Most Replayed Moment: The Role of Dopamine in Addiction and Motivation - Anna Lembke

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Steven Bartlett: You wrote one of the most iconic, well-known books about dopamine, which propelled the subject matter of dopamine into the public consciousness, but I guess the most important question I should ask you is why does dopamine matter?

Anna Lembke: Ah, good question. Good place to start. I mean, dopamine matters because it's fundamental to our survival. So it's the chemical that we make in our brain that tells us this is something we should approach, explore, investigate. So it's really almost the survival chemical.

Steven Bartlett: So what is dopamine? If you had to explain it to a 10-year-old, how would you go about explaining it?

Anna Lembke: So dopamine is a chemical that we make in our brain. It has many different functions, but one of its most important functions is that it helps us experience pleasure, reward, and motivation. It may be even more important for the motivation to do things than it is for the pleasure itself.

Steven Bartlett: For example, there's a very famous experiment in which rats were engineered to have no dopamine in the brain's reward pathway. And the scientists discovered that if they put food in the rat's mouth, the rat would eat the food, would seem to get some pleasure from the food, if you can determine that from watching a rat eat, which I think they felt like they could. But if you put the food even a body length away, the rat will starve to death.

Anna Lembke: The idea being that without dopamine, we're not motivated to seek out the things that we need for our basic survival. That's crazy. So you get a rat, you put the food an inch from its mouth, and it will starve to death because it doesn't have dopamine, the dopamine required to just reach out and eat.

Steven Bartlett: Yeah, essentially. Maybe it's not an inch, maybe it's a little more than an inch, but the idea being that dopamine is necessary to be motivated to do the work to get the thing that we need.

Anna Lembke: Having an understanding of dopamine, how might that improve my life? Having a basic understanding of how dopamine works, how we process pleasure and pain, and also what happens with dopamine as we go from adaptive recreational use to maladaptive addictive use is something that is really useful, especially for those of us living in the modern world, where now we're exposed to so many reinforcing substances and behaviors that we've all become vulnerable to the problem of addiction.

Steven Bartlett: And what are the biggest misconceptions on the subject of dopamine? Because it's kind of thrown around in society. I see it in my group chats, people saying, I need more dopamine or whatever, or, you know, that person just craves dopamine. What are the biggest misconceptions you've come across?

Anna Lembke: The main misconception is that somehow we can get addicted to dopamine. We're not getting addicted to dopamine itself. Dopamine is neither good nor bad. It's a signal to tell us whether or not something that we're doing is potentially useful for our survival. And also it's related to what we predicted about how rewarding or pleasurable something would be.

Steven Bartlett: And when you say relative, you mean, I mean, it's quite fitting for anyone that can't see. We have a set of scales on the table. And scales are relative to each other because if you pour in one end, the other end goes up. And if you pour in the other end, the other end goes up and this end goes down.

Anna Lembke: Yes, that's what I'm describing, yes.

Steven Bartlett: And what activities that I do every day have an impact on my dopamine?

Anna Lembke: Well, probably almost everything, you know, in some ways. I mean, every time we are doing something that's pleasurable, reinforcing, rewarding, that will affect dopamine. It's really the primary signal that lets us know that this thing is potentially important for our survival, as I mentioned. But even aversive stimuli can trigger dopamine.

Steven Bartlett: What's aversive?

Anna Lembke: Something that's painful or not pleasurable. Dopamine gets involved in that equation. Anything that's novel or new is something that triggers our dopamine in our reward pathway. Dopamine is fundamental for movement. So not just pleasure and reward, but also movement.

Steven Bartlett: So for example, Parkinson's disease, which is a disease related to stiffness and tremor, is caused by a depletion of dopamine in a part of the brain called the substantia nigra. And as dopamine gets depleted in that part of the brain, people lose the ability to move their bodies.

Anna Lembke: And it's probably no coincidence that the same neurotransmitter that is so important for pleasure reward motivation is also really important for movement because most organisms have to locomote toward the object of their desire. We want that thing. We have to exert effort, right? We have to put in the work to go get it.

Steven Bartlett: But in the world today, we really don't have to do that, right? We can swipe right. We can swipe left. And all of a sudden, it magically appears at the touch of a finger. And that's very confusing for our brains because that's not how we evolved. We really evolved for having to do quite a bit of upfront work for a tiny little bit of reward.

