Oct 11, 2008
Addiction Is a Brain Disease
An interview with Dr. Alan Leshner, director of the National Institute of Drug Abuse.
One of America's foremost experts on drug abuse discusses some of the latest knowledge about use, addiction, and treatment. Addictive drugs change the brain in fundamental ways, he says, producing compulsive, uncontrollable drug seeking and use. Leshner was interviewed by Contributing Editor Jerry Stilkind.
Question: Are there particular personality types or socioeconomic conditions that predominate among those who try a drug in the first place?
Leshner: There are different ways to approach this question. One, is to recognize that there are 72 risk factors for drug abuse and addiction that have been identified. They're not equally important. They operate either at the level of the individual, the level of the family or the level of the community. These are, by the way, the same risk factors for everything else bad that can happen -- poverty, racism, weak parenting, peer-group pressure, and getting involved with the wrong bunch of kids, for example. What these risk factors do is increase the probability that people with certain characteristics will, in fact, take drugs.
But you cannot generalize because the majority of people who have a lot of risk factors never do use drugs. In spite of the importance of these risk factors, they are not determinants.
So, what determines whether, say, Harry will use drugs, and whether Harry will become addicted to drugs? They're not the same question. Whether or not Harry will use drugs has to do with his personal situation -- is he under stress, are his peers using drugs, are drugs readily available, what kind of pressure is there to use drugs, and does Harry have a life situation that, in effect, he wants to medicate? That is, does Harry feel that if he changed his mood he would feel better, he would have a happier life? People, at first, take drugs to modify their mood, their perception, or their emotional state. They don't use drugs to counteract racism or poverty. They use drugs to make them feel good. And we, by the way, know a tremendous amount about how drugs make you feel good, why they make you feel good, the brain mechanisms that are involved.
Now, there are individual differences, not only in whether or not someone will take drugs, but in how they will respond to drugs once they take them. A Harvard University study published a few weeks ago demonstrated that there is a genetic component to how much you like marijuana. That's very interesting because the prediction, of course, is that the more you like it the more you would be prone to take it again, and the greater the probability you would become addicted. And so there's a genetic component to your initial response to it -- whether you like it or not -- and also to your vulnerability to becoming addicted once you have begun taking it. We know far more about this for alcohol than we do about other drugs.
Q: Do you mean that the genetic make-up of one person may be such that he gets more of a kick from taking cocaine than another individual? Is that what you mean by vulnerability?
Leshner: There's no question that there are individual differences in the experience of drug-taking -- not everybody becomes addicted equally easily. There's a myth that I was taught when I was a kid, and that was if you take heroin once, you're instantly addicted for the rest of your life. It's not true. Some people get addicted very quickly, and other people become addicted much less quickly. Why is that? Well, it's probably determined by your genes, and by other unknown factors like your environment, social context, and who you are.
Q: Is this true for people around the world -- in the United States, Western Europe, India, Colombia?
Leshner: The fundamental phenomenon of getting addicted is a biological event and, therefore, it's the same everywhere, and the underlying principles that describe the vulnerability, or the propensity to become addicted, are universal.
Q: What is addiction? How is it created in the body?
Leshner: There has long been a discussion about the difference between physical addiction, or physical dependence, and psychological dependence, behavioral forms of addiction. That is a useless and unimportant distinction. First of all, not all drugs that are highly addicting lead to dramatic physical withdrawal symptoms when you stop taking them. Those that do -- alcohol and heroin, for example -- produce a physical dependence, which means that when you stop taking them you have withdrawal symptoms -- gastrointestinal problems, shaking, cramps, difficulty breathing in some people and difficulty with temperature control.
Drugs that don't have those withdrawal symptoms include some of the most addicting substances ever known -- crack cocaine and methamphetamine are the two most dramatic examples. These are phenomenally addicting substances, and when you stop taking them you get depressed, you get sad, you crave the drug, but you don't have dramatic -- what we call "florid" -- withdrawal symptoms.
Second, when you do have those dramatic withdrawal symptoms with alcohol and heroin, we have medicines that pretty well control those symptoms. So, the important issue is not of detoxifying people. What is important is what we call clinical addiction, or the clinical manifestation of addiction, and that is compulsive, uncontrollable drug seeking and use. That's what matters. People have trouble understanding that uncontrollable, compulsive drug seeking -- and the words "compulsive" and "uncontrollable" are very important -- is the result of drugs changing your brain in fundamental ways.
