Science and the Origins of Addiction Drugs, alcohol, gambling, video games -- why do some people become addicted? Is it genetic, or something in the environment? Can study of the neurobiology of addiction lead scientists to a cure?
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Science and the Origins of Addiction

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Science and the Origins of Addiction

Science and the Origins of Addiction

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This is TALK OF THE NATION: SCIENCE FRIDAY. I'm Ira Flatow. If you look back in history, whenever we didn't understand a disease or an illness, our response to people who got sick was always the same: we blamed the person with the illness. There was a time when people who had cancer were stigmatized. No one would dare say the c-word out loud. The same was true, and still is, to a certain extent, for mental illness, such as depression.

But, through the ages, as we became more enlightened about disease and disease processes, we have come to understand that cancer or mental illness is not a moral failure or a character weakness, but a disease. The same can be said about our attitudes toward addiction. Only now are we beginning to understand that addiction is a disease - that there are real biophysical changes that occur in the brain that can make some people vulnerable to becoming addicted and make it nearly impossible for them to quit; time after time, they relapse.

This hour, we're going to be talking about what scientists are learning about addiction and how that knowledge is changing the way addicts are perceived and treated, and if you'd like to get in on our conversation, our number is 1-800-989-8255; 1-800-989-TALK.

But I need to remind you, as we always do, that we really cannot diagnose or treat your problem addiction or what is bothering you over the air, but we'll be happy to talk about it in a general sense; it's just not ethical to ask our doctors to sort of talk about your problems, so please don't do that.

Let me introduce my guests. Nora Volkow is the Director of the National Institute of Drug Abuse at the National Institutes of Health. She joins us here in our New York studios. Welcome to the program.

Dr. NORA VOLKOW (Director, National Institute of Drug Abuse, National Institutes of Health, Bethesda, Maryland): Thanks for having me here.

FLATOW: You're welcome.

Shelly Greenfield is associate professor of psychiatry at the Harvard Medical School and Associate Clinical Director of the Alcohol and Drug Abuse Treatment Program at McLean Hospital in Belmont Massachusetts. She joins us from WBUR in Boston. Thank you for being with us today.

Dr. SHELLY GREENFIELD, M.D. (Associate Professor of Psychiatry, Harvard Medical School; Associate Clinical Director, Alcohol and Drug Abuse Treatment Program, McLean Hospital): Thanks for having me.

FLATOW: You're welcome.

Rob Malenka is the Pritzker Professor in psychiatry and behavioral sciences at Stanford University. Dr. Malenka joins us by phone from the campus. Thank you for being with us today.

Dr. ROBERT MALENKA (Pritzker Professor in Psychiatry and Behavioral Sciences, Stanford University, Stanford, Connecticut): It's a pleasure to be with you today.

FLATOW: Let me begin with you, Dr. Volkow. Dr. Volkow, is there any question that addiction is a disease now?

Dr. VOLKOW: There is no question that addiction is a disease. Research has shown that it effects the brain in very specific ways that can help us understand why, through this damage, the person loses control of his or her action, as it relates to taking drugs. So it is recognized that it is (unintelligible) a disease. Despite this, it is still not accepted as a disease by most people.

FLATOW: You mean, even doctors - physicians themselves?

Dr. VOLKOW: Unfortunately, yes. Most, while they, in some instances, may just say, yes, it's a disease, and then they immediately put, but - and the moment that you hear the but, then you start to recognize all of the reasons why they start to counter that argument. So, yes, indeed, even physicians do not recognize that sometimes it's a disease.

FLATOW: Dr. Greenfield, you work in a clinic, you see people with addiction. Where does something cross the line from being a habit - a bad habit to something that's being addictive?

Dr. GREENFIELD: That's a good question, Ira. I think where it crosses the line is where we think of addiction as a compulsive use of a substance or a compulsive behavior that continues to take place in the life of someone, in spite of the negative consequences that that person actually acquires because of their use of the substance.

And this actually is quite different from a habit that might be somewhat annoying - annoying to the person or annoying to somebody else, but doesn't start to manifest itself in a number of negative consequences in that person's life.

FLATOW: So that the addiction becomes the overwhelming part of that person's life?

Dr. GREENFIELD: Sure. We have a number of things that we look for, in terms of when we begin to call something an addiction. We're really looking for adverse consequences in the person's life, such as a person spending more time using the substance, or using it in greater quantities than they want to, giving up activities because they're using the substance or recovering from it - that they continue to use something in spite of the fact that they know it jeopardizes their physical or their mental health.

So those are ways that we can distinguish between something that's what we might call a habit and something that actually has begun to be the disease we know as addiction.

