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JACK E. HENNINGFIELD AND NEAL L. BENOWITZ 139 or short-acting barbiturates; morphine-like opioids can also produce an overtly recognizable syndrome (O’Brien 1996). Deprivation after extended administration of cocaine and cannabis can also produce a diagnosable withdrawal syndrome; however, it is only since the mid 1980s that addiction experts have come to generally concur that these drugs can produce syndromes of withdrawal that can be distinguished from the lack of the effects of the drugs themselves; the role of the withdrawal syndromes in sustaining cocaine and cannabis use remains unclear (Gawin and Kleber 1986; O’Brien 1996). Acute deprivation from extended tobacco use produces a syndrome of withdrawal signs and symptoms that is intermediate between that of the opioids and cocaine in that it has been recognized for several decades, and is generally understood to serve as a barrier to even short-term efforts to achieve tobacco abstinence. Tobacco withdrawal can be occupationally and socially debilitating, but other than standing as a barrier to extended cessation, is not life-threatening in its own right (American Psychiatric Association 1996). Tolerance. A high degree of tolerance develops to the acute effects of nicotine, and some degree of tolerance is gained during each day of smoking and lost during the approximately 8 hours of tobacco deprivation during sleeping hours (Swedberg et al. 1990). Tolerance to nicotine has been systematically explored for more than a century (e.g. Langley 1905). Its mechanisms are diverse and the time course of gain and loss of tolerance varies across responses under evaluation (Collins and Marks 1989; Balfour and Fagerstrom 1996; Royal College of Physicians 2000; Perkins 2002). Comparing drugs of abuse on measures of tolerance is complicated by the varying potential range of measures that can be considered, however, the general degree of tolerance that is produced by repeated nicotine exposure is comparable to that produced by other addictive drugs that produce high levels of tolerance such as the opioids. Implications for treatment of tobacco dependence Although many people are able to quit smoking without formal intervention, this generally occurs only after many cessation attempts and after sufficient harm has been done to substantially increase the risks of premature mortality (Royal College of Physicians 2000; US DHHS 2000). For others, perhaps as a consequence of the pathological changes in brain structure and function produced by long-term nicotine exposure, achieving remission from dependence without treatment may be no more readily achievable than achieving remission from coronary artery disease or oral cancer without treatment. In fact, following surgery for coronary artery disease and lung cancer caused by smoking, many smokers resume smoking in face of the extraordinarily high risks (US DHHS 1988) (Fig. 6.1). The U.S. Clinical Practice Guideline: Treating Tobacco Use and Dependence (Fiore et al. 2000) and reports from the U.S. Surgeon General (US DHHS 2000) and Royal College of Physicians (2000) describe behavioral and pharmacological treatment interventions that approximately double
140 PHARMACOLOGY OF NICOTINE ADDICTION Fraction of Excess Risk 1.20 1.00 0.80 0.60 0.40 0.20 0.00 0 5 10 15 20 25 30 the chances of achieving cessation. These include intensive group behavioral counseling, other individualized behavior therapies and several types of pharmacotherapy. Pharmacotherapies include different nicotine replacement medications (gum, patch, lozenge, oral inhaler, and nasal spray) and bupropion, as well as medications that have been demonstrated to be effective but have not been explicitly approved or marketed for smoking cessation (nortriptyline and clonidine). Many other substances have been used but show little evidence of efficacy (Henningfield et al. 1998; Fiore et al. 2000; US DHHS 2000). Acknowledgements Duration of Cessation (Years) Lung Cancer Coronary Heart Disease COPD Fig. 6.1 Fraction of excess risk remaining with increasing duration of cessation. Modified from Burns 2000 Preparation of this paper was supported, in part, by a Robert Wood Johnson Foundation Innovators Combating Substance Abuse Award to Dr. Henningfield. Dr. Henningfield provides consulting services regarding treatments for tobacco dependence to GlaxoSmithKline Consumer Health Care through Pinney Associates, and also has a financial interest in a nicotine replacement product under development, and serves as an expert witness in litigation against the tobacco industry by the U.S. Department of Justice and other plaintiffs. Dr. Benowitz work was supported, in part, by U.S. Public Health Service Grants DA02277 and DA 12393. We greatly appreciate the editorial assistance of Christine A. Rose, whose efforts were supported by the Innovators award to JEH.