Q: How do drugs change the brain? What is it that makes you feel good and wants you to have more?
Leshner: Let's, again, separate initial drug use from addiction. Although addiction is the result of voluntary drug use, addiction is no longer voluntary behavior, it's uncontrollable behavior. So, drug use and addiction are not a part of a single continuum. One comes from the other, but you really move into a qualitatively different state. Now, we know more about drugs and the brain than we know about anything else and the brain. We have identified the receptors in the brain for every major drug of abuse. We know the natural compounds that normally bind to those receptors in the brain. We know the mechanisms, by and large, by which every major drug of abuse produces its euphoric effects.
Q: Including tobacco, alcohol, marijuana?
Leshner: Tobacco, alcohol, marijuana, cocaine, heroin, barbiturates, inhalants -- every abusable substance. We know a phenomenal amount. What we also know is that each of these drugs has its own receptor system -- its own mechanism of action. But in addition to having idiosyncratic mechanisms of action, each also has common mechanisms of action. That common mechanism of action is to cause the release of dopamine, a substance in the base of the brain, in what is actually a circuit called the mesolimbic reward pathway. That circuit has a neurochemical neurotransmitter, which is dopamine.
We believe that the positive experience of drugs comes through the mesolimbic-dopamine pathway. We know that because if you block activation of that dopamine pathway, animals who had been giving themselves drugs no longer give themselves drugs. In addition to that, about a week ago, Nature Magazine (a British science and medicine journal) published a study showing that the greater the activation of the dopamine system following the administration of cocaine the greater the experience of the high. So we know that this is a critical element, and we know that every addicting substance modifies dopamine levels in that part of the brain. That is to say, alcohol, nicotine, amphetamines, heroin, cocaine, marijuana -- all produce dopamine changes in the nucleus accumbens, in the mesolimbic pathway in the base of the brain.
We also know that in the connection between the ventral tegmentum and the nucleus accumbens -- in the mesolimbic circuit -- that at least cocaine, heroin, and alcohol produce quite similar changes at the biochemical level. That is, not only in terms of how much dopamine is produced but also in the similar effects these substances have long after you stop using the drug. So the point here is that we are close to understanding the common essence of addiction in the brain and we care about this because it tells us how to develop medications for drug addiction. That is the goal -- how to treat drug addiction.
Q: But over time, doesn't the brain of an addict release less and less dopamine? So how does he continue to feel good? How does he get his high if dopamine levels are reduced, rather than increased?
Leshner: Here is another indication of the difference between drug use and addiction. Initially, taking drugs increases dopamine levels, but over time, it actually has the reverse effect. That is, dopamine levels go down. And one of the reasons that we believe that most addicts have trouble experiencing pleasure is that dopamine is important to the experience of pleasure, and when the levels are low you don't feel so good. But once addicted, an individual actually does not take the drug to produce the high.
It is the case in heroin addiction that, initially, they take the drug for the high, but ultimately they take the drug to avoid being sick. The same is true, to some degree, in crack cocaine addiction. That is, we find that people coming off crack cocaine get depressed very badly, and so they are, in effect, medicating themselves, giving themselves crack cocaine to avoid the low. What they're trying to do is pump their dopamine levels up, which doesn't happen, but they keep trying to do it.
Q: Perhaps we should assure people that a certain level of dopamine is normally produced in the brain by pleasurable foods, or activities, and is necessary for human life. Is that correct?
Leshner: Dopamine is a very important substance in many different ways. It is, for example, involved in motor function. In order to maintain motor function, you must have a minimal amount of dopamine. Parkinson's disease is a deficit in dopamine levels, which results in motor problems. Both schizophrenia and depression have dopamine components to them, mostly schizophrenia. In fact, anti-psychotic drugs work on dopamine levels. And so, what you need to be doing is balancing your dopamine, not raising it or lowering it. You're trying to maintain dopamine at a normal level. And again, we think that people who are addicted have trouble experiencing pleasure because their dopamine systems are altered.
Q: If the working of the brain changes during addiction, is this alteration permanent, or can other drugs administered by physicians, or behavioral changes in various programs, bring the brain back to an unaddicted, unaffected state?
