How to Maintain Balanced Dopamine Levels in a World of Pleasure - An Interview With Dr. Anna Lembke

How to Maintain Balanced Dopamine Levels in a World of Pleasure - An Interview With Dr. Anna Lembke

What follows is a transcript for the podcast Dopamine - Dr. Anna Lembke - Neuroscience.

Topics within the interview include:

  • How dopamine is involved in the pleasure-pain balance
  • The role that serotonin plays in homeostasis
  • Why a world of indulgence has led to dopamine deficits
  • How flow states and human connections stimulate dopamine production
  • Evaluating the risk-reward of psychedelics and dopamine mechanisms
  • Leveraging hormetic activities to boost dopamine levels

How Dopamine is Involved in the Pleasure-Pain Balance

Daniel Stickler, MD: Welcome to the Collective Insights Podcast. I am your host for today's episode, Dr. Dan Stickler, and I have the pleasure of having Dr. Anna Lembke here. And this is someone who I've been wanting to have a conversation with after reading her book. She's a professor of psychiatry at Stanford University School of Medicine and chief of the Stanford Addiction Medicine Dual Diagnosis Clinic. Dr. Lembke is also a leading mind in the opioid crisis and the author of Dopamine Nation: Finding Balance in the Age of Indulgence, which explores how to moderate compulsive over consumption in a dopamine overloaded world. Welcome Dr. Lembke.

Anna Lembke, MD: Thank you. Thank you for having me.

Daniel Stickler, MD: Well, I have all kinds of questions for you. I want to start off with some basics to give people a bit of a background in what we're going to be talking about in this dopamine overload. Can you give us the neuroscience behind the pleasure-pain balance and how that works with dopamine?

Anna Lembke, MD: Sure. Dopamine is a molecule we make in our brain. It's a neurotransmitter. It's essential for the experience of pleasure, reward and motivation. It's also central to movement, and it's probably no coincidence that the same neurotransmitter involved in movement is also involved in pleasure, reward, and motivation. Things that are reinforcing or pleasurable release dopamine in the brain's reward pathway, which is a very specific neural circuit that's been identified over the past 50 to 100 years. The more dopamine that's released, the more potentially addictive the substance or behavior is.

Another really fascinating finding in neuroscience in the last 50 years or so is that pleasure and pain are co-located in the brain. What that means is the same parts of the brain that process pleasure also process pain, and they work like opposite sides of a balance. So if you imagine that in your brain, there's a beam on a central fulcrum, kind of like a teeter-totter in a kids' playground, and that balance represents how we process pleasure and pain. When we experience pleasure, we get a little release of dopamine in the reward pathway and the balance tips to the side of pleasure. And when we experience something painful, like touching our finger to a hot stove, the balance tilts to the side of pain.

But one of the overarching rules governing this balance is that it wants to remain level. It doesn't want to be deviated for very long to one side or the other. Hence, our brains will work very hard to restore homeostasis or a level balance after any deviation from neutrality. And that has lots and lots of implications, both for becoming addicted as well as implications for the ways in which our primitive wiring is mismatched for this modern ecosystem of overwhelming, overabundance. The bottom line is that the way that the brain restores homeostasis is first by tilting an equal and opposite amount to whatever the initial stimulus was.

So when I do something like eat a piece of chocolate, which I like, that releases dopamine. In the reward pathway, my balance tilts to the side of pleasure, I feel good, but no sooner has that happened than my brain adapts to that increased dopamine by down regulating my own dopamine production and transmission. And I imagine that is these little neuro adaptation gremlins hopping on the pain side of the balance to bring it level again, but the gremlins like it on the balance. So unfortunately, they don't get off right at that level position. They stay on until I've tilted an equal and opposite amount to the side of pain. That's that moment of wanting one more piece of chocolate.

Now, if I wait long enough, the gremlins hop off, the moment passes, and a level balance or homeostasis is restored. But if I naturally reach for a second piece of chocolate, which in this world of overwhelming over abundance is easy to do, then essentially what happens is oh, that over time, I accumulate more and more gremlins on the pain side of the balance until I have enough gremlins to fill this whole room. And then I'm in a dopamine deficit state, which is akin to the addictive brain. Now, I need that chocolate not to feel good, but just to restore a level of balance. And when I'm not using, I'm experiencing the universal symptoms of withdrawal from any addictive substance, which are anxiety, irritability, insomnia, depression, and intrusive thoughts of wanting to get my drug, otherwise known as craving.

