Growing Up Tobacco Free: Preventing Nicotine Addiction in Children and Youths (1994)

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Cigarettes and other forms of tobacco are addicting. Most smokers use tobacco regularly because they are addicted to nicotine. Furthermore, most smokers find it difficult to quit using tobacco because they are addicted to nicotine. Nicotine addiction develops in the first few years of cigarette smoking. that is, for most people during adolescence or early adulthood. Most smokers begin smoking during childhood or adolescence: 89% of daily smokers tried their first cigarette by or at age 18, and 71% of persons who have ever smoked daily began smoking daily by age 18 (table 2-1). The earlier in life a child tries a cigarette the more likely he or she is to become a regular smoker (that is, to smoke monthly or more frequently) or a daily smoker. For example, 67% of children who initiate smoking in the sixth grade become regular adult smokers, and 46% of teenagers who initiate smoking in the eleventh grade become regular adult smokers.1 Furthermore, the earlier a youth begins smoking, the more cigarettes he or she will smoke as an adult.2 Prevention of tobacco addiction and the related health consequences, therefore, requires early intervention for children and adolescents. To understand why youths use tobacco and why prevention measures are necessary and preferable to cessation measures to deter tobacco use by youths, it is useful to understand nicotine dependency. This chapter reviews (1) the general aspects of nicotine dependency, derived from research primarily in adults, and (2) the evidence of nicotine dependency and the factors that promote initiation and progression of tobacco use by youths.

*The terms "drug addiction" and "drug dependency" are used interchangeably in this report, as was done in the 1988 report of the surgeon general on nicotine addiction. which considered the terms to be "scientifically equivalent.''

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GENERAL ASPECTS OF NICOTINE ADDICTION

The Daily Nicotine Addiction Cycle

Given the pharmacologic properties of nicotine, a daily cycle of addiction can be described as follows. The first cigarette of the day produces substantial pharmacologic effects (pleasure, arousal, enhanced performance), but simultaneously the brain's chemistry changes and tolerance begins to develop. With subsequent cigarettes, nicotine accumulates in the body and is associated with the development of a greater level of tolerance. Withdrawal symptoms become more pronounced between successive cigarettes. The tolerance that develops over the day may be partially overcome by the transiently high brain levels of nicotine that occur immediately after the smoking of individual cigarettes, but the primary pleasurable effects of individual cigarettes tend to lessen throughout the day. As the day progresses, people tend to smoke more to relieve the symptoms of abstinence. Overnight abstinence allows considerable resensitization to the actions of nicotine, and the cycle begins again the next day.

What Is Addiction?

The World Health Organization (WHO) describes drug dependence as "a behavioral pattern in which the use of a given psychoactive drug is given a sharply higher priority over other behaviors that once had a significantly higher

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value."3 In other words, the drug comes to control behavior to an extent considered detrimental to the individual or to society.

Historically, drug addiction meant that tolerance developed to the effects of a drug during repetitive use, and that after cessation of such use withdrawal symptoms emerged (termed physical dependence). The prototypical addictive drug was heroin, and drug addiction has had a connotation of social deviance or criminal behavior in the United States. This historical view of addiction was revised by the 1964 Expert Committee of the World Health Organization. As discussed in detail in the 1988 surgeon general's report, such a definition is narrow and does not address addictions such as cocaine or binge alcoholism. A definition based on concepts of drug dependence developed by expert committees of WHO and in publications of the National Institute on Drug Abuse (NIDA) and the American Psychiatric Association includes compulsive drug-seeking behavior, effect of the drug on the brain, and usually a need for the drug to maintain homeostasis. Specific criteria for a drug that produces dependence or addiction have been presented by the U.S. surgeon general (table 2-2), and specific criteria for diagnosing drug dependence or addiction in individuals have been presented by the American Psychiatric Association (table 2-3).

Pharmacologic Aspects of Nicotine

The pharmacologic effects of nicotine are essential to sustaining cigarette smoking.4 Viewed another way, tobacco is used by people to deliver nicotine to

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the body. The primary physiologic effects of nicotine (reviewed in detail in the 1988 surgeon general's report) are listed below.

· Electroencephalographic desynchronization
· Increased circulating levels of catecholamines, vasopressin, growth hormone, adrenocorticotropic hormone, cortisol, prolactin, and beta-endorphin
· Increased metabolic rate
· Lipolysis, increased free fatty acids
· Heart rate acceleration

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· Cutaneous and coronary vasoconstriction
· Increased cardiac output
· Increased blood pressure
· Skeletal muscle relaxation

Smokers give various explanations for their smoking. Many report that smoking produces arousal, particularly with the first few cigarettes of the day, and relaxation, particularly in stressful situations. Many smokers report that smoking helps them concentrate and lifts their mood. Nicotine has been shown to increase vigilance in the performance of repetitive tasks and to enhance selective attention. Smokers commonly report pleasure and reduced anger, tension, depression, and stress after smoking a cigarette. The extent to which the enhanced performance and mood after smoking are due to the relief of symptoms of abstinence or to an intrinsic enhancement effect on the brain is unclear. A few studies do show improvement in the performance of nonsmoking subjects after dosing with nicotine, suggesting at least some direct enhancement.

Some of the gratifying effects of nicotine are due to the relief of the symptoms of nicotine withdrawal. When nicotine use is abruptly stopped, withdrawal symptoms emerge. The typical symptoms are listed below.

· Restlessness
· Eating more than usual
· Anxiety/tension
· Impatience
· Irritability/anger
· Difficulty concentrating
· Excessive hunger
· Depression
· Disorientation
· Loss of energy/fatigue
· Dizziness
· Stomach or bowel problems
· Headaches
· Sweating
· Insomnia
· Heart palpitations
· Tremors
· Craving cigarettes5

Most withdrawal symptoms reach maximal intensity 24 to 48 hours after cessation of tobacco use and gradually diminish in intensity over several weeks. Some symptoms, such as eating more than usual, weight gain, and craving cigarettes (particularly in stressful situations) may persist for months or even years after cessation.

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Actions of Nicotine on the Brain

The nicotine molecule is shaped like acetylcholine. Acetylcholine is a neurotransmitter, that is, a chemical naturally found in the body that is involved in transmitting information from one neuron to another. Receptors (specialized proteins that selectively bind drugs and initiate drug effects in the body) for acetylcholine are called cholinergic receptors. Nicotine acts on certain cholinergic receptors in the brain and other organs of the body. The receptors would normally be acted on by the body's own acetylcholine. By activating cholinergic receptors, nicotine enhances the release of other neurotransmitters and hormones including acetylcholine, norepinephrine, dopamine, vasopressin, serotonin, and beta-endorphin. The physiologic effects of nicotine include behavioral arousal and sympathetic neural activation. Release of specific neurotransmitters has been speculatively linked to particular reinforcing effects of nicotine (figure 2-1).6 For example, enhanced release of dopamine, norepinephrine, and seroto-

FIGURE 2-1  Source: Adapted from Pomerleau, O.F., and C. S. Pomerleau. "Neuro-regulators and the
Reinforcement of Smoking: Towards a Biobehavioral Explanation." Neuroscience Behavioral Review 8 (1984): 503-513.

