know, however, that people should resistance train in particular to offset the muscle loss. But retatrutide went through phase three at Lilly. People can lose up to a third of their body weight in a pretty short amount of time with some degree of muscle sparing. So this is also called GLP-3. It also seems to bypass some of the side effects that some of the previous GLPs, um, created, although no drug is perfect, of course. But the real reason retatrutide is interesting to me is that already people have realized that they can get much lower cost, um, and/or take lower doses of GLP drugs by going through compounding pharmacies. Lilly is working very hard to make sure that compounding pharmacies do not sell retatrutide. Compounding pharmacies and gray market sources already sell retatrutide. Many people are already taking it. It's not legal, but it's not necessarily enforced, and I'm not necessarily, uh, suggesting people do. But I think it's going to change society where in theory you could eradicate obesity, in theory. Um-

    7. DW

      Five years from now, what, what percent of Americans do you think are on GLPs?

    8. AH

      Well, I like to think that there's still some people who, because they've exercised good habits up until now, don't need them. I, I don't know why I like that, but I, I suppose if you can get away without having to take a drug and get the same result, that's better. Um, I'm guessing that more than half, especially, um, people who come from families or communities where there's a lot of obesity are, are gonna be taking them, probably taking them at lower dosages than are prescribed. Um, and I, I don't think that you can control the compounding pharmacies and gray market, mostly because, and I could be wrong here, so I wanna be careful, but I'm not aware of, of a major adverse event. You know, it's a little bit the same way that steroids were discussed in the '80s and '90s, but people were dying, going into rages. They were coming up with als- You know, they're having a lot of problems. I'm not aware of anyone dying from taking BPC 157. So there's a lot more room for experimentation. I'm not suggesting people do that, but the margins for error seem to be greater.

    9. DW

      Yeah.

    10. AH

      Yeah.

    11. DW

      I mean, my understanding is it's not the, like, uh, uh, the compounded drugs are probably generally safe, but it's the fear of contamination or-

    12. AH

      Yeah

    13. DW

      ... a meningitis ep- outbreak or whatever.

    14. AH

      Mm-hmm.

    15. DW

      It's happened in the past-

    16. AH

      Mm-hmm

    17. DW

      ... um, with compounding pharmacies being just less regulated-

    18. AH

      Yeah

    19. DW

      ... than traditional drug manufacturing.

    20. AH

      Yeah. I think it's really interesting, too, because I, as I watch this space, this peptide space emerge, which has mainly been, been around the GLPs, right, and BPC 157 body protection compound, which may or may not accelerate healing. In animal models, it's very clear that it can improve cartilage growth, nerve re-regrowth, as well as, uh, vascular growth, which is a little bit worrisome if you have a tumor. You don't wanna vascularize the tumor. No one has the right control experiment in themselves 'cause they'll say, "Oh, I injected my shoulder and it, I healed so much more quickly." But it goes systemically, so you can't, like, compare the two shoulders, and so... But no one wants to be in the control group.

    21. DW

      [chuckles]

    22. AH

      And the people are just assuming it's BPC. They're taking it. I mean, I think we probably would've heard of an adverse event by now, but who knows? Maybe some- something will pop up. I think that, um, when it comes to the GLPs in particular, there was a lot of debate for a while. The exercise fitness community were saying, "Oh, you know, you don't wanna take a drug. You just need to eat right and exercise." I disagree. I think that some people have accumulated so much adipose tissue that it's modified their metabolism and even, perhaps even brain circuitry and appetite, that it, it's really, really helps them. Um, and obviously behaviors and these drugs are gonna be the best combination, um, or just the behaviors if you can get away with them. I've never taken a GLP, so I can't talk about the experience of it. I have tried various peptides. I've tried BPC. I don't know if it helped me or not. I didn't have an injury. I didn't notice that I recovered any more quickly, uh, from exercise. I've tried pinealin as a sleep, uh, peptide. It gave me three hours a night of REM sleep, which was pretty awesome. Um, very little human data. So now I just-

    23. DW

      Are you continuing that?

    24. AH

      No, I just take AGZ, and that's the truth. I-

    25. DW

      So you want more data?

    26. AH

      I'm a little scared about taking something that in animal models has been shown to both improve the function of, but maybe also the proliferation of pinealocytes, which produce melatonin-

    27. DW

      Mm-hmm

    28. AH

      ...or the, they and other cells in the, in the pineal. Um, because anytime you're stimulating cell growth, you could, it could start going awry and maybe even get a tumor or something like that.

