infer that the risk of smoking-related cancer for sites other than the lungs would increase, at a given adult age, in inverse proportion to the age an adolescent begins smoking. Recent studies indicate that earlier onset of cigarette smoking is also associated with heavier smok- ing (Taioli and Wynder 1991; Escobedo et al. 1993). Nicotine Addiction in Adolescence Surgeon General's Report Heavier smokers are not only more likely to experience tobacco-related health problems, they are the least likely to quit smoking (Hall and Terezhalmy 1984; USDHHS 1989). Early use of cigarettes thus appears to influence intensity as well as duration of use and increases the potential for long-term health consequences. Introduction Nicotine dependency through cigarette smoking is not only the most common form of drug addiction but the one that causes more death and disease than all other _ addictions combined (USDHHS 1988). Most human research on nicotine addiction has been conducted with adult subjects, but the basic biologic processes that underlie this dependency appear to be similar in ad- olescents and adults. The research literature on nicotine addiction examines its chemistry and addiction poten- tial, its severity, and its pathophysiology and clinical course. Background and Nomenclature Drug addiction is the term most widely used to. label various medical and social disorders related to the compulsive ingestion of psychoactive chemicals. The primary criteria for drug dependence are that the behav- ior is highly controlled or compulsive, the chemical is one whose mood-altering or psychoactive effects are central elements of the drug’s activity, and the drug itself has the demonstrated capability of reinforcing behavior (Table 4). The American Psychiatric Association (APA) has identified two medical disorders that pertain to nico- tine addiction: nicotine dependence and nicotine withdrawal (APA 1987). Nicotine dependence is classified as a psychoactive substance-use disorder characterized by “a cluster of cognitive, behavioral, and physiologic symptoms that indicate that the person has impaired control of psychoactive substance use and continues use of the substance despite adverse consequences” (APA 1987, p. 166). In the case of nicotine, the most common form of use is cigarette smoking, in part because the rapid ab- sorption of nicotine through the processes of smoking ‘leads to a more intensive habit pattern that is more difficult to give up” than other forms of use (APA 1987, p. 181). Nicotine dependence also occurs through other routes of delivery, including smokeless tobacco and nicotine gum. 26 Health Consequences Nicotine withdrawal, an organic mental disorder induced by the removal of psychoactive substance, is described as “a characteristic withdrawal syndrome due to the abrupt cessation of or reduction in the use of nicotine-containing substances (e.g., cigarettes, cigars and pipes, chewing tobacco, or nicotine gum) that has been at least moderate in duration and amount. The syndrome includes craving for nicotine; irritability, frustration, or anger; anxiety; difficulty concentrating; restlessness; de- creased heart rate; and increased appetite or weight gain” (APA 1987, p. 150). Physical dependence refers to the condition in which withdrawal symptoms have been observed. Physical dependence can complicate the process of achieving and Table 4. Criteria for drug dependence Primary criteria Highly controlled or compulsive use Psychoactive effects Drug-reinforced behavior Additional criteria Addictive behavior often involves the following: Stereotypic patterns of use Use despite harmful effects Relapse following abstinence Recurrent drug cravings Dependence-producing drugs often manifest the following: Tolerance Physical dependence | Pleasant (euphoric) effects Source: Adapted from USDHHS (1988). Preventing Tobacco Use Among Young People maintaining drug abstinence, and the symptoms can be so unpleasant as to precipitate relapse (Jaffe 1985; USDHHS 1988). In surveys by the National Institute on Drug Abuse (NIDA), withdrawal and inability to main- tain abstinence are commonly attributed to cigarette smok- ing and heroin use (USDHHS 1988). The majority of ple monitored who regularly use other addictive drugs (including cocaine and marijuana) report that they have not experienced withdrawal, even though many of these people feel dependent and have been unable to maintain abstinence (USDHHS 1988). Severity of Nicotine Addiction Tobacco-delivered nicotine can be highly addic- tive. Each year, nearly 20 million people try to quit smoking in the United States (USDHHS 1990), but only about 3 percent have long-term success (Pierce et al. 1989; Centers for Disease Control and Prevention [CDCI, Officeon Smoking and Health, unpublished data). Even among addicted persons who have lost alung because of cancer or have undergone major cardiovascular sur- gery, only about 50 percent maintain abstinence for more thana few weeks (West and Evans 1986; USDHHS 1988). In a 1991 Gallup Poll, 70 percent of current smokers reported that they considered themselves to be “addicted” to cigarettes (Gallup Organization 1991). These findings are consistent with data from NIDA’s 1985 National Household Survey on Drug Abuse (NHSDA), which showed that 84 percent of 12- through 17-year-olds who smoked one pack or more of cigarettes per day felt that they “needed” or were “dependent” on cigarettes (Henningfield, Clayton, Pollin 1990). The NHSDA data show that young smokers develop toler- ance and dependence, increase the amount they smoke, and are unable to abstain from nicotine. These findings suggest that the addictive processes in adolescents are fun- damentally the same as those studied in adults (USDHHS 1988; Henningfield, Clayton, Pollin 1990). Several studies have found nicotine to be as addic- tive as heroin, cocaine, or alcohol (Henningfield, Clayton, Pollin 1990; Henningfield, Cohen, Slade 1991; Kozlowski et al. 1993). Moreover, because the typical pattern of tobacco use entails daily and repeated doses of nicotine, addiction is more common among all users than is true of other drug use, which tends to occur on a far less frequent basis (USDHHS 1988). For example, only about 10 to 15 percent of current alcohol drinkers are consid- ered problem drinkers, but approximately 85 to 90 per- cent of cigarette smokers smoke at least five cigarettes every day (Henningfield, Cohen, Slade 1991; Evans et al. 1992; Henningfield 1992b; Kozlowski et al. 1993). Only 2 to 3 percent of smokers (or about 7 to 10 percent of those who try quitting) stop smoking for one year (CDC 1993a), and most daily smokers report that they feel dependent on smoking and have experienced with- drawal symptoms (USDHHS 1988; Henningfield, Clayton, Pollin 1990). Chemistry and Addiction Potential Many behaviors that become regular, habitual, and hard to give up involve the ingestion of a substance. What sets drug addictions apart from less harmful habits is that the ingested substance releases a psychoactive drug with the demonstrated potential to addict. Several thousand chemicals are present