“I feel that any form of so called psychotherapy is strongly contraindicated for addicts. The question ''Why did you start using narcotics in the first place?'' should never be asked. It is quite as irrelevant to treatment as it would be to ask a malarial patient why he went to a malarial area.”
--William S. Burroughs
To say the least, addiction is variously interpreted by research scientists, drug treatment therapists, pharmaceutical managers, mental health professionals, drug education specialists, doctors, lawyers, and politicians. Well into the 1990s, the official “Decade of the Brain,” treatment for alcoholism and other addictions consisted almost exclusively of detoxification, followed by a stint in A.A.
“It was as if you had cancer,” said Dr. Janice Keller Phelps, “and your doctor's sole method of treatment consisted of putting you in a weekly self-help group." Dr. Phelps, then the director of the Alternatives in Medicine Clinic in Seattle, was the first physician to point out to me that, as late as the 1980s, it was rare to find a medical doctor who specialized in, or was clinically familiar with, the treatment of alcoholism, let alone other addictions. Feelings of therapeutic confidence are threatened when physicians discover that addicts frequently do not get better under their care.
It often seems as if drug addicts are at fault for perversely refusing to get well. Rarely do the treatment methods, or lack of them, come under question. The traditional view of the addict as an immature and irresponsible person, short on will power, low on self-esteem, and forever at the mercy of his or her “addictive personality,” works at cross-purposes with the goal of helping addicts recognize the need for treatment. Addicts have traditionally been taught to think of themselves the way Franz Kafka thought of himself in relation to his tuberculosis: “Secretly I don’t believe this illness to be tuberculosis, at least not primarily tuberculosis, but rather a sign of my general bankruptcy.”
Who is really at fault here—the patients, or the healers? Most of our current medical, legal, and psychiatric approaches to the prevention and treatment of drug addiction have failed—and are continuing to fail. As Susan Sontag has written: “Psychological theories of illness are a powerful means of placing the blame on the ill. Patients who are instructed that they have, unwittingly, caused their disease are also being made to feel that they have deserved it.”
In Samuel Butler’s classic utopian satire, Erewhon, sick people are thrown in prison, under a statute that makes it a crime to be ill. Is that our current approach to addiction? Does the drug problem belong in the Attorney General’s office, as it now stands, or in the Surgeon General’s office, where a growing number of researchers say it belongs? In light of new medical findings about addictive disorders, what is enlightened public policy, and what is not?
Recent research in neurophysiology, cell biology, and molecular genetics, coupled with breakthroughs in the science of brain imaging, have made it possible, for the first time, to venture a solid assault on the basic mysteries of addiction. The past fifteen years have been exhilarating times for biomedical researchers in general; a time when basic breakthroughs in the biomedical sciences have changed the way science approaches a variety of human afflictions. We have been used to thinking of such conditions as alcoholism, drug addiction, depression, and suicide in terms of causes rooted firmly in the environment. What events in a person’s life, what outside social factors, led to the problem? However, the new medicine is telling us that we have been looking in all the wrong places for causality.
When I first began following the scientific research on addiction and alcoholism, the field was small, the insights tentative, and the overall enterprise woefully underfunded. Today, more than a decade later, an interlocking maze of biomedical and psychiatric sub-specialties make up the world of addiction science. I can only hope to impart an introductory sense of the important work being done in addiction science. What I had originally viewed as a series of potential breakthroughs in addiction research very rapidly became the tip of an enormous iceberg: brain science, and the revolutionary new directions represented by modern biological psychiatry. The brave new sciences strongly suggest that, when it comes to addiction, the place to look is inside the brain itself.
