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March, 1987:

Nicotine: Harder To Kick…Than Heroin


LEAD: DESPITE OVERWHELMING EVIDENCE that tobacco is destroying their health and shortening their lives, 53 million Americans continue to smoke. Increasingly aware that their addiction is also harmful to their children and co-workers, they continue to puff away on 570 billion cigarettes a year.

DESPITE OVERWHELMING EVIDENCE that tobacco is destroying their health and shortening their lives, 53 million Americans continue to smoke. Increasingly aware that their addiction is also harmful to their children and co-workers, they continue to puff away on 570 billion cigarettes a year.

Many smokers are highly intelligent people with impressive levels of control over institutions, budgets, employees and political affairs. Yet, after repeated attempts to give up smoking, they find that they cannot control this one, seemingly uncomplicated, aspect of their behavior. Are smokers more weak-willed than nonsmokers or former smokers? Or do millions of people continue to smoke for reasons more powerful than previously imagined? What, for example, could possess a heart attack victim to light up a cigarette the moment he is wheeled out of the coronary care unit?

Interdisciplinary research in pharmacology, psychology, physiology and neurobiology is just beginning to shed light on the incredible hold that tobacco has on people. Scientists have found, for instance, that nicotine is as addictive as heroin, cocaine or amphetamines, and for most people more addictive than alcohol. Its hooks go deep, involving complex physiological and psychological mechanisms that drive and maintain smoking behavior and that even produce some ”good” effects, such as improved performance on intellectual, computational and stressful tasks.

The bad effects are legion. Tobacco use is the number one preventable cause of illness and death in the United States. The medical bill for individuals with fatal illnesses related to smoking has been estimated at $60 million a day, according to a 1985 study by the Congressional Office of Technology Assessment.

Since the first Surgeon General’s report on smoking in 1964, about 37 million Americans have quit. Those still addicted tend to smoke more cigarettes, but they should not lose hope. New strategies for quitting, based on a deeper understanding of the addiction, are in the wings. ”The known enemy is more easily overcome,” says Dr. Jack Henningfield, who specializes in the biology of dependence and abuse potential at the Addiction Research Center of the National Institute on Drug Abuse in Baltimore.

When the first warnings about tobacco were published more than 20 years ago, many experts thought that smoking was ”no different than compulsive potato chip eating,” says Dr. Henningfield. Not smoking was apparently just a matter of willpower. But it is now clear, according to Dr. Henningfield, that smoking is a subset of compulsive behavior in which the controlling factor, nicotine, profoundly affects the smoker’s central nervous system, producing pleasurable effects, dependency and, when it is taken away, withdrawal.

This finding has been long believed but only recently proved through tests that meet today’s scientific standards. It stems from extensive modern research into the nature of drugs of abuse, made possible through the development of highly specific testing equipment. Heroin, cocaine, alcohol, amphetamines and nicotine, it turns out, have many things in common. They affect the nervous system through different routes, but their end results are similar: people become dependent on them.

”Heroin addicts say it is easier to give up dope than it is to give up smoking,” says Dr. Sharon Hall, a psychology professor whose research at the University of California’s San Francisco medical school centers on methods of curtailing drug abuse.

LIKE HEROIN, NICOTINE IS AN alkaloid found in plants. The alkaloid kills insects by disrupting their neurotransmitters, substances released by the bug’s activated nerve cells. It so happens that humans have the same neurotransmitters. What is toxic to the insect, however, is pleasurable to the human when taken in the tiny amounts found in cigarettes.

Alkaloids exert their effects by binding to receptors in the brain and other nerve tissue. Heroin attaches to the brain’s natural painkilling receptors. Nicotine affects a major neurotransmitter system that is involved in the very conduction of nerve signals, memory and other critical functions. It also binds to white blood cells and is carried to most tissues throughout the body.

An addictive drug of abuse is defined as one that will be repeatedly self-administered, even though there is no medical reason for it. People take aspirin for a headache, but when the pain is gone, they stop taking the drug.

The classical experiment to test for self-administration involves humans or animals connected intravenously to both a source of the drug and to a saline solution. They are free to press two unmarked levers. One delivers the drug, the other the saline, but the subject does not know which is which. With an abusable drug, the rate of self-administration is regular, says Dr. Henningfield. Neither the animals nor the humans ”mistake” nicotine for saline, although they sometimes mistake nicotine for amphetamines. And both the animals and humans self-administer nicotine to keep the concentration of it in their blood relatively constant.

