Published on 10/2/2006

Amid the attention directed at the public health aspects of smoking, it is easy to lose sight of the intense struggle many smokers experience as they try to quit.

Amid the attention directed at the public health aspects of smoking, it is easy to lose sight of the intense struggle many smokers experience as they try to quit.

For a significant number of the 25 percent of adult Americans who smoke, breaking the habit requires far more than an act of will and a patch or stick of nicotine gum.

Researchers are charting a web of behavioral factors that both reinforce nicotine addiction and are reinforced by it. For individuals who have struggled unsuccessfully to quit, effective countermeasures, tailored to each smoker's particular set of dependencies, need to be readily available to all age and population groups.

The Facts:

One in five American deaths each year results from smoking cigarettes. Lung cancer kills 123,000; heart disease 98,000; chronic lung disease 72,000; other cancers 32,000; strokes 24,000; and other diagnoses, 81,000.(1)

Direct medical costs linked with smoking totaled at least $50 billion in 1993 — about $2 in avoidable costs for each of 23 billion packs of cigarettes sold that year in the U.S.(2)

Guidelines of the Agency for Health Care Policy and Research (AHCPR) point out that as little as 2-3 minutes of advice from a physician could double the rate at which American smokers quit, with even better results when nicotine gum or patches are added.

The AHCPR estimates that full smoking-cessation treatment — counseling plus medications — costs an average $2,587 per year of life saved. By comparison, medication for moderate hypertension was calculated in 1989 at $11,300 per year of life saved, and for elevated lipids $65,000 to $108,000 per year of life saved. (4,5)

Seven in 10 smokers see a physician at least once a year, but national surveys show that only half of these smokers receive even brief advice about quitting or help from their doctors.(13)

Interview:

Nicotine Receptors

Neil Grunberg, PhD, is Professor of Medical and Clinical Psychology and Neuroscience at the Uniformed Services University of the Health Sciences in Bethesda, Maryland. A psychobiologist who specializes in nicotine research, he led the psychobiology panel at the 1998 federal summit conference, "Addicted to Nicotine."(8)

Q. What happens when people smoke?

A. Not only can they, they must. When we are ill, we "mind" what is going on in our bodies, one way or the other. The way we respond to the stress of medical illness has a lot to do with not just the immediate problem but with the interpretation we put on it.

Disease-related pain, anxiety, and stress affect the way we cope with the illness in many ways. Conversely, how we manage these symptoms and cope with the illness can affect the body. Hypnosis is a simple state of highly focused attention, coupled with a heightened ability to put unwelcome thoughts, feelings, and perceptions outside of conscious awareness.

It's becoming increasingly clear that people can modulate those perceptions with hypnosis. They can change the painful and distressing effects of stressors on their minds and their bodies.

Q. How do you see this in your clinical work?

A. When you take one puff from a cigarette, you ingest 4,000 chemicals. Tobacco has about 500 chemicals in it; the other 3,500 are released when tobacco is burned. And of all those, nicotine is the one that addicts you.

Inhalation is the most effective way to distribute any psychopharmacological agent, whether it's nicotine, cocaine, or heroin. When tobacco smoke is inhaled into the lungs, nicotine circulates directly to the brain.

Q. Why do smokers want nicotine, despite its health hazards?

A. If you self-administer nicotine, by smoking or some other method, it makes you feel euphoric, it helps focus attention, it controls appetite and body weight, it helps you deal with stress, and it decreases pain. If you stop taking it after becoming accustomed to it, you'll have unpleasant feelings ranging from flu symptoms to extreme discomfort, irritability, sleeplessness, and inability to concentrate. You'll probably gain weight.

Q. How does it work?

A. Nicotine reaches the brain within 15 seconds of inhaling the smoke. Then it has a half-life of about two hours. This drug acts throughout the body at what are called "nicotinic cholinergic receptors." These are located in the brain and at muscle end plates and nerve endings. Each one resembles a closed microscopic necklace of five beads. Nicotine binds to the hole in the middle of the necklace. The receptors vary in makeup, so each one responds differently to nicotine, accounting for its diverse effects.

Most of the research on mechanisms underlying nicotine addiction has focused on dopamine, as this is fundamental to the euphoric effects of other drugs and alcohol. But with nicotine, much more is happening. Nicotine initiates a cascade of neurochemicals, including serotonin, norepinephrine, endogenous opioid peptides, and more. It stimulates hormone release in a way that may enhance the addiction process.

Q. Once you've taught people to hypnotize themselves, how often do they do it?

A. For smokers and those with pain, I recommend every one or two hours at first. I tell them any time you have an urge to smoke or feel pain, don't fight it. Go into a state of self-hypnosis for a minute or two, reestablish your commitment to protecting your body or altering the perception of pain, and go on about your business. After a while it may become second nature and they just sort of shift into a hypnotic state without realizing it.

