Suchitra Krishnan-Sarin

Time to First Cigarette in the Morning as an Index of Ability to Quit Smoking: Implications for Nicotine Dependence

An inability to maintain abstinence is a key indicator of tobacco dependence. Unfortunately, little evidence exists regarding the ability of the major tobacco dependence measures to predict smoking cessation outcome. This paper used data from four placebo-controlled smoking cessation trials and one international epidemiological study to determine relations between cessation success and the Fagerström Test for Nicotine Dependence (FTND), the Heaviness of Smoking Index, the Nicotine Dependence Syndrome Scale, and the Wisconsin Inventory of Smoking Dependence Motives. Results showed that much of the predictive validity of the FTND could be attributed to its first item, time to first cigarette in the morning, and this item had greater validity than any other single measure. Thus the time-to-first-cigarette item appears to tap a pattern of heavy, uninterrupted, and automatic smoking and may be a good single-item measure of nicotine dependence.

Varenicline Reduces Alcohol Self-Administration in Heavy-Drinking Smokers

BACKGROUND Alcohol and tobacco dependence are highly comorbid disorders, with preclinical evidence suggesting a role for nicotinic acetylcholine receptors (nAChRs) in alcohol consumption. Varenicline, a partial nicotinic agonist with high affinity for the alpha4beta2 nAChR receptor, reduced ethanol intake in rodents. We aimed to test whether varenicline would reduce alcohol consumption and alcohol craving in humans. METHODS This double-blind, placebo-controlled investigation examined the effect of varenicline (2 mg/day vs. placebo) on alcohol self-administration using an established laboratory paradigm in non-alcohol-dependent heavy drinkers (n = 20) who were daily smokers. Following 7 days of medication pretreatment, participants were first administered a priming dose of alcohol (.3 g/kg) and subjective, and physiologic responses were assessed. A 2-hour alcohol self-administration period followed during which participants could choose to consume up to 8 additional drinks (each .15 g/kg). RESULTS Varenicline (.5 +/- SE = .40) significantly reduced the number of drinks consumed compared to placebo (2.60 +/- SE = .93) and increased the likelihood of abstaining from any drinking during the self-administration period. Following the priming drink, varenicline attenuated alcohol craving and reduced subjective reinforcing alcohol effects (high, like, rush, feel good, intoxicated). Adverse events associated with varenicline were minimal and, when combined with alcohol, produced no significant effects on physiologic reactivity, mood, or nausea. CONCLUSIONS This preliminary investigation demonstrated that varenicline significantly reduced alcohol self-administration and was well tolerated, alone and in combination with alcohol in heavy-drinking smokers. Varenicline should be investigated as a potential treatment for alcohol use disorders.

Video-Gaming Among High School Students: Health Correlates, Gender Differences, and Problematic Gaming

OBJECTIVE: Video game playing may negatively impact youth. However, the existing literature on gaming is inconsistent and often has focused on aggression rather than the health correlates of gaming and the prevalence and correlates of problematic gaming. METHODS: We anonymously surveyed 4028 adolescents about gaming and reported problems with gaming and other health behaviors. A total of 51.2% of the sample reported gaming (76.3% of boys and 29.2% of girls). RESULTS: There were no negative health correlates of gaming in boys and lower odds of smoking regularly; however, girls who reported gaming were less likely to report depression and more likely to report getting into serious fights and carrying a weapon to school. Among gamers, 4.9% reported problematic gaming, defined as reporting trying to cut back, experiencing an irresistible urge to play, and experiencing a growing tension that could only be relieved by playing. Boys were more likely to report these problems (5.8%) than girls (3.0%). Correlates of problematic gaming included regular cigarette smoking, drug use, depression, and serious fights. Results suggest that gaming is largely normative in boys and not associated with many health factors. In girls, however, gaming seems to be associated with more externalizing behaviors and fewer internalizing symptoms. CONCLUSIONS: The prevalence of problematic gaming is low but not insignificant, and problematic gaming may be contained within a larger spectrum of externalizing behaviors. More research is needed to define safe levels of gaming, refine the definition of problematic gaming, and evaluate effective prevention and intervention strategies.

