Adjusted analyses included an e-cigarette dependence propensity score covariate calculated from a prediction model of e-cigarette dependence status regressed on 25 baseline variables, as detailed in the eAppendix in the Supplement. Additional and supplemental sensitivity analyses were conducted. Analyses were tested in Mplus statistical software version 7 using full information maximum likelihood estimating to account for missing data, and participants’ high school was accounted for using complex modeling. For primary analyses, Benjamini Hochberg multiple-testing corrections20 were applied to control study wise false-discovery rate at 0.05, based on 2-tailed corrected P values. Data were analyzed from March 2019 to December 2019. Sensitivity analyses of cross-tobacco product comparisons of dependence prevalence, severity, and symptom patterns that adjusted for age at onset and past 30-day use frequency of the 2 respective products yielded results that were similar to the primary results . Additional cross-product analyses restricted to dual users who vaped nicotine found differences on the same dependence outcomes as the primary results, although differences were less robust . Youth who use multiple tobacco products may have difficulty distinguishing the source of dependence symptoms; however, baseline past-year combustible cigarette use did not significantly moderate associations of e-cigarette dependence symptoms with subsequent vaping at 6-month follow-up . For descriptive purposes to examine whether results generalized across sex and non-nicotine substance use, tests of differences in cross-sectional and prospective analyses stratified by sex and number of nonnicotine substances used are reported in Tables 7, 8, 9,drying cannabis and 10 in the Supplement. They did not show marked differences by sex and concomitant substance use.
Past-month e-cigarette and combustible cigarette use patterns by past-month nicotine vaping days are presented in eTable 11 in the Supplement for descriptive purposes. Associations with additional behavioral health outcomes were tested for exploratory purposes, and analyses found that e-cigarette dependence was significantly associated with increases in ADHD symptom level at 6-month follow-up ; this association was amplified by the number of other substances used . Additionally, reporting 1 or more e-cigarette dependence symptoms at baseline was associated with heavier combustible cigarette smoking at follow-up, including more cigarette smoking days and more cigarettes smoked per day .This cohort study provides some of the most detailed evidence to date on the prevalence and symptom presentation of e-cigarette dependence and its association with future e-cigarette use among youth, to our knowledge. Previous studies have provided less comprehensive characterizations of e-cigarette dependence, without comparisons with combustible cigarette dependence.To our knowledge, this is also the first prospective longitudinal investigation of the association of e-cigarette dependence symptoms with subsequent vaping patterns. Our results suggest that e-cigarette dependence symptoms may be associated with future vaping patterns. In this study, the prevalence of e-cigarette dependence symptoms was relatively low and, consistent with prior research,primarily characterized by cravings and a perceived need to vape. Although prevalence and severity of dependence symptoms were approximately 2-fold as large for combustible cigarettes as e-cigarettes in users of both products, the most common and least common symptoms were similar across the 2 products, as were the qualitative profiles across all 10 symptoms. Importantly, the cross-product comparisons were conducted within-persons among dual users, eliminating confounding differences between smokers and vapers. Unlike combustible cigarettes, e-cigarettes and e-liquids vary in nicotine content and delivery.Few youth in this study likely used the now-popular pod mod–style e-cigarette products that deliver large amounts of nicotine efficiently.
Considering the elevated dependence symptoms reported among youth who vaped nicotine in this study despite low probability of pod mod use, these results suggest that e-cigarette dependence may be of notable clinical and public health significance. Electronic cigarette dependence symptoms were elevated in certain subgroups expected to be at higher risk, including youth who vaped recently, used e-cigarettes that contained nicotine, or used both e-cigarettes and combustible cigarettes. A 2018 study found that dual users had higher levels of nicotine biomarkers than users of e-cigarettes only. To our knowledge, this is among the first investigations to find that e-cigarette dependence symptoms were experienced even among youth who reported using only e-cigarettes without nicotine—a sizeable proportion of youth e-cigarette users.Nicotine-containing products may have been mislabeled, or youth with histories of nicotine vaping in early adolescence who later switched to only nicotine-free vaping over the past year may have experienced cravings triggered by cues associated with the act of vaping.Youth who used e-cigarettes and reported at least 1 e-cigarette dependence symptom were more likely to continue vaping and to vape more frequently and intensely 6 months later than their peers who did not report any dependence symptoms. This finding is consistent with a 2019 study that suggested that vaping continuation, with escalation of use frequency and dependence symptoms, is common. Our study further suggests that youth with dependence symptoms are at elevated risk for continuation and escalation. Symptoms of e-cigarette dependence may directly increase motivation to use, and increased use may recapitulate a cycle of worsening dependence. Although our observational study design precludes such causal inferences,ebb flow findings suggest that e-cigarette dependence may be associated with subsequent vaping patterns even after adjusting for dependence propensity defined by numerous potentially confounding influences.
