Essentials: Science of Stress, Testosterone, Aggression & Motivation | Dr. Robert Sapolsky

0:00Welcome to the Huberman Lab podcast where we discuss science and science -based tools for everyday life.

0:09I'm Andrew Huberman and I'm a professor of neurobiology and Ophthalmology at Stanford School of Medicine. Today, I have the pleasure of introducing Dr. Robert Sapolsky. Thank you so much Robert for joining us today. Well, this is glad to be here. I want to return to a topic that Near and dear to your heart, which is stress. What is the difference between short and long -term stress in terms of their Benefits and their drawback? How should we conceptualize stress? Basically, you started two graphs that won the draw. The first one is just all sorts of beneficial effects of stress, short term, and then once we get into the chronicities, just downhill from there, the sorts of chronic stress Raiders that most people deal with are just undeniably in the chronic range, like having spent the last 20 years daily traffic jams were abusive boss sort of something to think.

1:07The other curve that's sort of perpendicular to this is dealing with the fact that sometimes stress is a great thing. Like our goal is not to cure people of stress and because it's a right kind. We love it. We pay good money to be stressed that way. It's scary movie or roller coaster ride. What you want to see is when it's the right amount of stress, it's what we call stimulation. One thing that's really striking to me is how that physiologically the stress response looks so much like the excitement response to a positive event. But is there anything else that we know about the biology that reveals to us?

1:54What really creates this thing we call valence that an experience can be terrible or feel awful or it can feel wonderful depending on this somewhat subjective feature we call valence. On a really mechanical level, if you're in a circumstance that is requiring that your heart races and your breathing is fast and you're using your muscles and some such thing, you're going to be having roughly the same brain activation profile, whether this is for something wonderful or something terrible, with the one exception being that if the amygdala is part of the activation, this is something that's going to be counting as adverse.

2:38The amygdala in some ways is kind of the check point as to whether we're talking about excitement or terror. Let's use the amygdala as a transition point to another topic that you've spent many years working on and thinking about, which is testosterone and other sex steroid hormones. How should we think about the role of testosterone in the amygdala given that the engagement of the amygdala is fundamental in this transition point between a exhilarating positive response and a negative stressful response? Or maybe just broadly, how should we think about testosterone and its effects on the brain?

3:20Basically, almost everybody out there has completely wrong ideas to what testosterone does, which is testosterone makes your aggressive males and virtually every species out there of more testosterone and a more aggressive. And the reality is, testosterone does not cause aggression. And you can see this, but dangerally and in the amygdala, it lowers the threshold for the sort of things that would normally provoke you into the progressive so that it happens more easily. It makes systems that are already turned on, turn on the louder rather than turning on the aggressive music or something. It's not creating aggression, it's just uping the volume of whatever aggression is over there.

4:08And in terms of status and the relationship between individuals, either non -human primates or humans, can we say that relative levels of testosterone between individuals is correlated to status within the hierarchy? Yes, like you go back, whatever number of decades, the end of chronology texts, and they were choose totally reliable findings in there, which is higher levels of testosterone, predict higher levels of aggression in humans and other animals, higher levels of testosterone, predict higher levels of sexual activity. And the correlation is there, and when you look closely, we could cause an effect stuff, sexual behavior raises testosterone levels, aggression raises testosterone levels.

4:56Your levels beforehand are barely predicted what's going to happen. So with a response, rather than a cause, it's a great footnote. If you have the right type of willing to die in the trenches devotion, sort of think watching your favorite team play a sport will raise your testosterone levels as you sit there with the pitaterships in your armchair. So it's not the physicality of aggression, it's the psychological training of it. So yeah, testosterone is not causing that. And the great way to appreciate that is you do with a subtraction study, you remove the testes, and as I said before, levels of sexual behavior goes down.

