The Hijacked Brain

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Speaking with neuroscientists and addicts themselves, Bill Moyers unravels the mysteries of the addicted mind. Bill goes into the laboratory to follow researchers engaged in charting an image of desire in the brain.


TRANSCRIPT

WENDY WALKER: My dad was a wonderful father when he wasn’t drunk, but when he was drunk, he just — he wasn’t there. My dad was an alcoholic and so was his father.

WENDY WALKER: I had always been very interested in school. I loved school. And all of a sudden my motivation for school became unimportant. Drinking and hanging out became much more important than school.

HAL DUNNING: I got through college and graduate school on speed.

WENDY WALKER: I started drinking vodka and I fell in love with vodka.

HAL DUNNING: The first time I ever did coke — on my 25th birthday. Here we are in beautiful Miami. Within six months, I was a full-blown addict.

WENDY WALKER: It replaced everything in my life that I loved.

HAL DUNNING: Lake Havasu … During my cocaine days, I was drinking at least two to three six packs a day. Had to take the edge off, so it’s an incredible balancing act. You know, just the right high and the right low.

WENDY WALKER: I got introduced to heroin. My whole personality changed. I would fight.

HAL DUNNING: I started doing crystal meth in 1989. I mean, it — I could work forever and I did. I mean, I got promoted from general manager to vice president of quality assurance to executive vice president of quality assurance in three years.

WENDY WALKER: When I came out of my Mama’s womb, I didn’t say, ‘When I grow up I wanna be a drunk. wanna be a tramp.’ I didn’t say that. And I didn’t want that, but that’s what happened.

BILL MOYERS, host: How did it happen? How could it happen? I’m Bill Moyers. Now, at last, the mysteries of the addicted mind are beginning to unravel. Over the past decade, some extraordinary scientific expeditions into the workings of the brain have enabled us to understand how it is that some people will sacrifice everything — their family, their work, their health — to satisfy their hunger for a chemical fix. We’re learning how drugs enter the pathways of the brain, what scientists call the reward circuit where we experience joy, pleasure, euphoria, how they alter the brain to create something that didn’t exist before, and what all this means to motivation and behavior. Call them archaeologists of the brain, these neuroscientists, using new imaging technologies, they’re digging deep into the complex riddle of addition.

Dr. HANS BREITER: OK. While Terry’s getting her in the bit bar, we might want to hook up this component.

MARY: Adjust any way you need to.

HANS BREITER: Now do you feel like you’re hanging on? Just going to test this IV while they’re doing that.

Unidentified Man #1: OK. Lift just your head up straight up.

MARY: In you go, Denise.

BILL MOYERS: Denise is a cocaine user.

Man #1: I’ll get you some tape, Mary.

BILL MOYERS: She has volunteered for research at Massachusetts General Hospital in Boston, where neuroscientists are taking pictures of her brain on drugs.

MARY: OK, Denise, now you’re going to hear the beeps for about two minutes. Just slow, loud beeps. Hold real still. (Beeps heard)

Dr. STEVE HYMAN: (MD, National Institute of Mental Health): This gives us a picture of a thinking, feeling, living human brain as it processes information over time.

HANS BREITER: Those are good-looking images. (Beeps heard)

STEVE HYMAN: We literally see the activation of specific circuits in the human brain. (Beeps heard)

HANS BREITER: Nice-looking brain. Right. Let’s clear that component and get ready to replace the experimental slices. Excellent. This person had a significant amount of rush and high from the test dose. And so I suspect that we’ll get a — a wonderful effect here.

BILL MOYERS: Because she is awake and functioning, the scientists can talk to Denise while they X-ray her brain’s blood flow.

HANS BREITER: You’ll start to feel something in your left arm, that — that will be the infusion.

BILL MOYERS: It is a delicate and carefully choreographed process.

HANS BREITER: You may get two doses of saline, you may get two doses of cocaine or you may get one of ei — of either, OK?

BILL MOYERS: Dr. Hans Breiter is the team leader.

HANS BREITER: Let’s do it. (Beeps heard)

HANS BREITER: OK. We have 10 seconds until we start the infusion — six, five, three, two, one, now.

BILL MOYERS: Dozens of images taken over a short period of time show where in the brain the drug is active, where craving for the drug actually takes place.

MARY: Look at that screen.

BILL MOYERS: Dr. Steve Hyman once directed Harvard’s Initiative In Mind, Brain and Behavior. He now heads the National Institute of Mental Health.

STEVE HYMAN: So here it is, we tum on this checkerboard pattern.

HANS BREITER: Is that centered for her?

STEVE HYMAN: And now we’re going to be able to see whether even in the presence of cocaine we get the normal expected activation of the visual circuits.

HANS BREITER: OK. That’s a nice acquisition.

STEVE HYMAN: Mm-hmm. As the drug is coursing through her veins and getting into her brain, we’re gonna be able to get a picture of her brain as she is reporting to us.

BILL MOYERS: She can actually tell you what she’s thinking or feeling at any moment you’re taking a picture of the drug impacting on a part of her brain?

STEVE HYMAN: That’s exactly right. We’re getting a map of her feelings. We’re getting a map of what structures in her brain are active as she reports the feeling of high, as she reports later on after the drug wears off the sense of craving or wanting the drug. Literally what this allows us to do is get an image of desire in the brain.

Now this is not only interesting from the point of view of fundamental aspects of our humanity, it also has a practical significance for people who are addicted to drugs, because if we know where in the brain drug craving is, we can start to think about what chemicals are involved, what the timing is, and perhaps come up with better treatments, which can be administered to affect the right cells and very importantly at the right time.