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nin may be associated with pleasure as well as appetite suppression, the latter of which may contribute to lower body weight. Release of acetylcholine may be associated with improved performance on behavioral tasks and improvement of memory. Release of beta-endorphin may be associated with reduction of anxiety and tension.

Tolerance and Withdrawal

With prolonged or repetitive exposure to nicotine, the brain cells adapt in such a way as to compensate for the actions of nicotine, that is, to return brain functioning to normal. This process is called neuroadaptation. Neuroadaptation is associated with an increasing number of nicotinic receptors in the brain. Neuroadaptation results in the development of tolerance, that is, a given level of nicotine comes to have less of an effect on the body, and higher levels of nicotine are needed to produce the effects that lower doses formerly produced. Substantial tolerance develops to the behavioral arousal and cardiovascular effects of nicotine when a person smokes multiple cigarettes or uses multiple doses of smokeless tobacco, even within the course of a single day. Regular tobacco users regain sensitivity to the effects of nicotine, at least in part, after overnight abstinence from tobacco.

When the brain has adapted so as to function normally in the presence of nicotine, it also becomes dependent on the presence of nicotine for normal functioning. When nicotine is not available (such as when a smoker stops smoking), the brain function becomes disturbed, resulting in a number of withdrawal symptoms, as mentioned above.

Absorption of Nicotine from Tobacco

Nicotine from tobacco smoke is rapidly absorbed into the systemic circulation after inhalation, then is quickly carried to various body organs including the brain. Nicotine levels in the blood rise quickly after smoking, with arterial blood levels exceeding venous levels in the first few minutes (figure 2-2). Because nicotine is a weak base and is ionized at acid pH, there is little absorption of nicotine through the membranes of the mouth from the acidic smoke of blond (light-colored) tobacco. However, the smoke of pipes, cigars, and dark tobacco is more alkaline, so nicotine is absorbed through the mouth from these products. When oral snuff or chewing tobacco is used, nicotine is also absorbed through the mouth. Nicotine from oral snuff or chewing tobacco is absorbed more slowly than from cigarette smoke; peak plasma concentrations of nicotine in venous blood are similar.

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FIGURE 2-2  *Average values for 10 subjects. Shaded bars show the period of tobacco (or nicotine) use.
Vertical bars indicate ranges. Source: Adapted from Benowitz, Neal L., H. Porchet, L. Sheiner, and
P. Jacob III. "Nicotine Absorption and Cardiovascular Effects with Smokeless Tobacco Use:
Comparison to Cigarettes and Nicotine Gum." Clinical Pharmacology and Therapeutics (1988): 23-28.

Distribution and Elimination of Nicotine from the Body

A cigarette delivers nicotine to the brain within 10 to 19 seconds from the start of a puff. The rapid passage of nicotine from the lungs to the arterial circulation to the brain provides for rapid behavioral reinforcement for smoking and for the possibility for the smoker to control levels of nicotine in the brain and to modulate pharmacologic effects. Nicotine is also distributed extensively to other body tissues. Slow release from tissues explains in part the elimination half-life of 2 to 3 hours.

Nicotine is eliminated primarily by liver metabolism. The rate of metabolism is quite variable from person to person, so the same level of nicotine intake

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may be associated with different concentrations of nicotine in the blood of different people. The main metabolite of nicotine, cotinine, has a long half-life (on average 17 hours) and has been widely used by researchers as a biochemical marker of nicotine exposure.

Intake and Accumulation of Nicotine During Cigarette Smoking

On the average, smoking a cigarette results in the absorption into the blood stream of about I mg of nicotine, but the range is from 0.5 to 3.0 mg. The elimination half-life of nicotine is 2 to 3 hours. This means that the level of nicotine in the blood decreases by one-half every 2 or 3 hours. It also means that after a single use of tobacco nicotine remains in the body for 8 to 12 hours. With repeated smoking, nicotine levels accumulate over 6 to 8 hours, plateauing through the remainder of the day, then gradually falling overnight. Thus, regular cigarette smoking results in continued exposure of the brain and body to nicotine.

Addiction and the Light or Occasional Smoker

Among adults the light or occasional smoker, that is, one who regularly smokes 5 or fewer cigarettes per day or who does not smoke every day, is in general less addicted than are daily smokers of more than 5 cigarettes per day.7 Smoking appears to be reinforced for light smokers by the direct pharmacologic effects of nicotine, as described above, as well as by behavioral aspects of tobacco use, as described below. The use of tobacco in response to withdrawal symptoms is less of a factor in such tobacco users. Among adults, light or occasional smokers are relatively uncommon (less than 10% of adult smokers);8 they have higher success in smoking cessation than do heavier smokers, although not all light smokers are able to quit. In contrast, many more children than adults are light or occasional smokers; however, light smoking by children is often not a stable pattern but, rather, represents a stage in escalation to becoming daily smokers.

Nicotine Compensation

The "Low-Yield" Cigarette

Some tobacco advertisements indicate that particular brands of cigarettes deliver less nicotine and tar than their competitors' brands, implying a health benefit to low-yield cigarettes. Some people switch to low-yield cigarettes in an attempt to reduce the health consequences of smoking, but that is an unlikely result. A daily smoker tends to regulate his or her nicotine intake to a specific level in order to achieve desired effects and to minimize withdrawal symptoms.

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This nicotine regulation influences how smokers smoke cigarettes with various nicotine yields and how they respond to cutting down on the number of cigarettes they smoke per day. When smoking lower-yield cigarettes, smokers puff more frequently or more intensely than when smoking higher-yield cigarettes, presumably to obtain their usual specific level of nicotine from each cigarette. In switching from high-yield to low-yield cigarettes, smokers consume more nicotine from the low-yield cigarette than predicted by smoking machine tests. Conversely, smokers consume less nicotine than predicted from high-yield cigarettes.

The intake of nicotine, with blood cotinine or nicotine concentrations used as markers of nicotine intake, has been studied in large groups of people smoking their chosen brands of cigarettes.9 In such studies, nicotine intake correlates only weakly with the advertised yield. The slope of the regression line between advertised nicotine yields and blood nicotine or cotinine levels is shallow, suggesting only small differences of intake from cigarettes of widely different nicotine yields. Because of this compensatory smoking, having smokers switch to low-yield cigarettes reduces the risk of smoking to a much lesser degree, if at all, than suggested by the decreases in yield.

Smoking Fewer Cigarettes

The regulation of nicotine intake by daily smokers is also apparent when the number of cigarettes available to a smoker is restricted. In one study of heavy smokers, when the number of cigarettes was reduced from unlimited (average 37 per day) to 5 cigarettes per day, the average intake of nicotine per cigarette tripled.10 As a result, reducing the number of cigarettes to 15 per day had very little effect, and reducing to 5 cigarettes per day reduced the daily exposure to tobacco toxins only by 50%. This observation explains why many smokers who are instructed to quit report cutting down to about 10 cigarettes per day, but cannot reduce their consumption to fewer than 10. At 10 cigarettes per day smokers still can absorb adequate nicotine to maintain nicotine addiction.