  5. 18:37 – 25:16

    The Non-GLP Peptide Craze

    1. DW

      Maybe you can just sp- kind of speak more broadly about the non-GLP peptide craze.

    2. AH

      Mm-hmm.

    3. DW

      There's been-

    4. AH

      Mm-hmm

    5. DW

      ...a lot of kind of black market activity around Chinese peptides.

    6. AH

      Yes.

    7. DW

      Um-

    8. AH

      I love how that term has come about. Don't-

    9. DW

      There's look maxing. Like people-- What is a peptide?

    10. AH

      Sure.

    11. DW

      What do you recommend?

    12. AH

      Okay.

    13. DW

      What should people avoid?

    14. AH

      Sure. Um, short course, a peptide is, is just a short chain of amino acids make up a protein. Insulin's a peptide. Um, all the things we're talking about up until now are peptides. So the phrase peptides has been kind of co-opted, um, to mean a certain sort of a clique of peptides. Just like the word steroids, in people's minds, they think bodybuilders, but you know, a ster- estrogen is a steroid hormone.

    15. DW

      Mm-hmm.

    16. AH

      People are always shocked to hear that. You know, so if you take estrogen, you're on steroids. Okay, but we know what people are saying when they say on steroids. So they're androgenic steroids, they're estrogenic steroids, there's corticosteroid. Okay. Just in the same way, there are peptides that are to reduce hunger and appetite, the GLPs. Uh, Retatrutide being the newest generation, one soon to be released through Lilly, um, but already out on the market. From gray market sources are these sources that are sold all over the internet that are American or Canadian or whatever, and they list them as, uh, for research purposes only, not for human use. But they're selling them knowing that people are taking them. I mean, who's doing research on these peptides at home, right? This is not your-- unless you're my lab down the road or someone else's lab, like of course people are taking these. Um, they tend to be n- the gray market sources for research purposes only, not for human use, tend to be 99% purity, which means they've been cleaned of most things, except I do worry a bit about repeated injection of a substance that contains 1%, say, lipopolysaccharide, which can cause inflammation. So maybe not in one injection, but maybe repeatedly over time, as well as other contaminants. Black market sources, and when you hear Chinese peptides, are companies online. We don't know that it's all coming from China, by the way. They sort of get, get hit the hardest in this. But people refer to Chinese and black market peptides as people are going online, buying Retatrutide, and you have no idea if it's Retatrutide. In contrast to the gray market sources, where they might not be the cleanest, but you kn- we-- they give you a data sheet that says, "This was tested," and if it says Retatrutide, if it says BPC 157, that's what's actually in the vial and only that. Okay, so that's an important distinction. Compounding pharmacies have been compounding all sorts of things, selling drugs more cheaply than, um, drug companies. Um, they are controversial for that reason. We could talk about that. But other peptides that are interesting. [clears throat] Excuse me. BPC 157 for tissue repair, reducing inflammation, seems to have very, very high LD50. No one's really discovered it, and people have been injecting enormously high, um, amounts of this. I've not heard of an adverse event. I don't recommend doing that, however, because you don't want to vascularize a little tumor you might have on your liver or in your brain.

    17. DW

      Mm-hmm.

    18. AH

      Um, but maybe for short-term use to treat an injury, if that's within your margins of risk, you know, I mean, that's up to you. Um, ideally, you'd get it from a compounding pharmacy if you can, or from one of these gray markets, uh, sources before you would go to a black market source. Injectable l- injecting locally seems to be better than taking it systemically. Taking the oral forms, it's unclear how much of that BPC-157 gets into your bodily tissues. Pinealin, as I mentioned, for, for sleep, has become very popular. There's a whole category of what are called growth hormone secretagogues, which are very popular. Uh, Tesamorelin, Ipamorelin, Sermorelin, MK-677, these all stimulate the pituitary to release growth hormone, but they themselves are not growth hormone. They will increase the amount of deep sleep that you get at night. Typically, you'll take these 30 minutes before sleep, ideally not having eaten anything in the previous few hours. [clears throat] Will increase growth hormone and IGF-1. Some of those things I just mentioned are FDA-approved. So Sermorelin, for instance, I forget the exact indication, but, um, to increase height, for instance, or, uh, tissue repair after, um, after surgery, some, you know, increasing growth hormone can be beneficial. Some people will just take growth hormone, but growth hormone's very expensive, so Somatotropin, Omnitrope. Um, so that's what these peptides w- are very commonly used. Those have been researched, so assuming the sourcing is clean, we have a lot of human data on the ones I just described, as opposed to Pinealin and BPC 157, where you have basically no human data. So there are human data on things like Melanotan, which makes people tan from the inside, raises energy and libido dramatically, fat loss dramatically.