Anna Lembke: I just want to, before we move on, talk about this point you said, because I think it's quite foundational to everything we're going to talk about, about dopamine being relative to pain. And I have this set of scales in front of me. And here I have some chemicals that are likely to produce dopamine in my brain, I believe. Right? Alcohol. I have some rum. I have some whiskey. I have some vodka. And can you explain to me, using this rum whiskey and vodka, how dopamine is relative to pain and what's going on in my brain?

Steven Bartlett: Sure. Okay, I'll slide this over to you. Oh, okay. So one of the most exciting findings in neuroscience in the past 75 years is that pleasure and pain are co-located in the brain. So the same parts of the brain that process pleasure also process pain. And in a very simple reductionist kind of way, they work like opposite sides of a balance.

Anna Lembke: So imagine that deep in your brain's reward pathway, which is another exciting discovery, right, that there's this dedicated reward pathway of the brain that consists, broadly speaking, of the prefrontal cortex, which is this large gray matter area right behind our foreheads that's so important for future planning, for delayed gratification, for appreciating future consequences. You might think of it as like the brakes on the car, if we're going to analogize to an engine. And then deep, you know, in the brain, we've got what we call the limbic areas or the emotion brain. And there you have the nucleus accumbens and the ventral tegmental area that are rich in dopamine-releasing neurons, right? And they act like the accelerator on the car.

Steven Bartlett: So when you've got a healthy functioning brain, you've got enough accelerator, but not too much. And you've got a healthy prefrontal cortex putting the brakes on that dopamine release. When people become addicted, there's either a problem with the brakes, the prefrontal cortex, or the accelerator, or the nucleus accumbens and ventral tegmental area, or both, right?

Anna Lembke: What we're finding is that there's actually a disconnect. So there are large neuronal circuits and pathways between those deep limbic structures and the prefrontal cortex that literally get severed or disconnected when people become addicted.

Steven Bartlett: As we think about pleasure and pain being co-located in the same parts of the brain, working like opposite sides of the balance, in order to understand what happens in the addicted brain is to appreciate that there are fundamental rules governing this balance. And one of the most important rules is that the balance wants to remain level. It does not want to be tilted very long to the side of either pleasure or pain.

Anna Lembke: And in fact, what our brain does is first tilt an equal and opposite amount to whatever the initial stimulus is. So I'm going to try to illustrate that here. So let's say our initial stimulus is alcohol. Now, alcohol works through its own chemical pathway. It works on our endogenous opioid system, the opioids that we make. We have receptors for opioids in our brains. It works on our endogenous GABA system, which is our calming neurotransmitter. And at the end of the day, it releases dopamine in the reward pathway.

Steven Bartlett: So any potentially addictive substance will release dopamine in the reward pathway. The more that's released and the faster that's released in a given individual, the more likely that substance is to be addictive.

Anna Lembke: Another important concept here is what we call drug of choice, which is to say what releases a lot of dopamine in your brain may not release a lot of dopamine in my brain and vice versa, right? Which is this idea that people have predilections to different kinds of drugs. And by the way, people can get addicted to behaviors too. I should emphasize that.

Steven Bartlett: When you say drug of choice, you mean the brain has a particular sensitivity to that drug in terms of dopamine?

Anna Lembke: Yes. Okay, the more dopamine that's released, the faster that it's released, the more likely that drug is to be addictive for a given individual.

Steven Bartlett: So you're holding some whiskey there. I'm holding some whiskey. There could be a brain that is very sensitive to whiskey, and there could be a different brain that you could pour all the whiskey and you like, and the dopamine response is sort of limited.

Anna Lembke: Exactly. And for many of my patients who become addicted to alcohol, they will tell you that from the first moment they had alcohol, they knew they were either in trouble or had met their best friend or some combination. It was a very potent experience for them.

Steven Bartlett: All right. So let's go ahead and put this on the pleasure side of the balance. Dopamine is being released. But no sooner has that happened than my brain will work very hard to restore a level balance.