FLATOW: Mm-hmm. Dr. Malenka, let's get right down to the physiology of addiction. I know that's what you study and you specialize in. What happens in your brain when you take drugs or alcohol for the first time, and then something happens that makes you addicted to it?

Dr. MALENKA: Well, that's a very good question, but a complicated and difficult one to answer. I think - and again, Dr. Volkow also knows a lot about this topic, and she can, hopefully, pipe in. I think one of the breakthroughs in the addiction field was the realization that one common action of many different substances of abuse, whether it's nicotine or alcohol or cocaine or heroine, that they all work on something we call the brain's reward circuitry.

You know, through evolution, the brain has evolved to tell us what feels really good, what is rewarding, what is important for our survival. And we now know that all these different drugs of abuse act on this specific circuit in these specific brain areas.

We also know that an important chemical messenger in these brain circuits is a substance we call dopamine. It's a substance we term a neurotransmitter, and it turns out that all these different addictive substances increase the actions or the release of dopamine.

And then, in very complex ways that we're beginning to understand, but we have a long way to go, the release of this dopamine in certain brain structures leads to certain - tells the person that this substance is reinforcing or rewarding.

And then, for certain genetically vulnerable individuals, there are adaptations, long-lasting changes in these circuits that lead the person to believe that the pursuit of this substance is the most important thing in their life.

And I don't know how much detail you want me to go into, but there are changes - long-lasting changes in the connections between nerve cells as a consequence of the use of the drug - these connections we term synapses. So the communication between individual nerve cells that are part of this circuit start to change.

There are molecular changes in these cells that are part of these circuits. And we know - you know, we're beginning to learn a reasonable amount about what are these molecular changes, what are these changes in specific connections between nerve cells. And that's the first step towards trying to understand how to reverse those changes.

FLATOW: And so, Dr. Volkow, actually rewiring the brain during addiction?

Dr. VOLKOW: Correct. The brain learns by the experience produced by drugs, which is why not only that this experience is highly reinforcing pleasurable, but also highly salient. And one of the aspects that we've come to recognize is not just that drugs cannot be these reward centers by increasing the concentration of dopamine, but they do it in much more powerful and long-lasting ways than any of the other natural reinforcers.

So, as a result of that, it is believed that the brain tries to adopt to this very strong stimulation by drugs to compensate. And it is believed that these adaptations are the ones that lead to the changes that we - that occur in addiction.

One of the things about these reward centers is it's exactly the way that nature ensures that we will do behaviors that are indispensable for survival -ensures. So one of the mechanisms is not just that you feel pleasure, but in parallel to this experience, the areas of the brain in which you encode memories - and is not just the memory of the event, but the emotional memory -get activated by that experience in such a way that the next time that you get exposed to the drug, or to stimuli associated with the drug, it will recreate the sensation leading to the intense desire to procure the drug.

So it's not just the issue of experiencing pleasure, but the consequences in the memory that is associated, as you asked the question, with plastic changes, with the formation of new synapses that will then drive the behavior.

FLATOW: So then, any kind of memory of what started you - I'm getting to the idea about relapsing. Even if you've kicked the habit or the addiction the first time, it's very easy to relapse, should that little stimulus happen again.

Dr. VOLKOW: It's extraordinarily important what you are bringing up in the terms of why it's so difficult to treat addiction and why people, despite the fact that they face catastrophic consequences - not negative, catastrophic -and they don't want to take the drug anymore, they relapse. And it has to do with - it's almost like a reflex.

It's almost - when you think about something you like and you start to salivate; inside your brain, there is a release of dopamine when the person that's addicted sees stimuli associated with the drug that activate the motivational circuit almost in a reflex-like way. And that drives him or her to do that behavior. And that's evidently one of the mechanisms by way - why its -relapse occurs and it's so difficult to kick up the habit.

FLATOW: So finding a way to erase that original circuitry then was a challenge.

Dr. VOLKOW: I mean - and, indeed, that's one of the strategies that we're now trying to encourage investigators: to look at the development of medications that can either erase those memories associated with the drug or, alternatively, very important, can you create stronger memories that can overcome those learned responses, so that your behavior is not driven by what we call conditioning, but by these new learned experiences.

And there is ongoing research. It's - at this stage, it's predominantly done in laboratory animals, but there are some real interesting positive results that suggest that this strategy may, in fact, prove beneficial in helping through the therapeutic process.

FLATOW:: Mm-hmm. Well, we're going to take a quick break and then come back and talk lots more about addiction with my guests, Nora Volkow, Director of the National Institute of Drug Abuse at the National Institutes of Health; Shelly Greenfield, associate professor of psychiatry at the Harvard Medical School, Associate Clinical Director of the Alcohol and Drug Abuse Treatment Program at McLean Hospital in Belmont, Massachusetts; Rob Malenka, Pritzker professor in psychiatry and behavioral sciences at Stanford University.

