Joseph R. DiFranza

Initial symptoms of nicotine dependence in adolescents

OBJECTIVES It has been assumed that nicotine dependence has a slow onset and occurs only after prolonged daily use of tobacco. A cohort of young adolescents was followed to determine when the first symptoms of nicotine dependence occur with respect to the duration and frequency of tobacco use. DESIGN A cohort of 681 seventh grade students (age 12–13 years) from seven schools in two small cities in central Massachusetts was followed over one year. Detailed information regarding tobacco use was obtained in individual confidential interviews conducted in school three times over the year. The latency time to the onset of symptoms of nicotine dependence was measured from the time a subject first smoked at a frequency of at least once per month. RESULTS 22% of the 95 subjects who had initiated occasional smoking reported a symptom of nicotine dependence within four weeks of initiating monthly smoking. One or more symptoms were reported by 60 (63%) of these 95 subjects. Of the 60 symptomatic subjects, 62% had reported experiencing their first symptom before smoking daily or began smoking daily only upon experiencing their first symptom. DISCUSSION The first symptoms of nicotine dependence can appear within days to weeks of the onset of occasional use, often before the onset of daily smoking. The existence of three groups of individuals—rapid onset, slower onset, and resistant—distinguishable from one another by their susceptibility to nicotine dependence, is postulated.

Development of symptoms of tobacco dependence in youths: 30 month follow up data from the DANDY study

Objective: To determine if there is a minimum duration, frequency or quantity of tobacco use required to develop symptoms of dependence. Design and setting: A retrospective/prospective longitudinal study of the natural history of tobacco dependence employing individual interviews conducted three times annually in two urban school systems over 30 months. Detailed histories of tobacco use were obtained including dates, duration, frequency, quantity, patterns of use, types of tobacco, and symptoms of dependence. Participants: A cohort of 679 seventh grade students (age 12–13 years). Main outcome measures: The report of any of 11 symptoms of dependence. Results: Among 332 subjects who had used tobacco, 40% reported symptoms, with a median latency from the onset of monthly smoking of 21 days for girls and 183 days for boys. The median frequency of use at the onset of symptoms was two cigarettes, one day per week. The report of one or more symptoms predicted continued smoking through the end of follow up (odds ratio (OR) 44, 95% confidence interval (CI) 17 to 114, p < 0.001). Conclusions: Symptoms of tobacco dependence commonly develop rapidly after the onset of intermittent smoking, although individuals differ widely in this regard. Girls tend to develop symptoms faster. There does not appear to be a minimum nicotine dose or duration of use as a prerequisite for symptoms to appear. The development of a single symptom strongly predicted continued use, supporting the theory that the loss of autonomy over tobacco use begins with the first symptom of dependence.

Nicotine-dependence symptoms are associated with smoking frequency in adolescents

BACKGROUND Although many sociodemographic and psychosocial factors have been identified as related to adolescent smoking, few studies have examined the role of nicotine-dependence (ND) symptoms. The objective was to study the association between ND symptoms and smoking status among adolescents in the early stages of the smoking onset process. METHODS The McGill University Study on the Natural History of Nicotine Dependence is an ongoing 6-year prospective investigation of the natural history of ND among 1267 grade 7 students in ten Montreal high schools. The baseline response was 55.4%. Subjects for this cross-sectional analysis of baseline data, collected in 1999, included 241 past 3-month smokers (mean age [SD]=13.0+/-0.7 years at baseline). ND symptoms were measured in five indicators, including a measure based on the criteria for tobacco dependence in the International Classification of Diseases-10th Revision (ICD-10), the Hooked on Nicotine Checklist, and three symptom clusters (withdrawal, self-medication, and ND/cravings symptoms). The association between ND symptom indicators and each of sporadic, monthly, weekly, and daily smoking relative to less frequent smoking was investigated in multiple logistic regression analysis. RESULTS Despite low cigarette exposure, 16.6% (95% confidence interval [CI], 11.9%-21.3%) of past 3-month smokers were tobacco dependent. The proportion increased from 0%, 3.1% (95% CI, 0.0%-9.2%), and 4.6% (95% CI, 0.2%-9.0%) among triers, sporadic smokers, and monthly smokers, respectively, to 19.4% (95% CI, 5.5%-33.3%) and 65.9% (95% CI, 51.9%-79.9%) among weekly and daily smokers, respectively. ND/cravings consistently distinguished each smoking category from less frequent smokers; the odds ratios (95% CI) for ND/cravings symptoms were 1.16 (0.99-1.35) in sporadic smokers; 1.17 (1.06-1.29) in monthly smokers; 1.34 (1.19-1.50) in weekly smokers; and 1.39 (1.22-1.59) in daily smokers. CONCLUSIONS These data challenge current smoking onset models, which suggest that ND develops only after several years of heavy or daily smoking. ND symptoms are associated, at least cross-sectionally, with increased smoking in adolescents. To increase the likelihood of being effective, tobacco-control programs for children and adolescents will need to take early ND symptoms into account.