Daniel Stickler, MD: Now, is dopamine always associated with pleasure and reward in the brain? I mean, are there other areas of the brain, different receptors, D1, D2 that create different responses in that sense?

Anna Lembke, MD: Yeah. Great question. So this balance is an oversimplification of the way that we process pleasure and pain. In fact, dopamine is very sensitive to novel stimuli that are not necessarily pleasure or pain, but that are just a signal of news. This is something that you should pay attention to, which also speaks to why news in and of itself can be addictive and people can get actually addicted to things like checking on the news. And dopamine can also be released in response to painful stimuli. There's a very famous experiment showing that if you take a rodent and you expose it to a very painful foot shock, you will see the same arborization in the brain reward pathway, as you will to a single injection of cocaine. It's not just pleasure that stimulates dopamine release. It's really the signal that we need to pay attention to our environment.

The Role that Serotonin Plays in Homeostasis

Daniel Stickler, MD: Now, there's also serotonin in the brain and you hear a lot of people talking about, is the serotonin, dopamine balance out? And you haven't mentioned that yet, but how does that play into this homeostasis that we see?

Anna Lembke, MD: So addictive substances and behaviors or reinforcing substances behaviors work through many different biological pathways. In fact, what makes the substance addictive is that it mimics a chemical that our brain already makes, but it's usually in a much more potent plentiful form. For example, we have our own endogenous opioid system, right? We make our own opioids, but our endogenous opioids last about half an hour. Whereas, the opioids that we can make in a laboratory not only are much more potent than the endogenous opioids that we make, but they last much, much longer. Hence, they're very, very addictive because they're essentially hijacking this pathway.

Same thing with serotonin. Serotonin is another important feel-good neurotransmitter. It's the neurotransmitter that gives us that sense of attachment to others, love, that sense of merging with the universe and oneness. Indeed, there are chemicals like LSD that we ingest that release loads of serotonin, which is why we use them. That's the feeling that we're going for. So it's not just about dopamine, it's about all of these feel-good neurotransmitters and hormones, the endogenous cannabinoid system, the endogenous opioid system, which I had mentioned, the serotonin system, there's no epinephrine. But the final common pathway for all of these reinforcing chemicals in the brain is dopamine, which is why neuroscientists use it as a kind of common currency for measuring the addictive potential of drugs and behaviors.

How Flow States and Human Connections Stimulate Dopamine Production

Daniel Stickler, MD: Nice. So I do some, I delve into ecstatic states and states of awe. It's been an area that I've been very interested in over the years. Do you get the dopamine release with the states of awe as well?

Anna Lembke, MD: Oh, absolutely. That's a very powerful source. That's also accounts for the kind of flow state that people can get into with creative endeavors, this kind of spiritual transformation or transcendence that people get when they actively engage in meditative or prayer, or even more so collective religious experiences. So dopamine is very... One of the things that happens when we experience an emotion at the same time as other people is that we get a release of dopamine because dopamine is released when we make those intimate human connections. That's part of why we want to be connected because it feels good to do that. And of course, experiencing the same emotion, not just as one other person, but as a very large group of other people at the same time, that's very reinforcing, releases dopamine.

So a lot of these experiences that basically are fundamentally adaptive for us will release dopamine and we've evolved over millions of years to approach these kinds of dopamine-releasing substances and behaviors because for most of human existence that is adaptive for us, right? Finding food, finding clothing, finding warmth and shelter, finding a mate, having collective religious experiences that more tightly bind the social group together. These are all highly adapted. The problem is that now we have so much access to so many reinforcing drugs and behaviors, and they're so much more potent and the quantity is endless that now we've got this fire hose of dopamine that we really weren't adapted to deal with. And that's what we're struggling with today.

Daniel Stickler, MD: You've talked in that regard, at the societal level there, you've talked about a kind of a narcissistic individualization that society is promoting. This wasn't always the case. I mean, you can read back on Abraham Maslow's work, where he visited the Indians and the person that had the greatest respect in the community was the person that shared the most. It wasn't about being the best at anything. Why have we gone down this road? What kind of transitioned us into that state?