    19. DW

      Do we put that in the looks maxing category?

    20. AH

      I don't know. I... Or energy maxing or something. Yeah, it's kind of interesting. I mean, it, it-- I mean, um, there, there's a lot about... So Melanotan, um, and some similar peptides have been st- have been FDA approved for, um, hyposexuality in women. I think the Vyleesi is the drug for women. Men take it too. I have to sayThose drugs, um, melanotan is very risky. Some of the, the skin color changes, um, the kind of oranging of the skin can be permanent. So you have to-- This isn't the kind of thing you do to like go on vacation, right? [chuckles] Um, this is-- 'cause it, it might have more permanent effects.

    21. DW

      Not the pre-wedding.

    22. AH

      Right. And, and there's-

    23. DW

      Like, look

    24. AH

      ... a risk for men of priapism, which i- but you know, the, the last erection you may ever have. It might last eight hours, but that might be the last one you ever... It can cause damage to the nerves and penile tissue. So people, you know, people hear like erection, fat loss, energy, tan, like, "Oh, great." You know, and you think, uh, you gotta be real careful with these things with-- they, they do get abused. Um, but I just mention these, th- these things and, and, and the melanotan whole pathway is super interesting because it raises dopamine. Dopamine and pigmentation are linked through an enzyme called tyrosinase. Not to get technical here, but some animals are, um, are, uh, look like they're albino in the winter except they have dark eyes like an arctic fox, and then the summer, sunlight comes, hits this pathway, increases dopamine, pigments the fur-

    25. DW

      Hmm

    26. AH

      ... and they breed. So th- there's a relationship between sunlight, dopamine, fecundity, and these kinds of things. It's pretty interesting, right? The, um...

  6. 25:16 – 31:40

    Rogue Experiments and Low-Dose GLP

    1. AH

      So, um, people are taking these things, and they're getting them either through black market, which I don't recommend, gray market, which is risky, or compounding pharmacies, so now we're sort of ascending levels of stringency, and then you get to pharma sells it. You can buy sermorelin from one of the drug companies. You can buy retatrutide soon from Lilly. The cost tends to be, you know, three to 10 times higher. The dosage recommendations tend to be higher. People have figured out doing their own kind of rogue experiments that you can get by taking much lower doses of things. So I think one of the more interesting uses of GLPs that I'm hearing about mainly from people getting it from compounding pharmacy and gray market sources is that you can get by with taking much lower doses. Some people are using it for reducing alcohol craving-

    2. DW

      Mm-hmm

    3. AH

      ... for reducing just cognitive noise more generally, which I think is pretty interesting. Um, and this is probably a good opportunity to just mention things for focus since we were gonna talk about that. You know, if, if you ever have in your copious amounts of spare time, which I'm sure you never have, um, 'cause no one seems to have it anymore, [clears throat] there's some pretty interesting conversations that have taken place on X about drugs for focus because all the, all the, the other hackers, um, like to focus and program, um, and work. And so we all have heard of modafinil used to treat excess- excessive daytime sleepiness. It may have a slight cognitive enhancing effect, but it's mostly a focusing thing. You can-- it increases energy when you have poor sleep.

    4. DW

      Mm-hmm.

    5. AH

      Um, it was designed to treat narcolepsy and other things. There's a drug-

    6. DW

      Is it better than Adderall?

    7. AH

      Different than Adderall because Adderall is more of an amphetamine type stimulant. Um, a very interesting paper came out recently from WashU showing that Adderall, it wasn't really Adderall specifically, but Ritalin and other stimulants seem to improve focus about as well as a good night's sleep.

    8. DW

      Hmm.

    9. AH

      But a lot of people aren't getting the good night's sleep they need. It's-

    10. DW

      Because of it also.