Behavioral Aspects of Addiction

The behavior of smoking is maintained both by the direct pharmacologic effects of nicotine (including relief of withdrawal) and by learned responses. Anticipatory responses develop as a consequence of repetitive use of tobacco during which various kinds of gratifications from smoking occur in the presence of specific cues from the environment. For example, when a smoker encounters stressors or situational reminders of smoking, these stimuli revivify the pleasurable or other reinforcing aspects of smoking, which then generate the urge to smoke. Such recurrent anticipatory responses may persist 6 months or longer after physical dependence has been overcome, accounting for the relapses that

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occur beyond the first week or two after cessation of tobacco use. Such anticipatory responses probably also develop to some degree in occasional smokers.

There are various conceptualizations of the nature of the anticipatory response system. One is the conditioning model, in which learned associations between the effects of cigarette smoking and specific cues in the environment motivate smoking. Another model is self-regulation, in which high-risk situations activate cognitive processes in a form of pleasurable expectations and a reduced sense of personal control, which then increases the likelihood of smoking.11 Examples of common anticipatory reactions include smoking after a meal, with a cup of coffee or an alcoholic beverage, during a break from work, while talking on the phone, or while with friends who smoke.

Of note, aspects of the drug-taking behavior itself often become pleasurable in addition to the pleasure afforded by the pharmacologic effects of nicotine. For example, manipulation of smoking materials or the taste, smell, or feel of tobacco smoke in the throat can become associated with the reinforcing effects of smoking and can become pleasurable in themselves. When a smoker becomes abstinent, he or she must learn not only to forego the pharmacologic pleasures afforded by the drug, but also the pleasure of engaging in those aspects of drug-taking behavior that have become pleasurable through anticipatory mechanisms.

Behavioral factors other than anticipatory mechanisms may also influence personal susceptibility to drug addiction. For example, some smokers, particularly Caucasian women, smoke as a means of maintaining lower body weight.12 Certain characteristics of individuals appear to promote initiation of smoking and the development of nicotine addiction, as reviewed in more detail in a later section.

Addiction to Smokeless Tobacco

''Smokeless tobacco" (SLT) refers to oral and nasal snuff and chewing tobacco. Smokeless tobacco, commonly used by youths, particularly in rural areas, may be highly addicting.13 Considerable nicotine is absorbed from smokeless tobacco. A classification scheme for levels of SLT use or addiction is problematic. The nicotine content of smokeless products is not known to the public and the nicotine content of the tobacco provides only a rough estimate of actual nicotine intake. Recent laboratory analysis of popular brands of moist snuff revealed large differences in nicotine content, from 5.7 to 30.7 mg/g.14 Two studies found evidence for higher addiction levels and greater oral pathology among Copenhagen® users.15 The systemic dose of nicotine derived from smokeless tobacco can be estimated by measuring blood nicotine levels after SLT use. The systemic dose of nicotine from snuff is 3.6 mg, and for chewing tobacco it is 4.5 mg; an average dose from smoking a cigarette is I mg.16 No standard self-report measures exist for smokeless tobacco consumption, such as those for smoking. One way to estimate addiction level is to use the number of

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tins or pouches of SLT product consumed per week, the product used (high, medium, or low nicotine content), and the amount of time (minutes) the tobacco is in the mouth. In surveys, though not standardized, questions typically ask if the individual used one or more dips or chews in the past 7 days, used one or more dips or chews in the past 24 hours (or day), and uses dip or chew daily. In intervention studies, typical measures of the pattern and amount of SLT use have included the number of dips per day, the number of minutes the dip or chew is kept in the mouth, the number of days a tin or pouch lasts, and the number of tins or pouches used per week. All four measures of SLT intercorrelate significantly with saliva cotinine assays.17 Most users report using a tin or pouch every day or two, but adolescent boys report that a tin of snuff lasts 5 days and that they use an average of five dips a day.18

Most cessation studies define a "regular user" as someone who has used SLT daily for the past year. Schroeder and colleagues suggest categorizing the SLT user as a light, moderate, or heavy user according to the amount of nicotine consumed per week from chewing tobacco or snuff products.19 Other measures of the pattern of SLT use and addiction have been adapted from the smoking cessation literature. The Fagerström Tolerance Questionnaire20 has been adapted and used with a scale applicable to SLT users by simply converting cigarette-based items to SLT-use items, for example, "I chew or dip first thing in the morning or within 30 minutes of waking up in the morning."21 The scale has been validated by its correlation with saliva cotinine. Some items of this scale have been positively correlated with self-reported severity of nicotine withdrawal.22

Blood nicotine concentrations throughout the day are similar in regular smokers and people who also use smokeless tobacco.23 Plasma cotinine levels among regular users of smokeless tobacco are in many cases similar to those of cigarette smokers.24 Abstinence from smokeless tobacco use results in signs and symptoms of nicotine deprivation that are similar to those seen in smokers after they stop smoking.25 These symptoms are reversed by administration of tobacco or nicotine gum. Swedish oral snuff users report difficulty in quitting and many consider themselves to be addicted, reporting as much difficulty in giving up smokeless tobacco use as is reported by cigarette smokers trying to quit smoking.26 Finally, there is evidence that when deprived of snuff, regular snuff users will smoke cigarettes to satisfy their need for nicotine.27 The regular use of snuff or chewing tobacco by a child therefore increases the likelihood that subsequently the person will take up regular cigarette smoking.28

Comparison of Nicotine Addiction with Other Drug Addictions

It is obvious that all drugs of dependence share psychoactivity, produce pleasure, and are shown to reinforce drug-taking behavior. (For a detailed review of the comparison of nicotine and other drug addictions, see the 1988

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surgeon general's report.) The nature of nicotine's psychoactivity, which is generally subtle and is consistent with high levels of cognitive performance, is considerably different from that of heroin or cocaine, which produce intense euphoria and may be disruptive to performance. The subtle psychoactive effect of nicotine is experienced hundreds of times (puffs) per day, and exerts a powerful effect on behavior over time. Although the psychoactive effect of nicotine is less dramatic than that of other drugs, the strength of the addiction is as powerful or more powerful. The consequences of its addictiveness are clearly more dramatic, making tobacco use the number one health problem in the United States.

Compulsive use can be observed with all addictive drugs, but the compulsiveness is manifested in different patterns. Some drugs, such as cocaine and heroin, are used by some addicted persons only intermittently, that is, every few days or even at longer intervals, but the compulsion to use the drug does repeat. Cigarette smokers, on the other hand, rarely go more than a day without nicotine. At work or in other public places where smoking is proscribed, smokers may need to take numerous breaks throughout the day to smoke. No single physical dependence model describes the way in which drug use is continually compelled, but these compulsive behaviors are strongly controlled by the addictive actions of the drugs.

"Addiction is needing to smoke first thing in the morning, not just
when you are bored or hanging out with your friends. "
-adolescent in focus group

Use despite harmful effects confirms the difficulty that many persons have in quitting drug use. This is clearly evident to clinicians who treat alcoholics with chronic liver disease, heroin addicts with infective endocarditis, and cigarette smokers. For example, only 50% of smokers who suffer acute myocardial infarction quit smoking, despite a physician's admonition to do so.29 It has been argued that for many activities that entail risk, such as sex, sunbathing, and skiing, the individual assumes a risk and makes a free choice, and that the same is true of cigarette smoking. However, life-long smoking results in the premature death of one in three smokers and the disability of a great number of smokers from chronic lung disease, indicating a substantially different level of risk.