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Tobacco and Public Health: Science
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Tobacco and Public Health: Science
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Preface Tobacco: The public health
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PREFACE vii The cigarette companies
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dramatically. Once more, I am not s
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it impairs quality of life for year
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documents and through litigation by
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PREFACE xv it will not succeed. Now
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Stratton, K., Shetty, P., Wallace,
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Contents Preface v C. Everett Koop
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27 Tobacco and pancreas cancer 479
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Contributors Amanda Amos Reader in
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Stephen S. Hecht University of Minn
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Cecily S. Ray Project Assistant Epi
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Abbreviations AAA Abdominal aortic
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Introduction The publication of thi
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Part 1 Tobacco: History
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Introduction Chapter 1 Evolution of
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RICHARD DOLL 5 However, little atte
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RICHARD DOLL 7 lung’ (Doll and Hi
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Table 1.1 Principal diseases caused
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Table 1.4 Manufactured cigarette co
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in 1995 was approaching the maximum
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References Adler, I. (1912). Primar
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Introduction Chapter 2 The great st
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MICHAEL J. THUN AND JANE HENLEY 19
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it seems likely that some of this v
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steady increase in lung cancer occu
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cigarette smoking in deaths from co
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the effects of smoking and smoking
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Lung cancer death rate (per 100,000
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Lickint, F. (1929). Zeitschrift fur
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Chapter 3 Dealing with health fears
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LYNN T. KOZLOWSKI AND RICHARD J. O
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Table 3.3 Selected cigarette advert
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Part 2 Tobacco: Composition
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Introduction Chapter 4 The changing
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ILSE HOFFMANN AND DIETRICH HOFFMANN
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Table 4.4 (continued) Carcinogens i
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Table 4.5 Standard conditions for m
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Table 4.7 Comparison of experimenta
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the lung in rats treated with NNK (
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serve as the scientific basis in su
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Page 122 and 123: ILSE HOFFMANN AND DIETRICH HOFFMANN
Page 124 and 125: Senkus, M. (ed.) (1976). Leaf compo
Page 126 and 127: Introduction Chapter 5 Tobacco smok
Page 128 and 129: STEPHEN S. HECHT 95 Established pul
Page 130 and 131: STEPHEN S. HECHT 97 magnitude lower
Page 132 and 133: STEPHEN S. HECHT 99 generally great
Page 134 and 135: Table 5.1 1-Hydroxypyrene in the ur
Page 136 and 137: Table 5.2 NNAL and its glucuronides
Page 138 and 139: STEPHEN S. HECHT 105 Table 5.2 (con
Page 140 and 141: Table 5.3 Representative DNA adduct
Page 142 and 143: G No (Wang et al. 2001a) N 2 CHCH 2
Page 144 and 145: STEPHEN S. HECHT 111 N-Nitrosopyrro
Page 146 and 147: (Kozack et al. 2000; Seo et al. 200
Page 148 and 149: the DNA adducts resulting from toba
Page 150 and 151: Culp, S. J., Gaylor, D. W., Sheldon
Page 152 and 153: STEPHEN S. HECHT 119 International
Page 154 and 155: STEPHEN S. HECHT 121 Melchior, W. B
Page 156 and 157: STEPHEN S. HECHT 123 Rivenso, A., H
Page 158 and 159: Wang, M., McIntee, E. J., Cheng, G.