In an experiment with eight drug users, Dr. Henningfield tested the euphoric qualities of nicotine. Given intravenously in gradually larger doses, nicotine was rated as highly euphoric, with dose-response curves similar to those of cocaine, amphetamines and morphine. Asked to identify the injections, subjects frequently mistook cocaine for nicotine. Given intravenously in equal amounts, says Dr. Henningfield, ”nicotine was between 5 and 10 times more potent in producing a euphoric effect than cocaine.” But the effect is fleeting for regular smokers, since they inhale such tiny amounts of nicotine.

While the fundamental mechanisms are unknown, most drugs of abuse produce either tolerance or withdrawal. Nicotine does both. Tolerance means that, up to a point, more of the drug is required to achieve the same effect or that there is diminished effect when the same dose is used regularly. Dr. Henningfield took a survey of 741 smokers, all about 35 years old, whose smoking had increased from about three cigarettes to a pack a day over a period of eight years. All respondents indicated a rapid increase in the first few months of smoking followed by a gradual leveling off. According to Dr. Henningfield, a similar pattern of escalation followed by stable dosing is characteristic of dependence on alcohol, sedatives, stimulants and narcotics.

Withdrawal is a constellation of symptoms experienced after stopping the regular use of a drug. Nicotine withdrawal often includes anxiety, irritability, difficulty concentrating, restlessness, craving for tobacco, gastrointestinal problems, headaches, drowsiness, decreased heart rate, tremors and slowed metabolism.

”The popular media have exaggerated the withdrawal from opiates and downplayed the withdrawal from tobacco,” says Dr. Neal Benowitz, a clinical pharmacologist at the University of San Francisco medical school. ”If you take away the trappings of how the addicted person looks,” he adds, ”you can’t tell the difference.”

THE ADDICTIVE NATURE of nicotine is an important issue in cigarette liability cases. Is the smoker exercising free choice, and is he alone responsible for his behavior? Or has the smoker succumbed to an addiction not adequately disclosed by the manufacturer and perhaps even obscured by deceptive advertising?

Tobacco companies defend themselves by pointing out that they are simply marketing a legal substance. ”The idea that cigarette smoking is more addictive than cocaine or heroin is ludicrous,” says Scott Stath, a spokesman for the Tobacco Institute in Washington. ”The term ‘addiction’ is a debased coin worth nothing at all. You even see references to viewing sports as being addictive.”

According to one argument, substances like sugar are addicting because they affect neurotransmitters that improve mood. But Dr. Henningfield tested this notion and found that intravenous injections of glucose did not produce the mood changes characteristic of morphine, cocaine and nicotine. Drugs of abuse, he says, seem to tap into the brain’s wiring to control behavior in ways that other ”addicting” substances do not.

”We abuse drugs for many reasons,” says Dr. Henningfield. ”The effects that lead to compulsive behavior are diverse.” Nicotine is very different from most other drugs of abuse in important ways. Its effects are felt more rapidly than those of drugs taken intravenously. One-quarter of the nicotine in each drag reaches the brain in seven seconds. The nicotine concentration in the blood peaks at about the time that the cigarette butt is extinguished. The effects then fall off rapidly as nicotine is cleared by the liver and excreted in urine. Within a half hour, many smokers seek a new dose of nicotine. A pack-a-day smoker takes 70,000 drug ”hits” a year.

One astonishing property of nicotine is that it acts both as a stimulant and sedative. Shallow puffs tend to increase alertness, whereas deep drags relax the smoker. The reason is that low doses of nicotine facilitate the release of the neurotransmitter acetylcholine – which makes people feel alert – but high doses of nicotine block the flow of this compound.

Nicotine is the ”drug for all occasions,” says research psychologist Dr. Ovide Pomerleau, director of the behavioral medicine program at the University of Michigan in Ann Arbor. ”Its variable effects are available on demand and do not outlast the circumstances to which they are appropriate. Unlike other drugs, nicotine does not interfere with normal activity.”

Smokers are incredibly adept at maintaining a steady concentration of nicotine in their bloodstreams throughout the day, says Dr. Benowitz. There seems to be an internal sensing system, like a household thermostat, that knows when nicotine levels are too low. Called a ”nicostat,” it is what drives a smoker to light up when the nicotine level falls below his set point. Most smokers require about 10 cigarettes a day to maintain a ”comfort zone.” After a night’s sleep, smokers deeply inhale their first few cigarettes to raise the concentration of nicotine in their blood quickly. Later cigarettes are typically smoked more lightly.