in cigarette smoke. Some may conceivably modulate nicotine’s addictive effects, but the fact that different forms of nicotine delivery can be substituted for one another -(e.g., nicotine gum or transdermal patch in place of cigarettes) suggests that nicotine is critical in the addiction process (Henningfield 1984; Benowitz 1988; USDHHS 1988; Russell 1990). Nicotine is a naturally occurring alkaloid present in varying concentrations in different strains of tobacco. Most cigarettes sold in the United States contain about 8 to 9 milligrams of nicotine, of which the smoker typically in- gests 1 to 2 milligrams per cigarette (Benowitz et al. 1983; USDHHS 1988). Nicotine is both a lipid- and water- soluble molecule that can be rapidly absorbed in a mildly alkaline environment through the skin or the lining of the mouth and nose. Because of the massive area for absorp- tion in the alveoli of the lungs, nicotine inhaled deeply is almost immediately extracted from the smoke into the pulmonary veins; this sudden spike or bolus of nicotine is delivered to the brain, via arterial circulation, in approxi- mately 10 seconds (USDHHS 1988). In contrast, although smokeless tobacco has much higher levels of nicotine than cigarettes, the delivery of the drug is much more gradual; the effect peaks within approximately 20 minutes of use (Benowitz et al. 1988). The peak for nicotine replacement medications is even slower—30 minutes or longer for nicotine gum (Benowitz et al. 1988), several hours for the four commercially available transdermal patch systems (Palmer, Bucklet, Faulds 1992). In fact, because of the efficiency of the pulmonary route in extracting nicotine from inhaled tobacco smoke, nicotine may be 10 times more concentrated in arterial blood than in simultaneously sampled venous blood; these levels are much higher than those produced by nicotine replacement medications (Henningfield, London, Benowitz 1990). As vehicles for nicotine delivery, tobacco products are convenient to use, and they provide the experienced user with a means of regulating dose level. Such control does not, however, protect the user against drug depen- dency, since tobacco products appear to deliver the opt- mal addiction potential (or abuse liability) of nicotine. Chemicals can be tested for their addiction potential to Health Consequences 27 determine if they are psychoactive and if they can serve as reinforcers in animals and humans (Brady and Lukas 1984: USDHHS 1988; Fischman and Mello 1989; Henningfield, Cohen, Heishman 1991). These methods to test for abuse liability are reliable enough for the Food and Drug Administration (FDA) and the World Health Organization (WHO) to use them to develop policies regarding regulation of new drugs with possible addic- tion potential (USDHHS 1988; Barcelona Conference 1991). Nicotine meets the criteria for addiction potential in all of the standardized tests used by the FDA and the WHO (USDHHS 1987, 1988, 1991a). In humans and animals, nicotine produces discrete subjective effects more similar to those produced by cocaine than to those pro- duced by sedatives, and nicotine injections are biologi- cally reinforcing to humans and to at least five animal species (Henningfield, Miyasato, Jasinski 1985; Henningfield and Goldberg 1988; USDHHS 1988). Such’ findings confirm the conclusion of the 1988 report of the Surgeon General: nicotine is a drug with a liability for addiction (USDHHS 1988). Pathophysiology of Nicotine Dependence The pathophysiology of drug dependence and the clinical course of nicotine and other drug dependencies have been described in detail elsewhere (Jaffe 1985; USDHHS 1988; Benowitz 1992; Henningfield 1992a). In brief, exposure to a psychoactive chemical leads to re- petitive self-administration because of the chemical’s capacity to condition behavior. This powerful condi- tioning action of nicotine is mediated at least in part by the activation of nicotinic receptors in the brain (USDHHS 1988; Bock and Marsh 1990) and the modulation of levels of hormones such as epinephrine (adrenaline) and corti- sol (Pomerleau and Pomerleau 1984; Sachs 1987; USDHHS 1988). The mesolimbic dopaminergic reward system, which mediates the addicting actions of cocaine, is also thought to be involved in producing nicotine’s addictive effects (Pomerleau and Pomerleau 1984; USDHHS 1988; Bock and Marsh 1990; Balfour 1991a, b; Benwell and Balfour 1992). Behaviors that are followed by intense neural activation can become highly persistent and diffi- cult to modify (Pomerleau and Pomerleau 1984; Jaffe 1985; USDHHS 1988). Each year, the daily cigarette smoker may experience 50,000 to 100,000 such pairings of puffing on cigarettes and resultant effects in the brain, thus establishing a persistent need for cigarette smoking. Tolerance Tolerance refers to a diminishing response to a drug through repeated exposures (Jaffe 1985, USDHHS 1988). Tolerance is often demonstrated when increased dose levels are required to obtain the effects formerly 28 Health Consequences Surgeon General's Report produced by lower doses. Tolerance to nicotine appears to be acquired as people progress from initially smoking a few cigarettes to smoking greater numbers of cigarettes more often (see “Initiation Continuum of Smoking” and “Adult Implications of Adolescent Smoking” in Chapter 3 and “Developmental Stages of Smoking” in Chapter 4). The development of tolerance to the aversive effects of nicotine, such as nausea and dizziness, may also facili- tate the development of dependency (USDHHS 1987; Shiffman et al. 1990; Shiffman 1989, 1991; McNeill, Jarvis, West 1987). Tolerance of nicotine increases over time; experienced smokers can self-administer doses of nico- tine that would make nonsmokers ill. The tolerance the nervous system develops to nico- tine exposure can be at least partially overcome by increasing the dose. This effect was studied near the beginning of the 20th century and has been the subject of considerable study since then (Langley 1905; USDHHS 1988; Benowitz and Jacob 1993). Tolerance to various behavioral, physiologic, and subjective effects of nicotine has been studied (USDHHS 1988). For example, administering nicotine to a tobacco-deprived cigarette smoker can produce a substantial increase in heart rate and measures of euphoria, along with a decrease in the strength of the knee reflex. With repeated doses, the heart rate stabilizes at a level between that produced by the first dose and that which occurs when nicotine- deprived; subjective effects are minimal, and the knee reflex may become normal (Domino and Von Baum- garten 1969; USDHHS 1988; Swedberg, Henningfield, Goldberg 1990). Some tolerance of nicotine is lost each night as the smoker's nicotine levels fall; the nicotine from the first few cigarettes of the day produces effects on heart rate, mood, and other measures that are stronger than the effects produced by subsequent doses during the day (USDHHS 1988). Repeated exposure to nicotine leads to morphological changes in the brain that cause the devel- opment of new binding sites for nicotine receptors, which mediate the