Page 160 and 161: Part 3 Nicotine and addiction
Page 162 and 163: Chapter 6 Pharmacology of nicotine
Page 164 and 165: JACK E. HENNINGFIELD AND NEAL L. BE
Page 166 and 167: Pickworth et al. 1995; Shiffman et
Page 168 and 169: American Caucasians and Hispanics (
Page 170 and 171: (US DHHS 2001). At doses delivered
Page 174 and 175: References JACK E. HENNINGFIELD AND
Page 182 and 183: Introduction Chapter 7 Behavioral p
Page 184 and 185: BRIDGETTE E. GARRETT ET AL. 151 How
Page 186 and 187: (Fischman and Foltin 1991). Another
Page 188 and 189: following repeated, infrequent and
Page 190 and 191: BRIDGETTE E. GARRETT ET AL. 157 oth
Page 192 and 193: BRIDGETTE E. GARRETT ET AL. 159 cli
Page 194 and 195: to tobacco product ingredients and
Page 196 and 197: BRIDGETTE E. GARRETT ET AL. 163 Gom
Page 198 and 199: BRIDGETTE E. GARRETT ET AL. 165 Ris
Page 200 and 201: Introduction Chapter 8 Cigarette sc
Page 202 and 203: JEFF FOWLES AND DENNIS SHUSTERMAN 1
Page 204 and 205: ◆ The pressure drop of the filter
Page 206 and 207: Nitrosamines Nitrosamines are biolo
Page 210 and 211: Physical design features of cigaret
Page 214 and 215: Introduction Chapter 9 Nicotine dos
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Page 218 and 219: Table 9.2 The ranges of nicotine, n
Page 220 and 221: MIRJANA V. DJORDJEVIC 187 turing a
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Poland 19 1.4 n.a. n.a. 68−347 36
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MIRJANA V. DJORDJEVIC 191 cigarette
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MIRJANA V. DJORDJEVIC 193 Table 9.5
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MIRJANA V. DJORDJEVIC 195 MS wherea
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MIRJANA V. DJORDJEVIC 197 In recent
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MIRJANA V. DJORDJEVIC 199 Table 9.8
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MIRJANA V. DJORDJEVIC 201 Burns, D.
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International Agency for Research o
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Part 4 Tobacco use: Prevalence, tre
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Chapter 10 Tobacco in Great Britain
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Adult smoking PATTI WHITE 209 Since
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oys who were regular smokers report
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PATTI WHITE 213 cancer, and bringin
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Introduction Chapter 11 The epidemi
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since the late 1980s. In 2001, Phil
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YANG HONGHUAN 219 ◆ Among males,
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Table 11.1 Smoking among adolescent
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(57%) was higher than in males (45%
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20 cigarettes a day had double the
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Chapter 12 Patterns of smoking in R
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DAVID ZARIDZE 229 Ignatova et al. (
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DAVID ZARIDZE 231 Tyumen, respectiv
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References DAVID ZARIDZE 233 Alexee
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Chapter 13 Tobacco smoking in centr
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WITOLD ZATOŃSKI 237 The developmen
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especially post-Soviet countries, w
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No. of Cigarettes 3000 2500 2000 15
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WITOLD ZATOŃSKI 243 young men and
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DEATHS / 100,000 DEATHS / 100,000 7
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WITOLD ZATOŃSKI 247 According to d
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Unfortunately, available data on th
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Kaczmarczyk-Chalas, K., Gdulewicz,
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Chapter 14 The epidemic in India Pr
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aniseed, and musk, also available a
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PRAKASH C. GUPTA AND CECILY S. RAY
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Prevalence among youth PRAKASH C. G
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treatment and premature death were
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Although tobacco control legislatio
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PRAKASH C. GUPTA AND CECILY S. RAY
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Chapter 15 Tobacco in Africa: More
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In assessing tobacco use in Africa
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YUSSUF SALOOJEE 271 plug the gap th
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Table 15.2 Cigarette taxes as perce
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YUSSUF SALOOJEE 275 In recent years
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World Bank (2001). Economics of Tob
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Part 5 Tobacco and health. Global b
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Chapter 16 The future worldwide hea
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RICHARD PETO AND ALAN D LOPEZ 283 a
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UK male death rate at ages 35-69 ha
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Overview Chapter 17 Passive smoking
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evidence have proved to be effectiv
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JONATHAN M. SAMET 291 a thousand de
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Table 17.2 Occupational ETS exposur
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Table 17.3 Nicotine concentrations
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portable piezobalance to sample aer
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JONATHAN M. SAMET 299 Fetal effects
