[Congressional Record Volume 140, Number 26 (Thursday, March 10, 1994)]
[Extensions of Remarks]
[Page E]
From the Congressional Record Online through the Government Printing Office [www.gpo.gov]


[Congressional Record: March 10, 1994]
From the Congressional Record Online via GPO Access [wais.access.gpo.gov]

 
                               ADDICTION

                                 ______


                          HON. GEORGE W. GEKAS

                            of pennsylvania

                    in the house of representatives

                        Thursday, March 10, 1994

  Mr. GEKAS. Mr. Speaker, I would like to share with my colleagues some 
remarks made by Dr. Avram Goldstein, professor emeritus of pharmacology 
at Stanford University, before the congressional biomedical research 
caucus on Monday, February 28, 1994. The text of Dr. Goldstein's 
remarks follow:

       A 50-year-old man lies in a hospital bed, desperately ill. 
     Emphysema has destroyed his lungs, and the pitiful sound of 
     his labored breathing fills the room. Watch him! Incredible 
     as it seems, he begs his wife to bring him some cigarettes. 
     Cigarettes put him here, cigarettes will surely finish him 
     off. Why doesn't he quit? Why didn't he quit 25 years ago, 
     when the first Surgeon General's report on smoking, widely 
     publicized, had already made it clear what his future would 
     be if he continued his pack-a-day habit?
       This introduction could have started differently.
       A 50-year-old man gets off the bus in a seedy downtown 
     neighborhood. Just hours before, he was released after 
     serving a two-year sentence for burglary, his third time in 
     prison. His regular income as a grocery clerk had barely been 
     enough to support his wife and child, so burglary seemed the 
     only way to raise the large sums he needed for his heroin 
     habit. Watch him! Only a block from the bus terminal, he 
     makes his ``connection'', buys a syringe and needle and some 
     white powder. Heroin put him in prison three times, heroin 
     will surely finish him off. Why doesn't he quit? Why didn't 
     he quit 25 years ago, when he could see clearly enough what 
     his future would be if he continued using heroin?
       These are the opening paragraphs of my just-published book, 
     Addiction: From Biology to Drug Policy (WH Freeman, New York, 
     1994). They make two important points: First, that nicotine 
     addiction and heroin addiction are two examples of the same 
     biologic process. To the pharmacologist, licit or illicit 
     status has nothing to do with the addictive property of a 
     drug. Second, that an addictive drug can take control of 
     behavior, can lead to compulsive and self-destructive use 
     that seems to defy common sense and rationality.
       Albert Einstein once said, in connection with trying to 
     explain complex scientific matters: ``We should make things 
     as simple as possible, but not simpler.'' In my book--and 
     here today--I try to follow his advice.
       Forty years ago the prevalent view of drug addiction held 
     that it reflected ``poor will power'', an antisocial and 
     criminal temperament, or both. Then basic research on the 
     brain and behavior laid the basis of the disease concept of 
     addiction. The change in public perception came about first 
     with opiates and alcohol, beginning with research at the 
     federal narcotics hospital in Lexington, Kentucky in the 
     fifties. It had been thought that the reaction of addicts to 
     having their drug withdrawn--the ``withdrawal syndrome''--was 
     largely manipulative complaining in an attempt to get more 
     drug. The clinical research at Lexington established, for the 
     first time, that the withdrawal disturbances were truly 
     physical in nature, that they expressed a profound (possibly 
     even irreversible) alteration in the physiology of the brain.
       A further change in our perception of opiate addiction came 
     about as a result of two major research findings in the 
     sixties and seventies. Dole and Nyswander (with Mary Jeanne 
     Kreek, whose talk follows mine here today) showed that 
     maintaining antisocial and criminal heroin addicts on a 
     regular daily dosage of the long-acting opiate methadone, 
     given by mouth, could alter their compulsive drug-seeking 
     behavior and open the way to their total rehabilitation. And 
     basic neurobiology research revealed the existence of natural 
     morphinelike substances--the endogenous opioids 
     (``endorphins'')--which activate specific opioid receptors in 
     our brains, the same receptors on which the addictive opiates 
     act.
       These discoveries had profound implications. Since our 