effects of nicotine (Bock and Marsh 1990; USDHHS 1988, 1991a). Animal research has shown that nicotine exposure results in an increased expression (defined as up-regula- tion) of nicotine receptors in various regions of the brain (Ksir et al. 1985; Morrow, Loy, Creese 1985; Nordberg et al, 1985; Schwartz and Kellar 1985; Ksir, Hakan, Kellar 1987). Prenatal exposure to nicotine also produces up- regulation of nicotine receptors in tissue collected from newborn animals (Slotkin, Orband-Miller, Queen 1987; Slotkin et al. 1991; Smith, Seidler, Slotkin 1991). These data suggest the broad applicability of this up-regulation effect, which may be one of the ways in which tolerance of nicotine occurs (USDHHS 1989). Preventing Tobacco Use Among Young People Human research is more limited than animal re- search in this area, but there is evidence that cigarette smoking is associated with up-regulation of nicotine receptors in the human brain. Balfour (1989, 1991a) has conducted a series of studies that included the examination of postmortem brain tissue from smokers and nonsmokers. He and others found evidence of signifi- cantly elevated concentrations of nicotine binding sites as well as smoking-related changes in other binding sites (such as 5-hydroxytryptamine) (Benwell, Balfour, Ander- son 1988; Balfour 1989, 1991a; Grant, McMurdo, Balfour 1989; Bock and Marsh 1990). Morphologic changes in the nervous system are presumed to reflect part of the body’s adaptation (resulting in tolerance and physical depen- dence) to a prolonged exposure to nicotine (Marks and Collins 1982; Marks, Burch, Collins 1983; Marks et al. 1985, 1986;Marks, Stitzel, Collins 1985, 1986, 1987; USDHHS 1988). Physical Dependence Nicotine administered to animals and humans pro- duces altered spontaneous electroencephalograph (EEG) and evoked electrical potentials of the brain, altered local cerebral glucose metabolism, modulation of hormonal output by the adrenal glands, increased heart rate, and changes in skeletal muscle tension (USDHHS 1988). Most, if not all, of these effects are related to the dose of nicotine given, and tolerance develops to differing degrees across these effects. After a period of nicotine exposure that is assumed to be at least several weeks (APA 1987), physi- cal dependence on nicotine develops. The dependent person then appears to be functioning normally when under the influence of nicotine; conversely, the person may report feeling “abnormal” or “not right” when de- prived for more than a few hours (Casey 1987). Although basic pharmacologic research on nico- tine has been conducted primarily with adults, most people begin to smoke in adolescence and develop char- acteristic patterns of nicotine dependence before adult- hood (USDHHS 1988, 1991a). That adolescents develop physical dependence, as evidenced by their experience of withdrawal symptoms, has been well documented by the NHSDA (USDHHS 1991c). Moreover, quantitative characteristics of the withdrawal syndrome appear to be the same in adolescents and adults (McNeill et al. 1986; McNeill, Jarvis, West 1987). The magnitude of the withdrawal syndrome is related to the previous level of nicotine intake, although differences in just a few cigarettes a day may not be correlated with the severity of the syndrome (Killen et al. 1988; USDHHS 1988). Environmental context is also a factor; in a novel environment (e.g., a hospital setting), the symptoms of nicotine withdrawal may be less than in the smoker’s usual environment, with its various psychological cues for smoking (Hatsukami, Hughes, Pickens 1985).. The time course of withdrawal symptoms varies among individuals and for different responses. Most withdrawal symptoms peak within the first few days of nicotine abstinence and then begin to recover along a variable course; the most severe total withdrawal syndrome usually lasts about three to four weeks (USDHHS 1988; Gross and Stitzer 1989). For example, certain measures of brain function (such as P300-evoked electrical potential) recover within a few days, but others may take weeks or more (suchas N1 00-evoked potential, hunger, and craving). Powerful urges to smoke may recur for many years (Hughes and Hatsukami 1986; USDHHS 1988). Although questions remain, the pathophysiology of nicotine dependence clearly involves the brain, the endocrine system, and behavior, and the process begins when cigarette smoking is initiated. Moreover, although the effects of nicotine administration and deprivation are complex, they are orderly and are related to factors such as the amount of nicotine administered and the time since the last dose. The Clinical Course of Nicotine Dependence Like other drug addictions, nicotine dependence is a progressive, chronic, relapsing disorder. The level of dependence on nicotine in adults has been found to be inversely related to the age at initiation of smoking when measured by diagnostic criteria (APA 1987) of the APA (Breslau, Fenn, Peterson 1993) and by the Fagerstrom Tolerance Questionnaire Score (Henningfield et al. 1987). As is true for most drug addictions, tobacco use is not always constant from initiation on; the process of graduation from first use to addiction can take months or even years (USDHHS 1988). In fact, initial experiences with tobacco, as with other addictive substances, are sometimes negative and require social pressures and other factors to maintain exposure until the addiction develops (Haertzen, Kocher, Miyasato 1983). The per- centage of people who progress from smoking a few cigarettes to smoking at a regular, addictive level has been estimated to range from 33 to 94 percent. For example, Russell (1990) has reported that a survey of adults in Great Britain in the mid-1960s indicated that 94 percent of those who smoked more than three cigarettes became “long-term regular smokers.” These data, which precede widespread public awareness of the hazards of smoking, may have a limited applicability to current smoking behavior. Recently collected data in the United States and Great Britain suggest that between 33 and 50 percent of people who try smoking cigarettes escalate to regular patterns of use (Hirschman, Leventhal, Glynn 1984; McNeill 1991; Henningfield, Cohen, Slade 1991). Health Consequences 29 The chronic phase of the addictive process is highly resistant to substantial modification. For example, ef- forts to reduce tobacco smoke and nicotine exposure by smoking cigarettes with lower ratings of nicotine deliv- ery or to smoke fewer cigarettes are usually partially or completely thwarted by compensatory changes in how the cigarettes are smoked; smokers may compensate for “cutting back” by inhaling more deeply or smoking the cigarette farther down to its more potent and more toxic end (Kozlowski 1981, 1982; Benowitz et al. 1983; Benowitz and Jacob 1984; USDHHS 1988). Abstinence from smok- ing is generally short-lived; the majority of persons who quit on their own or in minimally supportive interven- tions appear to relapse within one week of their last cigarette (Kottke et al. 1989). In fact, in testament to the persistence of addiction, nearly