In one of Dr. Benowitz’s experiments, volunteers spent three days over a 10-day period hooked up to catheters that drew blood samples every two hours. On different days they smoked either their usual brand, True or Camel filter cigarettes, yet the subjects maintained essentially the same blood levels of nicotine. They smoked fewer of the strong Camels and more of the weak Trues than their regular brand, drawing harder on the Trues and more lightly on the Camels. In fact, Dr. Benowitz says, the smokers extracted 60 percent more nicotine per True cigarette than predicted by the Federal Trade Commission’s smoking machines. The people also inhaled about one-third more nicotine per cigarette from their own brands than from either the Camels or the Trues, probably, says Dr. Benowitz, because they enjoyed them more.

The nicostat does not, however, explain all smoking behavior. If it did, people would smoke in a clockwork fashion, on a fixed schedule. Factors other than blood concentration of nicotine can trigger the desire for a cigarette.

Tobacco is a ”package deal,” says Dr. Lynn Kozlowski, head of behavioral research on tobacco at the Addiction Research Foundation in Ontario, Canada. ”Nicotine’s significant but not debilitating psychoactive effects are combined with pleasant tastes and rituals.” For most smokers, certain situations trigger the desire to smoke, even though the body’s blood nicotine level has not fallen below the nicostat’s set point. Rituals such as drinking coffee, driving a car, talking on the phone or drinking alcohol at a party become inextricably linked with smoking. Once the patterns of smoking are set, they become regular from day to day and even from cigarette to cigarette.

THE SO-CALLED THERAPEUTIC effects of smoking, such as stress reduction and appetite control, are mediated through nicotine’s impact on a host of chemicals that modify the activity of neurotransmitters to regulate mood, learning, alertness and performance. The smoker uses nicotine to fine-tune his body’s reactions to the outside world. If its preferred mode of administration did not carry tar, carbon monoxide and thousands of poisons into the lungs, many scientists say, nicotine might not be such a bad drug. Current studies are proving that, for regular smokers, nicotine improves short-term memory, concentration and intellectual performance. It is not known, however, if the drug would produce these positive effects on nonsmokers. Nicotine also gives subjective relief from stress. Paradoxically, it induces the biological symptoms of stress, speeding up the heart rate and raising blood pressure. A smoker’s heartbeat is increased about 8 to 10 beats a minute all day and all night, according to Dr. Benowitz. This plus other changes induced by smoking, he believes, may produce excessive wear and tear on the heart over the years.

Smoking also appears to control weight. Dr. Neil Grunberg, associate professor of medical psychology and pharmacology at Uniformed Services Universities in Bethesda, Md., has found that smokers generally weigh less than nonsmokers of comparable age, sex and health. Intrigued by this, he conducted a series of animal experiments with tantalizing results. First, he found that male rats given nicotine over an extended period weighed less and ate less sweet food than other rats. When he took away their nicotine, the experimental rats ate more sweet food and gained weight.

In a second experiment, Dr. Grunberg let his nicotine-deprived male rats eat only bland food that was high in carbohydrates. They, too, ate more and became sluggish, although they did not gain as much weight as the rats who ate sweet food. But, while on nicotine, the rats weighed less than their ”nonsmoking” counterparts.

A subsequent experiment looked at male and female rats who were given and then deprived of nicotine. ”We were stunned to see that the females ate more high-carbohydrate bland food after nicotine withdrawal than the males did,” says Dr. Grunberg. The females lost more weight while on nicotine and gained more weight afterward. Both the males and females increased their consumption of sugary foods after nicotine was taken away.

Cautioning that his work is with rats and not people, Dr. Grunberg has developed some hypotheses. One is that nicotine might decrease circulating insulin levels, which would be consistent with less craving for sweets among smokers. Lowered insulin would also mean that smokers store less fat than nonsmokers.

Why females might have a stronger appetite for carbohydrates after they stop smoking than males do is a mystery, says Dr. Grunberg. Scientists theorize that carbohydrates exert a soothing, calming effect on people and that, perhaps, females seek the effect more than men. While some experts suggest that women find it harder to give up smoking than men do because they are more concerned about gaining weight, many other scientists say that the evidence is not convincing.

”It is quite interesting and more than a coincidence that alcohol, heroin and tobacco withdrawal seem to cause people to crave sweet foods and carbohydrates,” says Dr. Grunberg. ”I believe that, metaphorically, these substances shortcut neurochemical pathways, interfering with and modulating the regulation of body weight. The body comes to misinterpret these chemicals as if they are foodstuff.”

