Sherry A. McKee

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.

Stress decreases the ability to resist smoking and potentiates smoking intensity and reward

We have developed a novel human laboratory model to examine two primary aspects of stress-precipitated tobacco relapse: (1) Does stress reduce the ability to resist the first cigarette? (2) Once the first cigarette is initiated, does stress facilitate subsequent smoking? Using a within-subject design, daily smokers (n = 37) who were nicotine deprived overnight received a personalized imagery induction (stress or neutral) on two separate days, and then had the option of initiating a tobacco self-administration session or delaying initiation for up to 50 min in exchange for three levels of monetary reinforcement. Subsequently, the tobacco self-administration session entailed a 1-hour period in which subjects could choose to smoke using a smoking topography system. Following the stress induction, subjects were less able to resist smoking, smoked more intensely (increased puffs, shorter inter-puff interval, and greater peak puff velocity), and perceived greater satisfaction and reward from smoking. Stress significantly increased hypothalamus–pituitary–adrenal (HPA) axis reactivity, tobacco craving, negative emotion, and physiologic reactivity relative to the neutral condition. In addition, increased cortisol, ACTH, and tobacco craving were associated with reduced ability to resist smoking following stress. These findings have implications for understanding the impact of stress on smoking relapse and model development to assess smoking lapse behavior.

Nondaily smoking and alcohol use, hazardous drinking, and alcohol diagnoses among young adults: findings from the NESARC.

BACKGROUND Nondaily smoking and heavy alcohol use are prevalent behaviors among young adults, with nondaily smoking occurring primarily in the context of alcohol use. Although the relationship between drinking and daily smoking has been well characterized in young adults, few epidemiological investigations have investigated the association between nondaily smoking and drinking behavior. METHODS We examined Wave 1 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; Grant et al., 2003b; n = 43,093). Young adults (aged 18 to 25 years; n = 5,838) were stratified on current smoking behavior (daily, nondaily, and nonsmokers in the past 12 months) and differences in weekly quantity of alcohol use, frequency of alcohol use, frequency of binge drinking behavior, rates of NIAAA-defined hazardous drinking, and rates of DSM-IV alcohol diagnoses were investigated. College student status was examined. RESULTS Twenty-five percent were current smokers and 7% were smoking on a nondaily basis. Seventy-one percent were current drinkers, 39% reported binge drinking at least once a month, 41% met criteria for hazardous drinking, and 18% had alcohol use disorders. Across all measures of alcohol use, there was a significant effect of smoking status, with daily smokers having greater alcohol use patterns, compared with nondaily smokers, with nonsmokers consuming the least. Nondaily smokers were more likely to report any binge drinking in the past 12 months. However, daily smokers were more likely to report daily binge drinking. With regard to hazardous drinking and alcohol use disorders, nondaily smoking conferred the greatest risk, followed by daily smoking with nonsmoking as the reference group. Multinomial logistic regression demonstrated that the odds of being a hazardous drinker were 16 times greater (95% CI 9.46-26.48) in a nondaily smoker compared with a nonsmoker, whereas the odds for a daily smoker were increased by 7-fold (95% CI 5.54-9.36). A similar pattern of results was demonstrated for DSM-IV alcohol diagnoses. No differences across college student status were observed. CONCLUSIONS The increased risk of hazardous drinking and alcohol use disorders conferred by nondaily smoking supports the findings that nondaily smoking and drinking are highly concomitant behaviors. Results such as these suggest that interventions disengaging alcohol and cigarette use patterns (e.g., smoking bans in alcohol venues) might serve to limit the occurrence of hazardous drinking among young adults at heightened risk for this behavior.