Anna Lembke, MD: Well, I think it's just a natural byproduct of our economic system, which is not to say that capitalism is good or bad, but capitalism is about strivers and striving. It's about trying to get to the top of the mountain and stay there as long as possible. That's what capitalism fosters and promotes. And in many ways, that's positive because it does bring out that work productivity in people and that striving element in people, but the dark side of that is that as we further individuate and attempt to distinguish ourselves from the larger tribe, I believe we pay a psychological price for that. And the psychological price is a kind of a self-loathing and shame that comes on the heels of separating ourselves from the group. And so when we look at our society today, as you mentioned, one of the things that stands out is the kind of narcissistic self, a grandiose man, and individuation, and seeking of individual accomplishments.

But the other thing that really stands out is the kind of self-loathing that people seem to experience on a scale that was not true 200, 500, 1,000 years ago. And I think that self-loathing, contrary to popular wisdom, which would be to say is because we haven't given people enough self-confidence. I don't really think it's about that. I think it's because we're not connected to each other. We're not connected to a tribe. We're very focused on our individual wants and needs. We're basically isolated. And I think that is the cause of so much-

Daniel Stickler, MD: Why would that develop evolutionarily? I mean, it would seem like the dopamine hits for the individuation achievements in that regard would be less so than for the drive to contribute to the community and be part of a community, wouldn't it?

Anna Lembke, MD: I think it really depends on whether or not you're getting the social goods from that community that are actually sustaining. I mean, I think you make a good point. It's like we have more people living alone today than ever before in the history of humanity. Why is it that we seem to be progressing toward more and more isolation? I mean, I do think it's just a... I think it really is a byproduct of the social structure. It's amazing the impact of culture and social institutions on human behavior.

We like to think that it's sort of all about what we choose, but really we are very much at the mercy of the environment that we live in and the culture and social structures that we've created. And for reasons that I can't fully explain, we have created a culture which separates us to our detriment and certainly to our misery. And I think part of the corrective that has to happen is that we have to sort of come to a reckoning around that capitalism for all its virtues. In some regards, we've paid enormous price in terms of mental health and we need to figure out how to kind of get back to some semblance of community really.

Daniel Stickler, MD: And do societal norms dictate a lot of what we perceive as dopamine hits then?

Anna Lembke, MD: Absolutely. I mean, what society gives us accolades for, what we consider to be achievement, how we get awards. I mean, our heroes today are Jeff Bezos, Mark Zuckerberg, Sergey Brin. These are the people that we revere, and what have these people accomplished? I mean, I don't know any of these people individually, but they've managed to amass an enormous amount of money that they've essentially generated on the backs of other people's labor. So those are our heroes.

Daniel Stickler, MD: Well, and then social media shows all of these influencers and everybody with all of the flying on the private jets, enjoying the vacations in the Caribbean. And I think that's going to be a huge contributor as well.

Anna Lembke, MD: Yeah. And I think we think that's what we want, that kind of accumulation of material wealth. And it's so cliche, but still so very true that if we're able to be a part of that 1% of the 1% who amass all of that, I mean, those people are not happy. And it's not clear that they're actually contributing good to the world, so...

Daniel Stickler, MD: I mean, is there not the intrinsic happiness that we can generate versus the external validation for happiness?

Anna Lembke, MD: Well, I think we are such social creatures that we do need that external validation. I know in my younger years, I tried to convince myself that I didn't care what other people thought. Now, in my 50s, I openly admit, I really care. And I think that's not a bad thing. We're hive creatures, right? We do care what other people think. We should care. It does matter, but what are the sort of benchmarks for how to be a good person, how to live a good life? These are all things that I think we're having to reevaluate now.

Daniel Stickler, MD: Well, I spent the first 10 years of my medical career as a general and vascular surgeon. And I truly didn't care what anybody thought. I mean, I had zero empathy too. I mean, it was just not there. And it wasn't until really understanding the depth of love that I have for my partner, she was instrumental in that, but all of a sudden I have empathy and I'm like, “What is this?” I'd always intellectualized love and empathy, and then suddenly I'm feeling it. And I think societally, I had to shut down really feeling emotions and just really intellectualizing the emotions there.

Anna Lembke, MD: That's fascinating. What would you think were the factors that led you to have to shut down that emotional empathic part of yourself?