(Beeps heard)

ALAN LESHNER: There’s something about these biological changes that are going on at the neuron level, at the cellular level, at the molecular level that gets translated into compulsive, uncontrollable drug use. The electric current comes down the neuron, the little chemicals get released here — got it? These are the neurotransmitter dopamine coming out of the first cell.

BILL MOYERS: Dr. Alan Leshner is director of the National Institute on Drug Abuse which provides more than $400 million annual for research on addition.

ALAN LESHNER: …that addition is fundamentally a brain disease. Let me just show you a diagram.

BILL MOYERS: Leshner is often on the road to talk about the findings of addiction research. Today he’s at Eastern Middle School in Silver Spring, Maryland.

ALAN LESHNER: The problem is it’s not just a brain disease. Addiction itself is actually a result of a combination of environmental factors, historical factors, the physiological state of an individual like their genetic background. They all come together through the brain to produce addiction, but it’s not anyone thing all by itself doing it.

BILL MOYERS: You call it a disease.

ALAN LESHNER: It’s a disease because it’s a result, actually, of drugs changing the brain in fundamental and long-lasting ways. And it’s a chronic, relapsing disease because typically — sadly, but typically — people don’t have only one episode of addiction, they have repeat episodes.

Addiction is not a voluntary circumstance. It’s not a voluntary behavior. It’s not just a lot of drug use. It’s actually a different state.

WENDY WALKER: I liked the effects. I liked it. I liked it — what it did for me, because it took me from reality and put me wherever I wanted to be.

HAL DUNNING: I thought it made me smarter. I thought it made me more creative. I thought that I — I was more powerful. It made me complete, no question about it.

BILL MOYERS: For how long?

HAL DUNNING: For 20 minutes, and then I could do another line.

ALAN LESHNER: There are common mechanisms in the brain that are triggered by every major addicting substance. Now we don’t know for sure that this is the common essence of addition, but it’s very striking that all addicting substances cause a change in dopamine levels — that’s nicotine, heroin, cocaine, amphetamines, alcohol, marijuana — all produce changes in dopamine functioning in the same general area of the brain.

BILL MOYERS: Dopamine is part of our brain’s vast and intricate communications network. All of us have some hundred billion cells or neurons in our brains. They communicate with each other by electrical impulses and the release of chemicals. These chemical communicators are called neurotransmitters. Dopamine is one of them. When we have a pleasurable experience, the brain releases dopamine.

STEVE HYMAN: So, for example — normally, we might have a very positive experience and get a certain amount of dopamine released, we might have a wonderful meal, we might accomplish something, we might win a race and get a certain amount of dopamine. What the drug abuser finds is that they can literally fool the brain, they short circuit the brain. They take drugs, and they get this sense of well-being, of happiness, of euphoria and what’s really striking is that it’s reliable. When they take cocaine, when they take heroin, they can produce this again and again on a regular basis. None of the vagaries of; ‘Will this experience live up to expectation?’ And that’s what gets them in trouble, because by bombarding the nucleus accumbens and the rest of the brain with more dopamine than it had ever seen before, the brain adapts. It literally becomes dependent on the drug, it is changed by the drug. You can no longer feel OK, once you’re addicted, without the drug.

Unidentified Man #2: We can sort of put the …(unintelligible) in.

MICHELLE: Mmm-hmm.

STEVE HYMAN: Sounds like a reasonable idea?

MICHELLE: Yeah.

BILL MOYERS: In his lab at the National Institute of Mental Health in Bethesda, Maryland, Dr. Hyman and his researchers want to know more about how drugs chemically seduce the brain.

STEVE HYMAN: This crew here is really studying very directly how drugs and neurotransmitters, the chemicals that nerve cells use to talk to each other, make long-term changes in the functioning of the brain.

BILL MOYERS: Have you found the answer to his question about why the brain prefers drugs to broccoli?

Unidentified Man #3: Not yet.

MICHELLE: We’d all be out of business.

STEVE HYMAN: Well, you do know that. You know that — Right? — there’s nothing in broccoli that taps into brain reward pathways. All of the most addictive drugs are natural plant products, initially. So cocaine came from the coca leaf, tobacco produces nicotine, and opiates came from the opium poppy.

Now the chemicals in, say, the coca leaf that produced cocaine, fool the brain and literally reproduce, although in massive fashion, the equivalent of the release of dopamine. There’s nothing in broccoli that does that. Literally the chemicals in a small number of plants are Trojan horses, they’re masqueraders. They — they look just like natural chemicals found in the brain and they fool the brain.

BILL MOYERS: So they come in here and they say, ‘That was good,’ but it really wasn’t good.

STEVE HYMAN: That’s exactly right.

HAL DUNNING: And I’d go to a board of directors meeting — stand up there in a board of directors meeting and — and give a presentation, and I would give this image that I was fine, that I felt whole and that I was competent. And I knew that that night I was going to be going around the back gate of the local Marine base looking for more drugs.

WENDY WALKER: You don’t feel like a human being when you’re in the throes of this disease, Bill, because the things that you’re doing are inhuman. You’re lying, you’re stealing, you’re cheating.

STEVE HYMAN: People who are addicted will go to extreme lengths to get their drug of choice, despite incredible negative consequences, despite all kinds of trouble.

BILL MOYERS: Because this is telling them that they must have it and it’s changing their behavior to get it?

STEVE HYMAN: Absolutely. This has been hijacked. This part of the brain is there to say, ‘This is good, this is important, this is what makes the world good for you.’ And what’s happened is that in response to the drug we have made this part of the brain, an — and associated structures, unable to function without the drug. The brain has been compromised, usurped, changed, whatever. You’re a different person once you’ve been addicted.

HAL DUNNING: The last two years of my crystal use, it got worse and worse and worse and I knew I was in \deep trouble. And I’d be up for a second or third night in a row and I’d be in my apartment and I’d be sure that there was somebody outside the door. I’d be peeking out from behind the curtains, trying to catch them. I knew about this paranoia that happens sometimes when you’re a crystal addict. I knew it was there but I — I couldn’t stop it.