     brains actually contain and require substances that are like 
     heroin and morphine, excessive exposure to such drugs would 
     be expected to disturb the fine regulation of the brain's own 
     opioid systems. It also became possible to imagine (and to 
     look for) genetic abnormalities that might cause deficient 
     production or regulation of these endogenous opioids and 
     their receptors--abnormalities that could predispose to 
     addiction. If someone had too little of a brain component 
     essential to feelings of normality, might they then take a 
     drug that would act like the endogenous opioids, in effect 
     self-medicating?
       The change in public attitudes toward addictions was 
     accelerated by the 1988 Surgeon General's report summarizing 
     the evidence that nicotine is a powerfully addictive drug. No 
     longer could addicts be relegated to skid row or a criminal 
     underclass. Now a major segment of ``respectable'' middle-
     class society were recognized to be addicts. The long-
     persisting myth that alcohol and nicotine were not even drugs 
     began to break down.
       We now know that there are seven families of addictive 
     drugs. These seven (but no others) are capable, to varying 
     degrees, of producing the compulsive and self-destructive 
     use pattern that we call addiction. All of them, in 
     varying degrees, are dangerous to individual and public 
     health. They all alter behavior in varying degrees and in 
     different ways that are often harmful to the addict and 
     dangerous to others. Some cause grievous damage to the 
     fetus, leading to impaired brain development and long-
     lasting learning deficits and behavioral disorders. 
     Curiously, although some addictive drugs are much more 
     dangerous than others, there is no relationship between 
     the actual danger posed by a drug and its legal status. If 
     a legitimate role of government is to protect the public 
     health, the laws ought to be based on the biology ought to 
     be tailored to minimize the harm caused by each drug.
       Laboratory research has revealed where and how the 
     addictive drugs act in the brain. This knowledge, typically, 
     grew out of studies on rate behavior that had nothing to do 
     with drug addiction. B.F. Skinner had developed experimental 
     methods of studying behavior rigorously in pigeons and rats, 
     introducing new concepts about how rewards drive and control 
     behavior. James Olds, adapting some of Skinner's methods, 
     discovered that rats would press a lever to stimulate their 
     own brains with a mild electric shock--but only if the 
     electrodes were implanted in specific regions deep in the 
     brain. In other words, the rats ``liked'' to stimulate 
     certain nerve cells, which turned out to contain (and to 
     release when stimulated) the neurotransmitter dopamine. Years 
     of research in many laboratories have revealed that this same 
     dopamine ``reward pathway'' is stimulated by all the 
     addictive drugs.
       Cocaine, for example, prevents removal of the dopamine that 
     is released normally in small amounts at the nerve endings in 
     this pathway. As a result, greatly excessive amounts 
     accumulate, causing the extreme excitement, elevated mood, 
     and often frankly bizarre behavior seen during cocaine 
     binges. Morphine (produced from heroin in the body) 
     stimulates the same pathway by a different mechanism; it 
     prevents the release of an inhibitory neurotransmitter that 
     holds the dopamine nerves in check. In other words, morphine 
     removes the breaks, causing large amounts of dopamine to 
     flood the pathway. Nicotine, alcohol, marijuana, probably 
     even caffeine (weakly addictive though it is), act in a 
     similar way. Every addictive drug mimics or blocks the action 
     of one of the brain's neuotransmitters.
       What I have said is true, but I have violated Einstein's 
     dictum by oversimplifying. Forgive me; it would require a 
     whole course on the biology of addiction to deal with all the 
     subtleties. Obviously, each of these addictive drugs has it 
     own distinctive actions, so the common effect on the reward 
     pathway is only one of many diverse effects on the brain, 
     which can result in changes of mood, perception, 
     cognition, alertness, coordination, judgment, sense of 
     equilibrium, motor activity, and numerous other forms of 
     behavior--changes that are characteristic for each 
     addictive drug.
       An important question being addressed in current research 
     efforts is: What role does genetic predisposition play? 
     Obviously, addiction is influenced by the availability and 