When we come back, we're also going to bring on someone who has a firsthand experience with drug addiction, Marvin Seppala, who is Chief Medical Officer for the Hazelden Foundation. If you know anything about drug addiction, you know what the Hazelden Foundation is in Minnesota. He's going to join us. Hope you will stay with us, as we'll be right back after this short break.

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FLATOW: You're listening to TALK OF THE NATION: SCIENCE FRIDAY. I'm Ira Flatow. We're talking about drug addiction this hour with Nora Volkow, Director of the National Institute on Drug Abuse; Shelly Greenfield of Harvard Med School; Rob Malenka of Stanford. I also want to bring on now Marvin Seppala, who is Chief Medical Officer for the Hazelden Foundation. He joins us by phone from Oregon. Thanks for being with us today, Dr. Seppala.

Dr. MARVIN SEPPALA (Chief Medical Officer, Hazelden Foundation): Thanks for the opportunity, Ira.

FLATOW: I understand that originally you planned to be a surgeon. What happened?

Dr. SEPPALA: Well, originally I had no vocational plans and actually dropped out of high school as a result of addiction. And later, was hired into a research lab at the Mayo Clinic before I went to college. I applied to be a janitor, and I can't explain how I got this job, but somehow I was hired as a laboratory technician, and in that lab, you know, managed to get clean and sober attending self-help meetings.

I had already been through treatment, at 17, after dropping out of high school, but at this point, at 19, got clean and sober and was influenced by the physicians. There were fellows from all over the world doing fellowships at the Mayo Clinic. And, ultimately, decided I'd be a doctor and a surgeon like some of them.

And halfway through medical school, I saw how few doctors understood addiction and fewer cared about it. And I was complaining about this to friends and they said, Marv, you've got to quit complaining and do something about this. And it was at that point I chose to go into the field of addiction.

FLATOW: Mm hmm. The - are most of the people you treat at Hazelden seeking treatment for the first time or are they relapsing?

Dr. SEPPALA: You know, the bulk of them are seeking treatment after prior treatment, so relapsing. But we - most of our programs are residential programs, and that would usually be the case, that often people have failed other levels of care first.

FLATOW: Mm-hmm, Shelly Greenfield, do you find that to be true, too?

Dr. GREENFIELD: I find - do I find it to be true that people seeking care multiple times? I would say yes, in most circumstances people do seek care multiple times, and a lot of this is because of the kinds of neurobiological changes that Dr. Volkow and Dr. Malenka have talked about. One thing that's very helpful in understanding the neurobiology of the brain is it can help explain to patients and their doctors why moving past and getting well and into recovery can be so difficult.

On the other hand, the other part that's so important for people to understand is, like other types of medical disorders, addiction is a treatable disorder and people do actually get better. But like other medical disorders, like diabetes, hypertension, heart disease, people generally don't get better on a single treatment. They often require several different treatments, sometimes different types of treatments over time, in order to slowly but surely regain their health - their physical health and their mental health.

FLATOW: Mm-hmm, 1-800-989-8255, let's go to the phones. Jennifer(ph) in Boston. Hi, welcome to SCIENCE FRIDAY.

JENNIFER (Caller): Hi, how are you?

FLATOW: Hi, how are you?

JENNIFER: My question actually was - you know, I'm listening to your program, and I understand what you're saying when there is a substance involved, like how you, you know, how you can be medically addicted to let's say nicotine or alcohol. But I was wondering if you could talk a little bit about people's brains when they're addicted to a behavior, like gambling; do you see the same changes? And, you know, do you actually consider it the same type of addiction?

FLATOW: Mm-hmm. Let me ask Dr. Malenka first, and then I'll get to Dr. Volkow. Bob?

Dr. MALENKA: I think - and again, Dr. Volkow can comment on this - I think the general consensus is yes, that a lot of these other kinds of compulsive, especially rewarding behaviors, or reinforcing behaviors like gambling, like overeating, like perhaps even videogame playing, certainly effect these so-called reinforcement reward circuits, do effect the release of this chemical messenger dopamine. A little bit of the issue - the devil's in the details.

There's been some elegant work, in part done by Dr. Volkow, showing that it's not only the release of chemical messenger dopamine, but it's how much is released, and how fast it's released. And that has an important influence on the effects of that ingestion of a substance or that behavior has on your brain.