In clinical settings, e-cigarette dependence symptom screening questions may identify youth at risk for vaping progression who may benefit from intervention. In regulatory decision-making, dependence is a potential health consequence of e-cigarette use that should be considered. Adolescents are particularly vulnerable to nicotine exposure,and our findings suggest that dependence symptoms associated with nicotine exposure via e-cigarettes are associated with greater risk for escalation of vaping behavior. The development of dependence in youth is an important public health consequence that should not be overlooked.This study has some limitations. First, all participants were recruited from high schools in Los Angeles, California; therefore, extension to different regions would be informative. Second, data were collected in the 2016 to 2017 school year, before high-nicotine e-cigarettes became popular among youth.Third, all measures were self-reported and did not include clinical diagnosis of nicotine dependence. While the measure of dependence was selected for its presumed applicability to both tobacco products and its ability to capture key features of the dependence syndrome ,other measures of e-cigarette dependence that are correlated with nicotine exposure merit inclusion in future research to address varying aspects of the dependence syndrome.6 Fourth, the follow-up period was limited to 6 months, leaving unclear the long-term association of e-cigarette dependence with future use.Combusted tobacco use remains a major cause of premature disability and death around the world . Cigarette smoke contains an estimated 7000 different chemical compounds, of which at least 70 are proven or suspected human carcinogens including arsenic, benzene, formaldehyde, lead, nitrosamines, and polonium 210. Tobacco smoke also contains poisonous gasses: carbon monoxide, hydrogen cyanide, butane, toluene, and ammonia.Tobacco smoking causes about half a million U.S. deaths annually, of which 50,000 are among nonsmokers exposed to secondhand smoke . More than half of all long-term smokers die from a tobacco-caused disease, with an average loss of at least 10 years of life . Smoking causes 87% of lung cancer deaths, 61% of pulmonary disease deaths [chronic obstructive pulmonary disease and emphysema], and one in three cancer deaths. In the 50 years following the U.S. Surgeon General’s first report on tobacco , 20 million Americans died from smoking, and an estimated 1 billion people will die worldwide this century . For every person who dies from smoking, at least 30 people live with serious smoking-related illnesses costing >$300 billion annually, with nearly $170 billion in direct medical costs and $156 billion in lost worker productivity . The health harms of combusted tobacco use are now undeniable . With market and regulatory pressures to reduce the harms of nicotine delivery by combustion, the tobacco product landscape has diversified . Nicotine now comes in smokeless tobacco prepackaged pouches , in electronic devices that heat nicotine to an inhalable aerosol from a plug of tobacco or from an e-liquid , and in pharmaceutical grade nicotine replacement therapies . Cigars come in a variety of sizes down to little filtered cigars, some discernible from cigarettes only by their tobacco leaf wrapper.
Despite the diversification, conventional combusted cigarettes remain, by far, the most common nicotine product used by adults in the United States and in most places globally. Worldwide, there are approximately 1 billion smokers . While products of tobacco combustion are the main cause of smoking-induced disease, nicotine addiction sustains tobacco use . Nicotine addiction, in the form of cigarette smoking, causes more harm to public health than any other drug addiction. Reflected in the quote above, at least since the 1950s, the tobacco industry has researched and recognized, decades before it became generally understood in the scientific community, that nicotine is an addictive drug and central to their business . An understanding of the clinical features of nicotine addiction and the behavioral conditioning that occurs with frequent nicotine dosing is important for informing pharmacologic and behavioral treatment targets. We review current advances in research on nicotine addiction treatment and recovery. The “Tobacco Product Use and Nicotine Addiction” section covers the changing landscape of nicotine products with comparison of use patterns among adults and adolescents in the United States. The pharmacology of nicotine and effects on the brain are then reviewed, with consideration of particularly vulnera ble populations. The “Treating Nicotine Addiction in Adults, with a Focus on Conventional Cigarettes” section focuses on treatment of nicotine addiction with attention to counseling and behavioral approaches and cessation medications. The tobacco treatment literature is far more developed for combusted cigarettes and relatively sparse in other product areas. We focus on adults given develop mental differences in adolescents’ preferred nicotine product type, use patterns, addiction profile, and treatment efficacy. The tobacco treatment literature with adolescents largely consists of failed smoking cessation trials , and while youth nicotine vaping is drawing public health concern and policy attention, no study, to date, has evaluated an intervention to treat e-cigarette use in adolescents. The “Tobacco Control Population-Based and Policy Approaches” section gives greater attention to use in youth with review of the evidence for tobacco control policy interventions. The “Discussion: What Evidence Is Needed” section closes with discussion of emerging areas and consideration of new directions for advancing the field.Nicotine is a tertiary amine that can exist in a charged or uncharged form, depending on pH. Nicotine is a weak base with a pKa of 8.0 such that, at physiological pH , 69% is ionized and 31% is unionized. The unionized form of nicotine passes readily though membranes, such as the buccalmucosa, such that the pH of smokeless tobacco influences the rate and extent of systemic nicotine absorption. The more alkaline , the more rapidly nicotine is absorbed from smokeless tobacco. Cigarette smoke has an acidic pH of about 5.5 to 6, so little nicotine is absorbed through the mouth, while large cigars have an alkaline pH, facilitating oral absorption. The differences in pH of tobacco products depends on the strains of tobacco used and curing processes, as well as on chemicals used in processing. The pH of nicotine solutions also influences the pharmacology of e-cigarettes. The earliest forms of e-cigarette liquid contained mostly nicotine in free base form , which results in a considerable nicotine-related harshness during inhalation. Recently, e-liquids have used nicotine salts , with acidic pH , similar to that of cigarettes. This results in less irritation with inhalation and has been implicated in the current popularity of e-cigarette use in never-smoker adolescents . When cigarette smoke is inhaled, nicotine moves quickly to the lungs, arterial blood, and the brain in only 15 to 20 s , where it exerts its addiction-related effects. Rapidity of delivery to the brain is thought to be an important factor in the abuse liability of inhaled nicotine compared to other routes of nicotine administration. The importance of rapid delivery relates to higher arterial concentrations, nearly immediate psychological effects, and the ability to titrate doses to desired effects. Higher arterial levels also allow the smoker to overcome effects of tolerance to the desired psychological effects of nicotine. Inhaled nicotine from e-cigarettes potentially carries a similar abuse liability to that of tobacco cigarettes, but empirical data, to date, suggest that it is not the case.