Human Tobacco Smokers in Early Abstinence Have Higher Levels of β2* Nicotinic Acetylcholine Receptors than Nonsmokers

Nicotine, the addictive chemical in tobacco smoke, initiates its actions in brain through nicotinic acetylcholine receptors (nAChRs). In particular, nAChRs containing β2-subunits (β2*-nAChRs) the most prevalent subtype, mediate the reinforcing properties of nicotine. We hypothesized that abnormal numbers of β2*-nAChRs during early abstinence contribute to the perpetuation of addiction to tobacco smoking. Using molecular imaging, specifically single-photon emission computed tomography with the nAChR agonist radiotracer [123I]5-IA-85380 ([123I]5-IA), we imaged β2*-nAChR availability in human smokers. First, using nonhuman primates treated chronically with nicotine, we estimated the time interval necessary for smokers to abstain from smoking so that residual nicotine would not interfere with [123I]5-IA binding to the β2*-nAChR as ∼7 d. Thus, we imaged human smokers at 6.8 ± 1.9 d (mean ± SD) of abstinence. Abstinence was confirmed by daily assessments of urinary cotinine and expired carbon monoxide levels. In smokers, [123I]5-IA uptake was significantly higher throughout the cerebral cortex (26–36%) and in the striatum (27%) than in nonsmokers, suggesting higher β2*-nAChR in recently abstinent smokers. β2*-nAChR availability in recently abstinent smokers correlated with the days since last cigarette and the urge to smoke to relieve withdrawal symptoms but not the severity of nicotine dependence, severity of nicotine withdrawal, or the desire to smoke. Higher brain β2*-nAChR during early abstinence indicates that, when smokers quit smoking, they do so in the face of a significant increase in the receptors normally activated by nicotine. Greater β2*-nAChR availability during early abstinence may impact the ability of smokers to maintain abstinence.

Suppression of the HPA Axis Stress-Response: Implications for Relapse

This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim, Germany, in October 2004. This symposium explored the potential role of hypothalamic-pituitary-adrenal (HPA) axis dysregulation upon relapse. HPA axis stimulation induces the release of the glucocorticoid cortisol, a compound with profound effects upon behavior and emotion. Altered stress-responses of the HPA axis in abstinent alcohol-dependent subjects, therefore, may influence their affective and behavioral regulation, thus impacting their potential for relapse. Bryon Adinoff began the symposium with a review of HPA axis dysfunction in alcohol-dependent subjects, including recent studies from his lab demonstrating an attenuated glucocorticoid response to both endogenous and exogenous stimulation in one-month abstinent men. Klaus Junghanns presented his work demonstrating that a blunted ACTH or cortisol response to subjective stressors (social stressor or alcohol exposure) is predictive of a return to early drinking. The final two presenters examined the interaction between naltrexone and HPA responsiveness in alcohol-dependent or at-risk subjects, as naltrexone induces an increase in ACTH and cortisol. Falk Kiefer discussed the relationship between basal HPA axis responsivity and clinical outcome following treatment with naltrexone or acamprosate. Plasma ACTH significantly decreased over the course of the study in the placebo group, but not the medication groups [corrected] Lower basal concentrations of ACTH and cortisol were associated with quicker relapse in the placebo group only. Suchitra Krishnan-Sarin described her preliminary work, in which family-history positive (FH+) and family history negative (FH-) subjects were administered naltrexone, followed by an assessment of alcohol-induced craving. The cortisol response to alcohol was significantly and inversely related to craving in the FH+, but not the FH-, subjects. Alterations in HPA axis responsivity may therefore have a negative impact upon clinical outcome in alcohol-dependent subjects, and disinhibition of the axis with medication may have therapeutic potential.