one-third of those who have abstained for one year after quitting relapse later (USDHHS 1990; Giovino 1991). These patterns of relapse are similar to those observed with other drug addictions. Several potential predictive measures of the sever- ity of addiction in a person may forecast the severity of withdrawal and the outcome of an attempt to quit. These measures, which have been discussed in detail in the 1988 report of the Surgeon General (USDHHS 1988), include cotinine level in biological fluid such as saliva, blood, or urine; number of cigarettes smoked per day; score on the Fagerstrom Tolerance Questionnaire; and number of symptoms attributed from the Diagnostic and Statistical Manual of Mental Disorders (APA 1987). These measures tend to predict, although not perfectly, the difficulty of achieving abstinence, the severity of with- drawal symptoms, the rapidity of relapse, and the effi- cacy of replacement therapy (USDHHS 1988). One final source of vulnerability to nicotine depen- dence appears to be genetic predisposition. Research with animals has shown that the amount of up-regulation (increased binding in the brain) of nicotine receptors after Surgeon General's Report nicotine exposure is related to genetic constitution, as are certain behavioral and physiologic effects (Marks et al. 1989; Collins 1990). Data from studies with human twins have yielded indices of heritability for cigarette smoking similar to those for drinking alcohol (Hughes 1986; Kozlowski 1991; Carmelli et al. 1992). Nondrug Factors in Nicotine Dependence Nondrug factors can affect the prevalence of drug addiction in society as well as its severity in individuals. Some of the factors are the same as those that determine the prevalence and severity of other medical disorders resulting from exposure to toxins. Among the most important factors in determining the prevalence of drug addiction is the exposure to the addicting substance (USDHHS 1988). This factor is no less important in the spread of drug addiction than it is in the spread of disorders such as acquired immunodeficiency syndrome, malaria, and influenza infections. Moreover, social fac- tors can determine the type and frequency of exposure to the etiologic agent, as well as the time frame over which exposure continues. Many nondrug factors associated with both abstinence and relapse appear to operate simi- larly across addictions. These factors include illness induced by drug dependence (which will at least tempo- rarily interrupt drug use), ability to learn to manage cravings, social reinforcements for abstinence, availabil- ity of the substance, cost of the substance, and perception of the risk of using the substance (USDHHS 1988). Persons vary in their vulnerability to nicotine and other drug addiction, just as they vary in their vulnerabil- ity to other medical disorders; some people show a high degree of resistance to the disorder despite multiple exposures to the agent, and others very quickly become addicted (USDHHS 1988). Psychosocial factors affecting the vulnerability of the young and the onset of tobacco use are discussed in Chapter 4. Smoking as a Risk Factor for Other Drug Use Introduction The 1988 Surgeon General's report (USDHHS 1988) showed that among adolescents, cigarette smoking is a risk factor in the development of alcohol use and illegal drug use. The nature of the interrelationship be- tween tobacco and other drug use is complex; in several possible ways, tobacco use may heighten the probability that a young person will use other drugs (Slade 1993; see 30 Health Consequences “Smoking and Other Drug Use” in Chapter 3 and “Behav- ioral Factors in the Initiation of Smoking” in Chapter 4). Progression of Drug Use Kandel (1975) found that studies of the progression of drug use in the 1970s showed that cigarette smoking and alcohol use generally preceded marijuana smoking and other illegal drug use. In fact, Kandel’s study Preventing Tobacco Use Among Young People concluded that virtually everyone who used illegal drugs such as marijuana or cocaine had previously used cigarettes, alcohol, or both. These findings, primarily among white youths, have been repeatedly extended and replicated (e.g., Fleming et al. 1989; Kandel and Yamaguchi 1993). More recent data from the Monitoring the Future Project (MTFP) by NIDA (USDHHS 1988) confirm that illegal drug use is rare among those who have never smoked and that cigarette smoking is likely to precede the use of alcohol or illegal drugs. The 1985-1989 MTFP showed that first use of tobacco had occurred at the same age as first use of alcohol for 33 percent of the sample; cigarettes were used before alcohol by 49 percent of the sample. The same survey showed that among those who had used both cigarettes and marijuana, 23 percent be- gan using both in the same year, and 65 percent smoked- cigarettes before marijuana. The latter relationship was more pronounced for cocaine: 98 percent of persons who had used both cocaine and cigarettes smoked cigarettes first (see Tables 24-26 in Chapter 3). These findings were extended in another longitu- dinal study that assessed 12-, 15-, and 18-year-olds in New Jersey and reinterviewed them at three-year inter- vals (USDHHS 1987). This study showed that among 15- year-olds, the use of cigarettes, alcohol, or marijuana was the strongest predictor of cocaine use when these same persons were reinterviewed three years later; at that time, the persons using cocaine were likely to be using cigarettes and alcohol as well. Cigarette smoking in combination with alcohol use appears to be especially predictive of illegal drug use. A longitudinal study by Yamaguchi and Kandel (1984) examined initial data from students in the tenth and eleventh grades in New York State in 1971. When the authors reevaluated the same students in 1981 (av- erage age, 25 years), the most common sequence of drugs used was alcohol, cigarettes, marijuana, illegally used psychoactive or prescription drugs, and other ille- gal drugs. The investigators found that for 87 percent of the men, alcohol use preceded marijuana use; alco- hol and marijuana use preceded other illegal drug use; and use of alcohol, cigarettes, and marijuana preceded the use of other psychoactive drugs. For 86 percent of the women, a similar, but not identical, pattern emerged: alcohol or cigarettes preceded marijuana; alcohol, ciga- rettes, and marijuana preceded other illegal drugs; and alcohol and either cigarettes or marijuana preceded other psychoactive drugs. These findings were repli- cated with 1,108 high school seniors in New York in 1988 (Kandel and Yamaguchi 1993). This study confirmed the importance of cigarette and/or alcohol use in the progression of illegal drug use, with early cigarette 161-235 95-2 use being of particular importance in the develop- ment of other drug use among females. Early onset of cigarette smoking and/or alcohol use was a strong, pre- dictor of further drug use. The relationship between alcohol use and cigarette smoking is more complex than would be suggested by examining any one survey. In some studies, alcohol is more