     cost of a drug, the pharmacologic properties of a drug, by 
     stress, and by numerous environmental influences. Yet it is a 
     fact that with any addictive drug, of all who try it or even 
     use it socially, only a small fraction become addicted. Could 
     this mean that genetic vulnerability also plays a role? For 
     alcohol addiction there is solid evidence, from adoption and 
     other studies, that heritability is indeed a major factor. 
     Search for the responsible genes is under way, using 
     techniques of molecular biology that were developed without 
     any reference to the drug addiction problem. If those who are 
     especially vulnerable to addiction could be identified by a 
     simple test, prevention efforts might be more efficient and 
     cost-effective.
       The central problem in treating addicts is not how to get 
     them off the drug. For all the addictive drugs, that is a 
     relatively easy matter with proper medication and good 
     supervision. The real problem is the drug craving that sooner 
     or later can lead to relapse and readdiction. We do not 
     understand craving very well. It is difficult to study, 
     especially in animal experiments, but the attempt is under 
     way. If we could develop medications to block craving and 
     relapse, we could take a very big step forward in getting the 
     addiction problem under better control.
       Should addiction research be targeted? Of course it should! 
     But not at the expense of the free-wheeling untargeted 
     research that discovers new principles, opens new paths, 
     provides novel technologies. We need both targeted and 
     untargeted research, we need both laboratory and clinical 
     research. It goes without saying that to make progress in 
     preventing and treating drug addictions, we need to study 
     drug addictions. We need to understand the neurobiology, the 
     genetics, the behavioral aspects, the epidemiology, the 
     possible approaches to treatment. The National Institute on 
     Drug Abuse (NIDA) and the National Institute on Alcohol Abuse 
     and Alcoholism (NIAAA) have that specific mandate, and they 
     already support most of the relevant research in the 
     laboratory, in the clinic, and in human populations. We can 
     predict, however, that important breakthroughs are likely to 
     come unexpectedly from seemingly unrelated research, perhaps 
     funded by other institutes of the National Institutes of 
     Health or by other sources of support. History teaches us 
     that studies on isolated nerve cells from lowly squid and 
     sea slugs produced our basic knowledge about how nerves 
     carry messages and how neurotransmitters pass messages 
     from one nerve cell to another. Studies on the structure 
     and function of receptors, which help us understand how 
     all addictive drugs act, were carried out, by and large, 
     by investigators who had no interest whatsoever in 
     addiction. Such untargeted research has produced the 
     information infrastructure on which targeted addiction 
     research can draw. Who could have predicted that Skinner's 
     experiments with pigeons pecking at a lever to get a 
     kernel of corn--experiments that were ridiculed by some 
     politicians for their lack of relevance--would lead 
     directly to today's experiments on the reward pathway?
       It is becoming ever more clear that addiction is a disease, 
     some kind of neurobiologic disorder in the reward systems, in 
     which dopamine plays a key role. Our aim, as for any chronic 
     relapsing disease, should be harm reduction. Because the 
     addictive drugs stimulate and overstimulate the same brain 
     systems that are responsible for normal satisfactions, normal 
     reward, normal ``feeling good'', we cannot simply develop 
     drugs to block their actions. It would be unimaginable, for 
     instance, to destroy or permanently inactivate the reward 
     pathway. Thus, we need to learn much more in order to find 
     more subtle and specific ways of reducing the harm caused by 
     addictive drugs and forestalling relapse without disturbing 
     essential brain functions.
       In summary, addiction is primarily a public health problem, 
     complicated secondarily (for some drugs) by criminality. The 
     current budget proposal for the ``drug war'', which increases 
     the amount for prevention and treatment relative to that for 
     interdiction and law enforcement, is a move in the right 
     direction, consistent with our present understanding of the 
     biology of drug addiction and the need for a harm-reduction 
     approach in dealing with it.

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