And it turns out the highly addicting substances, like cocaine and heroin - and again, I'm actually talking about, in part, Dr. Volkow's work - really cause a much more rapid, stronger increase in this chemical messenger than, for instance, what I do all the time, which is eat donuts, or eat a quart of Haagen-Dazs ice cream, which is highly rewarding for me. But I can kick the habit when I choose to.

FLATOW: You mean you've given it up 100 times?

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Dr. MALENKA: Absolutely.

FLATOW: Dr. Volkow, please...

Dr. VOLKOW: Very interesting question that has started to intrigue many of the scientists; certainly, it has intrigued me for many years. And using imaging, me and my colleagues at Brookhaven National Laboratory have actually delineated some of the changes in the brain that are similar, specifically in pathological eating in obesity, versus those that we see in addiction. But at the same time, identify the differences. So yes, there are similarities, but there are also differences.

Where we find the similarities is in both conditions - in this case overeating versus addiction - there is a marked disruption of the function of the brain dopamine system, which is, again, the one that's directly affected by drugs, but it's also the one that motivates our behavior vis-à-vis natural activities like eating or doing social interactions or engaging in procreation - sexual behaviors.

So that system becomes dysfunctional. It's dysfunctional in both of these conditions. And it is believed that one of the reasons why there is a motivation to either continue taking the drug or to compulsively eat is that it's a mechanism to compensate for this deficit.

On the other hand, what's uniquely different, for example, in this case of pathologically obese individuals, is that their brain is particularly sensitive to the pleasurable aspects associated with food. And it is believed that, evidently, that is the reason why they are favoring these particular stimuli, in this case, food, over other ones. So this is why some people become addicted specifically to a certain substance and others may become addicted to behavior, because each one of our brains responds with a different sensitivity to the rewarding effects of the stimuli.

FLATOW: Mm-hmm. Okay, Jennifer?

JENNIFER: Yes, thank you very much.

FLATOW: Thank you. 1-800-989-8255. If you hooked somebody up to one of these brain scanners, could you see, in real time - and if you looked at the brain of someone who was craving a substance, see the changes that are going on in there?

Dr. VOLKOW: Yes, indeed. Multiple investigators have been trying to see which areas of the brain get associated, get activated when you're craving. And it took us by surprise, because what the first study started to show many years ago was it was not the limbic areas of the brain that we usually expected, but actually the famous frontal cortex, which is the area of the brain that does cognitive operations, that allows us to exert judgment.

But there's an area in the frontal cortex, just on top of your eyes, that is directly connected to the limbic brain, that is involved with assigning value to stimuli. So a stimuli may be very exciting on a given moment of our lives, but not in another one. And that's the area of the brain that gets activated when a person is craving. In parallel, also we see activation on some of the limbic areas of the brain. So, yes, indeed, you can see your brain when it's craving.

FLATOW: Mm-hmm. 1-800-989-8255. Bob, why does stress often cause people to relapse? And we are always under stress now. Do you have any idea?

Dr. MALENKA: Was that question directed to me, Ira?

FLATOW: Yeah, I'll ask you first, and then I'll ask Dr. Volkow.

Dr. MALENKA: Well, it turns out that the circuits in the brain that respond to stress, that release certain hormones in response to stress, that tell us that we're under stress, are heavily interconnected with the exact circuits we've been talking about, the so-called reward circuits, the circuits that use dopamine.

And work from many labs has shown that both in humans as well in animal models of addiction that stress is a very important factor in leading to relapse, in causing the continued use of a substance, as well as leading to relapse. And it turns out that, at least in certain instances, the brain's response to stress is actually pretty similar, under certain cases, to the brain's response to certain drugs of abuse.

FLATOW: Mm-hmm.

Dr. MALENKA: So a classic set of experiments has shown that if you train an animal to self administer a drug - or, again, this happens in human beings, too - and then you take the drug away for many weeks or months, that an acute stressful event can have that person or animal start using the drug again. We believe that's because that stress, as I said, is causing somewhat the same -perhaps the same release of dopamine even that the substance abuse causes.

FLATOW: Dr. Volkow, do you want to amplify?

Dr. VOLKOW: Yes, indeed. It's evident Dr. Malenka was commenting that there is overlap in the circuits and brain areas that's effected by drugs and effected by stress. And where does that come together? It comes together again, interestingly, in dopamine.

Dopamine is not only there to signal pleasure, but actually to signal saliency; and as you recognize, of course, pleasurable events are very salient. We need to learn from there. But a stress is also very salient, because if we do not learn from it, when we are exposed to it again we may not avoid it.

So anything that has importance, in terms of the survival of the species, that connotes a need to learn an experience so you can change your behavior accordingly, will involve dopamine. Such as, when you are exposed to a stress, you are going to be releasing dopamine. And that's going to, again, drive a similar circuitry to that that we see in drug addiction.