    11. AH

      Right. Exactly. And it's not increasing focus per se. It's increasing alertness, which allows you to allocate your focus. This is... The-- as far as I know, there are no drugs to increase focus per se. Now, the two things are tethered enough. You know, you need alertness to-- Alertness gates focus. Um, sleep gates alertness, unless you take a drug like Adderall or modafinil. There's a very interesting drug that I think is gonna become far more popular soon, which is already FDA approved called Sunosi, S-U-N-O-S-I, which is, um, approved for excessive daytime sleepiness. Did very well in a trial for ADHD, and it's a little bit of a dirtier drug in the sense that it doesn't just hit the dopamine and norepinephrine pathways that some of the other drugs I mentioned do. It also hits serotonin a little bit. Seems to have a much gentler arc of, uh, of alertness and focus. I confess I've tried it. Um, I'm-- it was a bit too much, and I was like, "I don't... I think I'm gonna stick with caffeine for now." People will take wellbutrin, the anti- the atypical antidepressant-

    12. DW

      Mm-hmm

    13. AH

      ... at low dosages to increase epinephrine, dopamine a little bit for focus. I mean, people are doing this all the time. Nicotine. So there's a lot of stimulant use right now for focus. So I do think that if there is a peptide that can be taken safely that can reduce the amount of noise in the system and allow people to be, uh, more focused and allocate their attention in a more deliberate way without having to take stimulants, I think that would be fantastic. I think there's an excessive amount of stimulant use, and this is coming from somebody who drinks a lot of caffeine and, and frankly would love to have a drug that could increase focus. But you always pay the piper somehow, either in sleep or in cardiac challenges. I mean, you, you don't wanna stimulate the sympathetic nervous system so much for so often. It can probably shorten your life.

    14. DW

      What does a proactive approach to health look like maybe five years from now, and what technology do you think needs to be built to enable that? M- maybe put another way, like you-- it feels like you've covered every single health topic on your podcast.

    15. AH

      Still going.

    16. DW

      What do you think you're gonna be covering in kind of '26, '27, '28?

    17. AH

      Yeah. We need to do autoimmune, cancer. We, we've got a bunch of things to go. But yeah, I, I mean, maybe this is a good opportunity to kind of weave in reading and writing to biology. So reading, I mean, people are wearing sleep sensors.

    18. DW

      Yeah.

    19. AH

      This is, like, commonly done now, right? Um, but you can't write to the sleep system yet.

    20. DW

      Mm-hmm.

    21. AH

      If you-- I think in five years we're gonna look back and we're gonna be like, "Can you believe it? We were, like, cooling the room to try and fall asleep." I think we'll still have cooling mattresses, but, like, it's gonna be so crazy 'cause there should be a way that you could just put like a l- a small, um-Like you can cool the core of the body more efficiently through the palms and the soles of the feet. Um, there's reasons for this. The, the vasculature there actually lacks capillaries, so you can pass... You're not really cooling the blood, um, directly, but you're essentially, um, dumping more heat. This is cool technology from Stanford. I mean, I think someday not long from now, you'll go to sleep with a little, little thing in your palm or on your, your feet, and your core body temperature will just drop.

    22. DW

      Yeah.

    23. AH

      You'll wear an eye mask that's moving your eyes back and forth, and within six minutes or less you'll be asleep. Um, when you wake up in the morning, you'll flip that thing on, it'll give you a burst of 10,000 lux light, and then you'll go outside. These are trivially straightforward technologies to build, but no one's really building them right now because we're like, "Oh, we'll just cool the whole room, and we'll, you know, and I'll, you know, look at a 10,000 lux, you know, thing over there while I..." It's, it's just, it's so easy to move these things to the body. So writing to our biology-

    24. DW

      Yeah

    25. AH

      ... around sleep is gonna be a big one. The read... The other forms of reading that I think are happening now that are soon gonna be writing as well, uh, well, I'd love to see not just real-time, um, glucose sensing. Love to see real-time cortisol sensing. Morning cortisol peak. Getting that, I, I mean, I can't overstate the importance of, for everyone, women, men, premenopausal, postmenopausal, pregnant, not pregnant, kids, you want a big morning cortisol pulse, and then you want that to trough in the late afternoon and stay low. You get that and you win 90% of the game. But we don't have real-time

  7. 31:40 – 44:39

    Real-Time Cortisol Sensing

    1. AH

      cortisol measures.

    2. DW

      Totally. People are, are working on these things. Like right now-

    3. AH

      Mm-hmm

    4. DW

      ... for our listeners-

    5. AH

      Mm-hmm

    6. DW

      ... there are continuous glucose monitors.

    7. AH

      Mm-hmm.

    8. DW

      And they put kind of a little piece of like dental floss under your skin that monitors glucose-

    9. AH

      Mm-hmm

    10. DW

      ... in real time, normally for diabetics.

    11. AH

      Mm-hmm.

    12. DW

      But people are working on kind of multi-biomarker-

    13. AH

      Mm-hmm

    14. DW

      ... sensors-

    15. AH

      Mm-hmm

    16. DW

      ... that could tell cortisol or a variety of things.