likely to precede than to follow cigarette smoking. This variability might be explained by the differing study criteria for alcohol use. For example, among many adoles- cents, alcohol consumption is characterized by the occa- sional light use of beer or wine—a pattern that often neither escalates into patterns of heavy drinking nor pre- dicts other drug use (Kandel, Marguilies, Davies 1978; Huba, Wingard, Bentler 1981; O'Donnell and Clayton 1982). This finding is consistent with the observation that approximately 85 percent of people who drink alcoholic beverages do so in patterns that do not meet criteria for abuse (USDHHS 1988). On the other hand, consumption of “hard liquor,” sometimes accompanied by heavy drink- ing patterns, appears to develop either along with or following the development of regular patterns of cigarette smoking (Kozlowski et al. 1993; DiFranza and Guerrera 1990). These observations are consistent with the find- ings of the 1985 NHSDA, which showed that among 12- through 17-year-old adolescents who had never smoked, only 3 percent had binged (i.e., had five or more drinksin a row) in the past 30 days, whereas nearly 40 percent of daily smokers in this age group had binged in the past 30 days (USDHHS 1988). The progression from cigarette smoking and occasional consumption of alcoholic beverages to heavier drinking and illegal drug use does not appear limited to any single population group. However, there is some evidence that boys with conduct disorders in school and at home may be at especially high risk of progression from any use of tobacco and alcohol to addictive patterns of multiple-drug use. A recent study of 61 males aged 14 through 18 who had conduct disorders found sequences of acquisition of drug usesimilar to those foundamong adoles- cents in general, but with higher rates of addictive use of the tobacco-alcohol-marijuana cluster and earlier initiation of these substances (Mikulich, Young, Crowley 1993). Cigarette Smoking and Other Drug Use Cigarette smoking is neither necessary nor sufficient for other drug abuse or dependence. Not all cigarette smokers subsequently abuse other drugs, and a small percentage of abusers of alcohol and illegal drugs do not use tobacco. However, several studies have revealed that cigarette smoking is a predictor of whether an individual is using other drugs and of what that individual's level of other drug use is. The 1985 NHSDA Health Consequences 31 (USDHHS 1988; Henningfield, Clayton, Pollin 1990) showed that 12- through 17-year-olds who had smoked cigarettes in the past 30 days were approximately 3 times more likely to have consumed alcohol, 8 times more likely to have smoked marijuana, and 22 times more likely to have used cocaine in the past 30 days than those who had not smoked cigarettes. Data from the 1985- 1989 MTFP showed that seniors who had smoked ciga- rettes in the past 30 days were about 1.6 times more likely to have consumed alcohol, 4 times more likely to have smoked marijuana, and 5 times more likely to have used cocaine in the past 30 days than those who had not smoked cigarettes (see “Smoking and Other Drug Use” and Table 23 in Chapter 3). The 1985 NHSDA (USDHHS 1988; Henningfield, Clayton, Pollin 1990) examined heavier drug use as a function of cigarette smoking. Having 5 or more drinks in succession in the past 30 days, using marijuana on more than 10 occasions, and using cocaine on more than 10 occasions were considered heavier usage of drugs. A strong association was observed between cigarette smok- ing and other drug use among all age groups in this study, although the percentage of the increases in drug use from the never-smoker to the daily-smoker levels was strongest in the 12- through 17-year-old group (Fig- ure 1). Among these youngest smokers, those who smoked daily were approximately 14 times more likely to have binged on alcohol, 114 times more likely to have used marijuana at least 11 times, and 32 times more likely to have used cocaine at least 11 times than those who had not smoked. . A similar correlation between frequency of alcohol use and level of cigarette smoking was found in a study of 7th- through 12th-grade students in New York State (Welte and Barnes 1987). In the Welte and Barnes study, as in the NHSDA, not only were smoking any cigarettes and drinking alcohol related, but daily smoking was a predictor of binge drinking. These data are consistent with those from a study of adult multiple-drug abusers, which found that severity of nicotine dependence, as measured either by a scale that assesses the strength of a given habit or by cigarettes smoked per day, was corre- lated directly with severity of alcohol consumption prob- lems, as measured by scores on the Michigan Alcoholism Screening Test (Kozlowski et al. 1993). These data indi- cate a strong direct relationship between level of nicotine dependence and alcohol abuse but do not in themselves show the direction of the relationship or rule out the possibility that other factors commonly determine the coincidental occurrence of high levels of tobacco and other drug use. Data from a longitudinal study in which 4,192 students (grades six through eight) were surveyed three times over four years extended the findings that the 32 Health Consequences Surgeon General's Report amount of tobacco use is directly related to other drug use (Bailey 1992). Specifically, this study showed that students who during follow-up periods escalated from low-level use of tobacco or alcohol to heavy-level use were more likely to begin using other psychoactive substances ‘or to increase their use of these substances than students who remained low-level users of tobacco or alcohol (Bailey 1992). Other studies suggest that the age at onset of cigarette smoking determines the probability of subse- quent use of marijuana and of heavy alcohol use. For example, Clayton and Ritter (1985) found not only that cigarette smoking, along with alcohol use, was the most powerful predictor of marijuana use, but also that the effect was strongest when smoking was initiated by age 17. Similarly, Keenan (1988) found that the age at onset of cigarette smoking was significantly younger in people with a history of alcoholism than in those who did not use alcohol. Another study estimated that the relative risk of alcoholism was increased tenfold among cigarette smok- ers and that people who heavily use alcohol represent approximately one-third of all cigarette smokers (DiFranza and Guerrera 1990). A further analysis of these and additional data led Kozlowski et al. (1993) to conclude that because the association between smoking and drinking is weaker among light smokers, the per- centage of heavier smokers who develop problems with alcohol might be greater than 30 percent. Of all drug users surveyed by the NIDA, cigarette smokers were by far the most likely to report experienc- ing various features of addiction. Among 12- through 17-year-olds who had used cigarettes, 27 percent were daily users and 20 percent felt dependent; of those who had used alcohol, 6 percent were daily users and 5 per- cent felt