Q. What effect does continued smoking have?

A. We have evidence that some receptors increase in number and decrease in sensitivity. This provides a molecular explanation of the development of drug tolerance. It helps explain why someone who starts smoking becomes less sensitive to nicotine and craves more.

As time goes by, a tobacco smoker's body adjusts to the presence of heightened levels of dopamine and the other chemicals I mentioned. That becomes its natural state. It needs the extra neurochemicals in order to function normally. This is the classic addiction scenario. It works the same with nicotine as with the most socially unacceptable — not to mention illegal — drugs.

Q. It sounds as though we can "cure" smokers by weaning them off nicotine through the use of patches, nasal sprays, and pills.

A. Those strategies clearly are valuable, but they ignore nicotine's other effects. Nicotine addiction results from the biologic actions of the agent, just as we've discussed. But that's intertwined with its behavioral, psychological, social, and environmental milieu.

When a smoker takes a cigarette from its pack, looks at it, puts it into his or her mouth, lights it and inhales, the smoker usually does this in the context of everyday life, perhaps while drinking a cup of coffee, or sitting in a bar socializing with friends. All the physical, social, visual, olfactory, and tactile cues become linked with nicotine addiction. The smell of cigarettes, the thought of cigarettes, the cue of other people smoking, an ashtray, the familiar coffee mug — all this becomes associated with the craving for nicotine.

Q. Is that such a difficult association to break?

A. I'll say. These learned associations are not something the smoker picked up after a few trials. This is not like training your dog on a weekend. Every cigarette is puffed an average of 10 to 12 times. At a rate of a pack or so a day, that's 200 to 300 events per day, or 2,000 smoking events a week, or 8,000 per month, or 100,000 per year. A 20-year smoker logs 2 million learning trials. You can see why nicotine substitutes alone do not break the powerful dependence and withdrawal phenomena that have been ingrained.

Because nicotine addiction is not a simple chemical dependency, we should give up the notion that we will find a magic bullet, some prescription that will "cure" the addiction.

Q. The number of smokers is dropping. Aren't we winning the battle against smoking?

A. Far from it. Roughly 50 million Americans smoke today. The number has been decreasing throughout this decade, but tobacco remains the number one killer in the United States and the world. Each year, more than 400,000 Americans die a smoking-related death. That's more than the total allied troop strength during the Persian Gulf conflict.

Imagine the public outrage if every one of those people had died in that war. The amount of public funds allocated to tobacco and nicotine research grossly under-represents the seriousness of the problem.

Interview:

'Gum, Patches Not Enough'

Kenneth Perkins, PhD, is Professor of Psychiatry, Epidemiology and Psychology at Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center. His nicotine addiction research has been widely published, especially in charting differences in responses to nicotine both among individuals and between the sexes.(9,10,11)

Q. How can we help people stop smoking?

A. First, it's important to note that smokers do need help to stop. Of those who try to quit on their own, only 5 percent or so succeed. Then we have to find out what it is about smoking that the individual craves most. Smoking offers a variety of "rewards" to the smoker. By identifying which rewards reinforce a person's decision to smoke, we stand a better chance of modifying that behavior.

Q. What are the different reinforcements?

A. First there's nicotine, and then there's everything else. Nicotine clearly is very important, the addictive element. People generally will not smoke anything that does not deliver nicotine. But there are other factors. Smokers become comfortable with taking in pack after pack, day after day. Even though that's a toxic and dirty way to take nicotine in, it comes to be rewarding in and of itself.

Q. It now looks as though there are as many women smoking as men. Is that true?

A. Just about. Today, 27 percent of men are smokers and 25 percent of women. A few decades ago, about 40 percent of men smoked and about 33 percent of women. It's dropped dramatically for both, but much more so for men than women, and there's still a long way to go.

One of the interesting aspects is that smoking per se is about equally reinforcing in men and women, but the relative contributions of nicotine and the behavioral factors differ. Nicotine seems to matter more to men. The behavioral factors seem to matter more to women.

Q. What evidence have you seen of that?

A. Look closely at the large-scale, nicotine gum and patch studies that have been done over the past 10 or 15 years. Women do worse than men in virtually every study. Sometimes there is not a significant difference because the sample sizes are too small, but when you look across them all, this trend always is present. One report concluded that a year after the largest nicotine patch study, 31 percent of the men were still not smoking, as opposed to 22 percent of the women.

Q. So women need behavioral counseling?

A. Everybody should get behavioral counseling, because everybody will have cravings and will need to learn how to avoid them. You can fool around with nicotinic receptors to identify drugs that will bind there and antagonize nicotine's effects, but the assumption that that's all you need to do is incorrect. If the standard of treatment is just to use the gum, patch, or whatever, smokers, especially women smokers, are not getting what they need.