WENDY WALKER: My mind told me to get on a window ledge. Well, I fell four stories down in a brownstone in Brooklyn and almost died.

HAL DUNNING: I let everything around me collapse. You know, my house went into foreclosure. I lost my car. I kept my phone bill paid because I had to have that connection to my dealer. Ended up losing my job. That’s always the last thing you lose, is your job because that supports your habit. I realized I didn’t have any control. I realized no matter how much I wanted to quit, I couldn’t. And it was — it was — it was the most fear I’ve ever felt in my life.

ALAN LESHNER: What we’re talking about is they’re being in a state where the drug has totally taken over their being. What that means, clinically, is that they’re in a condition where they suffer from compulsive, uncontrollable drug seeking and use. People are able to understand this now when they think about schizophrenic people who act in very bizarre ways. Why are they acting bizarrely? Well, there’s something wrong with their brain. That’s exactly what’s happening in addiction. Something is changed in the brain.

WENDY WALKER: You don’t know you’re falling in love with it. You don’t know that it’s beginning to take a priority. Except for one day you wake up, and you know you’ve got to have it because you can’t function.

ALAN LESHNER: Literally, what happens is that you take the drug for a prolonged period of time and it changes the biochemical processing in the brain. You stop taking the drug and that change persists. For example; with methamphetamine, we know that chronic use of methamphetamine reduces the ability to produce dopamine, while you’re taking methamphetamine for a long period of time. Then you stop taking methamphetamine and you still are less able to produce dopamine four weeks later, six months later, a year later, we believe — we haven’t proven this yet — but we believe that that then results in an ability to experience pleasure in a normal way.

BILL MOYERS: So you go back to the drug again and again just to feel normal, to feel right?

ALAN LESHNER: Absolutely. So what happens with crack cocaine is that you take cocaine initially to elevate dopamine. And then after you use it repeatedly, dopamine levels go down and then the person feels terrible.

HAL DUNNING: In the beginning it was absolutely pleasureful. It was exciting, it was erotic. You know, I really looked forward to it. I loved to get high. At some point, though, it was no longer exciting. It was just the way I was. It was j — I just did it to function. I did it to get out of bed; I did it to go to work; I did it — I mean, it was just the way I lived.

BILL MOYERS: Drugs, as a way of life, became a vicious cycle. Chronic use creates the brain’s need for more. Dopamine surges then subsides. Pleasure gives way to pain, until use and abuse spiral into addiction. To penetrate this puzzling and powerful vortex of drug addiction has taken some extraordinary detective work. Sherlock Holmes, meet George Koob.

PAT: Morning, George.

GEORGE KOOB: Good morning, Pat.

BILL MOYERS: At the Scripps Research Institute in La Jolla, California, Koob is investigating the common essence of all drug addictions, whether the substance is alcohol, nicotine, cocaine, amphetamine, heroin or marijuana.

GEORGE KOOB: And Tony is preparing these probes for an experiment.

BILL MOYERS: Koob and his colleagues are studying rodents to understand how prolonged and plentiful drug use depletes dopamine.

GEORGE KOOB: This goes right into the rain of the rodent.

BILL MOYERS: And how it affects other neurotransmitters.

GEORGE KOOB: So this is a very, very sensitive technique for measuring neurotransmitters. You can also see the membrane.

BILL MOYERS: What looks to the layman like a satellite photograph of Hawaii is actually the neural landscape of a rat’s brain. Koob ‘s team has identified where the dopamine is released, an important part of understanding how, during addiction, the brain’s reward system triggers a roller coaster of emotions.

GEORGE KOOB: … involved. And as you can see here in this diagram here, it’s — the work has focused in on an area called the — the nucleus accumbens, which is up here in the basal forebrain. But also, on this — an area called the central nucleus of the amygdala.

BILL MOYERS: If you published this as a map, would right here be the pleasure center of the brain, the sort of Times Square or Disney World?

GEORGE KOOB: Not so much a pleasure center but a pleasure circuit. This is the circuit of the brain that we believe is important for guiding our everyday life.

BILL MOYERS: To do the things we have to do, like eating to survive, sex to procreate?

GEORGE KOOB: Yes. And what we’re discovering is that drugs of abuse basically usurp this circuitry, they take it over. In other words, you no longer seek out natural pleasures because the drug is driving the system. Our bodies are built, in my view, to experience a certain amount of pleasure.

BILL MOYERS: A certain amount of pleasure to be sure. But in everyday life, most of us don’t go off the deep end with pleasure, our appetites for food, for sex, are governed.

GEORGE KOOB: So the issue is that something regulates that. Why aren’t we copulating all the time, why aren’t we over — always overeating? Why aren’t we overindulging in any of these things that we need to survive as a species?

BILL MOYERS: So there’s something in the original blueprint that seeks pleasure and at the same time regulates the pleasure I’m having?

GEORGE KOOB: In a — in a sense, there is some kind of control mechanism. Similar in my — in my view, similar to that that regulates body temperature. Basically, I think we have so much money in the bank in terms of pleasure in our lives. And we can expend that money over the course of a weekend in binging on cocaine, or we can expend it over a two-week period in the normal pleasures of everyday life. But if you expend these — this pleasure neurochemicals in one go and sor — such as a binge of drug addiction, then one pays for it. The system has to self-regulate, the p — the system has to re-regulate and return to homeostasis.

BILL MOYERS: What do you do for pleasure?

GEORGE KOOB: My favorite occupation when I’m not doing science is that I grow fruit trees, blackberries and peaches and nectarines.

BILL MOYERS: Koob’s curiosity leads him to look at how artificial pleasure created by drugs differs from natural pleasures.