In addition to cigarettes’ effects on eating habits, a new line of research has turned up another explanation of why people like to smoke. Dr. Jed Rose, a research psychologist at the Neuropsychiatric Institute of the University of California in Los Angeles and the West Los Angeles Veterans Administration Medical Center, anesthetized the upper airways and bronchial trees of smokers. The subjects said their smoking satisfaction was almost nil after anesthetization, even though they inhaled normal amounts of smoke and nicotine.

Intrigued, Dr. Rose used anesthesia to block the smokers’ senses of smell and taste and had them inhale, without knowing what they were getting, their own brand of cigarette, a low-nicotine cigarette, plain air or a l5 percent citric acid aerosol. The smokers rated the citric acid as being closest to their regular brand in strength and harshness. ”Since citric acid has no nicotine and is not in cigarettes,” Dr. Rose says, ”this demonstrates that there are nerve fibers in the tracheobronchial tree that help provide smoking satisfaction.”

Working with a group of chemists, Dr. Rose has developed various aerosols with all the tastes and aromas of popular cigarettes. Like tobacco smoke, the aerosols’ impact on the upper airways has a calming effect, he says. Smokers find them highly pleasurable and seem to enjoy them as much as cigarettes. Dr. Rose is conducting experiments to see whether the aerosols might make it easier for smokers to withdraw psychologically from nicotine.

New strategies for loosening nicotine’s physiological grasp are also being developed. ”If we accept the fact that the use of tobacco in its preparations is a form of drug addiction, even though a pleasant one not affecting criminal statistics, we can more readily help people when they find their habit has gotten out of hand,” says Dr. Henningfield.

Drugs, such as clonidine, used to treat opiate withdrawal, as well as naltrexone, which is given to heroin addicts, and mecamylamine, an antihypertensive medicine, seem to block some of nicotine’s effects. All are being used experimentally to help people stop smoking. In addition, an antidepressant drug called fluoxetine, which elevates mood and suppresses appetite, is being tried on smokers who are going through withdrawal.

Nicotine replacement therapies are promising because they satisfy the smoker’s physical dependence on nicotine while he concentrates on unlearning the psychological habits that drive smoking behavior. A nicotine gum, combined with behavioral intervention therapy, has helped an estimated one million smokers at least try to quit. In a one-year study, 31 percent of the participants who chewed nicotine gum, read a self-help manual on how to give up smoking and underwent counseling, stopped smoking. The gum doubled the effectiveness of the other two therapies. In addition, a nicotine nose spray is being tested in Europe, and a skin patch that releases nicotine slowly into the blood is being developed in the United States.

A type of aversion therapy called multicomponent rapid smoking has gotten the best results, with 70 percent of the people, who were under 35 and in good health, staying off cigarettes after one year, according to Dr. David Sachs, a lung specialist at Stanford University. Inhaling normally, smokers take a drag on a cigarette every six seconds until they literally feel sick. After 8 to 12 sessions of this, combined with intensive counseling, the smokers associate cigarettes with feeling bad, and they break the habit. Dr. Sachs, who says he owes his livelihood to American and British tobacco companies, has used the technique on about 200 patients with serious lung and heart diseases and found no ill effects. The therapy is not commercially available but is being tested at several universities.

For those who feel it is impossible to give up smoking, Dr. Ellen Gritz, director of the division of cancer control at the Jonsson Comprehensive Cancer Center at U.C.L.A., offers some encouraging statistics. ”There are 37 million success stories,” she says. ”People typically need to try several times before they succeed.”

Dr. Gritz describes the stages in getting ready to quit. ”Stage one is to set high motivation,” she explains. ”Make plans for quitting. Get rid of ashtrays. Set a date. Ask friends for help. Cut down on cigarettes smoked and identify your smoking patterns. Plan in advance how to deal with cravings.

”Stage two is acute nicotine withdrawal. Once you’ve stopped smoking, you might experience sleepiness, headaches, constipation, irritability, anxiety, tension, mood swings and cravings for different foods, but the symptoms only last about a week. Do not be afraid, and expect the worst. Think of it as a liberating experience. ”In stage three, the cravings become less frequent, but don’t let your guard down,” she cautions. ”Most relapses occur within three months. You go to a party and suddenly realize you are smoking. This should not be taken as a failure. You’ve been tripped up by some combination of environmental and social stimuli. Ask yourself, ‘Why did I do it and how am I going to deal with it the next time?’ ” Dr. Gritz stresses that there is always hope. ”Try a new method of treatment,” she says, ”and take into account everything you’ve learned from the past.”