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JONATHAN M. SAMET 301 Investigation
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Table 17.4 Summary of pooled random
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JONATHAN M. SAMET 305 also reported
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and involuntary exposure to tobacco
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Glantz, S. A. and Parmley, W. W. (1
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JONATHAN M. SAMET 311 O’Connor, G
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JONATHAN M. SAMET 313 US Department
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Introduction Chapter 18 Adolescent
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JOHN P. PIERCE ET AL. 317 would be
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JOHN P. PIERCE ET AL. 319 Indeed, t
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JOHN P. PIERCE ET AL. 321 reached i
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subsequent consumption. Most studie
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Burns, D., Garfinkel, L., and Samet
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JOHN P. PIERCE ET AL. 327 US Depart
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The epidemic Chapter 19 Tobacco and
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AMANDA AMOS AND JUDITH MACKAY 331 w
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AMANDA AMOS AND JUDITH MACKAY 333 T
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AMANDA AMOS AND JUDITH MACKAY 335 w
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AMANDA AMOS AND JUDITH MACKAY 337 p
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AMANDA AMOS AND JUDITH MACKAY 339 T
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AMANDA AMOS AND JUDITH MACKAY 341 o
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AMANDA AMOS AND JUDITH MACKAY 343 M
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such as Jewel and Madonna, who woul
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AMANDA AMOS AND JUDITH MACKAY 347 t
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particularly in developing countrie
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AMANDA AMOS AND JUDITH MACKAY 351 L
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Part 6 Tobacco and cancer
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Chapter 20 Cancer of the prostate F
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Table 20.1 Summary of results of ca
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Andersson et al. 1996 Sweden 256 ca
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Table 20.2 Summary of results of co
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cancer in younger or elderly men, w
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FABIO LEVI AND CARLO LA VECCHIA 365
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Summary Chapter 21 Laryngeal cancer
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12-year follow-up of the American C
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Hedberg et al. USA, 235, 81% P, 547
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cigarettes as compared to blond-tob
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of 3.78 and 11.47. An interpretatio
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Effect on survival In two studies f
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Cattaruzza, M. S., Maisonneuve, P.,
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USDHEW (1964). Laryngeal cancer. In
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Chapter 22 Smoking and cancer of th
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Table 22.1 Results from selected ca
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Asia Gao et al. 1994— Population
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EVA NEGRI 389 Ille-et-Vilaine, Fran
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Odds Ratio 2.5 2 1.5 1 0.5 0 0.30 2
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Garidou et al. 1996— Hospital ≤
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De Stefani, E., Barrios, E., and Fi
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Wynder, E. L. and Bross, I. J. (196
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Introduction Chapter 23 Tobacco use
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Table 23.1 Tobacco use and risk of
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Franceschi et al. Oral cavity, Oral
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Muscat et al. Oral cavity OR = 2.1
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Population-based case-control studi
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Lewin et al. Oral cavity, RR = 6.5
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TONGZHANG ZHENG ET AL. 411 the cont
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TONGZHANG ZHENG ET AL. 413 For smok
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TONGZHANG ZHENG ET AL. 415 per day
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TONGZHANG ZHENG ET AL. 417 than tha
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TONGZHANG ZHENG ET AL. 419 For exam
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TONGZHANG ZHENG ET AL. 421 decline
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Studies in India: Oral cancer is th
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carcinoma compared with other combi
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studies have demonstrated a positiv
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TONGZHANG ZHENG ET AL. 429 Garrote,
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TONGZHANG ZHENG ET AL. 431 Notani,
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Chapter 24 Smoking and stomach canc
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DAVID ZARIDZE 435 such as sex, age,
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DAVID ZARIDZE 437 (Kato et al. 1990
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DAVID ZARIDZE 439 respectively. The
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Gajalakshmi, C. K. and Shanta, V. (
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Pisani, P., Parkin, D. M., Bray, F.