5:43Good. We've just shown that testosterone is somewhat how caused is. Critically, they go down, but not down to zero, whether you are a rat or a monkey or a human, whatever, and what predicts how much residual sexual behaviors there, how much sexual behavior there was before castration. What that's telling you is by then that's behavior that's being carried by social learning and context, rather than by the hormone, exact same thing with aggression drops after castration doesn't go to zero. The more prior history of it, the more it just keeps constant along on its own eating without testosterone.

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9:12Again, that's drinkelement .com slash Huberman lab to claim a free sample pack. As I've heard you talk about testosterone today and over the years, I start to get the impression that as the most misunderstood molecule in human health in the universe, it has, it's clearly doing something very powerful. It's shifting the way that certain neural circuits work, adjusting the gain on the amygdala as you described. Is there any truism about testosterone and its relationship to effort or its relationship to resilience? In a way that maybe will help me and other people think about how to think about testosterone.

9:57Maybe three separate, excuse to that. The first one is, I think it's a fair summary to think that when it comes to motivated, strong behaviors, what testosterone does is make you more of whatever you already are in that domain. Such a rehearsal, libido, aggressiveness, spontaneous aggression, reactive aggression, things of that sort. It's uping the volume of things that are already strongly there. The second way to think about it is, well, here's my favorite finding about testosterone. This was some wonderful work by a guy John Wienerfield, who's one of the best behavioral and ecranologists out there.

10:45About 20 years ago, he formulated what was called the challenge hypothesis of testosterone action. What does testosterone do? Testosterone is what you secrete when your status is being challenged. It makes it more likely that you'll do the behaviors needed to hold onto your status. That's totally boringly straightforward. If you're a bagoon, if somebody is challenging your high rank, the appropriate response in your board is going to be aggression. We've just gotten through the back towards testosterone and aggression again. Then you get to humans. Humans have lots of different ways of achieving or maintaining status.

11:28All you need to do is go to some fancy private schools, annual auction, and you will see all these half -drunk alpha males competing to see who could give the most money away as a show of conspicuous property that they have. It is setting like that. I haven't been able to take your examples at those times. Unfortunately, but that shows the flip side of it. If you have the species that hands out status in a very different sort of way, testosterone is going to boost that also. That generates a totally nutty prediction. Wow. Take people in a circumstance, say, playing an economic game where you get status by being trustworthy and being generous in your interactions with the game.

12:19If you give people testosterone, does that make them more generous? That's absolutely the case. Totally cool finding. If we have a societal problem with too much aggression, the first culprit to look at is not testosterone. The first to look at is that we hand out so much damn elevated status for aggression in so many circumstances. The third thing about subtleties of testosterone is that, okay, some subtler behavioural effects, you give testosterone to people and they become more confident. They become more self -confident. That's good. People pay to take all sorts of non -sensical self -help courses that will boost your self -esteem.

13:04That's a good thing. Unless testosterone makes you more confident that is inaccurate and you're more likely to barrel into wrong decisions. What's shown in economic gameplay is that testosterone by making you more confident makes you less cooperative. Because who needs to cooperate because I'm on top of this all on my own, testosterone makes people cocky and impulsive and that may be great in one setting. But if in the others, you're absolutely sure your army is better over on the other country in three days. So, hell, let's start World War One and you get a big surprise out of it. Testosterone, altering risk assessment beforehand probably played a big role in that kind of miscalculation.

13:52Super interesting. I always think about testosterone and dopamine being close cousins in the brain because of dopamine's salient role in creating this bias towards exterroseption. When somebody takes a drug with that increases dopamine or they're chocoblockful of dopamine, they tend with, I want to highlight 10 because this is I'm really generalizing here, but they tend to focus on outward goals, things beyond the boundaries of their skin. Testosterone seems to do a bit of the same. It tends to put us into a similar mode of perceiving the outside world in ways that we're asking questions like, how do I relate to this other of my species?