Tobacco Promotion and the Initiation of Tobacco Use: Assessing the Evidence for Causality

OBJECTIVE. We sought to determine whether there is evidence of a causal link between exposure to tobacco promotion and the initiation of tobacco use by children. METHODS. We conducted a structured search in Medline, PsycINFO, and ABI/INFORM Global to identify relevant empirical research. The literature was examined against the Hill epidemiologic criteria for determining causality. RESULTS. (1) Children are exposed to tobacco promotion before the initiation of tobacco use; (2) exposure increases the risk for initiation; (3) there is a dose-response relationship, with greater exposure resulting in higher risk; (4) the increased risk is robust; it is observed with various study methods, in multiple populations, and with various forms of promotion and persists after controlling for other factors; (5) scientifically plausible mechanisms whereby promotion could influence initiation exist; and (6) no explanation other than causality can account for the evidence. CONCLUSIONS. Promotions foster positive attitudes, beliefs, and expectations regarding tobacco use. This fosters intentions to use and increases the likelihood of initiation. Greater exposure to promotion leads to higher risk. This is seen in diverse cultures and persists when other risk factors, such as socioeconomic status or parental and peer smoking, are controlled. Causality is the only plausible scientific explanation for the observed data. The evidence satisfies the Hill criteria, indicating that exposure to tobacco promotion causes children to initiate tobacco use.

Determinants of First Puff and Daily Cigarette Smoking in Adolescents

Few prospective studies of smoking initiation have investigated a wide range of time-varying and invariant predictor variables at the individual and contextual levels concurrently. In this study (1999-2005), 877 Canadian students (mean age = 12.7 years) who had never smoked at baseline completed self-report questionnaires on cigarette smoking and 32 predictor variables in 20 survey cycles during secondary school. Height and weight were measured in survey cycles 1, 12, and 19. School administrators completed questionnaires on school tobacco control policies/activities, and trained observers collected data on access to tobacco products in commercial establishments near schools. Younger age, single-parent family status, smoking by parents, siblings, friends, and school staff, stress, impulsivity, lower self-esteem, feeling a need to smoke, not doing well at school, susceptibility to tobacco advertising, alcohol use, use of other tobacco products, and attending a smoking-tolerant school were independent determinants of smoking initiation. Independent determinants of daily smoking onset among initiators of nondaily smoking included smoking by siblings and friends, feeling a need to smoke, susceptibility to tobacco advertising, use of other tobacco products, and self-perceived mental and physical addiction. Adolescent tobacco control programs should address multiple individual and contextual-level risk factors. Strategies that address nicotine dependence symptoms are also needed for adolescents who have already initiated smoking.

A Sensitization—Homeostasis Model of Nicotine Craving, Withdrawal, and Tolerance: Integrating the Clinical and Basic Science Literature

Recent reports suggest that nicotine withdrawal symptoms are common among adolescents after a few weeks of intermittent tobacco use. No current model of nicotine dependence had predicted the rapid development of symptoms of dependence and withdrawal before the development of tolerance. We present a model that integrates neuroscience with clinical observations regarding how nicotine dependence develops, progresses, and resolves in humans. The central tenet of this sensitization-homeostasis model is that nicotines dependence liability derives from its ability to stimulate neural pathways responsible for the suppression of craving. As a result of sensitization, the craving suppression produced by nicotine is magnified to superphysiological levels. The overinhibition of neurons responsible for craving initiates compensatory homeostatic measures that stimulate the craving pathways and result in craving when nicotine is absent. Separate homeostatic mechanisms are responsible for craving, withdrawal, and tolerance. The sensitization-homeostasis model is unique in its attribution of dependence to craving suppression, its attention to the temporal relationships among clinical features of nicotine dependence, and its extensive integration of clinical observations and basic science. It provides a framework for theory-based research.