GEORGE KOOB: I mean, it’s hard to make equivalent a 30-minute cocaine binge with my gardening, but if I were to do that, I would think that the pleasure that is derived under each circumstance could be more or less the same, it’s just condensed over time. And that, of course, explains why cocaine is such an unbelievably powerful reinforcing stimulus.

BILL MOYERS: It gets there very quickly.

GEORGE KOOB: It gets there very quickly and it activates those dopamine neurons much more quickly, presumably, than natural stimuli would do.

BILL MOYERS: Koob believes the speed and intensity with which addictive drugs work in our brains uses up our dopamine supply — no more dopamine, no more pleasure.

GEORGE KOOB: So your — your brain’s reward system is depleted. You get no pleasure from anything, except drugs, and even the drugs don’t do it anymore.

BILL MOYERS: Well …

GEORGE KOOB: So you have depleted the system, you’re out of money in the bank

BILL MOYERS: It’s not only that dopamine is depleted by chronic drug use. Other neurotransmitters are affected as well.

GEORGE KOOB: When we measure the amount of…

BILL MOYERS: Koob has recently discovered a neurotransmitter that jump starts the body’s stress system after plentiful drug-taking. To relieve the stress, the addict wants more.

GEORGE KOOB: And so alcoholics will report that they’re drinking to reduce stress, when, in fact, the alcohol is producing more and more and more stress in them and so — and then they start drinking to reduce the stress that the alcohol produced and you get into this vicious cycle that we were talking about earlier.

HAL DUNNING: Two feels good, so three is going to feel better. And then four would feel better. More is always better. That’s the addict mind, more is always better.

GEORGE KOOB: And so one of our passions right now, one of our major interests for which we don’t have a lot of the answers yet, but it’s not only us but many, many other laboratories across the country, are trying to understand how this cycle then translates into vulnerability, to future relapses and future drug addiction. And that’s pretty much where the action is. What we need to do is — is understand how this sequence of events leads to a vulnerability to relapse an — and why do people go back? Eighty percent of individuals who detoxify, within a year, go back to drug-seeking behavior an — and relapse.

BILL MOYERS: Have you ever had a relapse?

WENDY WALKER: Yes. Yes, I did. I relapsed after being in the program for seven years.

HAL DUNNING: And I was cleaning my house and I found this little yellow box that I used to stash my drugs. And before I knew it, I’d taken it. And it absolutely scared the hell out of me. I mean, it just — I could not believe that from where I’d been that I would relapse.

WENDY WALKER: Slick start talking. Slick is that little voice — that’s what I — we give it a name. Slick. I’m powerless over Slick, you know what I mean?

BILL MOYERS: Slick’s smarter than you?

WENDY WALKER: Slick is very smart, Bill. I mean, whatever Slick tells you to do, you — you can’t stop. You just — you just do what it says and Slick said, ‘Go ahead and get your drug of choice and get high. ‘

HAL DUNNING: If I’m feeling inadequate, if I’m feeling alone in the world, anything can trigger me, anything can make me think that I need to use.

Dr. ANNAROSE CHILDRESS: Relapse is really the cardinal and defining feature of addiction disorders. Patients always, with or without our help, will usually take a break from their drug use at some point, become drug free. So they go through a period of detoxification, rehabilitation, feel that they’re in pretty good shape, they may be in better physical condition than they’ve been in a long time, highly motivated, but the difficulty is staying that way. What happens for patients with addictions is that the tendency to return is powerful.

BILL MOYERS: What triggers that urge to use again, when the addict already knows the hard way that using can be deadly?

ANNAROSE CHILDRESS: I see.

BILL MOYERS: This question drives the research of Dr. Annarose Childress.

RON: She OD’d this morning I heard.

BILL MOYERS: Childress shows volunteer subjects videos she has made of drug-using situations …

RON: Meet me on the comer back here.

TONY: OK.

BILL MOYERS: The mere sight of a hypodermic needle, or a familiar street comer or another person using, even on television, can stimulate craving in the addict’s brain.

ANNAROSE CHILDRESS: And now that you’ve seen the videos …

BILL MOYERS: As her research volunteers watch the videos, Childress makes images of their brains with the new PET scan technology.

ANNAROSE CHILDRESS: Patients describe that many of their episodes of relapse are preceded by craving state. So this

work is directed toward seeing in the brain where this state occurs and it gives you a way of rationally beginning to talk about what craving is. So what we want to do …

BILL MOYERS: Annarose Childress is a psychologist at the University of Pennsylvania’s Treatment Research Center. She both studies addiction and teaches addicts how to deal with cravings.

ANNAROSE CHILDRESS: But this is pretty realistic, too. So where would you want to put the …

BILL MOYERS: She began her work 15 years ago using polygraph tests to indicate body changes when volunteers are exposed to cues that trigger craving.

Unidentified Man #4: All right, man. All right. Solid, man. Thanks, Jim.

ANNAROSE CHILDRESS: Yeah, the lighting on this is really good too.

LARRY: Beautiful, huh?

ANNAROSE CHILDRESS: So the best that we can do is bring in a videotape that’s true to life. And the way that we get

a good one is by using our patients as collaborators. They tell us when we’ve got the right thing. This is a pretty good close-up scene.

LARRY: Yeah. I’m getting the sweats just watching it.

BILL MOYERS: Before the session ends, Childress will work with her volunteers so they’re not left in a state of craving drugs.

RON: We’re going in there, right?

BILL MOYERS: On the streets of Philadelphia, Ron and Tony are helping Childress create authentic videotapes.

ANNAROSE CHILDRESS: OK. So let’s start talking a little bit about what the bag’s gonna be like, the fact that you heard it’s really good stuff.