14:36How do I relate to these goals? Is there anything that we can do to better conceptualize the relationship between testosterone and dopamine and motivation? Well, I think it's got lots to do with sort of this massive revisionism about dopamine. Everyone who since the Pharaoh's got brought up being taught that dopamine is about pleasure and reward turns out it isn't. It's about anticipation of reward and it's about generating the motivation, the goal of directing behavior needed to go get that reward. And before you know it, you're using like elevated dopamine your entire life to motivate you to do whatever is going to get you like entry into heaven after life's kind of, you know, it's doing that sort of thing.

15:23So it's really about the motivation and what testosterone does, even an individual supernotic resident and why testosterone replacement is often a very helpful thing for aging males is it increases energy, it increases a sense of verinous of presence of alertness, it increases motivation. Testosterone within minutes increases glucose uptake into skeletal muscle, you're just more awake and alert and all of that and that has a lot to do with what dopamine does. And as one might predict then, getting just the right levels of testosterone infused into your bloodstream feels great to lab or out. They will never press to get infused into the range that optimizes dopamine release.

16:15So you're absolutely right, they're deeply intertwined. I want to ask about estrogen. You know, we don't hear as about estrogen as often. And yet estrogen has a very powerful effects on both the animal brain and on the human brain of males and females. Are there any general themes of estrogen that are that people should be aware of or that you think that are generally misunderstood? Is it really all about feelings and empathy and making us more sensitive? I sense not. No. If you had a choice in the matter between having a lot of estrogen, your bloodstream or not, go for having a lot of estrogen.

16:55It enhances cognition, it stimulates neurogenesis and the hippocampus, it increases glucose and oxygen delivery, it protects you from dementia, it decreases inflammatory oxidative damage to blood vessels, which is why it's good for protecting from cardiovascular disease and contrast it to testosterone, which is making every one of those things worse. Estrogen is one of the greatest predictors of protection from Alzheimer's disease all of that, but it needs to be physiological. Just keep going, keep continuing what your body has been doing for a long time, versus let the whole thing shut down and suddenly try to fire up the cold stoves at the bottom of the basin kind of thing and get that going, there you get utterly different outcomes.

17:47Fascinating. I guess it raises the question about testosterone replacement too, whether or not people should talk to their doctor before too long, men and women talk to your physicians before too long to avoid these, whatever is happening in these periods where there isn't sufficient testosterone and or estrogen, sounds like it could cause longer term problems even when therapies are introduced. I'd like to briefly return to stress. You described a study once about two rats, one running on a wheel voluntarily, one who's basically stuck in a running wheel and is forced to run anytime rat number one runs.

18:31So in one case, the rat is voluntarily exercising and in the other case, the rat is being forced to go to PE class, so to speak and seeing divergent effects on biology. What do you think about stress mitigation and what should we do as individuals and as families and as a culture to try and encourage people to mitigate their stress, but in ways that are not going to turn us into rat number two, where we're being forced to mitigate our own stress and therefore it becomes more stressful. And what you see is rat number one gets all the benefits of exercise. Rat number two gets all the downsides of severe stress with this same exact muscle expenditure and movements going on perfectly yoked.

19:18A great example that it's the interpretation of your head. Anything I should say here, I should preface with reasonably good at telling people what's going to happen if they don't manage their stress, but I'm terrible at actually like managing stress or advising how to manage it. I'm much better with the bad and the aspect of it, but some people have massive stress responses, others not at all in between, enjoy it, like what are the building blocks of what makes psychological stress stress. Then the first one is exactly what is brought up by that running study. Do you have a sense of control? A sense of control makes stressors less stressful related to that is a sense of predictability.

20:08And that's enormously protective and protective. Others outlet for frustration, you take a rat who's getting shocked and he can not on a bar of wood. A stressor is less stressful. Unfortunately, if you have a rat or primate or human and they're stressed, the ability to aggressively dump on somebody smaller and weaker also reduces the stress response and displacement aggression. In the fact that displacement regression reduces stress accounts for a huge percentage of earth's unhappiness. All those variables get social support as well. That's a good one, interpreting circumstances, being good news rather than bad.