Daniel Stickler, MD: Well, I think as a surgeon, you almost have to really push empathy aside, but I would do it, I guess I did it more so than just being in surgery, I also did it when I was at home. I didn't understand the need for empathy. I was like, “Why would I want to feel what somebody else's feels?” I mean, I have compassion for them, but I don't want to feel their feelings.

Anna Lembke, MD: Uh-huh. Yeah. Well, thank you for sharing that. At the risk of sounding sexist, I do think this is a hard time for men and boys. I mean, I think it's a hard time paradoxically to be alive anyway. There are all kinds of unanticipated stressors having to do with having too much time and too many choices and too much access to cheap pleasures, as I talk about. But I do think it's an especially difficult time for men and boys to kind of figure out where they fit in here.

Daniel Stickler, MD: Yeah. We have five boys in their early 20s and watching them navigate this. Fortunately, we are with crowds of people here in Austin who are very open about what it means to be an adult. There are so many what we call adult children that never really get that rite of passage and understand what it is to be... And especially in the archetype of men, we see a lot of misconceptions around that. And I think that creates a lot of angst and they go for dopamine hits to kind of come through that.

Anna Lembke, MD: That's right, yeah. And I think these are really valuable and important questions. I'm so glad you're having them with your kids and in your community sort of trying to redefine what is the good life.

Evaluating the Risk-Reward of Psychedelics and Dopamine Mechanisms

Daniel Stickler, MD: That's an area I want to get into with you too, because I can remember I think it was some talk I listened to recently that you did and it was about psychedelics.

Anna Lembke, MD: Mm-hmm.

Daniel Stickler, MD: I'm involved with a bunch of the people in the Austin community. I mean, psychedelics are ubiquitous. I mean, you go out to a party and all of a sudden you see everybody's like in cuddle puddles or they're having these otherworldly conversations, but you had mentioned that you felt like the different psychedelics, and in psychedelics I'm also including the entactogens like MDMA. You had said that you felt that they were addictive, and I'd like to go down that and talk a little bit about that.

Sure. I think it's important to start with the definition of addiction. There's no brain scan or blood test for addiction. We base it on phenomenology, and the broadest definition is the continued compulsive use of a substance or behavior despite harm to self and/or others. Which means that mental preoccupation with using a drug again is one of the symptoms of addiction, as well as the comedown, which can also be quite subtle in the form of, again, these universal symptoms of withdrawal, anxiety, irritability, thinking of MDMA or thinking about blue Mondays, and those come owns are real. And the mental preoccupation with using the drug can also happens with psychedelics.

So even though people talk about this idea well, the physiologic tolerance develops so quickly that people don't tend to use again or repeat their use or want to use more over time. But that's not the sine qua non of addiction. The sine qua non of addiction is again, the continued compulsive use of a substance despite harm to self and/or others. And often that harm is not within our capacity to truly observe, but needs to come from the people around us saying, “Hey, you know, I've kind of noticed this or that.” And it can be quite subtle.

So I just think it's just a fact that if you are ingesting a drug that is massively changing your brain, whether the feelings that you get from it are happy or sad, that essentially your brain will have to adapt to that experience in ways that could lead you to compulsively invest a lot of time, energy, money, you name it into wanting to repeat that experience and to be avoidant with regular real life, which is at times boring, at other times, extremely difficult and challenging. And I really feel like our task as modern humans is to stop trying to alter our mental status so that we're not present and instead face the world as it is, and try to be fully present just with the brain chemistry we've been given.

Daniel Stickler, MD: I’ve had a different experience with that. Not that I have firsthand experience with it, but I have observed a bunch of my friends that are into using psychedelics periodically. And I don't see the criteria of addiction necessarily with them. From my medical experience of addiction, which is very limited, but I don't see the dependence on it. I don't see the withdrawal from it. I don't see the tolerance development from it. I mean, most of the people, if I see them take MDMA, they take it maybe once every quarter. Mushrooms, people will tell me, they say, “You don't want to do mushrooms more than every so many weeks. It's just, it's not... It doesn't feel that way.” So in my experience with it, the ones that I have seen that have been experimenting with it, and it's interesting because I see profound changes in them too. And I'm not talking about in a negative way, I'm talking about it in a very positive prosocial, pro community way that's beautiful to watch.

Anna Lembke, MD: Yeah. I'm really glad we're having this conversation. It's great. Let me just first say that just because a person can use a drug and not get addicted to the drug doesn't mean that the drug is not addictive, right? So the vast majority of people who drink alcohol don't get addicted to alcohol.

