What is the relationship between stress and eating and eating and the opioid system? Stress and eating is an interesting one. So most people when they feel stressed or, you know, I'm just going to ask you, do you eat more or less when you're stressed? Less, definitely. I feel like I can go two, three days without food when I'm really stressed.

But I came up in a profession where sadly for me, all-nighters were part of the regular until pretty recently, a couple of years ago when I just called an end to that. And no, it wasn't just because of procrastination, it was just work overload. But I can go a long period of time without eating, although I love to eat.

So I do point out that I do love to eat. And what does the body feel like when you're in that stress state, when you're not even hungry, you're kind of shut down in your digestion? That I have enough energy from my neural resources, from adrenaline. And generally, those periods of time when I'm not hungry coincide with a hyper focus on the stressor, the deadline, whatever it is in life that needs tending to.

And food just doesn't appeal to me as much. It doesn't taste as good and it's not as enticing. Yeah. So we think that your type of body temperament is high sympathetic. And so when you have a big stress response, your digestion is pretty much shut down. It would be the opposite.

Eating would be the opposite of what your body's telling you to do. I'm just going to, forgive me for interrupting. For those of you hearing sympathetic, we're not talking about sympathy. We're talking about the sympathetic arm of the autonomic nervous system, which is the so-called fight or flight arm, as opposed to the parasympathetic.

In any event, sorry to interrupt, but wanted to make sure that sometimes people hear sympathy and then they think emotional sympathy. I like to think I have that too. But okay. So I tend to lean more towards the sympathetic, meaning more alertness arousal on the seesaw of the autonomic nervous system.

And I'm a high sympathetic reactor. I lose weight when I go through, like writing my dissertation, I looked like a skeleton at the end. But that's not what most people complain about. It's not weight loss. Most people complain about overeating or binge eating when they're emotional, when they're stressed.

And that's the more common pattern. And what that, that looks different, both in the brain and biologically. And so what it looks like is that the stress response is driving cravings. And also, let's say high insulin or an insulin resistant state. And what goes along with that is tending to be overweight or have obesity.

And so just by whether it's through conditioning or genetics, having that kind of larger body with a big stress eating temperament, that is a challenge in life. And I've been, you know, I've worked with people with different eating conditions, eating disorders, binge eating. And it is a, what's hard about it is number one, it's very common and normative to just feel like you can't feel satiated.

So it's this compulsive eating tendency that stress brings you to. And so the, so what it means, we measure this, it's very easy to measure, it means that people feel like they can't control their eating, they don't get full, they think about food a lot. And so stress kind of exacerbates that tendency.

And that is a, you know, it's a common phenotype. Like we've studied it and maybe 50% of people with obesity have that. Do lean people have that? Some, not many, like less than 20%. But what they also have is this tremendous kind of diet, what we call dietary strain or control over their eating.

So they're, they are able to, to not overeat, even though they're thinking about food a lot. So that's, that is, you know, that explains that unusual body of someone who's really more has still has those compulsive traits. So why does this matter? Stress makes it really hard to eat well, because when you're stressed, you're craving the comfort food, the high fat, high sugar, high salt, depending on your temperament.

And that is, that means with repeated bouts of stress, you're just going to be gaining weight and particularly in the intra-abdominal area. That's what we've seen. We've seen it cross-sectionally, we've seen it in rat studies, and mice studies, and now we've seen it in people and many, for about 10 years I studied this.

And the question was, is what's happening in people the same thing that's happening in mice? If you stress them out and you give them Oreos, the mice develop binge eating, they get really compulsive and they get this, you know, terrible metabolic health profile, metabolic syndrome, where their, their round, you know, their, their belly fat basically expands like a cushion.

And that's because that's this really good immediate source of energy during stress. So like, we're really well wired to, if our body thinks we're under chronic stress, we're going to store stress fat or abdominal fat, so we can just mobilize that in a second. And then the second question we've asked is, can you reverse that with different interventions?

Can you, can you block the compulsive eating? So I can, I can tell you what we found there. But the opioid system that you mentioned is certainly involved. And in studies with people, lean people and people with obesity, my colleague, Rajita Sinhat-Yale, it's basically found that when you stress them out, people with obesity are having a different reward response.

And they're having, they're, the more insulin resistant they are, the more their reward center lights up during stress. And what's causal there? Like what's the chicken? What's the egg? So, because I can imagine these were people that at one time were not obese, who got stressed. The opioid system reacted in a particularly potent way to food and they were able to clamp their stress.

And so then they become binge eaters in the context of stress. And that leads to insulin insensitivity. I could also imagine that they were insulin insensitive, therefore they need to eat more in order to feel kind of an increase in satiety, as we know this now, based on brain and body mechanisms.

And then that set off a cascade of things leading to obesity. Not that it necessarily matters, but what's causal? Do we know if it's-- Oh, I think it really does matter. I think there's been a mistake of kind of confounding all obesity with food addiction and metabolic disease, and it's completely heterogeneous.

So I think it's the developmental path that you're describing, which is that there's a tendency toward having a bigger reward response and hunger during stress. So it becomes a way of coping, a lifestyle, and that is a pathway toward obesity. And so some obese people have a dysregulated stress response, but not all of them.

I mean, it really is a certain type of person. So that's why we target people with cravings in all of our intervention studies now. We want to know who has more of the compulsive eating type, because they need a different set of skills to cope with stress and to lose weight, if that's their goal.

There's a drug, I'm sure you're familiar with, naltrexone, which can block the opioid receptor. It's used to block the opioid receptor in the context of different types of addiction. Have people tried to use naltrexone in the context of binge eating, and does it help people lose weight? Because it presumably reduces some of the rewarding properties of food?