20:53Hooray, so you've got this very simple sort of like take home recipe to go out and get as much control and as much predictability as many outlets and as much social support as possible. And you're going to do just fine and you go out and do that and that's a recipe for total disaster because there's much much more subtle than that. And that's why stress management techniques about control and predictability wind up being far worse than neutral. If you're preaching that to somebody homeless or somebody with terminal cancer or somebody who's a refugee, tell a neurotic middle class person that they have the psychological tools to turn hell into heaven.

21:37And there's some truth to that. Do the same thing to somebody who's going through a real hell. And that's just privileged, you know, heartless to mess to do that because that doesn't work. It's not simple. It takes a lot of work to do it right because you do it wrong and it may temporarily seem like a great thing. But when it turns out to be completely misplaced face, you're going to be feeling worse than before you started. I'd like to take a quick break and acknowledge our sponsor, AG1. AG1 is a vitamin mineral probiotic drink that also includes prebiotics and adaptogens. As somebody who's been involved in research science for almost three decades and in health and fitness for equally as long, I'm constantly looking for the best tools to improve my mental health, physical health, and performance.

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24:55Again, that's Davidprotein .com slash Huberman. These days, there's a lot of interest in using physical practices to mitigate stress, trying to get out of the ruminating. And to some extent, take control of neural circuits in the brain by using exercise and using breathing and hypnosis. What are your thoughts on more for lack of a better way to put it more head -centered, cognitive approaches to stress mitigation versus going at the core physiology. Cold showers now are even a thing to some extent. Just to get people's stress acclimated, voluntarily taking cold showers. Transadental meditation, mindfulness, exercise, prayer, reflecting on gratitude, all that sort of thing.

25:46Collectively, they work on the average. They work in terms of the lower heart rate and cholesterol levels and have all sorts of good outcomes. But they come provisos. One is exactly the caveat that comes out of the running -neal study is it doesn't matter how many of your friends swear by this stress management technique. If doing it makes you want to screen your head off after 10 seconds, that's not the one that's going to work for you. So, read the fine printing, the testimonials, which is about to be something that works for you. Another one is the stress management type techniques that work.

26:25You can't save them for the weekend. You can't save them for when you're stuck on hold on the phone with the new sack for two minutes. It's got to be something where you stop what you're doing and do it virtually daily or every other day and spend 20, 30 minutes doing it. Whatever stress management technique you then do in those 20 minutes, you already 80 % of the way there simply by having decided your well -being is important enough that you're going to stop every single day and have that disparity. So, there's no magic breathing tool or exercise. It's any variety of those or one of those. Again, we come back to this idea that it's the one that you select and the one that you make enjoy that's going to work best in terms of physiology.

27:17That brings me to this question of, I find it amazing that how we perceive an event and whether or not we chose to be in that event or not can have such incredibly different effects on circuitry of the brain and circuitry of the body and biology of cells. And in some ways, it boggles my mind like how can a decision made presumably with the prefrontal cortex, although other parts of the brain as well? How can that change essentially the polarity of a response in the body? And I mean, you've talked before about type A personalities and we don't have to go into all the detail there for a sake of time, but it is interesting that the effects of endothelial cells, I mean, literally of the size of the portals for blood are in opposite direction depending on whether or not somebody wants to be in a situation is a highly motivated person.

28:15Maybe you could just give us the top contour of that. And then maybe if you would, you could just speculate on how the brain might have this switch to turn one experience from terrible to beneficial or from beneficial to terrible. It's really fascinating. You can think autonomic regulatory neurons into action in ways that only other animals can do with one extremes of environmental circumstances. We talk about the optimal amount of stress that counts as stimulation. And in general, that stress that's not too severe and doesn't go on for too long and is overall and it's been level and setting. And in those conditions, we love being stressed by something unexpected and had a control unpredictable and like a really interesting plot turn in the movie you're watching.