And in individuals that are addicted, the increase in dopamine by itself is a conditioned response. It's a learned memory response that's associated with the drug. And this is probably one of the reasons why, when a person that's going through recovery is stressed, and then they relapse in a way similar to the way they relapse when they get exposed to a stimulant that, in the past, they had associated with the use of drugs.

FLATOW: Dr. Greenfield, are doctors and nurses adequately trained to spot signs of substance abuse? I mean, even when they come into an emergency room for what appears to be something else.

Dr. GREENFIELD: Ira, that's a very important point. And actually, I think that, in fact, oftentimes, doctors and nurses in spite of their best efforts and desires to be helpful to patients are not always on - trained as well as they might be to think about drugs and alcohol in a variety of clinical settings.

In fact, as you know, drug and alcohol addiction are among the largest, most prevalent problems that we have; they present a major public health problem in addition to an individual and family problem. And, in fact, at almost every health care setting, whether it's a physical health care setting or mental health care setting, patients present themselves for other types of disorders and they also have a co-occurring substance use disorder.

And this, in fact, will present an opportunity for physicians and nurses to actually engage patients and screen them for whether they're using alcohol or drugs in a harmful way, or whether they already perhaps have become addicted or dependent on these substances. Sometimes it's helpful - and a doctor can actually catch a patient where something is just teeter tottering on moving forward into becoming a major abuse or dependence problem and can help by educating a patient and referring them to treatment, to intervening earlier on in the course of the disease process.

And, of course, in every area of medicine, what we try to do is intervene as early as possible. But often doctors and nurses haven't had adequate clinical training to screen and diagnose and to understand what the treatment processes are.

FLATOW: That raises all kinds of issues I want to get to, but I wanted to first remind everybody that I'm Ira Flatow. This is TALK OF THE NATION: SCIENCE FRIDAY, from NPR News.

One of the issues I want to get to is many times you see in Hollywood, or the Hollywood version of what happens in an emergency room or in a hospital. The same addicts show up. They get shoved into a corner. The nurses or the physicians say, oh, it's just so and so showing up again to dry out. And they never get that attention that they need. Is that an accurate portrayal?

Dr. GREENFIELD: Are you addressing that to me, Ira?


Dr. GREENFIELD: Well, I think in some circumstances it can be. You know, one of the things that I think is very important to understand is that the person who may come back time and time again into an emergency room, there are individuals like that who do require help who aren't necessarily referred on. But, you know, they represent also a very tip of the iceberg phenomenon. And, in fact, the vast majority of folks who have substance abuse disorder problems on -actually, many are working everyday. They are taking care of various kinds of responsibilities out in the world, and they are actually having problems with addiction. Some times those things manifest themselves at home rather than at work. Sometimes they may not show up in an emergency room, but they may show up, maybe, in a mental health care clinic or a physical health care clinic.

So I think this is not just in the emergency room with someone who's coming in acutely, multiple times, but it's much more generalizable to all sorts of health care settings where we, as medical professionals, can do a much, much, much better job at diagnosing early and referring for treatment many, many individuals who could actually benefit from all the available treatments that do exist and are actually effective.

FLATOW: Marvin Seppala, do you agree?

Mr. SEPPALA: I do agree. And, in fact, although the training for physicians and nurses is limited in regard to addiction, it has improved somewhat. There's a new emphasis and even now level 1 trauma centers, as one of their requirements to reach that designation, have to evaluate addiction and alcohol dependents in the population that comes into their emergency room settings. And that's the highest level of an emergency room that's designated.

FLATOW: 1-800-989-8255 is our number. We're talking about addiction this hour.

Before we go to the break, Dr. Volkow, is this something that your institute worries about a lot?

Dr. VOLKOW: Yes, I worry a lot about it. And, in fact, I was smiling because that question - when I have to cover the emergency room as a psychiatrist was a very frustrating one, where we would get the patients and we really didn't know what to do with them. So yes, it is frustrating, and I think that it's still ongoing, in the sense that a patient that is addicted when they have a job or they are referred by their physician is very different from the situation of a person that is homeless, that doesn't have a job, that doesn't have a family, that ends up in the emergency room and you are actually hand tied, in terms of what you can offer.

So yes, we are particularly interested on that issue from the National Institute on Drug Abuse about how to increase the education of the medical community vis-à-vis the early recognition and the evaluation and proper referral of a person that is addicted. Unfortunately, many physicians do not ask the question. Why don't they ask the question? Because drug addicts are stigmatized and they feel uncomfortable asking the patients, do they drink? Do they take cocaine? And they don't even know how to ask that question sometimes; and certainly, not recognize it.