Smoking and mental illness in the US population

Objectives Those with any psychiatric diagnosis have substantially greater rates of smoking and are less likely to quit smoking than those with no diagnosis. Using nationally representative data, we sought to provide estimates of smoking and longitudinal cessation rates by specific psychiatric diagnoses and mental health service use. Design and participants Data were analysed from a two-wave cohort survey of a US nationally representative sample (non-institutionalised adults): the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; 2001–2002, n=43 093; 2004–2005, n=34 653). Main outcome measures We examined smoking rates (lifetime, past year and past year heavy) and cross-sectional quit rates among those with any lifetime or past year psychiatric diagnosis (DSM-IV). Importantly, we examined longitudinal quit rates and conducted analyses by gender and age categories. Results Those with any current psychiatric diagnosis had 3.23 (95% CI 3.11 to 3.35) times greater odds of currently smoking than those with no diagnosis, and were 25% less likely to have quit by follow-up (95% CI 20% to 30%). Prevalence varied by specific diagnoses (32.4% to 66.7%) as did cessation rates (10.3% to 17.9%). Comorbid disorders were associated with higher proportions of heavy smoking. Treatment use was associated with greater prevalence of smoking and lower likelihood of cessation. Conclusions Those with psychiatric diagnoses remained much more likely to smoke and less likely to quit, with rates varying by specific diagnosis. Our findings highlight the need to improve our ability to address smoking and psychiatric comorbidity both within and outside of healthcare settings. Such advancements will be vital to reducing mental illness-related disparities in smoking and continuing to decrease tobacco use globally.

Survey of subjective effects of smoking while drinking among college students

Prevalence of tobacco use among the college-aged population is approximately 30%; a significant percentage of students initiate use or transition to regular use during their college years. This study examined the relationship between drinking and smoking rates, subjective reactivity of concurrent effects of alcohol and tobacco use, and expectations of smoking while under the influence of alcohol in first-year college students. The sample consisted of ever-smokers (n=217), who had smoked at least once in the past year, with a mean age of 19.67 years. Weekly alcohol consumption was 18.53 standard drinks per week, with 2.95 drinking episodes per week. Of the sample, 54% were classified as smokers (smoked more than 100 cigarettes in their lifetime) and 46% were classified as experimenters (smoked less than 100 cigarettes in their lifetime). Results demonstrated that 74% of all smoking episodes occurred while under the influence of alcohol. Smokers had higher levels of alcohol use and reported greater subjective effects from the simultaneous use of alcohol and tobacco. Smokers also were more likely to generate expectancies acknowledging an increase in smoking while drinking and for smoking to enhance reinforcement from alcohol. Experimenters were most likely to report positive reinforcement from smoking while under the influence of alcohol. Overall, smokers experienced stronger subjective effects of concurrent alcohol and tobacco use; however, results suggest that smoking while under the influence of alcohol is a positive experience even for relatively inexperienced smokers.

Nicotine withdrawal in U.S. smokers with current mood, anxiety, alcohol use, and substance use disorders

BACKGROUND The current study examined tobacco withdrawal symptoms and withdrawal-related discomfort and relapse in smokers with and without current mood disorders, anxiety disorders, alcohol use disorders (AUD), and substance use disorders (SUD). METHODS The subsample of current daily smokers (n=8213) from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, Wave 1, 2001-2002, full sample n=43,093) were included in these analyses. Cross-sectional data compared smokers with and without current psychiatric disorders on withdrawal symptoms using logistic regression models. The effects of having a co-morbid psychiatric disorder and AUD/SUD compared to a psychiatric disorder alone on nicotine withdrawal were also examined. RESULTS Participants with a current mood disorder, anxiety disorder, AUD, or SUD were more likely to report withdrawal symptoms and reported more withdrawal symptoms than those without current disorders. Having a current mood disorder, anxiety disorder, or SUD was also associated with increased likelihood of withdrawal-related discomfort and relapse. There were no significant interactions between psychiatric disorders and AUDs/SUDs on withdrawal symptoms or behavior. CONCLUSIONS Participants with a current Axis I disorder were more likely to experience tobacco withdrawal symptoms and withdrawal-related discomfort and relapse. Having a co-morbid psychiatric disorder and AUD/SUD did not synergistically increase the experience of withdrawal-related symptoms or relapse. It is important to identify Axis I disorders in smokers and provide these smokers with more intensive and/or longer treatments to help them cope with withdrawal symptoms and prevent relapse.