Q. You're investigating one of the more important behavioral factors in nicotine addiction. Tell us about that.

A. One of the things we're trying to do now is address the concerns women smokers have about gaining weight as a result of giving up cigarettes. From a health standpoint, women are better off quitting smoking and gaining the weight than by continuing to smoke, but their weight concerns are real. In our group, they tend to gain more than the 7 pounds that the literature reports as average. We've seen gains of 15 pounds and more.

A lot of women have an all-or-nothing attitude. They simultaneously stop smoking and vow to diet, or at least not eat anything extra. That's maladaptive. In a study of women smokers who wanted to quit, we tested three approaches: counseling that challenges the importance of a few extra pounds of weight; a weight control component; and a complete focus on smoking cessation without addressing the weight issue. The first group did the best of the three.

Q. If we learned how to teach smokers other ways to control weight, manage stress, improve their attention and so on, would we have a better chance of winning the tobacco war?

A. Those are health care developments that would help, but there also are financial considerations that are hurting our chances. Most people don't even get reimbursed for nicotine gum or patches. Some forward-thinking health plans offer a price break on them, but most don't. The optimum treatments with professional counselors cost several thousand dollars per successful "quitter." We're a long way from widespread implementation of what we know.

'The Antidepressant That Kills You'

Smokers with a history of depression probably need special help to kick the habit.

They find it twice as hard to quit as do other smokers, and they are twice as likely to suffer depression during withdrawal, even if their last bout with depression occurred as much as 10 years earlier, says Alexander Glassman, MD, Professor of Clinical Psychology at Columbia University, who has spent more than a decade studying the nicotine-depression connection.(7) Nicotine, says Glassman, is "an antidepressant drug that kills you."

A further complication: during withdrawal, depressed smokers may suffer greater declines in mood and in their ability to concentrate than non-depressed smokers.

In 1985, while testing a new drug for smoking cessation, Glassman and colleagues observed an astounding rate of major depression among the smokers who came to their clinic. Sixty percent reported a history of depression, compared to about 18 percent for the general population. A possible explanation: most of the smokers came from Columbia's medical school campus and were at increased risk of smoking-related depression because of their heightened awareness of the health risks.(6)

Researchers leading other smoking cessation trials also have discovered high rates of depression, ranging from 35 percent to 41 percent.

The usefulness of nicotine replacement therapy for these people in general, and depressed women in particular, is unclear, researchers say.(3) Behavior therapy tailored toward mood management rather than health education seems promising, but there too, they say, much work remains to be done.

"There seem to be genes that put you at risk to start smoking and to be unable to stop," Glassman says. "Do some of these genes lead to depression? We haven't nailed it yet."

What Works

"Absolute rates of successful quitting are enhanced by combined therapy compared with single therapies.... There is evidence both that behavior therapy enhances the efficacy of nicotine replacement therapy (NRT) and that NRT enhances the efficacy of behavior therapy. Typical long-term (6 to 12 months) abstinence rates for single therapies are on the order of 20-25 percent, while combined therapies can produce long-term abstinence rates as high as 35-40 percent. Thus, combined therapies produce quit rates greater than those generally produced by either treatment intervention alone and substantially better than general population quit rates of 5 percent or less."
— Maxine Stitzer, PhD
Johns Hopkins University School of Medicine
"Addicted to Nicotine: A National Research Forum"

Weight, Sex and Nicotine Patches

To help clinicians match patients with treatments, scientists at Stanford Research Institute recently reexamined the results of a 1991 nicotine patch study.(12) They learned:

Of 275 smokers wearing a 14 mg. patch, those with a body mass index greater than 26.4 returned to smoking after an average 48.1 days, compared to 70.2 days of abstinence by their non-overweight counterparts. Also, 91 percent of the overweight smokers relapsed, compared to 77 percent of the slimmer smokers. Heavier smokers, it was concluded, were not getting sufficient doses.

Of 262 people who tried the 21 mg. patch, 69 percent of the men went back to smoking after an average 90.5 days, compared to 78 percent of the women relapsing after 72 days. This suggests that nicotine replacement matters less to women than to men.

Less dependent men relapsed significantly later than those who were more dependent, suggesting that dependent men may need a slower schedule of lowered doses.

Women with low motivation to quit relapsed more quickly than highly motivated women. This indicates a need to reinforce women's reasons for quitting, enhance their social supports, and take other, similar measures.

Smoking and Drinking

The cliché of the smoke-filled barroom is not far off the mark. Smokers tend to drink heavily. They also tend to use illicit drugs. According to a 1996 National Household Survey on Drug Abuse, 12.8 percent of smokers were heavy drinkers (five or more alcoholic drinks on five or more days in the previous month) and 14.7 percent used illegal drugs. Among non-smokers, only 2.5 percent were heavy drinkers and 2.6 percent used drugs.