dependent; of those who had used marijuana, 18 percent were daily users and 10 percent felt dependent; of those who had used cocaine, 14 percent were daily users and 6 percent felt dependent (USDHHS 1988; Henningfield, Clayton, Pollin 1990). Cigarette smoking was also, by far, the drug use most commonly associated with withdrawal symptoms. Thus, cigarette smoking not only occurs early in the progression of drug use, it appears to be the first of these drugs to produce features of addiction in young people. Smoking as a Facilitator for Other Drug Use A number of mechanisms could explain how ciga- rette smoking facilitates the use of alcohol and illegal drugs. These mechanisms are not mutually exclusive. Moreover, other variables may operate to nondifferentially increase the use of tobacco and a wide range of other substances. For example, children with conduct disorders are at increased risk of using tobacco, heroin, alcohol, Preventing Tobacco Use Among Young People Figure 1. Use of alcohol, marijuana, and cocaine,* by age group, National Household Survey on Drug Abuse, 1985 42-17-year-olds ; 18-25-year-olds y' 50 y 50- 7 Hi Alcohol is Mi Alcohol 457 7 . 40-4 Marijuana 404 «Marijuana y wy . ee 35-| ME Cocaine 2 35-] Cocaine y 5 2 2° 3 6 36 255 be 25 4 5 s 5 2 20- < = g 2 15- o a 10- 5- 0 a4 never tried current never tried current Smoking history Smoking history 26-34-year-olds > 35-year-olds ”] 4 Alcohol Alcohol 454 a 45 a 40- Marijuana sot” Marijuana wn a 2 35 |] Cocaine > 35- Hi Cocaine sc S 5 30- 8 30- 6 6 5p 254 be 25- a 2 3 20-44 3 20-44 = S uv a = 15- & 15-4 & a 10 10- 57 5- 0- o- never tried current nevert tried? current Smoking history Smoking history Source: USDHHS (1988). *The criteria for current use are as follows: alcohol = drank five or more drinks in a row at least 1 day in the past 30 days; marijuana = used marijuana more than 10 times; cocaine = used cocaine more than 10 times (N = 8,814). *Values were under 1 for marijuana and cocaine use. + Values were under 1 for cocaine use. Health Consequences 33 cocaine, and other drugs (USDHHS 1988). Similarly, a longitudinal study showed that first-grade children who were characterized by their teachers as either shy or aggressive were significantly more likely than their peers to smoke cigarettes, drink alcohol, and use illegal drugs in their teenage years (Kellam, Ensminger, Simon 1980). Evidence of other predictive factors, however, does not rule out the possibility that young people who smoke have an increased risk of using other drugs. Morphologic changes in brain structure that have been induced by nicotine exposure might predispose persons to the abuse of other drugs; this mechanism, however, has not yet been experimentally investigated. One possibility is that common pathways of drug- produced reinforcement in the brain might be altered so that the reinforcement produced by subsequent drug exposure is intensified. Central nicotinic receptors are known to be critical mediators of the reinforcing effects of nicotine (USDHHS 1988). In turn, activation of these receptors leads to activation of the dopaminergic reward system, which is critical in mediating the reinforcing effects of a wide variety of abused drugs, including co- caine and heroin. Thus, it is a plausible, but unproven, hypothesis that nicotine exposure would lead toa height- ened sensitivity to the reinforcing effects of other drugs of abuse. This hypothesis is supported by the finding that the development of tolerance to nicotine is accompanied by the development of tolerance (“cross-tolerance”) to alcohol (Burch et al. 1988; Collins et al. 1988). Other research with animals also shows that nicotine exposure, either alone or in combination with other drugs, may alter the behavioral responses to drugs of abuse, including alcohol and cocaine (Signs and Schechter 1986; Horger, Giles, Schenk 1992). These data together suggest a plau- sible biological basis for a causal role for tobacco use in the development of other substance abuse patterns, even if this role is shared by other risk factors. Nicotine produces various effects that have been shown to be produced similarly by one or more other abused drugs; all of these findings were discussed in greater detail in the 1988 Surgeon General’s report (USDHHS 1988) and elsewhere (Pomerleau and Pomerleau 1984). Nicotine administration produces feel- ings of pleasure and euphoria that elevate the same scales on the Addiction Research Center Inventory as the effects of heroin, cocaine, alcohol, and other abused drugs (Henningfield, Miyasato, Jasinski 1985; USDHHS 1988). 34 Health Consequences Surgeon General's Report Human subjects report, and laboratory rats demonstrate, that nicotine produces acute effects that are more like a stimulant than a sedative (Henningfield, Miyasato, Jasinski 1985; USDHHS 1988). Nicotine administration causes cortical EEG activation (increase in alpha and beta frequency, decrease in beta power) that is associated with increased vigilance and improved cognitive func- tion (USDHHS 1988; Pickworth, Herning, Henningfield 1989). Conversely, nicotine deprivation leads to EEG deactivation and concomitant decreases in vigilance and cognitive function (USDHHS 1988; Pickworth, Herning, Henningfield 1989). Nicotine administration modulates the various levels of catecholamines, which are impor- tant in the regulation of mood and reactions to stressful stimuli (Pomerleau and Pomerleau 1984; USDHHS 1988). Partly through its effects on serotonergic systems in the brain, nicotine has some of the same effects on appetite as medications prescribed for this purpose. Nico- tine can reduce skeletal muscle tension and thereby con- tribute to the feelings of pleasurable relaxation often attributed to various abused drugs. For all of these drugs, including nicotine, the specific effect produced is related to the dose of the drug administered. Thus, depending on the dose of the drug or drugs taken, the time since the last dose, and other factors, theoretically the user may achieve certain effects with any of several drugs, achieve various maximal effects through drug combinations, or use certain drug combinations in an effort to reduce certain adverse effects (Gardner 1980). Certain trends in drug abuse that have become prominent over the past decade increase the potential role of cigarette smoking in the development of other forms of drug use. Specifically, there are increasing reports of smokable preparations of various drugs, in- cluding cocaine (“crack”), methamphetamine (“ice”), phencyclidine (“PCP”), and heroin, and marijuana con- tinues to be smoked by large numbers of people (USDHHS 1988). Drug administration via smoking re- quires the user to learn to regulate dose and to become tolerant of the rapid onset and aversive effects of smoke inhalation. These basic skills may be learned through the process of becoming dependent on tobacco, as is dis- cussed in “Developmental Stages of Smoking” in Chap- ter 4 of this report and in the 1988 report. Once learned, these skills can be transferred to other smoked drugs and can facilitate the process of experimentation