BILL MOYERS: Both Ron and Tony have been battling heroin addiction for decades.

TONY: Octopus was out and I did a shot of that — a bag of that one day. Man, I was crossing my knees, man, and my eyeballs …

RON: I like that. I ain’t had no dope where I crossed my knees in a long time, OK?

BILL MOYERS: Describe the pleasure you get out of that first high, that first rush.

RON: Hey, man, it’s a utopia. It’s like — it’s like — it’s like — pardon me, Doctor, it’s like when you — when you — when you reaching your climax, man.

BILL MOYERS: An orgasm?

RON: Yeah. It’s like when you come to your climax. Man I’ve seen at times — I say, ‘Wow.’

ANNAROSE CHILDRESS: That’s perfect.

RON: You know what I mean?

ANNAROSE CHILDRESS: In fact, he describes it spontaneously that way but our patients often use sexual terms to

describe this pleasure ’cause it’s certainly on that dimension. But what they will usually say is that it’s very often like orgasm, but many times more strong.

BILL MOYERS: All right.

RON: Yeah.

BILL MOYERS: But what happens the second and third time?

RON: That’s when — see, but that’s — this is one of the reasons you get hooked. Now we keep trying to find first — that first time, that first time is — is the greatest of all.

BILL MOYERS: You always want to get back to the first time, but you can’t.

RON: That’s why we — you keep going, keep going trying to get — find that — that first time again and you never find it.

TONY: I’ve been getting high for 30 years. I’m still trying to get it back again. I mean, the first time was just the ultimate, man.

BILL MOYERS: What was it? What drug?

TONY: Urn, the first time I shot was crystal meth.

BILL MOYERS: Crystal?

TONY: Meth — speed.

BILL MOYERS: Speed.

TONY: Yeah. It was like — I mean, it knocked me on my knees and I came in my pants, that’s how strong it was, the rush. And I’d go do about anything just to get a shot, sometimes. I mean, it takes away all my problems of the day or — it takes away everything, man. It just numbs you.

ANNAROSE CHILDRESS: And importantly, for all of these drugs, the vulnerability to return to use, the pull, the going

back, that tendency — it’s a cardinal feature of addictive disorders, across the board, and it’s there long after any withdrawal symptoms have ceased.

BILL MOYERS: So the body remembers?

ANNAROSE CHILDRESS: Long after. The — the body remembers and there’s this desire to recapture that experience and to relive it again and again and again.

TONY: I’ve been in jail a few times and I — I detoxed in a jail. You know, you’re sick for days and days. And like you say, Iíll never do this.’ Soon as you get out, man, you’re do — back doing the same shot again. I couldn’t be out an hour and I’d have it ag — you know, I’ve already kicked and times have been — gone by. I’ve been six months in jail.

BILL MOYERS: And you don’t want to go back to jail. You don’t want to go back to jail.

TONY: The first day I got out, man, I was — I did a shot.

BILL MOYERS: Why?

TONY: I just. ..

ANNAROSE CHILDRESS: It pulls you back.

TONY: I don’t know what — it just — I just love that high. I mean, it’s just like — it’s immense.

RON: It’s a magnet. It’s a magnet.

BILL MOYERS: What’s a magnet? ~ON:

Heroin. The feeling — it’s a magnet. You — I did three and a half one time, coming off — swore …

BILL MOYERS: Three and a half in jail.

RON: And swore I wasn’t going to and, man, I wasn’t home an hour. I wasn’t home an hour.

RON: You got the scratch?

TONY: Yeah, man. How about six?

RON: All right, my man.

BILL MOYERS: Many addicts report the same experience of being pulled back to using. It’s as if something turns on the autopilot to relapse.

ANNAROSE CHILDRESS: Talk a little bit about the feeling that you sometimes get as you’re about to get close to dope. It’s almost like you’ve already used it.

TONY: I mean, just knowing that you’re getting it is like — you can almost feel it, especially when you start cooking it up and smelling it. And it’s like…

RON: When you put that spark in there, boy, that smell that comes off of there, man, is …

TONY: That’s a high all — just by itself.

RON: Oh, man, you know, you’re getting ready to get high.

ANNAROSE CHILDRESS: That’s an important thing, actually.

BILL MOYERS: How’s that?

ANNAROSE CHILDRESS: He’s describing that when he actually begins to cook up, that before the drug ever gets in the syringe, before it ever touches his arm that he begins to feel a little bit of the high feeling before he even gets there. In animals, we’ve been able to see when you put down little probes in the brain, that when you have things that remind the animals that a cocaine injection is coming, or a heroin injection is coming, that it leads to an increase in the same chemical messenger, in advance of the drug ever getting there, that the real drug produces, like an increase in dopamine, the chemical messenger we’ve been talking about.

RON: Go around the block, man. Meet me back up on the comer.

ANNAROSE CHILDRESS: It’s the simplest kind of association learning and it’s very powerful.

RON: All right, man. Listen, I’m gonna — I’m gonna go back here and cop, hoping the dude’s here, man.

TONY: All right.

ANNAROSE CHILDRESS: So now, seeing a certain street comer or seeing someone get high on a videotape or even in real life, means opiates may be coming. It’s not exactly a memory of, ‘Oh, I was on 38th Street and I remember’ — it’s, ‘I know what this feeling was like. It takes me back to the feeling.’ So it’s a feeling memory and that’s important.

BILL MOYERS: An emotional memory.

ANNAROSE CHILDRESS: Emotional memory, feeling memory.

STEVE HYMAN: Emotional memory has literally the emotional content or meaning attached.ï What emotion does is it evaluates something, it gives it its significance for us. When you use drugs, for example, not only do you remember the experience, the euphoria, the high, but also the scene, the precise scene, who you used it with, where you used it.

