Mark L. Rubinstein

Smoking-Related Cue-Induced Brain Activation in Adolescent Light Smokers

PURPOSE To examine using functional magnetic resonance imaging whether adolescents with low levels of nicotine exposure (light smokers) display neural activation in areas shown to be involved with addiction in response to smoking-related stimuli. DESIGN/SETTING/PARTICIPANTS A total of 12 adolescent light smokers (aged 13-17, who smoked 1-5 cigarettes per day) and 12 nonsmokers (ages 13-17, never smoked a cigarette) from the San Francisco Bay Area underwent functional magnetic resonance imaging scanning. During scanning, the adolescents were shown photographic blocks of smoking and control cues. Smoking cues comprised pictures of individuals smoking cigarettes and smoking-related objects such as lighters and ashtrays. Neutral cues comprised images of everyday objects and individuals engaged in daily activities. FINDINGS For smokers, smoking cues elicited greater activation than neutral cues in the mesolimbic reward circuit (left anterior cingulate: t = 7.04, p < .001; right hippocampus: t = 6.37, p < .001). We found activation from smoking cues versus neutral cues within both the left and right frontal medial orbital regions (t = 5.09, p < .001 and t = 3.94, p = .001, respectively). Nonsmokers showed no significant difference in activation between smoking-related cues and neutral cues. CONCLUSION Our finding that smoking cues produced activation in adolescent light smokers in brain regions, similar to that seen in adult and teenage heavy smokers, suggests that adolescents exhibit heightened reactivity to smoking cues even at low levels of smoking. This article adds to the existing published data by suggesting that nicotine dependence may begin with exposure to low levels of nicotine, thus underscoring the need for early intervention among adolescent smokers.

Cotinine Levels in Relation to Smoking Behavior and Addiction in Young Adolescent Smokers

The goal of this study was to identify associations among self-reported nicotine exposure, nicotine addiction, and actual nicotine intake as measured by salivary cotinine levels in adolescent smokers. A total of 170 adolescent smokers with a mean age of 15 years were recruited from seven northern Californian public high schools. Data were collected on smoking behaviors, addiction, craving, and withdrawal. Nicotine dependence was assessed using a modified teen Fagerström Tolerance Questionnaire (mtFTQ), a modified Nicotine Dependence Syndrome Scale (mNDSS), and a simple self-rating. Withdrawal was assessed using the Minnesota Withdrawal Questionnaire, and craving was assessed using a survey created by the authors. Salivary cotinine levels were collected from and analysed in participants who self-identified as smokers; data from the 54 participants who smoked in the past 4 days and whose salivary cotinine levels were greater than 0.1 ng/ml were used in the analysis. Among this group of adolescent smokers, the mean number of cigarettes smoked per day was 3.51 (SD = 3.44) and the mean level of salivary cotinine was 44.1 ng/ml (Mdn = 24.2). Even at this low level of nicotine exposure, cotinine was highly correlated with measures of nicotine dependence such as the mtFTQ (r = 0.497, p = .001), NDSS (r = 0.439, p = .002), timing of craving in the morning (r = -0.601, p = .000), and self-rated addiction (r = 0.562, p = .000). Most interesting, cotinine levels reached a plateau at around 4-5 cigarettes/day.

Rate of Nicotine Metabolism and Withdrawal Symptoms in Adolescent Light Smokers

OBJECTIVES. The rate of nicotine metabolism may contribute to vulnerability in adolescents’ transition from smoking initiation to addiction. The objectives of this study were to examine the associations between the rate of nicotine metabolism and cigarette consumption, addiction, and withdrawal symptoms in a sample of adolescent light smokers. PARTICIPANTS. Twenty adolescent smokers between 13 and 17 years old, who smoked between 1 and 6 cigarettes daily for ≥6 months, were recruited from several San Francisco Bay area schools and pediatric clinics from 2006 to 2007. METHODS. Participants underwent 24 hours of supervised tobacco abstinence. Serum was collected at baseline and at 24 hours for measurement of the nicotine metabolites cotinine and 3′-hydroxycotinine. Participants also completed self-report measures, which included smoking behavior, nicotine dependence, and withdrawal scales at baseline and 24 hours after baseline. The ratio of serum 3′-hydroxycotinine/cotinine (the nicotine metabolite ratio), a measure of the rate of nicotine metabolism, was computed by using measurements from the 24-hour serum samples. RESULTS. Participants were divided into 2 groups: faster metabolizers (3′-hydroxycotinine/cotinine ratio ≥ 0.5; n = 5) and slower metabolizers (3′-hydroxycotinine/cotinine ratio < 0.5; n = 15). Faster metabolizers reported greater withdrawal symptoms after 24 hours of abstinence compared with slower metabolizers even after adjusting for the number of cigarettes smoked per day. The metabolite ratio was significantly correlated with self-described level of addiction. CONCLUSIONS. This is the first study to report a significant relationship between the rate of nicotine metabolism and withdrawal symptoms and self-reported addiction in adolescent light smokers. Given the association between withdrawal symptoms and nicotine addiction, adolescent smokers who are faster metabolizers of nicotine may be at greater risk for becoming addicted to nicotine compared with slower metabolizers.