with such drugs, as well as increase the potential for addiction. renting Tobacco Use Among Young People Prev Health Consequences of Smokeless Tobacco Use Among Young People Introduction Smokeless tobacco includes two main types: chew- ing tobacco and snuff. These products are made from the same type of dark- or burley-leaved tobacco. Most smoke- less tobacco is grown in Kentucky, Pennsylvania, Ten- nessee, Virginia, West Virginia, and Wisconsin. Leaves are generally aged one to three years, but snuff tobacco leaves are aged longer than chewing tobacco leaves (Shapiro 1981). People who use chewing tobacco place a wad of loose-leaf tobacco or a plug of compressed tobacco in their cheek; snuff users place a small amount of powdered or finely cut tobacco (loose or wrapped ina paper pouch) between their gum and cheek (USDHHS | 1992b). Smokeless tobacco users then suck on the to- bacco and spit out the tobacco juices with accompanying saliva. As a consequence of the way in which smokeless products are used, smokeless tobacco is sometimes re- ferred to as spit or spitting tobacco (USDHHS 1992b). The most notable health consequences associated with smokeless tobacco use include halitosis (bad breath), discoloration of teeth and fillings, abrasion of teeth, den- tal caries, gum recession, leukoplakia, nicotine depen- dence, and various forms of oral cancer (USDHHS 1986b, 1992a; WHO 1988). Specifically, smokeless tobacco use has been implicated in cancers of the gum, mouth, phar-. ynx, larynx, and esophagus (USDHHS 1986b; Winn 1988) and has also been indicated in early reports of the devel- opment of verrucous carcinoma (Winn 1988). Smokeless tobacco use may also play a role in cardiovascular dis- ease and stroke, through increases in blood pressure, vasoconstriction, and irregular heartbeat (Hsu et al. 1980; Gritz et al. 1981; Schroeder and Chen 1985). Since nearly 25 percent of adult smokeless tobacco users also smoke cigarettes (CDC 1993b), the effects on the oral cavity may be synergistic, and the risks of developing cancer of the oral cavity and pharynx noticeably increase (Blum 1980). Epidemiologic Evidence The 1986 Surgeon General's report on smokeless tobacco use concluded that there is no safe use of tobacco. Despite that report and subsequent legislation, restric- tions, and follow-up reports (USDHHS 1992a, b; see “Warning Labels on Tobacco Products” inChapter6and “Smokeless Tobacco Advertising and Promotional Ex- penditures” in Chapter 5), smokeless tobacco use in the United States remains a serious concern. The use of smokeless tobacco by adults has remained relatively con- stant at about 5 percent for males and 1 percent for females. However, smokeless tobacco use among high school males has become markedly more prevalent in the past two decades; about 20 percent report using smoke- less tobacco in the past month (see “Current Use of Smokeless Tobacco” in Chapter 3 for documentation and further discussion of the prevalence of smokeless tobacco use). In some states, nearly one out of three high school males uses smokeless tobacco. There is little indication that use among young people is significantly declining (Glover et al. 1988; Boyd and Glover 1989; USDHHS 1992b; see “Current Use of Smokeless Tobacco” in Chapter 3). . Smokeless tobacco use primarily begins in early ado- lescence; some research indicates an average age of onset of 10 years (USDHHS 1992b). Among high school seniors who had regularly used smokeless tobacco, 23 percent reported that they had first tried the product by the sixth grade, and 53 percent by the eighth grade (see “Grade When Smokeless Tobacco Use Begins” in Chapter 3). Health Consequences A recent report of the Office of Inspector General (USDHHS 1992b) concluded that smokeless tobacco use causes serious, but generally not fatal, short-term health consequences among young people. The primary health consequences during adolescence include leukoplakia, gum recession, nicotine addiction, and increased risk of becoming a cigarette smoker. Leukoplakia and/or gum recession occur in 40 to 60 percent of smokeless tobacco users (USDHHS 1992b). Leukoplakia has been defined by the World Health Organization as a lesion of the soft tissue that consists of a white patch (mucosal macule) or plaque that cannot be scraped off (Kramer et al. 1978; Axéll et al. 1984). Greer and Poulson (1983) examined 117 high school students who were smokeless tobacco users; oral soft-tissue le- sions were found in 49 percent of these students. Oral leukoplakias carry a five-year malignant transformation potential of about 5 percent (Pindborg 1980, 1985; Bouquot 1987, 1991). If smokeless tobacco use ceases, the leukoplakia appears to regress or resolve entirely (Chris- ten, McDonald, Christen 1991). Gingival tissue recession (or gum recession) com- monly occurs in the area of the oral cavity immediately adjacent to where smokeless tobacco is held. When smokeless tobacco remains exclusively in a specific intraoral location, gingival recession occurs among 30 percent (Weintraub et al. 1990) to over 90 percent (Schroeder et al. 1988) of users. Modéer, Lavstedt, and Ahlund (1980) found that snuff use among 13- and Health Consequences 35 14-year-old students could directly affect the gingival tissues, causing gingivitis, or gum inflammation. In a study of 565 adolescent male students with gingivitis in Georgia, Offenbacher and Weathers (1985) found that gingival recession was significantly more prevalent, and the odds of developing this condition were nine times greater, among smokeless tobacco users than among nonusers. Navy recruits from 45 states were examined to determine if smokeless tobacco use was associated with gingival recession (Weintraub et al. 1990). Results of the study showed that 31 percent of heavy users and 19 percent of nonusers or low users had gingival recession. Users’ age and the intensity of smokeless tobacco use were significant factors in ex- plaining variations in the degree of gingival recession. Two additional studies of adolescents failed to show an association between the use of smokeless tobacco and gingival recession (Wolfe and Carlos 1987; Creath etal. 1988), possibly because most of the users had been using the product for a short time. Nicotine Addiction The addictive qualities of smokeless tobacco are also a matter of major concern (Christen and Glover 1981; Glover, Christen, Henderson 1981; Glover et al. 1989; Hatsukami, Nelson, Jensen 1991). Smokeless tobacco users develop a nicotine dependency similar to that of cigarette smokers (Benowitz et al. 1988). This is not surprising, since smokeless tobacco users absorb at leastas much nicotine as smokers do (Russell, Jarvis, Feyerabend 1980)—perhaps as much as twice the amount (Benowitz et al. 1988). The high pH of saliva favors absorption of nicotine through oral mucosa, and the degree of absorption increases with the increasing pH of the tobacco product. The rate of absorp- tion of nicotine from snuff is particularly rapid (Russell, Jarvis, Feyerabend 1980; Edwards, Glover, Schroeder 1987). With continued use of smokeless tobacco, blood