Relapse rates after abstinence appear to be similar for tobacco, heroin, and alcohol; about 60%  of quitters relapse within 3 months and 75%  within 6 months.30 These relapse rates have been observed in clients discharged from treatment programs. It has been argued that the relapse rate for tobacco among spontaneous quitters might be lower than these rates. Recent data indicate that relapse rates for smokers who have undergone minimal intervention treatment in a physician's office and who have successfully abstained for 24 hours are 25% at 2 days, 50% at 1 week, and 75% at 2 months,31 whereas two-thirds of smokers who quit on their own relapse within 2 days.32

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Recurrent drug cravings have been described for each of the addicting drugs, although there has been considerable debate about the use of the term "craving." A better term might be "strong desire" to use a drug. When desires for different drugs were compared among polydrug abusers, most of whom smoked cigarettes, the reported intensity of desire for cigarettes when they are not available was as high as or higher than for heroin, alcohol, or cocaine when the latter were not available.33

Tolerance to the various drugs of abuse has been well documented, although the time course varies. Different time courses of tolerance might influence the pattern of drug use. For example, tolerance to many effects of nicotine develops quickly, within the day, and there is resensitization of many responses overnight. Intermittent high levels of nicotine in the brain from individual puffs might also overcome tolerance to some extent so that effects can be experienced from individual cigarettes. Presumably because of the daily cycle of tolerance and resensitization, daily doses of nicotine tend to stabilize, and, after a period of dose escalation in the first few years, many smokers smoke the same number of cigarettes each day. In contrast, tolerance lasts longer in an alcoholic who drinks all day and whose brain is more or less continually exposed to alcohol throughout the day. Tolerance likewise occurs during cocaine binges when progressively larger doses are used in an attempt to maintain a cocaine high; however, between binges, sensitivity to cocaine may be regained. One implication of the development of tolerance is that regular smokers are able to consume far greater amounts of tobacco smoke and associated toxins than if they had not become tolerant.

Physical dependence has been well characterized for smokers as well as for other drug abusers. It has been argued that a marked stereotypic syndrome occurs in a person after stopping use of heroin or alcohol, whereas the withdrawal symptoms after stopping smoking vary widely in nature and magnitude and, in one study, were not sufficiently present in 22% of quitters to constitute a diagnosis of withdrawal.34 Although it is true that smoking does not result in seizures or delirium tremens, withdrawal from smoking can be extremely disruptive to personal life. Nicotine withdrawal may be viewed as closer to that of withdrawal from other stimulants such as cocaine: the withdrawal syndrome is not life-threatening but it profoundly affects behavior and remains a strong impetus to recurrent drug use. Conversely, some persons dependent on heroin or alcohol stop their drug use abruptly without marked withdrawal symptoms.

Agonist drug "replacement" to modify withdrawal symptoms or to facilitate cessation has been used with narcotic abuse (methadone and L-acetylmethadol) and alcoholism (benzodiazepines) as well as with tobacco addiction (nicotine gum, transdermal nicotine, and nicotine nasal spray). In all cases the agonist relieves withdrawal symptoms. Methadone and nicotine can be used over several months, with gradual tapering, to facilitate cessation. Methadone is also used in the long term to maintain abstinence. While such use is not recommended for nicotine replacement, 6% to 38% of nicotine gum users do continue

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to use the gum for a year or more after stopping smoking, apparently as a sort of maintenance treatment.35

NICOTINE DEPENDENCY IN YOUTHS

Tobacco use begins with experimentation, often in early adolescence or in the preteen years. The immediate impetus to experiment is social, prompted by friends, or family members, or role models who smoke. Other factors involved in initiation and progression of smoking are discussed in detail in a later section. Estimates of the percentage of youths who experiment with smoking vary from 47% to 90%. Most who experiment smoke only a few cigarettes. Those who smoke three or more cigarettes have a high likelihood of becoming regular smokers.36 Once a smoker becomes a regular smoker, the number of cigarettes smoked per day tends to escalate over several years.37 Even when youths are smoking only a few cigarettes per day, they inhale tobacco smoke effectively and take in as much nicotine per cigarette as do adults, as shown in studies measuring salivary cotinine per cigarette smoked per day.

Epidemiology and Natural History of Cigarette Smoking

Data from the Youth Risk Behavior Survey for smoking initiation by high school youths in the United States are presented in table 2-4 (1990) and in table 2-5 (1991) for smoking within the past 30 days. Figure 2-3 shows that in 1990, by age 13, 56% of youths had tried smoking and 9% were regular smokers (that is, they smoked on 5-15 days or more in the past 30 days). The percentage of youths trying cigarettes increases with each year of age, so that by age 17, 77% of youths had tried smoking and 25% were regular smokers. This trend has been reported for current smokers (that is, who smoked within the last 30 days) in other recent surveys (table 2-5).

Data on the amount of cigarettes consumed by youths of various ages are provided in table 2-6. Younger children are less likely to be daily smokers; if they are, they smoke fewer cigarettes per day. Thus, at ages 12-13, 16.5 % of adolescent smokers are daily smokers, compared to 47.5% of teen smokers between 16-18 years old. At ages 12-13, 11% of smokers smoke 10 or more cigarettes per day, compared to 27.2% of smokers 16-18 years old.

The development of nicotine addiction has been characterized as a series of five stages:

1. Preparatory
2. Initial trying
3. Experimentation
4. Regular use
5. Nicotine addiction38

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The "preparatory" stage includes formation of knowledge, beliefs, and expectations about smoking. "Initial trying" refers to trials with the first 2 or 3 cigarettes (events that are discussed in more detail later in this section). "Experimentation" refers to repeated, irregular use over an extended period of time; such smoking may be situation-specific (for example, smoking at parties). "Regular smoking" by youths may mean smoking every weekend or in certain parts of each day (such as after school with friends). "Nicotine addiction'' refers to regular smoking, usually every day, with an internally regulated need for nicotine. Thus, for individual youths, there is a progression of smoking over time from initiation to experimentation with light smoking to regular and heavy smoking. Unlike adults, in whom intermittent or light smoking may be a stable and relatively nonaddictive pattern of smoking, children who are light smokers are often in a phase of escalation, with a typical interval from initiation to addiction of 2-3 years. The interval between initiation and addiction is based on a comparison of the cumulative prevalence curves for trying a first cigarette and smoking daily (table 2-1) and the interval between initiation of smoking and the rise of salivary cotinine concentrations to adult levels (figure 2-4).