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Introduction Chapter 25 Cigarette s
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attenuated in every study after con
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EDWARD GIOVANNUCCI 449 with a gener
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(Baron et al. 1994) of 352 colon ca
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(U.S. Dept. of Health Education and
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References EDWARD GIOVANNUCCI 455 A
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EDWARD GIOVANNUCCI 457 Kono, S., Ik
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Chapter 26 Smoking and cervical neo
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Tokuhata 1967* Williams 1977* Wigle
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Clarke 1985* Hellberg 1986* La Vecc
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ANNE SZAREWSKI AND JACK CUZICK 465
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case-control study nested in a scre
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five-fold risk of cervical cancer f
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(typically around two-fold), but be
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Introduction Chapter 27 Tobacco and
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Cigar, pipe, and chewing tobacco Wh
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Conclusion Overall, tobacco smoking
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Summary Chapter 28 Smoking and lung
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GRAHAM G. GILES AND PETER BOYLE 487
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quit for 20 years or more (Rogot an
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cancer and others where there is st
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Peto, R. (1986) Influence of dose a
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Chapter 29 Tobacco smoking and canc
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He further noted that case-control
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coefficients from the data in Table
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DIMITRIOS TRICHOPOULOS AND ARETI LA
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Epidemiology Chapter 30 Smoking and
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CRYSTAL N. HOLICK AND HARVEY A. RIS
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and at least the enteric variety of
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Chapter 31 Endometrial cancer Paul
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Table 31.1 Epidemiological studies
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studies (Terry et al. 1999, 2002a),
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Newcomer Population 740/2372 40-79
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PAUL D. TERRY ET AL. 531 levels, an
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Relative body weight Obesity is an
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Key et al. 1991 147 pre- and postme
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lood levels among current smokers,
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Table 31.7 Studies of cigarette smo
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of the association between cigarett
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Jensen, J., Christiansen, C., and R
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PAUL D. TERRY ET AL. 545 Weiderpass
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Part 7 Tobacco and heart disease
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citations of some of the best-known
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KONRAD JAMROZIK 553 because the dat
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KONRAD JAMROZIK 555 Fig. 32.2 Trend
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Table 32.3 Case-control studies of
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Table 32.5 Cohort studies of active
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Table 32.6 Effect of exclusion of p
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eadily addressed by cohort studies
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Specificity The entries in Table 32
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Table 32.8 Application of Bradford
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KONRAD JAMROZIK 569 arterial CVD re
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elationship goes beyond statistical
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Garland, C., Barrett-Connor, E., Su
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National Health and Medical Researc
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Part 8 Tobacco and respiratory dise
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Introduction Chapter 33 Chronic obs
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Many of the constituents in both th
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DAVID M. BURNS rate of growth in lu
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Death rates from COPD in smokers an
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Fraction of Excess Risk 1.20 1.00 0
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DAVID M. BURNS Higgins, M. W., Enri
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Part 9 Tobacco and other diseases
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Introduction Chapter 34 Smoking and
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ALLAN HACKSHAW 595 several mechanis
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Table 34.4 Studies that reported re
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Table 34.5 Cohort studies that repo
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than non-smokers; they have about h
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Table 34.8 Cohort studies that repo
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esults from cohort studies. There i
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ALLAN HACKSHAW 607 (DiFranza and Le
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Table 34.12 Cohort studies that rep
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Caries and tooth loss Because perio
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Table 34.16 Summary of disorders in
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References ALLAN HACKSHAW 615 Allar
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Johnsen, R., Forde, O. H., Straume,
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Seddon, J. M., Willett, W. C., Spei
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Part 10 Genetics, nicotine addictio
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Chapter 35 Genes, nicotine addictio
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Cotinine (ng/ml) 750 500 250 OXCHEC
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MICHAEL MURPHY ET AL. 627 of those
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MICHAEL MURPHY ET AL. risk associat
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Table 35.2 (continued) Gene map Chr