Leshner: Drugs of abuse have at least two categories of effects. One is what I will call "brain damage." That is, they literally destroy cells or functions in the brain. For example, if you use inhalants, you literally destroy brain tissue. If you use large doses of methamphetamine, we believe you literally destroy both dopamine and serotonin neurons. In most cases, however, we believe changes in the brain associated with addiction are reversible in one way or another, or they can be compensated for. We know that the brain of an addicted individual is substantially different from the brain of a non-addicted individual, and we have many markers of those differences -- changes in dopamine levels, changes in various structures and in various functions at the biochemical level. We know some of those changes, like the ability to produce dopamine, recover over time. What we don't know is if they recover to fully normal.
Secondly, we know that some medications can compensate, or can reverse some effects. If the change is reversible, your goal is to reverse. If it's not reversible, but you still need to get that person back to normal functioning, you need a mechanism to compensate for the change.
Q: That moves us into the question of prevention and treatment programs. First, what kinds of prevention programs are known to work?
Leshner: One problem in the prevention of drug abuse is that people think in terms of programs, rather than in terms of principles. But the truth is, like anything else that you study scientifically, stock programs that you apply anywhere around the world in exactly the same way do not work. Rather what you want are guiding principles. And we have now supported over 10 years of research into prevention, and have actually been able to derive a series of principles of what works in prevention, and have just issued the first ever science-based guide to drug-abuse prevention. And some of those principles are fairly obvious once you state them, but if you don't say them you don't do them. For example, prevention programs need to be culturally appropriate. Well, people say that all the time, and then they look at a prevention program and they say, "Oh good, I'm going to just take that one and put it in my country." Then they're shocked when it doesn't work. Well, you need to have the cultural context to whatever you do.
Another obvious principle is that programs need to be age appropriate. Everyone knows that youngsters early in adolescence are a different species from those late in adolescence. So, you need to deal with them differently. The messages have to be different. The advertisement industry has done a very good job with that.
In addition, people frequently like "one-shot" prevention programs. Go in, do something, and then the problem's solved. Well, they never work. You need to have sustained efforts with what we call "boosters." You make your first intervention, then you go back and give another intervention, and then another, and finally you successfully inoculate the individual. There are a whole series of principles outlined in a pamphlet we recently published -- "Preventing Drug Use Among Children and Adolescents: A Research Based Guide" -- and a checklist against which you could rate programs.
Q: Is this booklet on your web site?
Leshner: Yes. You can find this prevention booklet by going to -- www.nida.nih.gov -- and looking under publications. You can download the whole thing.
Q: Which have been found more effective in treating addicts -- behavioral or medical programs? Or do they need to complement each other?
Leshner: I believe that addiction is a brain disease, but a special kind of brain disease -- a brain disease that has behavioral and social aspects. Therefore, the best treatments are going to deal with the biological, the behavioral, and the social-context aspects. Now that's difficult for people to understand, I think, but it's a very important principle. We have studies that show that although behavioral treatment can be very effective, and biological treatment can be very effective, combining the two makes them more effective. In addition to that, remember that people who are addicted typically have been addicted for many, many years, and, therefore, they have to almost relearn how to live in society. And that's a part of treatment.
Q: Such a comprehensive approach sounds pretty expensive. Is it more expensive than a prevention program?
Leshner: The question boils down to whether you're going to try to compare treating an individual once addicted, which involves doing a cost-benefit analysis of what that individual's habit is costing society, versus a massive prevention program that might cost only three cents per person but which only affects the one or two people who would have used the drug in the first place. So, it's not a comparison that you can actually make. However, I can tell you that even the most expensive treatments -- inpatient, therapeutic communities that cost, depending on the particular kind of program, between $13,000 and $20,000 a year per person, are a lot less than imprisoning people. Incarceration costs $40,000 a year per person. So the cost-benefit ratio always is in favor of the treatment approach.
Q: How many drug addicts are there in the United States and around the world?
Leshner: We believe that there are about 3.6 million individuals in the United States who are addicted to heroin, crack cocaine, amphetamine,marijuana -- the illegal drugs. So, at least that many are in need of treatment. Then heavy users add to that number. It's impossible to know exactly the total number who are in need of treatment, but it's probably between four and six million people. I don't know what the comparable figures are internationally.
Jerry Stilkind writes on drugs, environment and other subjects for the United States Information Agency.
USIA Electronic Journal, Vol. 2, No. 3, June 1997