The natural history of the smoking experience for an individual provides insight into the pharmacology of the addiction process. The first cigarette smoked is often perceived as aversive, producing coughing, dizziness, and/or

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nausea. With repeated smoking, tolerance develops to the noxious effects of cigarette smoking, and smokers tend to report positive effects of smoking. As the daily intake of nicotine increases, the development of physical dependence, that is, experiencing withdrawal symptoms between cigarettes or when cigarettes are not available, becomes established. Thus, there appears to be a progression over time from smoking initially for social reasons to smoking for pharmacologic reasons. The latter includes both smoking for positive effects of nicotine and smoking to avoid withdrawal symptoms, as discussed above in the section on general aspects of nicotine dependence.

Evidence for Nicotine Dependence in Youths

Many youths describe themselves as being dependent on tobacco, and there is evidence that nicotine dependence does become established in youthful smok-

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FIGURE 2-3  Source: Data from  1990 Youth Risk Behavior Survey, presented in Escobedo,
Luis G., Stephen E. Marcus, Deborah Holtzman, and Gary Giovino. "Sports Participation,
Age at Smoking Initiation, and the Risk of Smoking Among U.S. High School Students."
Journal of the American Medical Association 17(11) (1993) 1391-1395.

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ers. The evidence reveals that (1) youths consume substantial levels of nicotine, (2) youths report subjective effects and subjective reasons for smoking, (3) youths experience withdrawal symptoms when they are not able to smoke, and (4) youths have difficulty in quitting tobacco use.

That youths consume substantial amounts of nicotine was shown in a 3-year study of 197 London schoolgirls who entered the study between the ages of 11 and 14. Saliva cotinine concentrations in girls who were smokers throughout the 3 years were higher at each year's evaluation. Average salivary cotinine levels were 103, 158, and 208 g/ml.39 The level of 208 ng/ml is similar to that of many adult daily smokers. The ratio of salivary cotinine per cigarette per day, an index

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of the amount of nicotine taken in per cigarette, was similar for girls with various levels of cigarette consumption, and similar to that for adults. Thus, there seems to be the same intake of nicotine per cigarette among adolescent girls as among adults. Also of note in the study was that smokers who smoked at the time of all three surveys, as well as smokers who were occasional smokers or nonsmokers at the time of the first survey but who subsequently became daily smokers, showed escalation of cigarette consumption (figure 2-4) and saliva cotinine levels each year.

FIGURE 2-4  Source: McNeill, A. D., M. J. Jarvis, J. A. Stapleton, R. J. West, and A. Bryant.
"Nicotine Intake in Young Smokers: Longitudinal Study of Saliva Cotinine Concentrations."
American Journal of Public Health 79 (1989): 172-1.'5.

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FIGURE 2-5 *Difference is statistically significant. Source: McNeill, Ann D., Martin Jarvis, and Robert West.
"Subjective Effects of Cigarette Smoking in Adolescents." Psychopharmacology 92 (1987): 115-117.

That youths experience pharmacologic effects of nicotine from tobacco smoke was reported in an earlier study by the same researchers.40 A smoking questionnaire asked a group of 170 British schoolgirls ages 11-17 about the five subjective effects of smoking specified in figure 2-5. Feeling high or feeling more alert, which are stimulant-like effects, were described by only a few respondents. Feeling calmer was the most common effect described, and was more likely to be reported by daily smokers than by occasional smokers. There was also a significant correlation between salivary cotinine concentrations and

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the response of feeling calmer. Feeling calmer may be a beneficial effect that is particularly desirable to youths with high levels of anxiety or depression (as will be discussed later). Alternatively, feeling calmer could represent the reversal of nicotine withdrawal symptoms. In any case, there is clear evidence that youthful smokers do smoke for the pharmacologic effects of tobacco, presumably the effects of nicotine.

That youths experience withdrawal symptoms when they try to give up smoking has been demonstrated as well. McNeill and colleagues queried 191 schoolgirls 11-17 years old who were current cigarette smokers about how they felt when they tried to stop smoking.41 Of the group of smokers, 71% of the daily smokers and 72% of the occasional smokers had made at least one attempt to quit and had failed. Of these subjects, the average cigarette consumption by the daily smokers (69 girls) was 6.8 cigarettes per day, with an average salivary cotinine of 182 ng/ml. The average salivary cotinine concentration in the occasional smokers (47 girls) was 22 ng/ml; 74% of the daily smokers and 47% of the occasional smokers experienced one or more of the six symptoms of nicotine withdrawal graphed in figure 2-6. The withdrawal score correlated significantly with salivary cotinine concentration and with weekly cigarette consumption. This study demonstrates that adolescent smokers experience withdrawal symptoms when they try to quit and that many youths have difficulty quitting. It should be noted that the data on nicotine consumption, pharmacologic effects, and withdrawal symptoms are based on studies of schoolgirls; no data are as yet available on boys. However, based on the difficulty of quitting smoking that is experienced by both boys and girls (described below), it is likely that dependence develops to a similar degree in boys as it does in girls. This issue of the natural history of the development of addiction to nicotine in youths requires further research.

Other studies further reveal that many youths want to quit but have difficulty doing so. Townsend and colleagues reported that 60% of adolescent smokers evaluated in a general medical practice made an agreement with the practice doctor or nurse to give up smoking.42 Stone and Kristeller surveyed tenth grade students in suburban Massachusetts; 14% of the students were daily smokers and, of these, 28% reported that they continued to smoke because they were addicted.43 The Monitoring the Future Project, which looked at high school seniors in the United States, asked about interest in quitting smoking and prior attempts at quitting (table 2-7). Of smokers (1985-1989) who had smoked at all in the past 30 days, 42.5% reported a desire to stop smoking. Of this group, and of the subgroup who smoked daily, 28% and 39%, respectively, stated that they had tried to stop in the past and could not.44

Another perspective on the difficulty of quitting is youths' expectations regarding their future smoking behavior. Seniors in high school were asked, "Do you think you will be smoking cigarettes 5 years from now?" Among the respondents who were occasional smokers (less than one cigarette per day) 85%

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FIGURE 2-6  *Difference is statistically significant. Source: McNeill, Ann D., Robert J. West, Martin Jarvis, et al.
"Cigarette Withdrawal Symptoms in Adolescent Smokers." Psychopharmacology 90 (1986): 533-536.

stated that they probably or definitely would not be smoking in 5 years, as did 32% of those who smoked one pack per day or more (table 2-8). However, at follow-up 5-6 years later, of those who smoked occasionally only 58% had quit and 28% had actually increased their cigarette consumption. Of those who had smoked one pack or more per day, only 13% had quit and 70% still smoked one pack or more per day. Smokers of 1-5 or about 10 cigarettes per day at the time of the initial questionnaire also were less likely to quit than they had predicted, and on average escalated their smoking over the subsequent 5 years (table 2-9).45

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Thus, consistent with the concept of addiction, smokers' expectations of future smoking behavior shows little relationship to their actual behavior; that is, youths think that they will be able to quit but underestimate the power of their addiction. Even those who smoke only a few cigarettes per day during high school have a high risk of becoming heavy smokers as adults.