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.

Message framing for smoking cessation: the interaction of risk perceptions and gender.

Because quitting smoking is clearly linked to preventing health problems such as lung cancer, research on health message framing based on prospect theory suggests that gain-framed messages (i.e., emphasizing the benefits of quitting smoking) would be more persuasive in promoting cessation than loss-framed messages (i.e., emphasizing the costs of continuing to smoke). However, because women tend to anticipate greater perceived risk from quitting smoking than men, this may affect how receptive they are to specific message framing interventions. Data from 249 participants (129 females, 120 males) in a clinical trial of message framing for smoking cessation with bupropion were used to examine how gender differences in perceptions of the risks associated with quitting influence the effects of framed interventions using number of days to smoking relapse as the criterion. Perceived risk of quitting scores were dichotomized using a median split for the entire sample. Women reported a higher perceived risk of cessation than men. Participants who anticipated high risks associated with quitting smoking reported fewer days to relapse. Further, females in the gain-framed condition who reported low perceived risks of cessation had a greater number of days to relapse, as opposed to females in the loss-framed condition. These findings suggest that message framing interventions for smoking cessation should consider the influence of gender and risk perceptions associated with quitting on the effectiveness of framed interventions.

Mood-Induced Increases in Alcohol Expectancy Strength in Internally Motivated Drinkers

This study investigated whether exposure to musical mood induction procedures (MMIP) differentially increases the strength of specific alcohol expectancies for coping motivated (CM) versus enhancement motivated (EM) drinkers. Participants were 86 undergraduates who had elevated scores on either the CM or EM subscale of the Drinking Motives Questionnaire (M. L. Cooper, 1994). Participants were randomly assigned to either a positive or negative mood condition. The Alcohol Craving Questionnaire (E. G. Singleton, S. T. Tiffany, & J. E. Henningfield, 1994) was administered at baseline and after MMIP to assess phasic changes in alcohol expectancy strength. Consistent with hypotheses, only CM drinkers in the negative mood condition reported increased relief expectancies, and only EM drinkers in the positive mood condition reported increased reward expectancies. Theoretical and clinical implications are discussed.

Risk factors for treatment failure in smokers: Relationship to alcohol use and to lifetime history of an alcohol use disorder

Little is known about the impact of alcohol involvement on smoking cessation relapse or possible mechanisms for these associations. We addressed these issues using data from a randomized clinical trial of two types of framed messages (gain vs. loss) in conjunction with open label sustained-release (SR) bupropion (Toll et al., 2007) (N = 249). Participants were categorized according to whether or not they were diagnosed with a lifetime alcohol use disorder (AUD; i.e., current or past alcohol abuse or past alcohol dependence) and according to three levels of alcohol use: abstinence, moderate, or hazardous use. Alcohol use categories were established for drinking at baseline, during the 6-week treatment period and through 12 weeks post-quit. There were few significant differences by baseline alcohol use level or AUD history for a series of predictors of smoking cessation failure (e.g., depressive symptoms). During treatment and follow-up, the probability of any smoking on heavy drinking days was significantly higher than the probability of smoking on moderate drinking or abstinent days. AUD history did not predict smoking cessation relapse in any analysis, nor were any alcohol usexAUD history interactions significant. Moderate alcohol users and, to a lesser extent, abstainers from alcohol at baseline were less likely than hazardous drinkers to have relapsed at 12 weeks post-quit. Based on these findings, it appears that risk of any smoking and of relapse was associated primarily with heavy drinking days and a hazardous pattern of use respectively, rather than with moderate drinking.