Anna Lembke: Balance. And by the way, a level balance is what neuroscientists call homeostasis, okay? And one of the overarching physiologic drives for all living organisms is to return to homeostasis. Homeostasis is that parameter of what's often called affordances or states of being that are adaptive and healthy for the organism. For example, like we have a certain homeostasis of body temperature. And if we go much beyond that either too high or too low, we will disintegrate and die, right? So homeostasis is that states of being that are compatible with existence and potentially advantageous too. Sort of baseline level.

Steven Bartlett: That's right. Yeah, baseline level. And by the way, we're always releasing dopamine at a kind of tonic baseline level in our brains. I sometimes think of it as the heartbeat of the brain.

Anna Lembke: So what's happened here for people that can't see is you poured a little bit of whiskey into one end of the scale, the pleasure side of the scale, and the other side of the scale has risen because now there's whiskey in the pleasure side, which I guess has released dopamine? Exactly.

Steven Bartlett: So now we've released dopamine in the reward pathway. Okay. Because the pain side went up, does that mean there's now less pain in the brain?

Anna Lembke: Well, I think, you know, again, this is a metaphor. It's an oversimplification. The idea here is just when we press on the pleasure side, we're releasing dopamine in the reward pathway and experiencing pleasure.

Steven Bartlett: But no sooner has that happened than our brain will try to compensate or adapt to increased dopamine firing by down-regulating dopamine transmission, for example, by involuting postsynaptic dopamine receptors. What does that mean?

Anna Lembke: Okay. Okay. So our brain is a bunch of wires, you know, that conduct these electrical signals. And these long spindly cells are called neurons. And the thing about neurons is that they don't actually touch end-to-end. There's a little gap or space between them, and that gap is called the synapse. And that gap or synapse is bridged by what we call neurotransmitters, and dopamine is one of those neurotransmitters, okay? And when the presynaptic neuron pulses and releases dopamine, it crosses the synapse and binds to a receptor on the postsynaptic neuron, which either continues or aborts that electrical signal. Does that make sense?

Steven Bartlett: Okay. So one of the ways that our brain can decrease the effects of dopamine, decrease dopamine transmission, is by involuting or taking inside the neuron the postsynaptic receptor. That way, when dopamine is released, it has nowhere to bind. Oh, okay. So it's like removing the docking station.

Anna Lembke: Exactly. Very good. It's removing the docking station. So essentially, getting back to our scale, we've ingested alcohol, we've increased dopamine firing in the reward pathway. But remember, our pleasure-pain balance wants to return to a level position, level with the ground, homeostasis. So it's going to decrease dopamine transmission by, for example, involuting those postsynaptic dopamine receptors. But one thing about the brain in its process of trying to get back to homeostasis, and again, I like to think of this neuroadaptation process as these gremlins hopping on the pain side of the balance to bring it level again.

Steven Bartlett: You don't have gremlins here. You have these little rocks. But let's go ahead and put a rock on the pain side of the balance. And these rocks are our friends, right? Their job is to level the balance because, remember, we've got to go back to homeostasis. So I'm going to put a rock on, and you're going to see, oh, my gosh, it overshot, right? Now I've got it pressed down on the pain side of the balance. But that's exactly what happens in our brains.

Anna Lembke: In this process of neuroadaptation, those gremlins hopping on the pain side of the balance don't get off as soon as the balance is level. They stay on until we're tilted an equal and opposite amount. So is that what a hangover is or a come down? As they would say when people take drugs, they say, I have a come down.

Steven Bartlett: Exactly. That's exactly what it is. That's the hangover, the come down, the blue Monday, or on a much smaller scale, just that moment of craving, right? That moment of wanting to have one more shot, right? Why does it overshoot? Why can't it just perfectly hit homeostasis?

Anna Lembke: Such a great question. Because then we'd feel fine. Yeah. Why did Mother Nature do that to us? So cruel, right? Yeah. Okay. I'm going to tell you an evolutionary just so story. What we mean by that is we don't really know why, you know, this mechanism exists. But from an evolutionary perspective, if you're living in a world of scarcity and ever-present danger, this is the perfect mechanism to make sure that we're never satisfied with what we have, that we're always wanting more. It's made us the ultimate seekers.

Steven Bartlett: Okay, because immediately after getting something, I'm now feeling a lack of pleasure, and I'm at a deficit, you know, on the pain side of the scale, which means that I'm going to go seeking out more dopamine. And in a world where everything is quite scarce, that could mean going on another four-hour hunt the next day to go kill a gazelle or something. Perfect. You've got it perfectly.

