Emily L.R. Harrison

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.

Acute Disinhibiting Effects of Alcohol as a Factor in Risky Driving Behavior

Automobile crash reports show that up to 40% of fatal crashes in the United States involve alcohol and that younger drivers are over-represented. Alcohol use among young drivers is associated with impulsive and risky driving behaviors, such as speeding, which could contribute to their over-representation in alcohol-related crash statistics. Recent laboratory studies show that alcohol increases impulsive behaviors by impairing the drinkers ability to inhibit inappropriate actions and that this effect can be exacerbated in conflict situations where the expression and inhibition of behavior are equally motivating. The present study tested the hypothesis that this response conflict might also intensify the disruptive effects of alcohol on driving performance. Fourteen subjects performed a simulated driving and a cued go/no-go task that measured their inhibitory control. Conflict was motivated in these tasks by providing equal monetary incentives for slow, careful behavior (e.g., slow driving, inhibiting impulses) and for quick, abrupt behavior (fast driving, disinhibition). Subjects were tested under two alcohol doses (0.65 g/kg and a placebo) that were administered twice: when conflict was present and when conflict was absent. Alcohol interacted with conflict to impair inhibitory control and to increase risky and impaired driving behavior on the drive task. Also, individuals whose inhibitory control was most impaired by alcohol displayed the poorest driving performance under the drug. The study demonstrates potentially serious disruptions to driving performance as a function of alcohol intoxication and response conflict, and points to inhibitory control as an important underlying mechanism.

Alcohol and distraction interact to impair driving performance

BACKGROUND Recognition of the risks associated with alcohol intoxication and driver distraction has led to a wealth of simulated driving research aimed at studying the adverse effects of each of these factors. Research on driving has moved beyond the individual, separate examination of these factors to the examination of potential interactions between alcohol intoxication and driver distraction. In many driving situations, distractions are commonplace and might have little or no disruptive influence on primary driving functions. Yet, such distractions might become disruptive to a driver who is intoxicated. METHODS The present study examined the interactive impairing effects of alcohol intoxication and driver distraction on simulated driving performance in 40 young adult drivers using a divided attention task as a distracter activity. The interactive influence of alcohol and distraction was tested by having drivers perform the driving task under four different conditions: 0.65 g/kg alcohol; 0.65 g/kg alcohol+divided attention; placebo; and placebo+divided attention. RESULTS As hypothesized, divided attention had no impairing effect on driving performance in sober drivers. However, under alcohol, divided attention exacerbated the impairing effects of alcohol on driving precision. CONCLUSIONS Alcohol and distraction continue to be appropriate targets for research into ways to reduce the rates of driving-related fatalities and injuries. Greater consideration of how alcohol and distraction interact to impair aspects of driving performance can further efforts to create prevention and intervention measures to protect drivers, particularly young adults.

Experimenting and daily smokers: Episodic patterns of alcohol and cigarette use

Alcohol use may facilitate the development of nicotine dependence. Alcohol is often paired with cigarette smoking, particularly in those experimenting with smoking. However, little research has examined episodic patterns of alcohol and cigarette use. This study examined patterns of alcohol and cigarette use in a college-aged sample (n=237) designated as experimenters or smokers based on their smoking history. Participants reported their consumption of drinks and cigarettes by hour, for each hour, of a typical drinking and smoking episode. Self-reported pleasure and desire associated with smoking generally and while drinking was assessed. No group difference was observed in total number of drinks. However, experimenters delayed smoking until more drinks were consumed, suggesting they smoked after reaching binge levels of alcohol. By contrast, smokers smoked after fewer drinks. Both groups reported increased smoking while drinking and increased pleasure and desire when smoking while drinking. The increase was greater in experimenters. Concurrent alcohol and cigarette use may facilitate the development of tobacco dependence and interventions interrupting their pairing might impede the transition from experimenter to smoker.

Driver training conditions affect sensitivity to the impairing effects of alcohol on a simulated driving test (corrected)

Research shows that prior behavioral training in a challenging environment reduces alcoholinduced impairment on simple psychomotor tasks. However, no studies have examined if this relationship generalizes to driving performance. The present study examined simulated driving performance and tested the hypothesis that a challenging training history would protect against the impairing effects of alcohol on driving performance. The challenging training history involved driving in a visually-impoverished environment. Thirty adults were randomly assigned to one of three groups. Two groups were tested under alcohol (0.65 g/kg) after prior experience performing the task under either a visually-impoverished environment or a normal visual environment. The remaining group served as a control and was trained and tested under the visually-impoverished condition environment. Results showed that individuals trained in the impoverished environment displayed sober levels of performance when their performance was subsequently tested under alcohol. By contrast, volunteers trained in a normal environment showed impairment under alcohol. The findings suggest that differences in driving training history can affect a driver’s sensitivity to the impairing effects of alcohol.Research shows that prior behavioral training in a challenging environment reduces alcohol-induced impairment on simple psychomotor tasks. However, no studies have examined if this relationship generalizes to driving performance. The present study examined simulated driving performance and tested the hypothesis that a challenging training history would protect against the impairing effects of alcohol on driving performance. The challenging training history involved driving in a visually-impoverished environment. Thirty adults were randomly assigned to one of three groups. Two groups were tested under alcohol (0.65 g/kg) after prior experience performing the task under either a visually-impoverished environment or a normal visual environment. The remaining group served as a control and was trained and tested under the visually-impoverished condition environment. Results showed that individuals trained in the impoverished environment displayed sober levels of performance when their performance was subsequently tested under alcohol. By contrast, volunteers trained in a normal environment showed impairment under alcohol. The findings suggest that differences in driving training history can affect a drivers sensitivity to the impairing effects of alcohol.