A Randomized Trial of Nicotine Nasal Spray in Adolescent Smokers

OBJECTIVES. Nicotine nasal spray has been 1 of the most successful forms of nicotine-replacement therapy in adult populations. The nasal sprayer has not been studied in adolescent smokers. The objective of this pilot study was to determine the feasibility and utility of using nicotine nasal spray for adolescent smokers who wanted to quit smoking. METHODS. Forty adolescent smokers who were between 15 and 18 years of age and smoked ≥5 cigarettes daily for at least 6 months were recruited from several San Francisco Bay area schools from 2005 to 2007. Using a randomized, open-label, 12-week trial, adolescent smokers were assigned to receive either weekly counseling alone (control) for 8 weeks or 8 weeks of counseling along with 6 weeks of nicotine nasal spray. Self-reported smoking abstinence was verified by both expired-air carbon monoxide and salivary cotinine. RESULTS. There was no difference in cessation rates, the numbers of cigarettes smoked per day, or cotinine levels at 12 weeks. Fifty-seven percent of participants stopped using their spray after only 1 week. The most commonly reported adverse effect was nasal irritation and burning (34.8%) followed by complaints about the taste and smell (13%). CONCLUSIONS. The unpleasant adverse effects, poor adherence, and consequent lack of efficacy observed in our pilot study do not support the use of nicotine nasal spray as an adjunct to counseling for adolescent smokers who wish to quit.

Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products

HIGHLIGHTSElectronic cigarettes are often promoted as a safer alternative to combusted cigarettes.Human and animal research supports that nicotine contributes to the adverse effects of gestational tobacco exposure on fetal development.Nicotine exposure during adolescence is associated with cognitive deficits.Measures to protect pregnant women and adolescents from nicotine exposure are warranted. ABSTRACT While the health risks associated with adult cigarette smoking have been well described, effects of nicotine exposure during periods of developmental vulnerability are often overlooked. Using MEDLINE and PubMed literature searches, books, reports and expert opinion, a transdisciplinary group of scientists reviewed human and animal research on the health effects of exposure to nicotine during pregnancy and adolescence. A synthesis of this research supports that nicotine contributes critically to adverse effects of gestational tobacco exposure, including reduced pulmonary function, auditory processing defects, impaired infant cardiorespiratory function, and may contribute to cognitive and behavioral deficits in later life. Nicotine exposure during adolescence is associated with deficits in working memory, attention, and auditory processing, as well as increased impulsivity and anxiety. Finally, recent animal studies suggest that nicotine has a priming effect that increases addiction liability for other drugs. The evidence that nicotine adversely affects fetal and adolescent development is sufficient to warrant public health measures to protect pregnant women, children, and adolescents from nicotine exposure.

Adolescents Discriminate between Types of Smokers and Related Risks Evidence from Nonsmokers

Many studies concerning cigarette smoking and smoking-related outcomes among adolescents use categories such as “casual” or “regular” smoker to define different types of smokers. It is not clear whether adolescents themselves differentiate between different types of smokers. The present study sought to examine whether and how adolescents discriminate between categories of smokers and how these discriminations engender different perceptions of risk attributable to smoking. Five hundred and fifty ninth graders (mean age 14) who reported never smoking tobacco completed a self-administered survey concerning smoking attitudes and beliefs. Adolescents discriminated significantly between nonsmokers, casual smokers, smokers, and addicted smokers, based on both frequency of smoking and the number of cigarettes smoked. Addicted smokers were perceived as having the greatest chance of experiencing negative outcomes, followed by the smoker, the casual smoker, and last, the nonsmoker. Finally, adolescents ascribed a far greater chance of quitting smoking to casual smokers than they did to either regular or addicted smokers. Understanding how adolescents define and discriminate between types of smokers has important implications for smoking-related interventions, especially concerning how we communicate about risks of smoking.