Parent’s Socioeconomic Status, Adolescents’ Disposable Income, and Adolescents’ Smoking Status in Massachusetts

OBJECTIVES This study examined the association between parental socioeconomic status (SES) and adolescent smoking. METHODS We conducted telephone interviews with a probability sample of 1308 Massachusetts adolescents aged 12 to 17 years. We used multiple-variable-adjusted logistic regression models. RESULTS The risk of adolescent smoking increased by 28% with each step down in parental education and increased by 30% for each step down in parental household income. These associations persisted after adjustment for age, sex, race/ethnicity, and adolescent disposable income. Parental smoking status was a mediator of these associations. CONCLUSIONS Parental SES is inversely associated with adolescent smoking. Parental smoking is a mediator but does not fully explain the association.

Sources of tobacco for youths in communities with strong enforcement of youth access laws

AIM To determine how youths obtain tobacco in communities with strong enforcement of tobacco sales laws. SETTING Ten communities in Massachusetts with merchant compliance rates at or above 90%. METHODS Paper surveys and focus group discussions with 68 adolescent smokers. RESULTS Parents and friends are the primary sources of tobacco for new smokers. When stealing from parents can no longer satisfy the need for cigarettes, young adolescents ask strangers to buy them tobacco. For high school age smokers, teenage store clerks are a major source. Teenage clerks sell to other teenagers, steal tobacco, and help their friends steal from their employers. Friends who are 18 years of age or over are a second major source for older adolescents. Parents often purchase tobacco for older adolescents. CONCLUSION Recommended actions include raising the minimum age for the purchase of tobacco to 21 years, and prohibiting individuals less than 21 years of age from selling tobacco.

Susceptibility to Nicotine Dependence: The Development and Assessment of Nicotine Dependence in Youth 2 Study

OBJECTIVES. The purpose of this work was to identify characteristics that predict progression from the first inhalation of a cigarette to dependence. We studied a cohort of 1246 public school 6th-graders in 6 Massachusetts communities (mean age at baseline: 12.2 years). METHODS. We conducted a 4-year prospective study using 11 interviews. We assessed 45 risk factors and measured diminished autonomy over tobacco with the Hooked on Nicotine Checklist and evaluated tobacco dependence according to the International Classification of Diseases, 10th Revision. Cox proportional-hazards models were used. RESULTS. Among 217 youths who had inhaled from a cigarette, the loss of autonomy over tobacco was predicted by feeling relaxed the first time inhaling from a cigarette and depressed mood. Tobacco dependence was predicted by feeling relaxed, familiarity with Joe Camel, novelty seeking, and depressed mood. CONCLUSIONS. Once exposure to nicotine had occurred, remarkably few risk factors for smoking consistently contributed to individual differences in susceptibility to the development of dependence or loss of autonomy. An experience of relaxation in response to the first dose of nicotine was the strongest predictor of both dependence and lost autonomy. This association was not explained by trait anxiety or any of the other measured psychosocial factors. These results are discussed in relation to the theory that the process of dependence is initiated by the first dose of nicotine.

Genetically decreased CYP2A6 and the risk of tobacco dependence: a prospective study of novice smokers

Objective: Case control studies in adults suggest that defective alleles in the gene that codes for the hepatic cytochrome P450 2A6 (CYP2A6) protect against nicotine dependence (ND) and higher levels of cigarette consumption. These two hypotheses were tested in young adolescents. Design: Self reports of tobacco use and ND symptoms were collected every 3–4 months in a prospective study of 1293 grade 7 students from a convenience sample of 10 schools. Subjects: 281 smokers with genetic data were analysed; those who were not already tobacco dependent and who had inhaled (n  =  228) were followed 29.9 months on average, until they became dependent or were censored. Main outcome measures: The association between metabolic activity, represented by CYP2A6 genotype, and conversion to dependence was analysed using Cox’s proportional hazards model. Results: During follow up 67 subjects (29.4%) became dependent. Relative to CYP2A6*1/*1, having 1–2 copies of the inactive CYP2A6*2 or *4 variant was a strong risk factor for developing dependence (hazard ratio 2.8, 95% confidence 1.3 to 6.3). Subjects with 1–2 partially inactive CYP2A6*9 or *12 variants were not at increased risk. Mean past-week cigarette consumption at the end of follow up (controlling for age, sex, and number of months since first inhalation) among dependent subjects was 29.1 among normal inactivators, compared to 17.2, and 12.7 among slower (1–2 copies of *9 or *12), and slowest (1–2 copies of *2 or *4) inactivators, respectively (p  =  0.09). Conclusion: Adolescents with 1–2 copies of CYP2A6*2 or *4 are at substantially increased risk of becoming dependent but smoke less once dependent. Genetic risk for ND may need to be considered in the conceptualisation of tobacco control programmes for adolescents.