    17. AH

      Yeah. I think that, you know, real-time cortisol would be very interesting. Of course, you'll get little blips of cortisol as you stress throughout the day, and the real question is can you bring your cortisol back down afterwards?

    18. DW

      Mm-hmm.

    19. AH

      These blips in cortisol aren't a problem if they come back down. Sometimes if that whole curve gets shifted to the right a bit, there's actually worse cancer outcomes, reduced longevity. There are a lot of reasons to want that cortisol spike really big and then have it trough into the afternoon. Um, so that's one that I'd love to see. Um, and then once you see that, you know, if at 5:00 or 6:00 PM your cortisol's riding high, you know, you'd love to be... have a way that you could dial it down, and you could do that through conventional methods like long exhale breathing or short meditation, maybe eating some starchy carbohydrates. People forget that cortisol's main job is to deploy energy in the body.

    20. DW

      Mm-hmm.

    21. AH

      This is why it gives you a glucose bump. And there's a reason why starchy foods we call comfort foods, is that it provides this sort of energy that allows cortisol to come down. This is why a lot of people who follow very low starch diets oftentimes feel really stressed or at the edge of stress. I can't sleep well unless I've had enough starches during the day.

    22. DW

      Interesting.

    23. AH

      Now, if I haven't done any exercise or anything, I don't really need many starches. But if you're weight training, you're busy, you're using your mind, you're moving about, and then, you know, it's 11:00 at night and you're fried and you fall asleep, and then you're up at 3:00 in the morning, I'm willing to bet that had you had maybe a bowl of rice with dinner [chuckles] you might actually sleep a lot better. People don't talk about this, especially in the context of ketogenic diets, which sure, you'll have more energy, but it can really mess up your sleep.

    24. DW

      You heard it here. You can have carbs at dinner.

    25. AH

      Do it.

    26. DW

      I love that.

    27. AH

      Please do it. Please. In fact, if you're gonna have carbohydrates at any time, should be within a couple hours after resistance training or, you know, maybe three, four hours before sleep, maybe even a couple hours before sleep. It... People who reduce their carbohydrate intake too much are... You're not going to sleep well. You're just not. Um, not nearly as well as you could if you had some moderate carb intake. Um, obviously you wanna try not to eat too close to bedtime-

    28. DW

      Yeah

    29. AH

      ... and so forth. So I think that the, the... I do think that the whole peptide thing is, you know, the, the horse is out of the stable. I think in five years, you and I are gonna have a little cocktail. It's gonna be one injection or one pill, and it's gonna be a little bit of pineal in at night combined with something else. It's gonna be in the morning something. Whatever it is that you need to, um, not you specifically, of course, but whatever I need to, you know, ramp up my dopaminergic system a little bit to, um, make sure that I'm getting enough micronutrients that, uh, maybe I'm gonna put a little clofo in there to protect me against Alzheimer's. I mean, I think all of that stuff is, is gonna be commonplace. The same way that people are not afraid of vitamin D or they're taking some creatine or magnesium. People are taking... Magnesium's kind of the next wave of, of accepted supplements, I think, that feel safe enough for most, not all people, but safe enough. I think, um, most everyone is going to be doing that, and I think the cost is going to be low enough that that statement, most everyone, is a real statement.

    30. DW

      I love the read versus write breakdown. I think on the read side, it feels very clear where the world is going. Like, ChatGPT is already an incredible doctor.

  8. 44:39 – 50:36

    The Pet Octopus and AI Communication

    1. DW

      Last question. You have a pet octopus?

    2. AH

      I do.

    3. DW

      That is unusual.

    4. AH

      Yeah.

    5. DW

      Tell us about him or her. [chuckles]

    6. AH

      Van Gogh. Um-

    7. DW

      Van Gogh.