Daniel Stickler, MD: I was just going by the criteria of addiction that we use in medicine.

Anna Lembke, MD: Sure. So what you're observing is that anecdotally in your community or in the people that you know, you don't see addiction playing out, but I can tell you, in my population, I see people getting addicted to psychedelics repeatedly pursuing use of that drug at a very high cost.

Daniel Stickler, MD: Any particular one that you see more commonly?

Anna Lembke, MD: I've seen them all. It really depends on the drug of choice, right? Some people get addicted to pornography, some people to cannabis, and some people to ecstasy or psychedelics [inaudible 00:24:29].

Daniel Stickler, MD: Is that like alcohol though, where you have 10% to 15% of the population that are more prone to be addicted versus the ones that are not?

Anna Lembke, MD: That's right. That's right. But the other thing to keep in mind too, which is an increasingly common picture that we're seeing in addiction medicine is the problem of polypharmacy. So folks who may use MDMA once a quarter, but they're using cannabis on the other days and alcohol in some of those days and psilocybin on some days, so that the net effect is that frequently, like maybe every day, they're essentially ingesting some kind of-

Daniel Stickler, MD: Looking for an alteration.

Anna Lembke, MD: Right. Exactly. Exactly. So I think the other thing, the other danger here with psychedelics, because it sounds like... First of all, let me just also go back to saying, it sounds like anecdotally, you're seeing benefit in these people's lives and that's great. And I believe you, and that's why these agents are being studied. But I think we can't put the cart before the horse and say, these agents have medicinal value without the data and we don't have the data yet. The data are really not impressive for the use of psychedelics and MDMA and frankly, ketamine as well as having therapeutic benefits for mental health disorders.

A recent study comparing an SSRI Lexapro to psilocybin in the treatment of, I think it was major depression, showed that they were sort of equal and that both had sort of modest effects. If that's true, we're not dealing with like a groundbreaking drug here to treat depression, we're dealing with something that seemed to, in a small cohort, in a limited design study, a work sort of about as well as Lexapro. And Lexapro we know is safe. It's been FDA approved. It's been in the community for a really long time. People don't get persistent hallucinogen disorders from it. People don't become psychotic from it. So I think that's my concern. We've got this sort of like kind of a narrative that the media has really promoted that number one, they're not addicted. And number two that people have this spiritual awakening and it can treat their mental health disorder. Well, wait a minute, wait a minute, let's way back up and really look at the evidence. Because the evidence, at least the scientific evidence that we rely on now is not robust.

Daniel Stickler, MD: Yeah. I had a conversation with a Gul Dolen researcher at Hopkins about a year and a half ago, and she was doing the research with MDMA out there. One of the interesting aspects of that is she found that single dose of MDMA opened up the social developmental window of the brain for about a 10-day period after taking it, and that she felt that there were a lot of benefits from that in the fact that people who have... You know, we typically closed that social developmental window by 15, maybe at most get to 20, and then we're kind of locked into our social developmental aspects. But here we are, 20, 30 years after that, and we're still in that social developmental stage. Could there not be a benefit from the MDMA in that situation?

Anna Lembke, MD: Well, I guess a couple questions, how did she measure that? How did she measure-

Daniel Stickler, MD: Well, she was working predominantly with autistic children at that point, but she also had some rat studies on it. I mean, her big dive was in the parvocellular versus magnocellular oxytocin receptors in the hypothalamic brain.

Anna Lembke, MD: Okay. I mean, I guess I really want to read the study. In general, those studies are very short term. They're a small end, so not very many participants. And I think subsequent studies have not borne out some of the early promise.

Daniel Stickler, MD: Mm-hmm.

Anna Lembke, MD: So I just think it's important. It's not to say that... I believe that people can have enriching experiences that can change their lives in a positive direction with psychedelics. I have encountered people, friends in my own life, friends and acquaintances who attest to that, but that's still to me, not yet sufficient to say this is a therapeutic way to treat this disorder. That's a very, very different things. As they always talk about in the psychedelic world, set and setting matter. And to assume that the office setting of a psychiatrist is necessarily going to be a therapeutic setting for psychedelics, I think is premature.