These data are evidence that nicotine addiction develops during adolescence, and that most adolescents who are daily cigarette smokers (as well as some who are occasional smokers) are addicted to nicotine. Once adolescents are addicted, cessation is difficult, as it is for adults; thus, interventions are needed at early stages to prevent an established pattern of addiction. The likelihood of successful quitting among adolescents is greater the sooner the adolescent tries to quit after initiating tobacco use, and the fewer cigarettes he or she has smoked.46

Risk Factors for Smoking Initiation

Understanding why children begin to smoke is important in planning and developing effective prevention strategies. The numerous major factors that influence or predict initiation and escalation of tobacco use were recently reviewed extensively in the 1994 surgeon general's report, and are listed in table 2-10. In general, the psychosocial risk factors can be described as a continuum

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of proximal to distal factors. Proximal factors directly affect an individual's choice to use tobacco, whereas distal factors do so indirectly. For example. being offered a cigarette at a party is a proximal factor, but prior exposure to advertising showing young adults smoking at a party would be a distal factor influencing the decision to use tobacco. Although proximal factors may seem more influential because of their immediacy, distal factors:

. . . acquire potency if they are pervasive and provide consistent, repetitive messages across multiple channels. Distal factors are also powerful because, over time, they affect proximal factors as these influences become interpreted and internalized, particularly among adolescents as they try to shape a mature self-identity.47

The degree to which any of these risk factors influences smoking behavior varies for each risk factor and among research studies. The reader who wishes a de-

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tailed discussion of the risk factors should refer to the surgeon general's report. This section provides only an overview of those issues most pertinent to the policy questions addressed in this report.

Initiation of cigarette smoking is influenced by several kinds of factors: environmental, behavioral, personal, and sociodemographic.48 Among the environmental factors that influence initiation of smoking is having friends who smoke, having a best friend who smokes, and/or having many friends who smoke strongly influences initiation. Parental smoking is more important in establish-

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ing smoking as a normative behavior, and is associated with more positive and fewer negative perceptions of the health consequences of smoking. Advertising and exposure to smoking in other mass media (for example, television, movies, and sports events) reinforces the idea that smoking is an adult, sophisticated, attractive, and sexy behavior, and downplays the adverse health consequences of smoking (see chapter 4 on advertising).

Behavioral analysis indicates that cigarette smoking is often an early manifestation of problem behavior. School children manifest such problem behaviors as poor school performance, low aspiration for future success, school absences, and the intention to drop out of school or actually dropping out. Other problem behaviors linked to cigarette smoking include alcohol and other drug use and other risk-taking or rebellious behaviors.

A number of personal characteristics of adolescents have been linked to cigarette smoking: (1) low self-esteem, poor self-image, low perception of self-efficacy, and susceptibility to peer pressure; (2) sensation-seeking, rebelliousness, sense of invulnerability; (3) low knowledge level of the adverse effects of cigarette smoking; (4) depression and/or anxiety; and (5) pharmacologic response. Considerable recent research has shown a high prevalence of depression among current smokers. Smokers are more likely than nonsmokers to have a history of major depression, even preceding initiation of smoking,49 and smokers with a history of depression have been found to have lower smoking cessation rates than smokers without depression.

Various pharmacologic responses to smoking (presumably to nicotine) from the first cigarette may also predict the likelihood of progression to regular smoking. Hirschman and colleagues found that a report of dizziness after smoking the first cigarette predicted a high rate of progression to the next cigarette, whereas reports of adverse effects, such as coughing, were not associated with progression.50 While the mechanism of such a link between dizziness and smoking progression is not apparent, a pharmacologic link between cigarette smoking and depression is reasonable. Nicotine is known to release dopamine, norepinephrine, and serotonin in the brain in animals. Antidepressant drugs have similar effects. Thus, it is possible that pharmacologic responses to nicotine promote tobacco use in people who are depressed.

Evidence from studies of twins suggests a moderate genetic influence both on initiation and on maintenance of cigarette smoking.51 Possible mechanisms include genetically determined differences in the pharmacologic response to nicotine, differences in personality, and the presence or absence of an affective or other psychiatric disorder, particularly depression. There is a high concordance of cigarette smoking and alcoholism, and studies in twins suggest that these addictions share, to some extent, a common genetic determinant.52  Some proportion of the genetic predisposition to tobacco addiction thus appears to be specific, but some appears to be linked to alcoholism or to other drug addictions.

The factors that influence initiation may be predominantly of one type, and

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those that influence the progression of cigarette smoking of another type. Hirschman and colleagues studied 386 urban public school children, grades 210, to determine how many had ever tried smoking, and then how many had progressed to a second and third cigarette. The main risk factors for the 47% of children who had tried at least one cigarette were grade level in school (that is, the higher the grade level and the older the child, the higher the likelihood of trying a cigarette), having a best friend who was a smoker, and risk-taking behavior (reported on a questionnaire). Progression to a second cigarette (32% of those who smoked one cigarette) was predicted by life stress (predicted rapid progression), friends who smoked (predicted slow progression), lack of negative attitudes toward smoking, and an experience of dizziness when smoking the first cigarette. Progression to a third cigarette (in 77% of those who had smoked two cigarettes) was predicted by best friend being a smoker, feelings of helplessness, and rapid progression to the second cigarette.53 These analyses support the idea that initiation of cigarette smoking is primarily a consequence of environmental factors, whereas progression appears to be more influenced by personal and pharmacologic factors.

Sociodemographic factors that predispose youths to cigarette smoking include low  socioeconomic status, low  level of parental education, and the individual's developmental state of adolescence. With respect to the latter, the transition years from elementary to high school, grades 7-10, (ages 11-16) appear to be a particularly high-risk time for initiation (table 2-4).

Ethnic Differences in Nicotine Dependency

Differences in tobacco use by youths are specific to and consistent within ethnic groups. The rates for daily smoking for twelfth graders in 1991 were highest among non-Hispanic whites (21%), next among Hispanics (12%), and lowest among African Americans (5%); the rates in 1991 for smoking one or more cigarettes in the preceding 30 days were 32% for non-Hispanic whites, 25% for Hispanics, and 9% for African Americans.54 A striking trend of decline in smoking has occurred among African-American high school seniors: from 26.8% in 1976 to 4.4% in 1993 for smoking daily during the preceding 30 days55 (figure 2-7). Differences in the smoking habits of various ethnic groups are notable and may influence the addictive process. Compared to whites, African Americans show a consistent preference for menthol brands, higher tar levels, and higher nicotine levels; and they smoke fewer cigarettes per day. These factors influence inhalation patterns and health risks. For instance, because menthol cigarettes ''provide a sensation of cooling when smoked," they may "promote deeper and more prolonged inhalation."56 Although current initiation rates are lowest for African Americans, there is evidence that adult African Americans are more highly addicted to tobacco than are whites. The cotinine levels of adult African Americans are higher than those of whites, even though

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FIGURE 2-7  Source: Monitoring the Future Project, University of Michigan, 19761993.

they smoke fewer cigarettes;57 this suggests that African Americans consume higher levels of nicotine from each cigarette than do whites. A greater dose of nicotine per cigarette may be explained in part by the smoking of menthol cigarettes, as discussed previously. In addition, this observation is consistent with the generally lower income level of African Americans compared to whites, and an economic pressure to extract more nicotine per cigarette. Cessation rates for African-American adults are lower than for whites, which seems to indicate a higher level of addiction for African Americans.58 The explanation for the apparent inconsistency between lower current initiation rates but higher levels of addiction in adult African Americans is not clear. Possibly this difference reflects a cohort effect, and in the future fewer adult African Americans will be addicted. Alternatively, it may reflect initiation of cigarette smoking later in life among African Americans compared to whites. Further research is needed to clarify these issues. The use of smokeless tobacco is highest among whites and Native Americans, with relatively low levels among African Americans and

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Hispanics.59 The reasons for ethnic differences in tobacco use among youths are unclear.