Characteristics of Adolescent Intermittent and Daily Smokers

INTRODUCTION Intermittent smoking is common among adolescent smokers, but little is known about adolescent intermittent smokers (ITS). This study describes a cohort of adolescent ITS and compares them to adolescent daily smokers (DS) for the purpose of providing a more detailed characterization of adolescent ITS, specifically patterns of smoking, level of self-reported addiction, and experience with cessation METHODS Participants were 124 ITS and 55 DS. ITS were defined as smoking at least monthly but <30 days per month; and DS as smoking daily. Participants completed demographic, smoking and addiction surveys including the HONC and mFTQ. RESULTS ITS started smoking at an older age, smoked fewer cigarettes per day and scored significantly lower on addiction scales, but had similar difficulty to DS in quitting smoking with similar numbers of reported quit attempts. These differences remained after adjusting for years of smoking. ITS were more likely to smoke in social situations, while DS were more likely to smoke when angry. Both groups were equally likely to report smoking when drinking alcohol. CONCLUSIONS We documented significant differences in smoking related behaviors between adolescent ITS and DS. Importantly, we also found that, despite low level infrequent smoking, ITS reported difficulty in quitting smoking. Given the risks from light and intermittent smoking, it is essential that we develop a greater understanding of adolescent ITS, including their difficulty in quitting and the contextual factors influencing their smoking, so that we may develop new targeted interventions.

Frequent marijuana use is associated with greater nicotine addiction in adolescent smokers.

BACKGROUND Marijuana and tobacco are the substances used most commonly by adolescents and co-occurring use is common. Use of one substance may potentiate the addictive properties of the other. The current study examined the severity of nicotine addiction among teen smokers as a function of co-occurring marijuana use. METHODS Participants were 165 adolescents (13-17 years old) who reported smoking at least 1 cigarette per day (CPD) in the past 30 days. General linear models examined the association of marijuana use with multiple measures of nicotine addiction including the Modified Fagerström Tolerance Questionnaire (mFTQ), Hooked on Nicotine Checklist (HONC), ICD-10, and the Nicotine Dependence Syndrome Scale (NDSS). RESULTS The adolescent sample (mean age=16.1 years, SD=0.95) averaged 3.0 CPD (SD=3.0) for 1.98 years (SD=1.5). Most (79.5%) also smoked marijuana in the past 30 days. In models controlling for age, daily smoking status, and years of tobacco smoking, frequency of marijuana use accounted for 25-44% of the variance for all four measures of adolescent nicotine dependence. CONCLUSIONS Marijuana use was associated with greater reported nicotine addiction among adolescent smokers. The findings suggest a role of marijuana in potentiating nicotine addiction and underscore the need for treatments that address both smoked substances.

Adolescent Exposure to Toxic Volatile Organic Chemicals From E-Cigarettes.

Given the urgent need to understand the safety of e-cigarettes in adolescents, we sought to identify exposure to toxicants associated with e-cigarette use among adolescents. BACKGROUND: There is an urgent need to understand the safety of e-cigarettes with adolescents. We sought to identify the presence of chemical toxicants associated with e-cigarette use among adolescents. METHODS: Adolescent e-cigarette users (≥1 use within the past 30 days, ≥10 lifetime e-cigarette use episodes) were divided into e-cigarette–only users (no cigarettes in the past 30 days, urine 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol [NNAL] level <1 pg/mL of creatinine; n = 67), dual users (use of cigarettes in the past 30 days in addition to e-cigarettes, NNAL level >30 pg/mL; n = 16), and never-using controls (N = 20). Saliva was collected within 24 hours of the last e-cigarette use for analysis of cotinine and urine for analysis of NNAL and levels of 8 volatile organic chemical compounds. Bivariate analyses compared e-cigarette–only users with dual users, and regression analyses compared e-cigarette–only users with dual users and controls on levels of toxicants. RESULTS: The participants were 16.4 years old on average. Urine excretion of metabolites of benzene, ethylene oxide, acrylonitrile, acrolein, and acrylamide was significantly higher in dual users versus e-cigarette–only users (all P < .05). Excretion of metabolites of acrylonitrile, acrolein, propylene oxide, acrylamide, and crotonaldehyde were significantly higher in e-cigarette–only users compared with controls (all P < .05). CONCLUSIONS: Although e-cigarette vapor may be less hazardous than tobacco smoke, our findings can be used to challenge the idea that e-cigarette vapor is safe, because many of the volatile organic compounds we identified are carcinogenic. Messaging to teenagers should include warnings about the potential risk from toxic exposure to carcinogenic compounds generated by these products.

Scanning the brain for answers about effectiveness of graphic warning labels

We know that smokers who perceive greater risks to their health from smoking are more likely to quit.1 Thus, while ‘traditional’ cigarette pack imagery helps to reinforce cigarette advertising and promote purchasing behaviour,2 ,3 graphic warning labels (GWLs) may serve as a form of ‘reverse’ advertising—increasing smokers’ knowledge about the risks associated with smoking and promoting behavioural change by preventing smoking initiation and fostering cessation.4–6 In fact, as a smoking cessation and prevention intervention, GWLs are particularly valuable since they are located directly on the product and delivered at the point of use. Moreover, if smoking is associated with a lapse of judgment and temporary disregarding of health consequences, messaging by highlighting the risk of smoking coincident with use may be most beneficial.7 ,8 While there remains some controversy …