Now one of the things about emotional memory, which is so important, is that they are powerful and long-lived because they’re associated with survival. You know, if sex weren’t rewarding, nature’s experiment with sexual reproduction would have been a failure.

BILL MOYERS: If we didn’t have sex, we wouldn’t recreate ourselves. But when we have sex, we say, ‘Hey, that was good. Let’s do it again.’

STEVE HYMAN: You remember it. In the case of positive emotional memories, we think that the chemical dopamine is what’s involved as marking them as survival enhancing. So when you encounter a wonderful new food, a wonderful new experience, dopamine is released. The next time, when you anticipate getting that new food, having that experience again, dopamine is now released in anticipation. Now where the emotional memory is stored in response to these survival-enhancing, positive memories is not yet entirely clear. Actually the amygdala may play a role, so might the nucleus accumbens which we’ve been talking about, but so might other parts of the brain. And one of the long-term hopes of — of this kind of approach in humans is that we’ll be able to map exactly where these emotional memories are stored.

BILL MOYERS: The amygdala, an almond-shaped structure in the brain, lights up on the screen when Childress takes PET scans of the brain during drug craving.

ANNAROSE CHILDRESS: What we’re able to see is that when our patients are viewing videos that remind them of their drug and entering this state of craving or desire, this structure seems to be differentially activated. When they’re looking at nature videos from public television, the amygdala is not really all that interested.

Another structure in the brain that seems to be differentially activated during this state is something called the anterior cingulate. So what we see here as sort of a developing signature of craving in the brain is that these structures are saying, ‘Something emotional, significant, is about to happen.’

OK. To what degree — zero to nine — are you feeling any craving or desire for heroin at the moment?

Unidentified Man #5: Eight.

ANNAROSE CHILDRESS: If we ignore these desire states, that seem to persist long beyond the last use of the drug, long beyond the last sign of any withdrawal symptom, then we’ll be missing the boat. And so part of our effort here has been to focus on developing strategies, whether they’re behavioral strategies, in — in terms of talking therapies, to help people cope with these states when they’re triggered, or whether it’s medications that we would basically like to have that would be helpful in tuning down the compelling quality of this craving. Not to the point that a person is without desire, because a person without desire is …

BILL MOYERS: A zombie.

ANNAROSE CHILDRESS: .. .is numb. And no one would want to live that life. But to put them in a range that would be more manageable.

Unidentified Man #6: Di — double shot of DNA?

STEVE HYMAN: Yeah.

BILL MOYERS: Scientists working in the addiction field are studying all kinds of medications, vaccines and therapies for their potential use in treatment. Their research often comes back to real-life experience.

MICHELLE: I have been touched by many people who have been profoundly affected by addiction, both — one branch of my family and one of my closest girlfriends, who is my age, just passed away several months ago from longtime abuse of alcohol and cocaine. So if — if — if I could do one thing in my — in my life, it would be to discover some possible pharmacological treatment that would give people — individuals who find themselves profoundly addicted to these substances — just something that would even take the edge off for long enough to enable them to get on their feet just enough to give them a chance through — through psychotherapy, through group work with — with other people like themselves and fulfill their potential as humans.

BILL MOYERS: Is the brain of the addict different?

GEORGE KOOB: I think it’s clear that after they’ve become a drug addict their brain is changed, and it’s probably changed forever. The real question is: Is the brain of a potential addict different than the brain of a non-potential addict? And that’s an issue that’s still being explored. Large proportions of people who use drugs do not become addicted.

BILL MOYERS: Most people who drink don’t become alcoholics, most people who take cocaine don’t become addicts.

GEORGE KOOB: And actually a large proportion of people who use heroin don’t become heroin addicts.

BILL MOYERS: Why can I have two glasses of wine and want no more? And yet, my good friend can’t stop at six? Is that what you’re asking?

GEORGE KOOB: Yes. I mean, we can only speculate at this point, but maybe someone has higher endogenous levels of stress hormones, maybe someone has a deficit in dopamine function, or a hyper dopamine function. We don’t know at this point. That’s gonna be the real challenge for future work.

BILL MOYERS: Trying to identify who’s at risk?

GEORGE KOOB: Who is at risk and how to translate the information that we gain from the animal studies to the human studies.

STEVE HYMAN: One explanation is simply that you induce processes that degrade the RNA.

BILL MOYERS: One clue to discovering who’s at risk for addiction lies in the genetic code that makes every human

being different. That gives each brain its own signature.

STEVE HYMAN: What’s the first gene you’re gonna put in the cells? This group of people is discovering genes that are regulated by drugs and what they do inside nerve cells.

MICHELLE: There’s no vibration. There are no…

BILL MOYERS: What researchers want to know is how biology and biography produce addiction.

STEVE HYMAN: It is clear that the brain is built in interactions between your genes — what you inherit in your

DNA — and the environment. It’s really striking. There are about 100,000 genes that go into making up a human being, about 70,000 of them are expressed in the brain. So the environment has to work together with the genes to build a brain.

Having said that, we emerge in childhood, or — or later on, with real differences in our dopamine system, in our nucleus accumbens, in different parts of our amygdala. That’s part of our own natural diversity. It’s that combination of th — the thermostat being set differently in all of the different circuits in the brain that makes one person more likely to try drugs …

BILL MOYERS: Right.

STEVE HYMAN: …makes a person more likely to get caught if they use drugs. But, obviously, none of these things are genes alone, or environment alone.

BILL MOYERS: Your father was an alcoholic.

HAL DUNNING: And so was his father.

BILL MOYERS: Your grandfather.

HAL DUNNING: Mm-hmm.

BILL MOYERS: Any others in your family?

HAL DUNNING: I’ve got two sisters who are also drug addicts, alcoholics. It’s throughout my family.