Daniel Stickler, MD: Yeah. I agree with that. Yeah. I followed the research on this a lot because I'm hoping at some point that the MDMA therapy will be available because I've seen some really good results. One thing we use in our clinic is ketamine nasal spray. The hardest thing for me to ever wean somebody off of... I mean, harder than those addicted to cocaine has been SSRIs. And most of them are prescribed for reasons of just feeling bad and not true depression, and these people are locked in on that. And we see brainwave changes. We do qEEG on all of our clients every year and we see some significant changes that are occurring relating to those SSRIs.

We found this accidentally, we do neuromodulation with neurostimulation and we found that ketamine nasal spray facilitates the uptake of patterns when we're inducing them. This is all anecdotal. We're hoping to get in a larger study with University of Texas here in Austin. But we accidentally found that people can come off SSRIs and rather quickly. You don't even have to go through the weaning process and they have no distress over coming off of them when they use the ketamine nasal spray, and then they just stop the ketamine nasal spray and they're all good.

Anna Lembke, MD: Mm-hmm.

Daniel Stickler, MD: I mean, do you have any experience with that or why is that so difficult to get people off of? I mean, you talk about addiction. I think SSRIs are one of the biggest addictions.

Anna Lembke, MD: Yeah. So I mean again, sort of physical dependence and addiction certainly overlap, and I agree with you that some people have a very hard time getting off of SSRIs and have neuroadaptive changes that are difficult to reverse and require very slow taper over time. I've certainly seen that clinically. I suspect a lot of it depends on quantity and frequency, how big the dose is, over what length of time you're using it, which then does speak to the level of neural adaptation to that chemical. The higher the dose and the longer the person's on it, the more neural adaptation there will be and the harder it will be to get off. And I suspect that would be true for ketamine too.

And again, you're going to have people... There's this whole drug of choice concept, which is really important. You're going to have some people who are susceptible to ketamine addiction and K-holes and things, and other people who aren't, and that's true for cannabis and alcohol and you name it. And it's not going to be the same person necessarily. So one person who might be very vulnerable to an alcohol addiction might not be vulnerable to a ketamine addiction and vice versa.

So I think it's just a matter of really having kind of a humble and healthy respect for these molecules to be really careful and thoughtful and explore how they might be helpful, but make sure that we simultaneously are looking for other ways in which these things can go wrong. Because I think there's just too many examples throughout the history of medicine of saying, “Oh, this is going to be the miracle cure. This is going to be the thing that, you know, relieves physical and mental pain with no addictive potential and no... ” And then, you know, whether it's one year or five years or 20 years down the road, we've got a major addiction problem. So just like a little bit of a cautionary kind of request.

Daniel Stickler, MD: Yeah. I mean, I see a lot of that in the community of people attributing these characteristics to the psychedelics that we don't know. And they're promoting this with other people and I'm just like, “No, that's... We don't know. That's not the case.” And they act like they're safe because it's plant medicine.

Anna Lembke, MD: Right. Right.

Daniel Stickler, MD: No, you got to be careful with that stuff.

Anna Lembke, MD: Yeah.

Leveraging Hormetic Activities to Boost Dopamine Levels

Daniel Stickler, MD: So I want to get back to dopamine. We kind of got sidetracked there for quite a while. I appreciate you opening that up and really allowing my questions on it. So I would be remiss if I didn't mention. My son, Nathan, works at this place called Kuya here in Austin and they do float tanks and they do cold plunge and sauna. He is a huge fan of getting in the cold plunge, hanging out in there, and then running over and sitting in the sauna.

Anna Lembke, MD: Mm-hmm.

Daniel Stickler, MD: And you mentioned in the book about the dopamine hit that occurs with cold plunge. So I want to go into that a little bit.

Anna Lembke, MD: Yeah. So this is the science of hormesis, and hormesis is Greek for, to set in motion. Essentially, what it is, is this idea that by exposing ourselves intentionally to mild to moderate toxic or painful stimuli, we actually do the body good. And why is that? Because the body senses injury and then starts to upregulate or increase production of our own feel-good neurotransmitters and hormones. So instead of ingesting them from the outside, we make our own. And ice cold water plunges are clearly a way to do that. There are studies showing that if you immerse yourself... There was a study taking adult males and immersing them in an ice cold water bath for an hour, and measuring dopamine levels in their brains and finding that dopamine levels increased gradually over the course of the ice cold water bath. But most importantly, dopamine levels remain elevated for hours afterwards, before going back down to baseline levels. And we all have a baseline tonic level of dopamine firing.