Anna Lembke: Yeah. Okay, so that's going to motivate me, because... Jesus, people that have hangovers don't seem very motivated. Right. So now that's it. So why is that, right? It's because alcohol is a product of human engineering that releases so much dopamine all at once in the reward pathway that our brains are reeling to compensate, right? We really weren't evolved for this much pleasure with this much easy access. As you said yourself, we were really evolved to have to do quite a lot of work up front and to be hungry and to be lonely and to be tired and then get a little bit of reward that would then bring us back up to homeostasis.

Steven Bartlett: Does that make sense? Yeah. So you telling me essentially that we all wired to be addicted Because if this is how our brain works in a world it designed to seek out more dopamine But the problem we have now is we have all this synthetic dopamine, effectively, like this synthetic chemicals and synthetic things and, you know, an internet that is wiring us to give us so much dopamine so easily. That means that our brains are effectively, like, mismatched to the world that we live in, and therefore, why to be addicted? Yeah, I think you actually said that. I found a quote you said in an interview where you said, we're all wired to be addicted. And if you're not addicted yet, it's right around the corner. Right. Coming to a website near you. Yes. I guess I would qualify that a little bit by saying we're wired for survival in a world of scarcity. That's not the world we live in now. We live in a world of overwhelming overabundance. And so there is a mismatch between this ancient wiring that has us relentlessly pursuing pleasure in order to survive, and a world that's so infused with pleasure and so many rewarding stimuli that now we're overwhelming our reward system and our brains are reeling in response to try to compensate.

Steven Bartlett: So what happens to this scale then in such a world where I can get a big hit of dopamine all the time using some of these synthetic things or the internet or pornography or whatever else? What's going on with this scale over and over again? Okay, great. So let me get there. Let me first say, though, that remember, after we do something that's highly pleasurable, our brain compensates with neuroadaptation, tilting an equal and opposite amount to the side of pain, and then restoring our balance back to the level position, right, or what we call homeostasis. So this doesn't last forever, right? It's to pleasure, then it's to pain, then it's back to the level position. But if we continue to consume our drug of choice over days to weeks to months and we add in a whole bunch of other drugs and now we're consuming, you know, pornography and smoking pot and eating donuts and, you know, you name it all at the same time, then essentially what happens is those gremlins on the pain side of the balance end up camped out there. For anyone that can't see, she put all of the rocks into the pain side to represent all of the addictive behaviors that this individual has now taken on. Right. And now we've entered addicted brain, by which I mean that we've changed our hedonic or joy set point to the side of pain. Now we need more and more of our drug in more potent forms, not to get high and feel good, but just to level the balance and feel normal. And this is not going to be enough. To level the balance, I would have to keep filling this much more than this container can hold. And that would be in pursuit really of just trying to level that balance so that we can feel normal. And when we're not using, we're walking around with a balance tilted toward the side of pain, experiencing the universal symptoms of withdrawal from any addictive substance or behavior, which are anxiety, irritability, insomnia, depression, and craving. So if I managed to get enough vodka, whiskey, rum, and pour it into the pleasure side of the scale, now that all the rocks are in the pain side of the scale, I managed to outweigh it, it would, it would, what would then happen? More rocks. More rocks would be added. Yes, more rocks. So momentarily, I would maybe be in a little bit of pleasure. Yes. But then my brain would remove those docking stations again, remove more of them, and more rocks would go in and I'd slam down on the pain side again, which means I need more alcohol to try and get up to pleasure. Okay, so really you want to, you want to like dopamine fast. You need to just balance this. And this is so difficult because of the world we live in. It's almost, it's funnily enough because this little scales experiment analogy here has given me a huge amount of empathy for people that are addicts. Oh gosh, I'm so glad you said that because I think that is the key to empathy for the disease of addiction, as well as for people with the disease having empathy for themselves, is recognizing that on some level it's out of their control, right? Because when we are tilted to the side of pain, the overwhelming drive to restore a level balance or restore homeostasis as quickly as possible overwhelms any other rational thought about the consequences of my drug use, right? It's just like, get back to the level position because if I do that, I'll at least feel temporarily better.

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