There's another element to it. Even if they do know how to ask the question, they don't necessarily know what to do then with that particular person, where to refer to, how to follow them up. And there's another element that is very, very relevant. Unfortunately, there is no parity for the treatment of drug addiction. So, as a result of that, many medical insurances will not cover the cost of doing an evaluation for drug addiction and proper referral.

FLATOW: All right, Dr. VOLKOW. Hang on there. Everybody else, hang on with us. We have to take a short break, pay some bills. We'll be right back after this. Stay with us.

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FLATOW: You're listening to TALK OF THE NATION: SCIENCE FRIDAY. I'm Ira Flatow.

We're talking this hour about addiction with my guests: Dr. Nora Volkow, Director of the National Institute on Drug Abuse; Dr. Shelly Greenfield associate professor of psychiatry at Harvard Med School; Dr. Rob Malenka, Pritzker professor in psychiatry and behavioral sciences at Stanford. Dr. Marvin Seppala is Chief Medical Officer for the Hazelden Foundation.

Our number, 1-800-989-8255. Let's see if we can get a few phone calls in. Mark in Boston. Hi, Mark.

MARK (Caller): Hi. My name is Mark. Great show, I love you so much.

FLATOW: Thank you.

MARK: So I have an interesting story - a comment that goes along with the question.

My father was actually the head of a halfway house which was, for many years was helping hundreds of people with drug and alcohol addiction, many successfully. So he's an example to this community and for over 20 years was completely sober. And then, suddenly he relapsed and he's been completely gone. And me and other members of my family have had a funeral for him pretty much because he's still alive, but he's not the person we once knew and there's really no hope of getting him back.

So that's the story. It's just we've seen personally how addictive tendencies can totally rewire someone's priorities and irrevocably change who they are.

I was wondering, is there any evidence that the later one gets in life, the more fixed patterns get, the more less plastic their brain gets, the more irrevocable they are? Is there any kind of pattern of addiction recovery being easier earlier on in life, or becoming more intractable later on in life?

FLATOW: Let me ask Marvin Seppala first - that question.

Dr. SEPPALA: I think it's certainly more difficult to address addiction in the older population. I think your description, in regard to questions of plasticity in the brain, are fairly accurate, that plasticity does decrease with age. I think the researchers should address that aspect of it. But we've done a great deal of work with the older population and find that they have to address their addiction slower, allowing more time and in a way - you're a little bit different than most of the people we see, because family members often deny that there's a problem in an older person, and most often, it's kind of like you can't teach an old dog new tricks, and that's not necessarily true, because we see good outcomes in an elderly population.

MARK: Well, that's good to hear, but I think what's one of the worst things about this situation is that some people, if they have this, they become actually positively dangerous and you can't really rely on their affections for family or their morals or any of those other things to protect you in those situations. So the family often has an unfortunate choice to where they have to cut off all contact for their own safety and also material and also mental safety. So - but I appreciate the work that you're doing, and this is a great program.

FLATOW: Thanks for calling. Good luck to you.

1-800-989-8255. Shelly Greenfield is that a common take that you hear?

Dr. GREENFIELD: I was listening to the caller's story and, obviously, I think one of the things that he points is that addiction is an individual problem, but it's also one that effects families and effects communities. And I think he's talking about a situation that, you know, I wouldn't say is so very common.

I think, in fact, overall, people do relapse; but, in fact, there are many, many available treatments that are quite effective across the entire population range, from the very young, early adolescents, all the way through, actually, the very old. And I do think there's a lot of variability amongst individuals, in terms of their own inherent vulnerabilities to the substance, in terms of how long and severe their use was, how much abstinence they had, and also what other kinds of co-occurring disorders they might be battling, such as depression or anxiety or an eating disorder. Many individuals with substance abuse disorders are also battling other types of mental health problems, as well, and so there's a lot of individual variation.

I think, in fact, though, that we are able to treat a vast majority of folks, and actually, in many instances, have people who are in recovery for many years sometimes with relapses that occur periodically. Hopefully, if they remain connected to treatment and to a treatment community, they can recognize a relapse quickly and associate themselves again with treatment that's been helpful and shorten the actual duration of their actual relapse or lapse.

And that's what we aim for: to keep people as healthy as we can over time, and if they do slip - a relapse - to shorten the duration of that and to return them as quickly as possible to their best-functioning selves.

FLATOW: Dr. Volkow, are there any drugs, or potential drugs, that are on the horizon or might be developed, that are waiting to be developed, that might not just treat the addiction but reverse those brain wiring pathways?

Dr. VOLKOW: Very challenging question, indeed. And, we are trying, again, encourage investigators using laboratory animals to do exactly that. Can you strengthen certain pathways that have been damaged by the chronic use of drugs?