This is really powerful because what it says is, hey, there's a way we can get our dopamine by paying for it upfront and doing these things that are painful. Exercise is another perfect example of that. Intermittent fasting is probably another example of that. And any kind of mind-body work that requires this effortful engagement, contrast that with intoxicants where we take it and we immediately get a spike in dopamine followed very quickly on the heels by dopamine free fall, not just to baseline levels, but actually below baseline, that dopamine deficit state, which then drives craving for another hit. Now, if we can withstand the craving and we have enough brain plasticity, then we'll eventually get back up to baseline firing. But what it means is that it does make us vulnerable to this over consumption, repeated use, which ultimately can reset our hedonic or joy set point. Whereas ice cold water, bath exercise, and other hormetic forms, get us our dopamine indirectly without that dopamine deficit state.

Daniel Stickler, MD: Okay, so you don't get addicted to the cold baths, cold plunges because of the prolongation of the dopamine release? Is that what you're saying?

Anna Lembke, MD: Well, basically it's much harder to get addicted to dopamine release.

Daniel Stickler, MD: Got it. Okay.

Anna Lembke, MD: You still can. I mean, I've had patients addicted to exercise. I had a patient that I talk about in the book who was on his way to getting addicted to ice cold water baths, kept upping the ante. First, he got a meat locker, then he got a motor to circulate the water to keep it colder, and then he had to make it so cold that he was breaking the ice on the surface of it. So yeah, you kind get addicted to pain, but it's just much harder because you have to put in so much effort up front to tolerate the pain and so much less likely to get to that point. Of course, I will say in this day and age where scientific innovation has allowed technology to enhance all human experiences, it has become easier to get addicted to things like exercise, which would've been much harder to do 50 or 100 years ago.

Let's just take the treadmill as an example, or our other gym machines. Those machines, in part because they make it convenient and easy to exercise year round, the repetitive nature of it probably has a soothing quality. The way that we can quantify our heart rate, the distance we covered, the elevation, enumerating things, or giving them numbers, makes them more reinforcing. We also know this from social media or video games, the likings, the rankings. And for all those reasons, we can take something like exercise, which really is fundamentally healthy and we can drugify it and make it more addictive.

One of the experiments that I absolutely love that I about in the book is that neuroscientists used to think that the running wheel in a rat's cage was just a measure of healthy exercise or movement, but what they slowly came to realize was that the rodents could actually get addicted to the running wheel. And some rodents would run so much on the running wheel that they would actually run themselves to death. And some of them, they would run so much that if they made the running wheel smaller and smaller, they would curve up their tails to match the shape of the running wheel and eventually end up with the tails permanently curved. So rats got addicted to running wheels.

Anna Lembke, MD: And then my absolute favorite experiment from the Netherlands where they put a running wheel in nature thinking, well, here we are in nature, there's going to be no animal that's going to use the running... No, it turns out all kinds of animals came in and use it. Like, there's something about that going against gravity in that horizontal and vertical way, like an amusement park ride that organisms find reinforcing, including humans. So I just think it's interesting to think about how we've reached this point where really everything has become drugified.

Daniel Stickler, MD: Yeah. I just wish we could sustain it, you know?

Anna Lembke, MD: Yeah, right. That's the problem. I mean, if it's that really good feeling all at once, it's probably a dangerous,

Daniel Stickler, MD: It's like the yin yang, you can't know the highs without knowing the lows.

Anna Lembke, MD: That's true. That's true.

Daniel Stickler, MD: Well, this has been a very enlightening talk and I love that you kind of finished it out with all these hormetic things in life, because I think that's the key is to constantly keep the body off guard from normalcy, from routine. And you talk a little bit about that with the dopamine fasting, which I encourage everybody to read this book and dig into some of these topics and some of the how-tos that Dr. Lembke goes into. So I appreciate your time today and I appreciate you indulging me on my off script questions for you.

Anna Lembke, MD: Yeah. No, I love it. That's great. I think we have to have these conversations. We shouldn't be afraid of them. So I really appreciate our dialogue today.

Daniel Stickler, MD: Awesome. Well, thank you very much.

Anna Lembke, MD: You're very welcome.

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