In moments of weakness, it may help struggling ex-smokers to remember that over the years many people have quit cold turkey, surviving withdrawal without the benefit of nicotine gums and patches, medication, counseling and other aids. In fact, it may be easier to give up tobacco now than ever before because of changing attitudes that make smoking less socially acceptable.

GIVEN THAT TOBACCO is a legal substance that generates enormous wealth for governments throughout the world, the substance is not likely to be banned, says Dr. Henningfield. But if tobacco were declared an illicit drug, there is abundant historical evidence that people would risk their lives to obtain it. For example, in the Middle East during the 17th century, people had their hands and heads chopped off for smoking forbidden tobacco, which did not prevent their fellow countrymen from risking life and limb to secure the substance.

A few decades earlier, when tobacco was introduced to England, it became worth its weight in silver. King James I then banned the cultivation of tobacco in England so that he could exercise complete control over its price. ”Seeing that people would pay almost any price for tobacco,” says Dr. Henningfield, ”monopolies were started so that governments could benefit from the desires of their people. Taxes were implemented, and governments became dependent on revenue generated from nicotine addiction.”

This economic dependence seems to be yet another factor contributing to the power of nicotine. In what might be called a nationwide experiment in the sociology of smoking behavior, many local governments have waged public health campaigns against smoking and instituted legislation that restricts or bans smoking in public. The results are encouraging: less than 30 percent of all American adults smoke cigarettes, compared to 40 percent 20 years ago. While half the world’s population still smokes, the United States is the first country to see a decrease in tobacco use. KICKING THE HABBIT A number of programs, many of them free, are available to the smoker who wants to quit. The following use a combination of behavior modification and group-support techniques. The American Cancer Society’s FreshStart Program consists of four free group-counseling sessions, led by former smokers, to help participants analyze why they smoke and how to stop. Included are strategies for dealing with two of the biggest obstacles to quitting permanently – stress and weight gain. Contact your local chapter of the American Cancer Society; in New York, at 19 West 56th Street (586-8700). For those who want to quit on their own, ”FreshStart: 21 Days to Stop Smoking” is available on audio- and videocassette at many bookstores. The audiocassette can also be purchased through the mail for $9.95 (order number 61783-4) from the audio division of Simon & Schuster, 1230 Avenue of the Americas, New York, N.Y. 10020. The video ($29.95) can be ordered by calling 800-445-3800. The New York Lung Association’s Kick-the-Habit Program devotes the first three of its six free 90-minute sessions to helping people figure out why they smoke and the rest to support after quitting. The association also publishes a manual, ”Freedom From Smoking,” available with a $7 contribution, and a video, ”In Control,” for $59.95. Contact the New York Lung Association, 22 East 40th Street, New York, N.Y. 10016 (889-3370), or your local affiliate of the American Lung Association. The Seventh-day Adventists’ Breathe-Free Plan to Stop Smoking consists of five days of instruction and support-group activities, and at least one follow-up session. Participants are encouraged to give up caffeine and alcohol, at least for the duration of the program, because they often trigger the desire for a cigarette. The course and activities are free, although a small donation for materials is requested.

Contact the Adventist Information Center, 12 West 40th Street, New York, N.Y. 10018 (382-2939 or 800-832-2210). Smokenders offers a six-session course that teaches participants how to withdraw gradually from cigarettes. During the first four sessions, people are allowed to smoke, but are restricted to certain times and places. The program, offered at several locations, costs $295. Call 800-243-5614. The LifeSign Smoking Cessation Program is offered with eight individual therapy sessions at the American Health Foundation. Each participant is given a pocket-sized computer that beeps when smoking is permitted. The beeps occur at gradually increased intervals, ceasing entirely in two to four weeks. The foundation’s program normally costs $400, but when it is taken as part of a research project, there is no fee, except for a $100 deposit for materials (and motivation) that is refunded after completion. Contact the American Health Foundation, 320 East 43d Street, New York, N.Y. 10017 (953-1900). Smokers can purchase the LifeSign computer with an instruction booklet for $73.95 by contacting Health Innovations, 13873 Park Center Road, Suite 336, Herndon, Va. 22071 (800-543-3744).

Correction: April 5, 1987, Sunday, Late City Final Edition