nicotine levels remain relatively high; these levels fall more slowly after smokeless tobacco is removed from the mouth thanaftera cigarette has been smoked (Benowitz et al. 1988). Adolescents develop physical dependence from smokeless tobacco use, as is evidenced by their experi- ence of withdrawal symptoms when they try to quit (see “Smokeless Tobacco Cessation” in Chapter 6). Smokeless tobacco cessation produces withdrawal symptoms that are similar to those for smoking cessa- tion (Hatsukami, Gust, Keenan 1987), including cravings, irritability, distractibility, and hunger. Adolescents who are most addicted to nicotine appear to be less able to quit (Eakin, Severson, Glasgow 1989). Thus, as is seen with cigarette use (see “Adult Implications of Adoles- cent Smoking” in Chapter 3 and “Adolescent Smoking Behavior as a Risk Factor for Subsequent Smoking” in 36 Health Consequences Surgeon General's Report Chapter 4), adolescents who are heavy smokeless to- bacco users are likely to become adult users. The addictive potential of smokeless tobacco use is aggravated by the fact that some smokeless products are highly effective in the initiation process and are even termed “starter products” by one smokeless tobacco com- pany (Marsee v. United States Tobacco Company 1989; Henningfield and Nemeth-Coslett 1988). These prod- ucts tend to be low in nicotine concentration and low in pH (thus reducing absorption); some are in a unit dosage form (“tobacco pouch”), which helps first-time users avoid placing too much of the substance in their mouths. These products may have contributed to the reversal of the demographics of smokeless tobacco users from 1970 to 1986. In 1970, the majority of smokeless tobacco users were 50 years old and older; by 1986, the majority were 35 years old and younger (USDHHS 1987, 1988). As is discussed in Chapter 5 (see “Smokeless Tobacco Adver- tising and Promotional Expenditures”), marketing and advertising factors have been identified as having in- stilled the general perception that smokeless tobacco products are safe and socially acceptable (Connolly et al. 1986; USDHHS 1987; Glover et al. 1989). Marketing strategies included a heavy reliance on distributing free samples of product types designed to introduce new users to what one company termed the “graduation process” (Marsee v. United States Tobacco Company 1989). Advertising strategies then encouraged new users to experience greater “satisfaction” and “pleasure” by switching to maintenance products higher in nicotine concentration and pH (Marsee v. United States Tobacco Company 1989; Henningfield and Nemeth-Coslett 1988). Smokeless Tobacco Use as a Risk Factor for Cigarette Smoking Young people who use smokeless tobacco appear to be at greater risk to smoke cigarettes than are nonus- ers. Among smokeless tobacco users, 12 to 43 percent also smoke cigarettes (Eakin, Severson, Glasgow 1989; Williams 1992; CDC 1993b; Stevens et al., in press; see Table 23 in Chapter 3). In the 1986-1989 MTFP, 44 percent of high school seniors had tried both smokeless tobacco and cigarettes; of those, 63 percent had tried smokeless tobacco either before or at about the same time as cigarettes (see Table 38 in Chapter 3). Ina prospective study, Ary, Lichtenstein, and Severson (1987) found that smokeless tobacco users were significantly more likely than nonusers to initiate cigarette smoking. Smokeless tobacco users were also more likely to increase their use of cigarettes over a one-year period. For adolescents who use both smokeless tobacco and cigarettes, cessation of one substance may lead to a direct increase in the other (Biglan, La Chance, Benowitz, unpublished data). preventing Tobacco Use Among Young People smokeless Tobacco Use as a Risk Factor for Other Drug Use Smokeless tobacco use is also predictive of other drug use. Ina study of more than 3,000 male adolescents interviewed twice at nine-month intervals about their use af various psychoactive substances (Ary, Lichtenstein, Severson 1987), the main findings were that (1) smokeless tobacco users were significantly more likely to use ciga- rettes, Marijuana, or alcohol than nonusers, (2) users of 16 years/> grade 10 8.2 3.9 5.3 5.7 Never smoked 48.3 39.9 39.8 41.4 Sources: 1989 TAPS: Centers for Disease Control and Prevention (CDC), Office on Smoking and Health (OSH) (unpublished data); 1991 NHSDA: CDC, OSH (unpublished data); 1991 MTFP: Institute for Social Research, University of Michigan (unpublished data); 1991 YRBS: CDC, Division of Adolescent and School Health (unpublished data). *In TAPS, the NHSDA, and the YRBS, respondents reported the age at which they had first smoked; in the MTFP, respon- dents reported the grade in which they first smoked. *Includes 17- and 18-year-old respondents to the 1989 TAPS who had completed the 11th grade and who still attended school. Response categories were constructed using the questions, “Have you ever smoked a cigarette?” and “How old were you when you smoked your first whole cigarette?”(N = 687). Includes respondents to the 1991 NHSDA between the ages of 17 and 18 years who had completed the 11th grade and responded to the question, “About how old were you when you first tried a cigarette?” (N = 979). SIncludes high school senior respondents to the 1991 MTFP survey who responded to the question, “When if ever did you first do each of the following things . . . Smoke your first cigarette?” (N [weighted] = 2,012). ‘Includes 12th-grade respondents to the 1991 YRBS who responded to the question, “How old were you when you smoked a whole cigarette for the first time?” (N = 3,127). Table 9. Age or grade when respondents began smoking daily, National Household Surveys on Drug Abuse (NHSDA), Monitoring the Future Project (MTFP), Youth Risk Behavior Survey (YRBS), United States, 1991 NHSDA' MTFPt YRBS5 Age/grade* % % J < 12 years/< grade 6 3.3 2.3 3.3 13-14 years/grades 7-8 4.0 8.5 6.1 15-16 years/grades 9-10 10.4 11.9 10.2 > 16 years/> grade 10 4.6 6.0 4.5 Never smoked daily 77.5 71.2 76.0 Sources: 1991 NHSDA: Centers for Disease Control and Prevention (CDC), Office on Smoking and Health (unpublished data); 1991 MTEP: Institute for Social Research, University of Michigan (unpublished data); 1991 YRBS: CDC, Division of Adolescent and School Health (unpublished data). *In the NHSDA and the YRBS, respondents reported the age at which they had begun smoking daily; in the MTFP, respon- dents reported the grade in which they had begun smoking daily. ‘Includes 17- and 18-year-old respondents to the 1991 NHSDA who had completed the 11th grade who responded to the question, “About how old were you when you first started smoking daily?” (N = 959). Hncludes high school senior respondents to the 1991 MTFP survey who responded to the question, ‘When, if ever, did you first do each of the following things . .. Smoke cigarettes on a daily basis?” (N [wtd.] = 2,074). SIncludes 12th-grade respondents to the 1991 YRBS who responded to the question, “How old were you when you first started smoking cigarettes regularly? (at least one cigarette every day for 30 days)” (N = 3,074). 50 Epidemiology