MARC SCHUCKIT: The risk for developing alcohol dependence is fourfold increased over the general population if you have a close relative with alcohol dependence.

WENDY WALKER: Alcoholism runs deeply in my family.

BILL MOYERS: Your parents?

WENDY WALKER: My parents, my grandparents. It cost me my mother. My mother died from cirrhosis of the liver when she was 35 years old. My father died when he was 39.

MARC SCHUCKIT: Alcohol has for centuries been an integral part of most societies. People accept it as a normal part of our culture and dance around the issue that other people are at risk, but they’re not. Take a little bit more.

BILL MOYERS: At San Diego’s VA Hospital, Dr. Marc Schuckit has been conducting a landmark study into who is at risk for alcoholism.

MARC SCHUCKIT: We’ve got how many more minutes for him?

Unidentified Woman #1: Three more minutes.

MARC SCHUCKIT: Keep on going.

BILL MOYERS: For two decades, he has tracked a group of 450 men to determine who will become an alcoholic.

MARC SCHUCKIT: It should be kind of interesting. Just kind of watch what your own reactions to things are. To develop a problem with alcohol or other drugs — it’s a combination of biological vulnerability and environment. I’d like to study both. It turns out that the biology is a little easier to study than the effects of the environment.

Unidentified Man #7: Now I want you to pick up your feet there. March in place a little bit.

BILL MOYERS: Each new volunteer is given alcohol, followed by tests that measure body sway and brain waves.

Man #7: Pick up your feet again.

BILL MOYERS: Motor function and memory.

Man #7: Steady as you can now, here we go.

MARC SCHUCKIT: We looked for a theme. That is, is there a characteristic that people might be inheriting that increases the risk for alcoholism?

Man #7: Try to remember as many as you can. So go ahead and look at the screen there. Here we go.

BILL MOYERS: Schuckit has found that those with the proverbial hallow leg, who at first could drink and drink without showing serious effect, were more likely to be headed for trouble down the road.

Unidentified Man #8: Valley. I got a valley.

MARC SCHUCKIT: So what we did is started a study to try and see whether it’s possible that as a group, children of alcoholics would show a low level of response to alcohol.

Man #8: Here we go.

BILL MOYERS: They did. An initial low response to alcohol, combined with a family history of alcoholism can be a double whammy.

MARC SCHUCKIT: If you are a son of an alcoholic with a pretty good sensitivity to booze, you got pretty high with a modest amount of alcohol, your risk for alcoholism 10 years later was about 15 percent. That isn’t 0, it’s 15 percent. Whereas, if you were a son of an alcoholic with this very low response to alcohol, the risk was 60 percent. That’s 60 percent alcoholism risk, even though these guys had all been highly functional, they had jobs, or they were in school at the time that we originally tested them.

HAL DUNNING: I just drank and drank and drank, you know, 26 beers in one — in one sitting and — and it — this — this was no big deal.

MARC SCHUCKIT: Number one: It runs in families, which doesn’t tell you genetics or environment, but says, ‘There’s something there worth looking at. ‘

BILL MOYERS: So how much higher, then, is the risk of alcoholism among the children of alcoholics?

MARC SCHUCKIT: Fourfold.

BILL MOYERS: Fourfold.

MARC SCHUCKIT: Yes. The second bit of information regarding genetics …

BILL MOYERS: Schuckit is professor of psychiatry at the University of California San Diego’s Medical School. He alerts aspiring doctors to the significance of the family tree when diagnosing and treating alcoholism.

MARC SCHUCKIT: Identical twins, one of whom is alcoholic, have a much higher risk for alcoholism in the second twin.

BILL MOYERS: His own study of adoption and addiction is now part of the scientific cannon.

MARC SCHUCKIT: The third — and I think the most convincing — is that adopted away sons and daughters of alcoholics still have that fourfold increased risk for alcoholism, even when raised by non-alcoholics. So if we look at his pattern of use of alcohol, we see problems in one, two, three, four, five categories.

Unidentified Man #9: Mm-hmm.

BILL MOYERS: Schuckit and his research group are currently conducting thousands of in-depth interviews with alcoholics and their families.

MARC SCHUCKIT: Did we finish off the …

BILL MOYERS: It’s part of a six city, multimillion-dollar genetic study with other researchers in the field that’s funded by the National Institute on Alcohol Abuse and Alcoholism. While the genetic search on alcoholism digs deeper, several risk factors, genetic and cultural, are already apparent.

MARC SCHUCKIT: Are they people who are relatively impulsive and easily bored? Probably higher risk for alcoholism. Are they people with a low level of response to alcohol? Probably higher risk for alcoholism. Are they people who come from traditions of never drinking, or never drinking to the point of drunkenness, an environmental factor that probably decreases any predisposition that’s there. But the real risk factor? Tell me your family history of alcoholism.

BILL MOYERS: So you’re not saying that anyone is destined to become an alcoholic?

MARC SCHUCKIT: No. Even if we’re talking about your mother and father were alcoholic and your families were loaded with alcoholism, the risk is still about 60 percent, as a rough guess. So that — nobody is predestined to become an alcoholic that I can think of. But everyone enters life with various levels of vulnerability, some to diabetes, some to heart disease, some to cancer, some to alcohol dependence, and I think that knowing something about those vulnerabilities gives you the opportunity of taking the steps to minimize the chance that this thing’s gonna happen to you.

If you know the causes, maybe you can find things that help people to avoid developing the problems, and by looking at causes, maybe you can find people who have unique needs in treatment. The good news is, most drug-related problems are reversible or at least tremendously improvable, although it’s a matter of trying to survive long enough for the body to be able to improve.

BILL MOYERS: Schuckit is also clinical director at the Scripps McDonald Center, a private treatment facility in La Jolla…

MARC SCHUCKIT: How?