β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking

CONTEXT Available levels of nicotinic acetylcholine receptors containing the beta(2) subunit (beta(2)*-nAChR) are higher in recently abstinent tobacco smokers compared with participants who never smoked. Variations in beta(2)*-nAChR availability during the course of abstinence may be related to the urge to smoke, the extent of nicotine withdrawal, and successful abstinence. OBJECTIVE To examine changes in beta(2)*-nAChR availability during acute and prolonged abstinence from tobacco smoking and to determine how changes in beta(2)*-nAChR availability were related to clinical features of tobacco smoking. DESIGN Tobacco smokers participated in up to 4 iodide 123-labeled 5-iodo-A-85380 ([(123)I]5-IA) single-photon emission computed tomography (SPECT) scans during abstinence at 1 day (n = 7) and 1 (n = 17), 2 (n = 7), 4 (n = 11), and 6 to 12 (n = 6) weeks. Age-matched nonsmokers participated in a single [(123)I]5-IA SPECT scan. All participants completed 1 magnetic resonance imaging study. SETTING Academic imaging center. PARTICIPANTS Tobacco smokers (n = 19) and an age-matched nonsmoker comparison group (n = 20). Main Outcome Measure The [(123)I]5-IA SPECT images were converted to distribution volume and were analyzed using regions of interest. RESULTS Compared with nonsmokers, beta(2)*-nAChR availability in the striatum, cortex, and cerebellum of smokers was not different at 1 day of abstinence, was significantly higher at 1 week of abstinence, and was not different at 4 or at 6 to 12 weeks of abstinence. In smokers, beta(2)*-nAChR availability was significantly lower in the cortex and cerebellum at 6 to 12 weeks compared with 1 week of abstinence. In addition, cerebellar beta(2)*-nAChR availability at 4 weeks of abstinence was positively correlated with craving on the day of the SPECT scan. CONCLUSIONS These data suggest that higher beta(2)*-nAChR availability persists up to 1 month of abstinence and normalizes to nonsmoker levels by 6 to 12 weeks of abstinence from tobacco smoking. These marked and persistent changes in beta(2)*-nAChR availability may contribute to difficulties with tobacco cessation.

E-cigarette Use Among High School and Middle School Adolescents in Connecticut

INTRODUCTION There is limited evidence on electronic cigarette (e-cigarette) use among U.S. adolescents. METHODS Cross-sectional, anonymous surveys conducted in 4 high schools (HS; n = 3,614) and 2 middle schools (MS; n = 1,166) in Connecticut in November 2013 examined e-cigarette awareness, use patterns, susceptibility to future use, preferences, product components used (battery type, nicotine content, flavors), and sources of marketing and access. RESULTS High rates of awareness (MS: 84.3%; HS: 92.0%) and of lifetime (3.5% MS, 25.2 % HS) and current (1.5% MS, 12% HS) use of e-cigarettes was observed. Among those who had not tried e-cigarettes, 26.4% of MS and 31.7% of HS students reported being susceptible to future use. Males (OR = 1.70, p < .01), older students (OR = 1.39, p < .05), Caucasians (OR = 2.01, p < .001), ever cigarette smokers (OR = 13.04, p < .001), and current cigarette smokers (OR = 65.11, p < .001) were more likely to be lifetime e-cigarette users and to report greater future susceptibility (males: OR = 1.30; Caucasians: OR = 1.14; ever cigarette smokers; OR = 3.85; current cigarette smokers; OR = 9.81; ps < .01-.001). Among MS students who were lifetime e-cigarette users, 51.2% reported that e-cigarette was the first tobacco product they had tried. E-cigarettes that were rechargeable and had sweet flavors were most popular. Smokers preferred e-cigarettes to cigarettes. Current cigarette smokers were more likely to initiate with nicotine-containing e-cigarettes, and ever and never cigarette smokers to initiate with e-cigarettes without nicotine. Primary sources for e-cigarette advertisements were televisions and gas stations and, for acquiring e-cigarettes, were peers. CONCLUSIONS Longitudinal monitoring of e-cigarette use among adolescents and establishment of policies to limit access are imperatively needed.