Use of Smokeless Tobacco by Children and Youths

Initiation of smokeless tobacco use begins in the preteen and early teen years. In 1991 smokeless tobacco was used by about 11% of high school seniors (table 2-11). The prevalence of smokeless tobacco use varies considerably in different regions of the country, with lowest rates generally in the Northeast, and lower rates in cities than in rural areas. Of note, the prevalence of smokeless tobacco use is greater than that of cigarette smoking by youths in several states, including Alabama, Idaho, South Dakota, Colorado, Wyoming, and Montana. The prevalence of moist snuff tobacco use by youths has risen dramatically, with a 10-fold increase for 16- to 19-year-olds between 1970 and 1985.60 There was a brief reduction in 1986-87, but sales of smokeless tobacco products are now increasing, with a 70% overall increase in moist snuff sales from 1982 to 1992.61 Smokeless tobacco is used primarily by males in all ethnic groups except American Indians and Alaskan natives, where the prevalence of use is similar for males and females.

As discussed earlier, nicotine and cotinine concentrations in the blood of adults who use smokeless tobacco are comparable to those measured in smokers. No such data are available for children. Addiction of youths to smokeless tobacco is documented by reports that many users of smokeless tobacco have tried to quit but have been unsuccessful. According to the 1986-1989 Teenage Attitudes and Practices Survey, 21% of current smokeless tobacco users (12- to 18-year-olds) had tried to quit four or more times unsuccessfully, which is consistent with a high level of addiction.62

Factors influencing the initiation of smokeless tobacco are in general similar to those that are associated with initiation of cigarette smoking.63 One difference of note, however, is that smokeless tobacco use has been associated with participation on sponsored athletic teams (for example, baseball, wrestling, football, rodeo), whereas smokers are less likely to participate in such teams. As noted earlier, smokeless tobacco use is a risk factor for cigarette smoking, and vice versa. The exchangeability of tobacco use supports the idea that nicotine addiction can be maintained by tobacco from any source.

NATURE OF TOBACCO PRODUCTS

Nicotine addiction is maintained by use of tobacco, the only significant source of nicotine. Certain teas and vegetables contain low levels of nicotine, but the amounts available are so low that it is impossible to consume pharmacologically active doses of nicotine from sources other than tobacco. Tobacco is smoked as cigarettes, cigars, and in pipes, but can also be used

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without smoking by applying smokeless tobacco directly to mucous membranes. Several types of smokeless tobacco are available—oral snuff, nasal snuff, and chewing tobacco.

Production of Tobacco Products

Tobacco products in the United States are made by blending different types of tobacco leaf, to which sugar and other flavorings are added. Lighter tobaccos, which are found in most American cigarettes, produce acidic smoke when burned. Darker tobaccos, such as are used in cigar and pipe tobacco, produce alkaline smoke. As discussed elsewhere, the pH of the smoke determines the extent to which nicotine will be absorbed through the mouth.

In addition to different types of shredded tobacco leaf, tobacco sheet or reconstituted tobacco is also blended into many cigarettes. Tobacco sheet uses scraps and stems of tobacco as well as various additives, which are combined into a homogeneous mixture that can then be incorporated into tobacco. The manufacturing of tobacco sheet allows for production of a relatively uniform composition of tobacco, since additives can be used to achieve the end product.64

Reports have been made of evidence that tobacco manufacturers manipulate the nicotine content of cigarettes.65 One way in which manufacturers control the nicotine content of tobacco is by extracting the nicotine from the tobacco, then adding it back in controlled amounts as tobacco extract. Tobacco companies also hold patents for spraying nicotine solutions onto cigarette tobacco, although it is unclear if this practice is actually used in the manufacturing of cigarettes. Tobacco manufacturers state that the reason nicotine is extracted and then reapplied to tobacco is that nicotine in the natural tobacco leaf exists in very uneven concentrations. By extracting and re-adding nicotine, it is possible to provide a more consistent tobacco product, which delivers a consistent amount of nicotine. It has also been suggested that the amount of nicotine in tobacco is controlled so as to ensure a level adequate to maintain nicotine addiction. In support of this idea was an internal memorandum, discovered in recent ligitation, from a Phillip Morris Tobacco Company scientist: "The cigarette should be conceived not as a product but as a package. The product is nicotine . . . smoke is beyond question the most optimized vehicle of nicotine and the cigarette is the most optimized dispenser of smoke."66 That the pharmacologic actions of nicotine are important determinants of why people smoke is supported by research both by the tobacco industry and by non-industry researchers.67

In the United States, four primary types of smokeless tobacco are manufactured: loose leaf, plug, twist or roll, and oral snuff.68 Loose leaf chewing tobacco consists of tobacco leaf that has been heavily treated with licorice and sugars. Plug tobacco is produced from leaves that are immersed in a mixture of licorice and sugar and then pressed into a plug. Twist tobacco is made from leaves that are flavored and twisted to resemble a rope. Oral snuff is available in

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dry and moist preparations. Dry snuff is powdered tobacco that contains flavor and aroma additives. Moist snuff consists of fine particles of tobacco that contain considerable moisture; many varieties are prepared with flavorings such as wintergreen or mint. The oral use of snuff, called "snuff dipping," involves placing a pinch of the tobacco between the cheek or lips and the gum, or beneath the tongue.

Starter products and distribution of free samples might introduce users to a graduation process of moving from low-nicotine to higher-nicotine snuff products. For example, products low in nicotine and low in pH (which reduces buccal absorption) and products sold in a teabag-like unit dose, would make it easier for first-time users to adapt to snuff products. The use of such low-nicotine-delivery products could be the beginning of a graduated process toward nicotine addiction.

Modifying Cigarette Yields

Tobacco smoke contains more than 4,000 chemicals, many of which are known toxins. Some of the better-known toxins include carbon monoxide, hydrogen cyanide, nitrogen oxides, ammonia, benzene, formaldehyde, nitrosoamines, vinyl chloride, polycyclic hydrocarbons, polonium-210, arsenic, and lead.

Tobacco smoke is an aerosol of droplets containing water, nicotine, and other alkaloids, and tar. Tar is what is left in the particulates after water and alkaloids are removed. Particulates are suspended in a gaseous mixture, which contains carbon monoxide, nitrogen oxides, and other gases.