I plead guilty in advance of succumbing to the temptation of attempting to summarize complex scientific data without committing egregious errors of fact. I have endeavored to be honest about the evidence, or lack of it, and have attempted to add qualifiers when they seemed warranted. For the sake of readability, I have chosen to forego footnotes in favor of informal, in-text citations where appropriate. This is not a textbook, or a scholarly work. I have tried to smooth the toughest scientific sledding by employing a minimum of medical jargon--but the story is a scientific one, and can’t really be made into anything else. Interested readers can track down additional material by consulting the selected bibliography.
I have also felt compelled to leaven the laboratory findings of hard science with what addicts themselves have to say about addiction. The common understanding and experience of addicts in Alcoholics Anonymous and Narcotics Anonymous is impressive, and much of it amplifies, rather than contradicts, various strands of the medical research. Some of the most powerful insights into addiction come from addicts themselves. In the world of medical science, this is “anecdotal evidence,” but I would feel remiss if I did not include it.
No one knows how many addicts there are. U.S. public health officials commonly settle on a figure of between 10 and 20 per cent of the population. Whatever the actual frequency, addiction is a potentially lethal human health condition that, until recently, has been more or less completely misunderstood. Up until the late 1980s, almost everyone had gotten it wrong. Addiction wasn’t what the experts said it was. Most of the doctors, parents, politicians, priests, and police officers charged with educating our children about the perils of drugs got it wrong.
Much of the traditional thinking about addiction can be boiled down to three basic viewpoints—psychological, sociological, and biochemical: 1) Psychological theories focus on factors in early childhood or psychological and cognitive conflicts later in life, and hold that the secret to treating addiction is to be found in the mind of the addict. 2) Sociological theories assert that adverse societal conditions cause addiction, and that the cure lies in changing the social and environmental factors that mold the psyche in the first place. 3) Biochemical theories begin with the observation that key elements of drug withdrawal are distinctly physical in nature, and argue that the key to addiction is to be found in the structure of the drug molecule and its direct effect on certain cells in the central nervous system. The key to treating addiction, in other words, is chemical.
The basic science upon which this book is built is called neuropharmacology, or sometimes psychopharmacology: the study of the effects that drugs have on the brain.
In essence, this book is the story of what happens to a molecule of cocaine, or a molecule of gin, or a molecule of heroin once it wends its way inside the human brain. Once that has happened, an alchemical combination of molecular messengers—serotonin, dopamine, norepinephrine, and glutamate—operate at specific receptor sites in the portion of the brain known as the limbic system. Everything that follows, from behavioral problems to broken marriages, from jail time to rehab, is a result of changes in infinitesimally small amounts of these chemicals in the brain.
A neurotransmitter is a chemical substance, like serotonin or dopamine, which carries impulses from one nerve cell to another. Neurotransmitters are manufactured by the body and are released from storage sacs in the nerve cells. A tiny junction, called the synaptic gap, lies between brain cells. (Think of Michelangelo’s Sistine Chapel, with the finger of Adam and the finger of God not quite touching, yet conveying energy and information.) Neurotransmitters squirt across the synaptic gap, and this shower of chemical messengers lands on a field of tiny bumps attached to the surface of the nerve cell on the other side of the synaptic gap. These bumps are receptors, and they have distinctive shapes. Picture these receptors, brain researcher Candace Pert has suggested, as a field of lily pads floating on the outer oily surface of the cell.
Neurotransmitter molecules bind themselves tightly to these receptors. The fact that certain drugs of abuse also lock tightly into existing receptors, and send messages to nerve cells in the brain, is the key to the mystery of addiction.
What is distinctive about the many different kinds of neurotransmitters is that they all have different three-dimensional shapes. The lock-and-key arrangement of neurotransmitters and their receptors is the fundamental architecture of action in the brain. Glandular cells are studded with receptors, and many of the hormones have their own receptors as well. If the drug fits the receptor and elicits a response, it is called an agonist. If it simply blocks the receptor site without stimulating a response, it is an antagonist. Still other neurotransmitters have only a secondary effect, causing the target cell to release other kinds of neurotransmitters and hormones.