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MICHAEL MURPHY ET AL. pre-clinical
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Steps to carcinogenesis Exposure to
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DNA repair As previously alluded to
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MICHAEL MURPHY ET AL. Lichtenstein,
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Part 11 Tobacco and alcohol
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Table 36.1 Comparison of alcohol an
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Although gene therapy has rarely be
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20+ TABAC 5.1 10-19 0-9 3.4 12.3 0-
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Heavy drinking is known to cause ga
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Treatment issues and co-dependence
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ALBERT B. LOWENFELS AND PATRICK MAI
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Part 12 Tobacco control: Successes
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Introduction Chapter 37 Global toba
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NIGEL GRAY (sometimes at state leve
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NIGEL GRAY The first attempt to red
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per litre of smoke. Reduction of th
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Borland, R., Cappiello, M. and Owen
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Chapter 38 Lessons in tobacco contr
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entangling relationships with negot
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successful country advocates deeply
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Thus, when the opportunity arose, t
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Chapter 39 A brief history of legis
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Committee, mentioned above, little
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4. Tobacco and its related processi
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RUTH ROEMER 683 advertising and adv
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or shows, and distribution of free
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RUTH ROEMER 687 threat to the peopl
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RUTH ROEMER 689 The case was settle
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Another study by Harvard researcher
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At the end of 2003, 83 countries ha
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Chapter 40 Roles of tobacco litigat
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NGOs obtained sanctions against tob
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RICHARD A. DAYNARD 699 In a 1980s c
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RICHARD A. DAYNARD 701 Fourth, the
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even impossible. Such a statute pre
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RICHARD A. DAYNARD 705 Daynard, R.
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Introduction Chapter 41 Impact of s
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in this chapter, is evidence that s
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RON BORLAND AND CLAIRE DAVEY 711 Wh
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RON BORLAND AND CLAIRE DAVEY 713 On
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RON BORLAND AND CLAIRE DAVEY 715 ro
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you are subject, but this does not
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RON BORLAND AND CLAIRE DAVEY 719 to
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RON BORLAND AND CLAIRE DAVEY 721 fo
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RON BORLAND AND CLAIRE DAVEY 723 (E
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RON BORLAND AND CLAIRE DAVEY 725 th
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advanced. Although in countries lik
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RON BORLAND AND CLAIRE DAVEY 729 Da
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RON BORLAND AND CLAIRE DAVEY 731 Pr
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Introduction Chapter 42 Effective i
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PRABHAT JHA ET AL. 735 India (Gupta
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Average price or tax per pack (US$)
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PRABHAT JHA ET AL. 739 Bans on adve
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PRABHAT JHA ET AL. 741 Table 42.2 T
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PRABHAT JHA ET AL. 743 antismugglin
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Farrelly, M. C., Pechacek, T. F., a
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PRABHAT JHA ET AL. 747 Raw, M., Mc
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Part 13 Treatment of dependence
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Introduction Chapter 43 Treatment o
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Nocturnal sleep-disturbing nicotine
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MICHAEL KUNZE AND E. GROMAN 755 tob
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Fifteen different products were ide
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In summary, tobacco dependence amon
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medications for OTC sale in 1996, t
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MICHAEL KUNZE AND E. GROMAN 763 US
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Chapter 44 Regulation of the cigare
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as these correlate quite well with
Page 802 and 803:
NIGEL GRAY 769 within three major g
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of carcinogens and toxins in its wa
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Index abdominal aortic aneurysm see
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aromatic amines 58, 60, 98 DNA addu
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central and eastern Europe (CEE) (C
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coronary thrombosis 5 see also myoc
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epinephrine 169 epoxide hydrolase g
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health professionals advice on smok
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laryngeal cancer (Continued) animal
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Morris, Philip 207 see also Philip
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nursing home residents 718 nutritio
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Polish Central Statistical Office (
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smoke, tobacco (including cigarette
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Sweden female smoking rates 330-1 l
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United Nations agencies 680-1 Unite
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Tobacco and Public Health - TCSC Indonesia

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