There are some very interesting compounds that, for example, are targeting more the disruptions that exist in the memory circuit. We're also looking to strengthening the ability of your brain, through cognitive operations, to regulate your emotions and your desires. And this is, of course, a pathway that is badly eroded by the usage of drugs.

Those compounds are currently being investigated in animal studies, some with actually fascinating positive results. But it's very difficult to get these compounds into the clinic, because, first of all, it's very, very expensive. And, in general, the major burden of developing these medications has relied on the pharmaceutical industry; and here in the pharmaceutical industry it's not one of their primary interests. And there are many reasons why that is so.

But one of them is that drug addiction is stigmatized. There's - as we were mentioning for, there's not even parity for drug addiction, so that does not help the - certainly doesn't help the translation of potentially promising medications into the practice.

FLATOW: But let me just stop you. But there are potentially so many people who could be helped by this, though. You always hear drug companies saying, well, it's not a big enough market for a drug that we might produce. It seems like there would be a big enough market here for that.

Dr. VOLKOW: Yes, indeed, and particularly because what we're starting to recognize is that there may be medications, if you're developing a medication, you don't necessarily need to address it a medication for cocaine addiction, but rather a medication for addiction, in general. And then you can start to recognize that, indeed, the market could be very large.

The other aspect about it, as we were discussing before, is because some of these processes also underline some of the behavior of compulsive disorders, such as pathological gambling, or compulsive eating. These medications could also be beneficial in addressing some of the disruption that we see in these individuals.

So yes, I agree that there is a market. But, as I said, unfortunately, stigmatization has not helped. And there's always the sense and fear - and I can understand the pharmaceutical and where they come from, because they have to make a profit, of course - is the sense that a person will be reluctant to take a medication that is useful for depression, because it also seems to be a medication that is being used, for example, for the treatment of (unintelligible) addiction.

So there's always fear about that, how can that effect the perception of a given medication. And that has influenced the pharmaceutical.

FLATOW: And so you haven't been able to talk them into working on it?

Dr. VOLKOW: Indeed. I would say that that is changing. I think that the pharmaceutical industry has been much more open over the past five years to start a dialogue and explore the feasibility, I think, in terms of not just from the perspective of (unintelligible) we're going to make a profit, but they recognize the importance that this would have to the community.

The ability to be able to develop, for example, a medication to treat methamphetamine addiction would be quite extraordinary.

Dr. SEPPALA: And, Ira, if I can add in - another reason the pharmaceutical industry is beginning to pay attention is our understanding of the neurobiological basis of addiction has advanced enormously, in large part because of the efforts of NIDA over the last ten or 20 years. So they're beginning to realize, you know, this is a biological problem that can be attacked with modern biomedical research efforts and that there's really some hope.

You know, 20 or 30, or whatever it was, 40 years ago, when we had really very limited understanding, there was no way to rationally develop pharmacotherapies for various addictions. And now that there's been such great progress, you can start thinking of many different approaches to take.

FLATOW: Go head. Somebody wanted to jump in there.

Dr. GREENFIELD: Yeah, I was going to jump in. I would also echo that this stigmatization has really held back the general public understanding of all the gains that have been made over the last 20 years both in the basic biology, but also we have 20-plus years of treatment-related research on many different models of treatment; both behavioral and pharmacotherapeutic, singly and in combinations that have been demonstrated in multi-site trials funded by the National Institute on Drug Abuse, by the National Institute on Alcohol Abuse and Alcoholism, and other federal agencies, that have demonstrated time and time again that this treatment actually works; people actually get better; people do much better.

And so our public ideas, whether it's the public, in general, or the public, in terms of medical professionals, patients, families, are behind the times - very much so - in catching up with this vast amount of research that has been done over the last 20 years, that really shows this over and over again. From the basic biology, it's a classic bench to bedside story - basic biology and treatment-related research demonstrating over and over again that many, many patients can be helped.

FLATOW: So, Dr. Volkow, we have these drugs, they've have been tried out, we just can't get them to market.

Dr. VOLKOW: We cannot. Well, we cannot get them into the clinics. We cannot get that translation from the animal experiments into the humans as fast as we could, because of restriction and budgets. The government has to carry the costs that are associated with these medication developments.

But I do want to make a point that Dr. Greenfield was covering, because I think it's very important. There are many treatments, not just medications, but there's actually behavioral cognitive group therapies that have been unequivocally shown that they work. They are effective in the treatment of drug addiction, and yet they are not necessarily all the time accepted as such. And what we've come to recognize, actually very much through the insight of Dr. McClellan, is one of the reasons has been that people expect the person that goes to treatment to be miraculously cured after going through a rehabilitation program.