That's one of the very few drug combinations that has been used for binge eating. So it was a combination of naltrexone and Welbutrin. And I'm not sure at this moment how much that's favored for binge eating, but certainly the early trials showed that it really does damp down on the compulsive eating.

Interesting. There's a commonly prescribed kit of drugs now for obesity. I know there's a lot of excitement nowadays about these semaglutide analogs, because they do seem very effective in blocking hunger, especially in type 2 diabetics. I don't know if you're familiar, but there's all the rage, mostly because people saw the before and after photos of Elon, he had a shirt off on a boat and there were some not so nice comments made about him, and then sometime later he was quite a bit lighter and he announced that he'd been taking one of these semaglutide agonists.

I really hope that we come up with safe and effective drugs. And one thing to think about is that the challenge that we all have, particularly if we're prone to obesity, is the toxic food environment, and particularly the refined sugar. And regardless of what we're on, metformin or one of these drugs, we override it with our diet.

And really, the improved nutrition is the only way to solve it as a public health problem. I mean, the drug companies are saying everyone should be, everyone with a certain BMI should be on one of these new drugs, and it's just rubbish, and it's not going to lead to long-term health.

Well, I know you have a colleague there at UCSF, Dr. Robert Lustig, who's been talking about sugars and hidden sugars for years and the problems with that. And we don't want to demonize sugar as the only cause of the obesity epidemic, but it's certainly one of them. At least that's my belief, according to the data.

Yes. And Rob is the biggest proponent of helping people understand the big problem and the root is in the processed food and the sugar, and that the drugs don't touch that. We override effects of any drugs with our diet. And so it's been a losing battle, really, because of the force of big food and big pharma.

So let me go back to the compulsive eating. So there are some clues about how to break that cycle. So one is in our weight loss trials or our healthy, mindful eating trials, we find that mindful eating is not going to cause a lot of weight loss, period. And if the people who benefit most from learning this kind of calm self-regulation where you check in with your hunger, you slow down, you increase your awareness of your body, so interoceptive awareness, that type of skill is really critical for people with compulsive eating.

And so in our trials, we find that people with compulsive eating, if they get randomized to the mindful eating, they do better in terms of their insulin resistance and their glucose and their long-term weight loss. So that's one good clue. Another is the positive stress pathway looks important for breaking the compulsive eating cycle.

So high-intensity interval training or maybe some of these other ways that we've been talking about to increase the bodily stress in these short-term ways to metabolize stress in our body can help with the cravings. So what would that look like in the context of – let's say somebody has the opposite phenotype to me.

They get stressed and they find themselves reaching for snack food or that they simply can't reach satiety. They just want to eat and eat and eat. What are some of the – aside from naltrexone and wellbutrin and some of these prescription approaches, because I always say while I value – certainly value prescription drugs in certain contexts, I always feel like behavior should come first, do's and don'ts, then nutrition, then supplementation, and then if and only if it's still needed, prescription drugs.

But that's just my bias based on my observations. Pretty reasonable. I like to think so. It also is a – it starts at a zero-cost endeavor. I mean behaviors require time, but it certainly includes everybody, not just those that have insurance or that live in a particular region of the U.S.

or the world. So anyway, that's my bias and at least for the time being, I'm sticking with it. It's the basis of a lot of what we talk about on this podcast. But nonetheless, if somebody is finding themselves in that category of binge eating or heading towards binge eating or using food to comfort or alleviate stress, how should they intervene in their own thoughts and behavior?

We talked about the bins, top-down strategies, changing the body, changing the scene. We need all of those. I mean the compulsive drive to eat is one of our strongest impulses if we've developed that pathway. And so we train people, for example, in mindful awareness of separating out emotions from hunger.

So they get really wrapped up together. So just labeling how you're feeling, labeling your hunger from one to ten, and figuring out am I really hungry or is it boredom. That helps people. And if you do that check-in right before you eat, that helps the most. So that's the top-down mindful check-in.

The other thing we help people do is like ride the craving, surf the urge. So we deal a lot with soda drinkers and it is addictive and there is nothing worse than drinking sugar soda for our body. So we help people by having them watch their craving pass and knowing that it's a matter of time that they can surf the urge without jumping to consuming.

And so that practice helps some people, especially with practice. The push-ups, the taking a walk, the changing the scene, getting away from food is always going to be a huge strong strategy if you can get yourself away from it. The problem is, as you know, is that the cravings get you to the buffet.

They drive you to the soda, etc. And so just creating safe environments both at home and in the workplace where you don't have soda is really important. So we tried that at UCSF. My colleagues and I, including Rob Lustig, the anti-sugar doctor, we just saw the absurdity of being a medical center.

People come with these chronic diseases and what are they served in a cafeteria or even at their bedside? Sugared Coke. In the hospital. In the hospital. And so my colleague, Laura Schmidt, who's partly responsible for the soda tax, she rallied all the – we went top down to administration but bottom up to vendors, got rid of all the soda in all of our hospitals and campuses.

And we found two things. Number one, people who were heavy drinkers lost weight in the most important place, their waist. Heavy soda drinkers? Mm-hmm. So when we took it out of the workplace, they actually – their health improved. And number two, those with compulsive eating, they score high on our little scale for reward based drive.

It didn't help them. So then we randomized half of them to get some extra boost. We call it motivational interviewing where we're really supporting them more and helping them think of goals like being with their grandchildren, not getting diabetes, and that little bit of support helped them tremendously. And so now we're trying to roll that out in a big controlled trial.

But at least 100 hospitals have adopted the stop selling sugary drinks because people don't want to be sick but they can't help it if they have the reward drive and if they have the compulsivity and it's right there at work. We're just working against health.