The fact that certain drugs mimic the shapes of certain neurotransmitter receptors, and essentially “fool” receptors into receiving them, is one of the most important and far-reaching discoveries in the history of modern science. It is the reason why even minute amounts of certain drugs can have such powerful effects on the human nervous system.
Two of the most important neurotransmitters are serotonin and dopamine. There are many others, including norepinephrine and glutamate, but the unfolding story of addiction science, at bottom, is the story of what has been learned about the nature and function of these two chemicals, and the many and varied ways they effect the pleasure and reward centers of the brain. The emergence of a sound understanding of how this mechanism operates has helped explain what happens to drug abusers when they “fool with mother nature.” Relapses on the part of “recovering” addicts have always been so distressingly common that clearly some major piece of the puzzle has been missing. The real story of alcoholism and other addictions can now be told in biochemical terms, like any other medical disorder.
One of the crucial neurotransmitter discoveries dates back to 1948. Three researchers--Maurice Rapport, Arda Green, and Irvine Page--were looking for a better blood pressure medication. Instead, they succeeded in isolating a naturally occurring compound in beef blood called serotonin (pronounced sarah-tóne-in). It was known chemically as 5-hydroxytryptamine, or simply 5-HT. The researchers determined that serotonin had something to do with vasoconstriction, or narrowing of the blood vessels, and in that respect resembled another important chemical messenger in the brain--epinephrine, better known as adrenaline.
Serotonin turned out to be one of nature’s signature chemicals—a chemical of thought, movement and behavior, as well as digestion, ejaculation, and evacuation. The body’s all-purpose neurotransmitter, involved in sleep, mood, appetite, among dozens of other functions. The cortex, the limbic system, the brain stem, the gut, the genitals, the bowels: serotonin is a key chemical messenger in all of it.
A human body contains approximately 10 milligrams of serotonin, but it must be in the right places, at the right quantities, for the body and brain to function normally. This cannot be accomplished by simply injecting serotonin into someone’s arm. It must be produced in the body, using the amino acid tryptophan as a building block.
The neurotransmitter dopamine, along with serotonin, is considered to be one of the brain’s primary “pleasure chemicals.” This somewhat misleading designation denotes neurotransmitters that share pathways of transmission in areas of the brain linked to experiences of pleasure and joy.
Dopamine pathways play a role in carrying signals related to attention, movement, problem solving, pleasure, and the anticipation of reward. Dopamine is one of the reasons why, after you have a pleasurable experience with food, drink, sex, or certain drugs, you are likely to feel a desire to repeat the experience. Dopamine is implicated in not just the drug high, but in the craving that accompanies withdrawal as well.
Feelings of pleasure, or joy, are natural drug highs. The fact that they are produced by chemical alternations in brain state does not detract from the feelings themselves, any more than fear or anger feel any less real if you happen to know that they are identifiable biochemical brain states. The familiar “fight-or-flight response” triggered by extreme fright or excitement—increased heart rate, shallow respiration, elevated blood pressure, dilated pupils, and higher levels of glucose in the blood and muscles—is a function of the aforementioned norepinephrine/adrenaline.
An area of the brain behind and below the cerebral cortex, known as the limbic system, is the locus of attention for any modern discussion of addictive drugs. The cerebral cortex is the seat of the higher faculties—logic and rational thought, but the limbic system is the command and control center for the expression (or curtailment) of primal emotions—fear and joy. A subset of the limbic system—a set of various bodies and sites with names like the locus coeruleus and the nucleus accumbens, combine to form what is commonly referred to as the brain’s pleasure pathway, or reward center. Addictive drugs, we now know, target this part of the brain in ways both straightforward and insidious. We can now map these changes visually, with state-of-the-art scanning systems. We know for certain that there are well-documented neurochemical and genetic reasons why alcoholics and other drug addicts cannot, in so many cases, “just say no.”