    8. AH

      Van Gogh. Yeah, it's a starry night octopus, hence Van Gogh. And then it got even more eerie because Van Gogh lost one tentacle in the, in the fan, so it was like a... Um, so when my lab was in San Diego, before I moved to Stanford, I worked on a different cephalopod called cuttlefish, which are like little underwater monkeys. They're incredibly intelligent. They're known for being great camouflagers. There's also this twist in their, uh, sociobiology where the males will, um, camouflage as females, infiltrate, and then mate with the females. Um, so I was studying their vision. They're very interesting because they can see in panorama, and they're very placid. But then when they wanna hunt, their eyes translocate to the front and they generate depth perception, stereopsis to, to hunt. And I was very interested in whether or not they had two visual systems and, uh, I'm very interested in depth perception and, and prey capture and how that relates to bodily states. Just to weave this into what we were talking about earlier, um, when your eyes are focused on a single point, your levels of, of arousal and e-energy, attention go up. When your eyes are sort of di- when your gaze is dilated, like you're viewing the corners of the room and the ceiling and the floor, that tends to make, put us into a calmer state. Some animals only exist in one or the other. We, we are unique that we can switch back and forth. Some other animals can. But I was studying that in cuttlefish. When I moved to my current home, I converted an art gallery into a living space. I put a gym. I put a place to work downstairs where there's no Wi-Fi. I don't bring my phone down there. That's where I prepare for podcasts. I do s- drawing. I'm doing some illustrations these days for my book and a few other things. And then it's like, oh, I've always loved aquaria. I'm gonna put a freshwater discus tank, and I put a huge fresh- freshwater discus tank. I was like, "You know, I think I need cephalopods again." So I got an octopus. I got a starry night octopus. And here's what I'm trying to do with the octopus. This has everything to do with AI. I'm trying to get the octopus to report to me what it's thinking, because I do think they're very intelligent, and we say, "Oh, they're like aliens. They're so intelligent." But, uh, we get the camouflage. They're very interactive. Um, but an underwater iPad and the appropriate use of, of touchscreen and AI, I'm hoping will allow this or another octopus to communicate something about what it's thinking. Okay, so how would you do this, right? So y- you can't apply a typical large language model. So you have to do it based on the coloration patterns, on the camouflage patterns. So it turns out AI can actually learn a lot by correlating the behaviors of an octopus with its camouflage patterns.

    9. DW

      Mm-hmm.

    10. AH

      The problem has always been that you have to do that in real time as the animal's swimming around and hunting and doing various things. So the challenge now is to get it to interact with stimuli that will give enough information so that this model, I don't know what we call it, I, uh, we don't have... Someone more clever than I can come up with something that's not LLM. I don't know. It's something else, uh, something related to camouflage patterns. Could start revealing that certain camouflage patterns relate to certain behaviors which relate to, um, certain nuance in the behaviors, and then it could start teaching itself. Um, and then the idea would be that the A- AI would present something to Van Gogh or another octopus, I've got more on the way, that, um, would start to influence behavior. There could be, uh, not just conversations between octopi, but where maybe I could speak. It would, it would, uh, translate that into octopus, [chuckles] whatever you call it. And then we could communicate. And here's the reason for doing this, okay? So there's this idea that other animals have all this intelligence. Normally, we measure that through behavior or through some, you know, highly specialized aspect of their nervous system or body, like barn owls or, you know, they all do these fantastic feats. Or y- what you find, and I don't like it, for instance, when I see, oh, this guy taught an octopus how to use a piano. I saw that. That's not interesting. Actually, all that tells you, it, that tells you more about how hard humans are willing to work to train a different organism to do something pretty rudimentary compared to what humans can do. Tells you everything about humans' obsession with teaching other animals to be more human. I'm interested in what the octopus understands about the world and can communicate that to me because I don't know that stuff. I can learn to play a piano. Why would I wanna teach an octopus to play a piano? That's silly.

    11. DW

      That's fascinating.

    12. AH

      So-

    13. DW

      I think you need a whole podcast outlining your experience.

    14. AH

      Yeah. Well, maybe this is what happens when we run out of topics to put on the, on the HLP.

    15. DW

      [chuckles]

    16. AH

      But, and I'm probably not thinking about this as cleanly as I, I could or should, but it was... I have to say, just in kind of, you know, wrapping this, you know, monologue, it, y- you get to the point doing public-facing health information where you can kind of feel the saturation point, and we need more technologies and tools, and I think that's great, and I really am excited for what's coming. But the, at some point, the conversations become, um, clear that we need more, right? And then you think about this whole vast landscape of animal intelligence, and people have placed this thing on the oc- on the cephalopods, like they're really smart. They know. I mean, they might be idiots for all we know, just, uh, dazzling us with colors. I don't think they're idiots. I think that they are accessing, um, a certain perceptual landscape, and they're thinking hard about what's there based on things I've observed and others have observed. But we really need to figure out a way to let them tell us what they're thinking.

    17. DW

      Amazing. Andrew Huberman, thank you for coming on the a16z Show.

    18. AH

      Thanks for having me here.

Episode duration: 50:50

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