Also, smoking is often compared with drinking alcohol: both have serious health consequences, and both are legal. But nicotine is far more addictive.

According to the Centers for Disease Control and Prevention: "Addiction to nicotine is far more common than addiction to cocaine, heroin, or alcohol, and the rate of graduation from occasional use to addictive levels of intake is highest for nicotine."(14,15)

Eighty-five to 90 percent of persons who drink alcoholic beverages are not considered "problem drinkers," but as many as 90 percent of all smokers escalate to become daily smokers and smoke more than five cigarettes a day.

This means that state of the art nicotine addiction treatments need to be geared to the special needs of smokers with other chemical dependencies.

'Addicted'

Much of the material in this Facts of Life is drawn from Addicted to Nicotine: A National Research Forum, a 121-page book of summaries of presentations at a July 1998 "summit conference" describing state-of-the-art science in the fields of nicotine addiction, treatment, and prevention. The book is available online at www.nida.nih.gov. Primary sponsors of the Bethesda, Maryland, conference were the National Institute on Drug Abuse and the Robert Wood Johnson Foundation.

The Research

Centers for Disease Control and Prevention (1997), Morbidity and Mortality Weekly Report, 46:(4) 48-51.

Centers for Disease Control and Prevention (July 8, 1994), "Medical Care Expenditures Attributable to Cigarette Smoking — United States, 1993," Morbidity and Mortality Weekly Report.

Covey, L et al. (1998) "Cigarette Smoking and Major Depression," Journal of Addictive Diseases, 17(1): 35-46.

Cromwell, J et al. (1997) "Cost Effectiveness of the Clinical Practice Recommendations in the AHCPR Guidelines for Smoking Cessation," JAMA, 278:1759-1766.

Cummings, SR et al. (1989) The Cost-Effectiveness of Counseling Smokrers To Quit," JAMA, 261:75-79.)

Glassman A (1997) "Cigarette Smoking and Its Comorbidity," National Institute on Drug Abuse, Research Monograph No. 172: 52-58.

Glassman, A (April 1993) "Cigarette Smoking: Implications for Psychiatric Illness," American Journal of Psychiatry, 150(4): 546-553

Grunberg, N et al., "The Psychobiology of Nicotine Self-Administration," a chapter in Handbook of Health Psychology, Baum, A et al., eds. Lawrence Erlbaum Associates. (in press)
Perkins, K et al. (1997) "Addressing Women's Concerns about Weight Gain Due to Smoking Cessation," Journal of Substance Abuse Treatment, 14 (2): 1-10.

Perkins, K (1996) "Sex Differences in Nicotine Versus Nonnicotine Reinforcement as Determinants of Tobacco Smoking," Experimental and Clinical Psychopharmacology, 4 (2): 166-177.

Perkins, K (1995) "Individual Variability in Responses to Nicotine," Behavior Genetics, 25 (2): 119-131.

Swan, G et al. (1997) "Behavior Genetic Investigations of Cigarette Smoking and Related Issues in Twins," Handbook of Psychiatric Genetics, pp. 387-406.

Swan, G et al. (1997) "Subgroups of Smokers with Different Success Rates After use of Transdermal Nicotine," Addiction, 92(2): 207-218.

Tomar, SL et al (February 1996) "Do Dentists and Physicians Advise Tobacco Users To Quit?" JADA, Vol. 127.

US Department of Health and Human Services (1988) "The Health Consequences of Smoking; Nicotine Addiction." Report of the Surgeon General, DHHS Publication No. (CDC) 88-8406.

US Department of Health and Human Services (1989) "Reducing the Health Consequences of Smoking, 25 Years of Progress." Report of the Surgeon General, DHHS Publication No. (CDC) 89-8411.

This report was prepared with assistance from:

Academy of Behavioral Medicine Research
Academy of Psychosomatic Medicine
American Academy of Nursing
American College of Neuropsychopharmacology
American Psychiatric Association
American Psychological Association
American Psychological Association-Division 38
American Psychological Society
American Psychosomatic Society
American Sociological Association
American Society of Psychiatric Oncology
College on Problems of Drug Dependence
Institute for the Advancement of Social Work Research
International Psycho-Oncology Society
International Society for Traumatic Stress Studies
Society of Behavioral Medicine
Society for Developmental and Behavioral Pediatrics
Society for Public Health Education

The Center for the Advancement of Health, a nonprofit institute, promotes the science that explores health as a complex and dynamic system of relationships among biology, behavior, psychology, and social context and works to integrate this knowledge into public awareness, health care policy, and health care practice. The Center was founded by the John D. and Catherine T. MacArthur Foundation and the Nathan Cummings Foundation, which continue to provide core funding.