Non-daily smoking predicts hazardous drinking and alcohol use disorders in young adults in a longitudinal U.S. sample

BACKGROUND It is known that daily smoking is associated with the development of alcohol use disorders. However, non-daily smoking is prevalent in young adults and is associated with increased rates of problematic alcohol use in cross-sectional data. It is unknown whether non-daily smoking is predictive of hazardous drinking and alcohol use disorders using longitudinal data. The primary aim of the present investigation was to explore the temporal relationship between non-daily smoking and drinking in young adults, and secondarily, whether college status modified this relationship. METHODS Using Waves 1 (2001-2002) and 2 (2004-2005) of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC), we examined the predictive relationship of smoking status at Wave 1 and change in college status between Waves on alcohol drinking, hazardous drinking, and alcohol abuse and dependence disorders at Wave 2. The sample was restricted to individuals aged 18-25 years at Wave 1. FINDINGS Daily and non-daily smokers at Wave 1, compared to nonsmokers, were at a greater risk for hazardous drinking and alcohol use disorders at Wave 2, after controlling for Wave 1 drinking. College status did not modify smoking and drinking interactions. CONCLUSIONS The findings indicate non-daily smoking is predictive of increased, problematic alcohol use among young adults longitudinally and they support increasing evidence that non-daily smokers represent an important population. Future research should be conducted to continue developing targeted interventions. Early treatments for smoking behavior might have a beneficial effect on reducing the development of problematic patterns of alcohol use and alcohol use disorders.

Effects of the nicotinic receptor antagonist mecamylamine on ad-lib smoking behavior, topography, and nicotine levels in smokers with and without schizophrenia: a preliminary study.

Individuals with schizophrenia have higher plasma nicotine levels in comparison to non-psychiatric smokers, even when differences in smoking are equated. This difference may be related to how intensely cigarettes are smoked but this has not been well studied. Mecamylamine (MEC), a non-competitive nicotinic acetylcholine receptor (nAChR) antagonist, which has been shown to increase ad-lib smoking and to affect smoking topography, was used in the current study as a pharmacological probe to increase our understanding of smoking behavior, smoking topography, and resulting nicotine levels in smokers with schizophrenia. This preliminary study used a within-subject, placebo-controlled design in smokers with schizophrenia (n=6) and healthy control smokers (n=8) to examine the effects of MEC (10mg/day) on ad-lib smoking behavior, topography, nicotine levels, and tobacco craving across two smoking deprivation conditions (no deprivation and 12-h deprivation). MEC, compared to placebo, increased the number of cigarettes smoked and plasma nicotine levels. MEC increased smoking intensity and resulted in greater plasma nicotine levels in smokers with schizophrenia compared to controls, although these results were not consistent across deprivation conditions. MEC also increased tobacco craving in smokers with schizophrenia but not in control smokers. Our results suggest that antagonism of high-affinity nAChRs in smokers with schizophrenia may prompt compensatory smoking, increasing the intensity of smoking and nicotine exposure without alleviating craving. Further work is needed to assess whether nicotine levels are directly mediated by how intensely the cigarettes are smoked, and to confirm whether this effect is more pronounced in smokers with schizophrenia.

Longitudinal Associations Between Smoking Cessation Medications and Alcohol Consumption Among Smokers in the International Tobacco Control Four Country Survey

BACKGROUND Available evidence suggests that quitting smoking does not alter alcohol consumption. However, smoking cessation medications may have a direct impact on alcohol consumption independent of any effects on smoking cessation. Using an international longitudinal epidemiological sample of smokers, we evaluated whether smoking cessation medications altered alcohol consumption independent of quitting smoking. METHODS Longitudinal data were analyzed from the International Tobacco Control Four Country (ITC-4) Survey between 2007 and 2008, a telephone survey of nationally representative samples of smokers from the United Kingdom, Australia, Canada, and the United States (n = 4,995). Quantity and frequency of alcohol consumption, use of smoking cessation medications (varenicline, nicotine replacement [NRT], and no medications), and smoking behavior were assessed across 2 yearly waves. Controlling for baseline drinking and changes in smoking status, we evaluated whether smoking cessation medications were associated with reduced alcohol consumption. RESULTS Varenicline was associated with a reduced likelihood of any drinking compared with nicotine replacement (OR = 0.56; 95% CI = 0.34 to 0.94), and consuming alcohol once a month or more compared to nicotine replacement (OR = 0.43; 95% CI = 0.27 to 0.69) or no medication (OR = 0.63; 95% CI = 0.41 to 0.99). Nicotine replacement was associated with an increased likelihood of consuming alcohol once a month or more compared to no medication (OR = 1.14; 95% CI = 1.03 to 1.25). Smoking cessation medications were not associated with more frequent drinking (once a week or more) or typical quantity consumed per episode. Medication effects on drinking frequency were independent of smoking cessation. CONCLUSIONS This epidemiological investigation demonstrated that varenicline was associated with a reduced frequency of alcohol consumption. Continued work should clarify under what conditions nicotine replacement therapies may increase or decrease patterns of alcohol consumption.