Nora Volkow, Director of the National Institute on Drug Abuse, separates the drug addicts from drug users.

Question: What makes somebody become addicted to a drug?

Nora Volkow: Many surprising findings have come across the studies that have completely destroyed all of the hypotheses that we initiated with. For example, when we first started doing these studies, one of the things that I had postulated, not because it was my great idea, but because a lot of people had been postulating it and in animal models, there was evidence that that could be the case, that people that were addicted because drugs were more rewarding, more pleasurable. And thus, their brain will have a much greater release of dopamine in these limbic areas when they took it. And so, that was the idea. But we did the studies and consistently now in three independent investigations that we've done in our laboratory, and similar findings have been reported by others at Columbia University, we've shown exactly the opposite. Which is fascinating! What we're observing is that in cocaine addicted individuals, and individuals addicted to alcohol, that in these subjects, the ability of drugs to increase dopamine is actually markedly decreased and their subjective experience of the drug is also decreased. But what's fascinating is that this fact, almost in contradiction, in contrast to these decreased responses, when they take the drug, they immediately, it's almost like triggers the desire of more, of more, of more. Like, almost like you open the faucet and there's this intense drive to want more drug and this inability to get satiated.

And I always try to understand when someone is telling me this experiences, have I ever felt that way? And I've never been addicted to anything, but I am a very compulsive person, and I can get into stages, certainly for example, with food, certain foods, I generate, and you eat a chocolate chip cookie and it tastes so good that you immediately know that you want more and you do another bite, and you already in your brain are saying, "I'm going to want more." So when I think about it, this is the closest it gets. Or when you've been incredibly, incredibly thirsty. I actually, I just start to drink water, it seems like you need more and more and more water, right? Eventually, of course, you just get bloated and that's the end of the water. But in the person that's addicted, that's what seems to happen.

So the reward center itself is decreased, but it triggers a response that is abnormal, that you don't see in people that are not addicted. And our imaging studies, of course, we've been trying to understand then, what is driving this different response, even though you have less reward, why are they generating this response? And what we have shown and certainly other investigators have looked at that is, that you've shifted the response to the drug to add stimuli that is associated with the drug and this is done through memory and learning, condition. We all know about conditioning, because Pavlov taught us that if you show a dog, taught him hear a sound when they get meat, and you do that repeatedly and repeatedly and then one day you bring the dog and you just show the sound, that animal will salivate with the sound. There's no meat, they salivate. That's a transfer of the physiological response that initially was triggered by the meat into the sound. And that's what we call conditioning.

Now, you can look inside the brain and try to understand what happens, why is this dog salivating with the sound? It just makes no sense. Well, the learning, the brain has automatically linked the meat with the sound so in the moment that the brain inside listens to the sound, it's predicting that the pleasure will come, it's predicting the meat. So just automatic they've learned. The brain needs to learn in order to be prepared and that's exactly what happens when people become addicted to drugs, they get conditioned to a wide variety of stimuli.

So, for example, a person that is snorting cocaine with a $20 bill, when they see that $20 bill will do the equivalent of salivation, except inside their brain, and what's going on is, their brain, in expectation of getting cocaine, is releasing dopamine. So they've transferred what was a pharmacological response, a response to cocaine, an action of the drug affecting specific areas in the brain, is now triggered by observing a $20 bill. Now what happens when dopamine goes up, because they see that $20 bill, is that that activates the motivational circuit that drives you into action. So, the brain is saying, this is motivational salient, this is relevant, remember? All of the circuits were generated for us to survive, to do behavior crucial for survival, it, sex for procreation.

So these are hard wired across evolution. So your brain is immediately, automatically responding and it becomes an automatic response. So in that moment, the person desires and takes action to take the drug. They have all of these learning responses and memory that actually just automatically triggers a behavior that becomes compulsive and repetitive.

And they cannot stop it. It's basically, when the brain engages in such a state, and the normal mechanisms by which we sort of control our desires and our behaviors, all of us, all of us. I think that if we are honest, on a daily basis have things that tell us, "I want that! But I shouldn't do it, it's a bad idea. I just can think of a million reasons why it's a bad idea." And so we have to relinquish things that we want on a daily basis. How can we do that? Well, we judge, we analyze, and it's always a balance about how much we want this and how bad it is to go and do this.

So dopamine actually there plays a very important role because it regulates the brain areas that are making the analysis, that are judging. Is this worth the effort? Is this worth the punishment? And in base of that, that judgment, you then stop. Stop the behavior. No matter how much you want it, if your judgment is not worth the risk, you'll stop it. And that's also regulated by the pathways. So when you've been taking the drug repeatedly, you basically disrupted all of these normal mechanisms that allow you to exert judgment and to decide, no, it's not worth the risks. Or basically you decide, "No, I don't think it's a good idea. If I take cocaine, I'll end up, my probation officer will put me in jail." You cannot stop it.

Recorded on November 6, 2009