To estimate the amount of various constituents that smokers are exposed to, cigarettes are routinely tested with a standardized smoking machine test. This test has been referred to as the Federal Trade Commission (FTC) method. The FTC performed and published test results in commercial cigarettes from 1967 until 1985; since that time the tobacco industry has conducted these tests. The FTC test procedure consists of placing a cigarette into a holder and igniting it; then 35-ml puffs are taken via a syringe over 2 seconds, once every minute until the cigarette is burned to a specific butt length. The smoke that is collected is passed through a filter to collect the particulate material (tar and nicotine). The gases that pass through the filter are collected for determination of carbon monoxide and other constituents. Thus, values for yields of tar, nicotine, and carbon monoxide for each cigarette are reported from this type of testing procedure.

Lowering the yields of tar and other toxic constituents of cigarettes smoke makes intuitive sense as a way to reduce the health risks of cigarette smoking. Tobacco companies widely promote cigarettes that are lower in yield, implying a health benefit compared to smoking higher-yield cigarettes. However, the low-yield cigarette concept is in many ways deceptive. To understand why this is so, it is useful to examine how low-yield cigarettes are engineered.

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There are several ways in which cigarettes can be engineered to be low-yield by smoking machine tests. The most obvious way is filtration, in which case a filter is placed at the end of the cigarette. This filter can remove a significant amount of tar. In the United States, 95% of cigarettes are filtered. Another way to reduce yields is to reduce the content of nicotine or other toxic substances in tobacco per se. This appears not to be the case with commercial cigarettes. When the nicotine concentration of tobacco in cigarettes of differing yields was measured, it was found that, on average, cigarette tobacco had a nicotine concentration of about 1.6%.69 There was a significant inverse correlation between concentration of nicotine in tobacco and yield, suggesting that low-yield cigarettes are made with tobacco that contains more, rather than less, nicotine than higher-yield cigarettes. In any case, it is clear that low-yield cigarettes are not low-yield because the contents of nicotine or tar are lower in the tobacco per se. Low-yield cigarettes are engineered to be low-yield based on the standardized smoking machine protocol. This can be done by shortening the cigarette length, increasing the burn rate of the paper, or increasing the length of the filter overwrap so that the machine is able to take fewer puffs before the cigarette is burned to its specified length. Placing less tobacco in each cigarette by using expanded tobacco and/or smaller diameters of cigarettes can also reduce yield. Diluting the mainstream smoke through the use of porous paper or ventilation holes in the filter tipping paper can substantially reduce yields. In the latter case, when the cigarette is inhaled from the tip, considerable room air is drawn in to dilute the tobacco smoke.

Unfortunately, the addicted smoker does not smoke like an FTC smoking machine. Smokers take deeper and more frequent puffs than the machine on average, and can easily alter their smoking behavior as desired. Smokers learn, without realizing what they are doing, that placing their lips or fingers over the cigarette tip improves the draw characteristics of the cigarette. They are actually blocking the ventilation holes so that they are inhaling more tobacco smoke and less room air. Many studies in which the actual intake of nicotine, carbon monoxide, or other constituents of tobacco smoke have been measured in smokers, have shown a very weak relationship, if any, to nominal nicotine yield. Thus, once a smoker becomes addicted to nicotine, he or she can easily adapt smoking behavior to obtain the desired dose of nicotine from any cigarette. Of note, the ultra-low-yield cigarettes (that is, tar less than 1 mg, nicotine less than 0.1 mg) do seem to make it more difficult for smokers to obtain levels of nicotine that they can from high-yield cigarettes.70 The observation that sales of these ultra-low-yield cigarettes are relatively low suggests that there may be a threshold for nicotine delivery, below which nicotine addiction is not easily maintained. As typically smoked, low-yield cigarettes are not less harmful than higher-yield cigarettes. Because smokers take in much more tar and other toxins than estimated by machine yields, the risk of smoking-caused disease is not significantly reduced by using low-yield cigarettes.

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In summary, people smoke cigarettes largely to obtain the nicotine they desire. They do not smoke in a standardized way as do smoking machines, and therefore machines are poor predictors of actual human exposure. Human exposures can be estimated by direct measures of levels of tobacco smoke constituents in biological fluids of smokers. Such markers include nicotine, its metabolite, cotinine, carbon monoxide, adducts of various reactive chemicals to hemoglobin or DNA, and mutagenic activity of the urine.

CONCLUSIONS AND RESEARCH RECOMMENDATIONS

Having reviewed the research literature on nicotine addiction and tobacco use, the committee finds the following conclusions to be warranted:

1. Long-term tobacco use is maintained by addiction to nicotine.

2. Use of any form of tobacco can result in addiction, and smokeless tobacco is becoming an increasingly prevalent behavior among youths. Smokeless tobacco is not a healthful alternative to cigarettes.

3. Once addicted, a person finds it difficult to quit using tobacco.

4. Children and youths begin tobacco use. Youths rapidly become addicted to nicotine; the addiction maintains their tobacco use in adulthood.

5. When youths begin using tobacco, they overestimate the proportion of tobacco use in society, underestimate the addictive nature of tobacco and the risk that they will become addicted over a long term, and underestimate the danger that they will incur tobacco-related disease. Thus, children and youths become addicted to nicotine before they are able to appreciate fully the consequences of their behavior.

6. There is considerable individual variation in susceptibility to nicotine addiction. Environmental, behavioral, personal, socioeconomic, and ethnic factors influence susceptibility to initiation and addiction.

7. The recognition that youths become addicted to nicotine should be incorporated into the design, evaluation, and dissemination of treatment programs for youths to stop tobacco use; as proven strategies emerge, they should be made easily accessible to youths.

8. Among adults the prevalence of cigarette smoking has declined from 1966 to the present. The prevalence of smoking by youths declined through 1980, but subsequently has been stable, except for African-American youths, for whom there has been a sharp decline. The prevalence of smokeless tobacco use by boys has increased steadily for the past 15 years and represents a significant growing addiction to tobacco.

9. Available evidence indicates that cigarette manufacturers control the level of nicotine in cigarettes and the nicotine delivery of their products in deliberate ways. However, "low-yield" cigarettes are not low in nicotine content and do

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not in general deliver less nicotine or tar to smokers than do higher-yield cigarettes.

10. Prevention of nicotine addiction among youths is an essential part of any policy for reducing tobacco use in society as a whole. Approaches to prevention can be targeted toward the various factors that initiate and maintain tobacco addiction, as will be discussed in subsequent chapters.

The Committee makes the following recommendations for research on nicotine addiction:

1. Research should be conducted to determine individual susceptibility to nicotine addiction. Particular areas that need research are genetic factors, affective states, and ethnic influences. Such information could facilitate the identification of high-risk children and could lead to more effective prevention strategies.

2. For all forms of tobacco products, research should be conducted on the characteristics of nicotine addiction in the early stages, that is, in the first few years during which the transition between experimental and addictive nicotine use occurs. Such information could contribute to more effective intervention before youth become highly addicted adult tobacco users.

3. Research should be conducted on the relationship between the characteristics of tobacco products and addiction. For example, as a basis in developing regulatory guidelines, it would be useful to know the minimal level of nicotine delivery from a tobacco product at which addiction will develop and/ or be sustained.

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25. Hatsukami, Dorothy K., S. W. Gust, and R. M. Keenan. ''Physiologic and Subjective Changes from Smokeless Tobacco Withdrawal." Clinical Pharmacology and Therapeutics 41:1 (1987): 103107.

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