So they go through the rehabilitation program, they stop taking the drugs. Six months later something happens in their lives and they relapse, and that is then used as an argument. You see? Treatment does not work. Of course, we would never use that argument for someone that is being treated with anti-hypertensive medication for high blood pressure. The moment he or she stops taking the medicine their blood pressure goes up; you'll never use the argument, you see, that does not work.

So we've been treating the problem of drug addiction, again, and this relates to the whole stigmatization aspect of it, very differently from the way that we treat other diseases, and the same thing, in terms of what we expect of the treatment of drug addiction. We expect a cure, yet we know that it's a chronic disease. So we are treating; very rarely do we cure right now.

FLATOW: We're talking about drug addiction this hour on TALK OF THE NATION: SCIENCE FRIDAY, from NPR News.

Does someone want to jump in here?

Dr. GREENFIELD: Yeah, I did.

FLATOW: Dr. Greenfield, was that you? Go ahead.

Dr. GREENFIELD: It was me. I wanted just follow up on what Dr. Volkow just said, because it's so important.

Actually, if you follow along on that model and continue to think about it -for someone who's being treated for diabetes or heart disease or hypertension, what you hope you would do is you would help them in the acute first illness that they had, and then you enter them into treatment. And you want them to be followed up over the long term to keep them healthy, and hopefully to prevent any more acute episodes.

This is very similar to substance abuse treatment. People come in acutely, you treat them, and then what you'd really like to do is enter them into care where they're followed to keep them as healthy as possible. If people are connected to care, if there is a stressful life event or something else that comes up, they're already hooked into care and they can usually continue how they're doing or circumvent any exacerbation in their condition, hopefully avoiding, if possible, another major episode.

And this is truly a model of keeping people well over time; that it's really important we begin to implement for people with substance use disorders. We have many models in chronic disease care that work. We know that this is a kind of model that will work for substance abuse, as well, over the long term.

FLATOW: Dr. Malenka, I'm going to give you my famous blank check question, which is, if you had a blank check and you could spend it anywhere. And you needed a breakthrough or some medical equipment or some sort of laboratory experiment that you would like to perform, what would it be so you could learn more about this?

Dr. ROB MALENKA: Oh, wow. Are you really going to give me that?

FLATOW: Well, a hypothetical - the same check I give everybody.

Dr. MALENKA: I think I would just - actually I would do a little bit - a lot more of what NIDA and other agencies are currently doing. I would put more money into really defining both the molecular changes in the brain that happen in response to substances of abuse or during addiction, but really, beef up the imaging approaches so we can really understand, because the devil is always in the details. Which specific brain areas, which specific connections, which circuits in the brain are really being modified in a semi-permanent way during addiction?

I would also probably put a lot of the money, if I had a blank check, into trying to identify either both genetically and through other approaches, those people who're going to be most vulnerable to developing addiction. Trying to get kids, you know, I think - and, again, Drs. Volkow and Greenfield can speak on a more sophisticated level about this - but I believe people really start developing their problems mostly during adolescence, late adolescence to early adulthood, and I think it would be wonderful if we could identify those specific individuals that are going to be particularly susceptible and vulnerable to (unintelligible) addictions.

FLATOW: Let me give someone who handles money, Dr. Volkow, the last 30 seconds to tell us what she would do with the money, if she had it.

Dr. VOLKOW: Well, I'd like to be able, with the money, to create the knowledge that would allow us to have piety for substance abuse; the knowledge that would drive and motivate and intensify the pharmaceutical industry to be able to fund medications into clinical practice. And finally, to use that knowledge to create more targeted prevention, such that less people get exposed to drugs.

FLATOW: And as Dr. Malenka was saying, identify kids at a younger age that might be susceptible?

Dr. VOLKOW: The earlier we start, the better off we are; because if we can indeed intervene early, we may be able to cure addiction.

FLATOW: Thank you very much, all, for joining me.

Dr. Nora Volkow, Director of the National Institute on Drug Abuse; Shelly Greenfield, associate professor of psychiatry at Harvard Med School and Associate Clinic Director of the Alcohol and Drug Abuse Treatment Program at McClean Hospital in Belmont, Massachusetts; Dr. Robert Malenka, Pritzker professor in psychiatry and behavioral sciences at Stanford University, and Dr. Marvin Seppala, Chief Medical Officer for the Hazelden Foundation in Minnesota.

Thank you all for taking time to be with us today.

Dr. SEPPALA: Thank you for covering this topic.

Dr. GREENFIELD: Thank you very much.

Dr. VOLKOW: Goodbye.

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