Trends in use of electronic nicotine delivery systems by adolescents

Electronic nicotine delivery systems (ENDS) have been gaining in popularity. The few prevalence studies in adults have found that most ENDS users are current or former smokers. The objectives of this study were to estimate the prevalence of ENDS usage in adolescents, and examine the correlates of use. Self-administered written surveys assessing tobacco use behaviors were conducted in multiple waves as part of a larger intervention study in two large suburban high schools. The prevalence of past-30 day ENDS use increased from 0.9% in February 2010 to 2.3% in June 2011 (p=0.009). Current cigarette smokers had increased odds of past-30 day ENDS use in all study waves. When adjusted for school, grade, sex, race and smoking status, students in October 2010 (Adjusted OR 2.12; 95% confidence interval (CI): 1.12-4.02) and June 2011 (Adjusted OR 2.51; 95% CI: 1.17-4.71) had increased odds past-30 day ENDS use compared to February 2010. The prevalence of ENDS use doubled in this sample of high school students, and current cigarette smoking is the strongest predictor of current use. Continued monitoring of ENDS is needed to determine whether it increases the likelihood of cigarette smoking initiation and maintenance in youth.

Contingency management for smoking cessation in adolescent smokers.

This pilot study evaluated the use of contingency management (CM) procedures in combination with cognitive-behavioral therapy (CBT) for smoking cessation in adolescents. Twenty-eight treatment-seeking adolescent smokers participated in a 1-month, school-based smoking cessation program and were randomly assigned to receive either CM with weekly CBT or CBT alone. In the CM+CBT group, biochemical verification of abstinence was obtained twice daily during the first 2 weeks, followed by daily appointments during the 3rd week and once every other day during the 4th week. Participants were monetarily reinforced for abstinence on an escalating magnitude schedule with a reset contingency. At the end of 1 week and 1 month of treatment, abstinence verified using quantitative urine cotinine levels was higher in participants in the CM+CBT group (1 week: 76.7%; 1 month: 53.0%) when compared with the CBT-alone group (1 week: 7.2%; 4 weeks: 0%). These preliminary results provide a strong initial signal supporting the utility of CM techniques for smoking cessation in adolescents and demonstrate the feasibility of implementing such a program in a school setting.

High School Students’ Use of Electronic Cigarettes to Vaporize Cannabis

BACKGROUND AND OBJECTIVES: Electronic cigarette (e-cigarette) use is increasing rapidly among high school (HS) students. Of concern, e-cigarettes can be used to vaporize cannabis, although use rates among adolescents are unknown. We evaluated lifetime rates of using e-cigarettes to vaporize cannabis among all lifetime e-cigarette users (27.9%), all lifetime cannabis users (29.2%), and lifetime users of both e-cigarettes and cannabis (18.8%); common means of vaporizing cannabis including hash oil, wax infused with Δ-9-tetrahydrocannabinol (THC), and dried cannabis; and demographic predictors of using e-cigarettes to vaporize cannabis. METHODS: In the spring of 2014, 3847 Connecticut HS students completed an anonymous survey assessing e-cigarette and cannabis use. RESULTS: Vaporizing cannabis using e-cigarettes was common among lifetime e-cigarette users, lifetime cannabis users, and lifetime dual users (e-cigarette 18.0%, cannabis 18.4%, dual users 26.5%). Students reported using e-cigarettes to vaporize hash oil (e-cigarette 15.4%, cannabis 15.5%, dual users 22.9%) and wax infused with THC (e-cigarette 10.0%, cannabis 10.2%, dual users 14.8%) and using portable electronic vaporizers to vaporize dried cannabis leaves (e-cigarette 19.6%, lifetime cannabis 23.1%, lifetime dual users 29.1%). Binary logistic regression indicated that male students (odds ratio [OR] = 2.05), younger students (OR = 0.64), lifetime e-cigarette users (OR = 5.27), and lifetime cannabis users (OR = 40.89) were most likely to vaporize cannabis using e-cigarettes. Rates also differed by HS attended. CONCLUSIONS: Rates of vaporizing cannabis using e-cigarettes were high. These findings raise concerns about the lack of e-cigarette regulations and the potential use of e-cigarettes for purposes other than vaping nicotine.