HAL DUNNING: So it’s the drugs, not the lack of sleep.

BILL MOYERS: …where Hal sought treatment in 1994.

MARC SCHUCKIT: Yeah. I think that the genes probably explain 40 percent of the risk, and that other things that I don’t understand that are environmental, and behavioral and learned explain 60 percent.

HAL DUNNING: I believe that I was born an alcoholic. I grew up in a family of alcoholics and I don’t think I had any choice. I think once I started drinking, I was gonna be an alcoholic, and once I started using I was gonna be a drug addict.

BILL MOYERS: Does the fact that the brain has been hijacked — does that relieve the addict of — of a moral responsibility, of accountability? Does it — ‘I have a disease, my brain is doing this to me. There’s nothing I can do?’

STEVE HYMAN: Right. I — you know, this is — this is the — the downside of a disease model of addiction. People will say, ‘Well, nothing I can do, Doc. I’d like to say no, but I’m just a helpless tool of my DNA.’ But the fact is that the brain is not just one thing, or one synapse. So this critical part of the brain is altered. It’s not working right. It is giving us a perverted sense of priorities. But it doesn’t mean that the whole brain has been hijacked. We can still engage people and ask them to take responsibility for themselves. Now it’s difficult and I can tell you, even well-trained doctors sometimes really lose faith. But you have to be literally implacable. You must never give up with an addicted person. You have to come back again and again and again, because — I mean, this is not a trivial thing that’s happened to their brain. But you can still engage them, you can still treat them as a moral agent. Indeed, I think that success is getting people into treatment demands that you still treat them as a moral agent.

ALAN LESHNER: The stigma associated with drug abuse and addiction is one of the biggest problems we have in dealing with it. People hate addicts. Addicts commit crimes. People are nervous that addicts are going to do something to them. The truth is, though, an addict has an illness. Whether you like the person or not, you’ve got to deal with it as an illness.

WENDY WALKER: Part of why people get so angry — and I believe this — when someone says to them, ‘Why don’t you just stop?’ because they don’t have an answer. They don’t know why they don’t just stop. But when they go to the — to — to treatment, they learn why they don’t stop and it makes sense to them.

BILL MOYERS: What does it mean to realize that you have a disease called alcoholism?

HAL DUNNING: For me, what it did was relieve me of shame. I don’t have to be ashamed of what I am, of what I did. What I need to do is take the medicine.

BILL MOYERS: And the medicine is?

HAL DUNNING: Recovery.

BILL MOYERS: And treatment is a kind of post-graduate course in what you have?

WENDY WALKER: Yeah. It’s like a college. It’s like walking into a schoolhouse.

MARC SCHUCKIT: You stop me and you say, ‘No, no, no.’

ALAN LESHNER: It’s not about punishment, making them pay up. We believe that we have to focus on that which we can change. What we can change is the brain state.

BILL MOYERS: What happens to the brain during treatment?

STEVE HYMAN: Well, we’re not exactly sure. We are fairly certain, from animal models, that some of the adaptations, some of the changes in the brain caused by drugs reverse in a matter of weeks. Other changes take a longer time. These emotional memories that can be activated by reminders of the drug experience, these may really last a lifetime and require a great deal of vigilance from somebody who has been treated for drug abuse, lest they relapse even years after they’ve been treated.

ALAN LESHNER: People have to learn how to care for other people. People have to learn normal social skills Over again.

Unidentified Woman #2: You want to try some of this?

ALAN LESHNER: People have to learn how to be a responsible employee. Sometimes people have to learn work skills that they never acquired very well in the first place. We can’t put people, some of whom took drugs because they had life failures, back into a failure situation and expect them not to use drugs again.

WENDY WALKER: It’s quite a difference waking up and having some place to go. Going to work — you know, getting ready to go to work, like everybody else, as opposed to waking up wondering, ‘Where am I going to get my next drug from?’ And I see a different Wendy.

Looking good. Looking good, guys.

HAL DUNNING: Absolutely.

Woman #2: Yeah.

STEVE HYMAN: Interpersonal interactions have a profound effect on our nervous system …

Woman #2: That was pretty intense. I mean …

STEVE HYMAN: …and we know that groups can create support and comfort. And there’s something about supportive group interactions, something about belonging, which can create a powerful and safe holding environment.

MARC SCHUCKIT: I’ve got to protect myself.

HAL DUNNING: Literally, you are retraining your brain. You’re learning new things. So that you don’t end up in this same old pit once again. It’s a lot of hard work. It’s the hardest thing I’ve ever done — recovery — but it’s also the most rewarding. And I think that’s something I’ve really learned in recovery, is that the most rewarding things come with work, and my addict mind wants that immediate gratification, wants something quick, you know, an — and now I’m finding it doesn’t come quick. You don’t learn to climb a mountain in a weekend. You’ve got to work towards it.

BILL MOYERS: Hal Dunning was promoted last year to regional manager at a San Diego company three months after starting work there. It’s been how many years now that you’ve been recovering and sober?

WENDY WALKER: I’m working on 14 years, a day at a time.

BILL MOYERS: Wendy Walker last year became senior counselor at Hazelden New York, a private treatment center.

WENDY WALKER: What my immediate concern is, is when he comes in, put him on house safety. People are dying, you know; young people, old people, successful people, poor people. I don’t believe anyone is making a choice to have this illness.

ALAN LESHNER: We need to understand everything from the molecule to managed care. Because if we look for a silver bullet, or a magic bullet, we will fail. This is the most complex phenomenon that’s facing our society. And our strategy for dealing with it has got to be equally complex. We have to bring a multiple discipline approach to the problem and that’s what I hope the science will give us.

(Beeps heard)

STEVE HYMAN: Beautiful.

This transcript was entered on April 16, 2015.

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