The biological view of addiction assumes metabolic individuality—Some people are prone to addiction, and some people are protected from it, primarily, but not exclusively, because of their genetic endowment. For a minority of users, drugs that most people can easily go without manage to exert the kind of driving, compulsive control over behavior typically associated with the primary survival drives--food, water, and sex. How are those who suffer from addiction different from those who are not?
Addiction is not a single, monolithic condition triggered automatically by excessive use of mood-altering drugs. Little more than a decade ago, brain scientists were arguing over whether to consider alcoholism a drug addiction. Cocaine, once considered by many drug experts to be a non-addictive substance, is now widely viewed as one of the most fiercely addictive drugs of all. LSD, once assumed to be addictive, is not addictive at all. And hippies who scoffed at the notion of getting “hooked on pot” now routinely turn up at drug treatment clinics as self-confessed marijuana addicts, despite a notable lack of scientific evidence to support their contention. Is sugar an addictive drug? Are habit-forming behaviors like gambling and sex in the same class as addiction to Jack Daniels or crystal meth? If addiction is a disease, why can’t we cure it? We will explore two case histories in particular: anti-craving drugs for cigarettes, the first success story in the field; and anti-craving drugs for carbohydrate overeaters, the first disaster in the field.
Drugs kill. Nonetheless, not all drug use is abuse, and not all drug abuse is addiction. There is a difference between a drug habit, which non-addicts can develop, and a full-blown drug addiction. Most people understand that daily drinkers are not necessarily addicted to alcohol. Forced to stop drinking, these people do not find themselves undergoing excessive cravings or an unstoppable desire for a drink. Many people have trouble extending this perspective to drugs like heroin, cocaine, and marijuana. The idea of so-called “hard” and “soft” drugs may not, in the end, shed much light on the process of addiction. As one prominent neuroanatomist at the National Institute of Mental Health once put it to me, “There’s this arbitrary line drawn between legal and illegal drugs--and that line has nothing to do with addiction.”
Much of this books focuses on alcoholism, because it is the most extensively investigated drug of addiction, and also because it is the nation’s primary drug of abuse. The past few years have also seen a deeper understanding of addictive mechanisms at work in the nation’s other over-the-counter drug of abuse, nicotine. Tobacco kills as many as 400,000 people a year, according to the Journal of the American Medical Association. (“A thousand funerals a day,” as former Surgeon General C. Everett Koop used to say.) Alcohol, in turn, kills twenty times as many people as “hard drugs.”
It may seem odd to mention LSD and alcohol in the same discussion, but the distinction between legal and illegal is of little use from a research point of view. But by any estimates at all, the drug trade, licit and illicit, is the largest, most lucrative industry in the world. As a nation, our stance with respect to this industry has been wildly inconsistent: From real cocaine in turn-of-the-century Coca-Cola to the crack “epidemic” of the 1980s. From Carrie Nation and prohibition to the “romantic” alcoholic of the 1940s and 1950s. From “No Hope Without Dope” to “Just Say No” within the space of 25 years. By any estimate at all, the drug trade, licit and illicit, is, and probably always has been (if you are willing to count spices), the largest, most lucrative industry in the world.
This book is not a straightforward scientific detective story. The narrative is more diffuse, because the overall understanding of addiction has proceeded by fits and starts, involving thousands of scientists, therapists, and institutions. It is by no means fully articulated, even today. The explosion of knowledge has been historic, but “if you’re trying to come to a simple conclusion,” a scientist at the National Institutes of Health observed, “you’ve got a problem.”
Recent work has led to the discovery of a class of medications that reduce the craving for drugs and alcohol in certain addicts. Craving—known to research scientists as drug-seeking behavior--is the basic engine that drives relapse. And so craving has been one of many points of attack for addiction scientists. Today, the first generation of “anti-craving” medications has become a major new addition to the arsenal of treatment options medical science can now offer drug and alcohol abusers who want to quit, but find, repeatedly, that they cannot.
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