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.

A preliminary study on the effect of combined nicotine replacement therapy on alcohol responses and alcohol self-administration.

BACKGROUND AND OBJECTIVES: Limiting alcohol consumption may help prevent alcohol-mediated smoking relapse in heavy drinking smokers. This pilot study examined whether combining a nicotine patch with nicotine nasal spray has stronger attenuating effects on alcohol response and consumption than a nicotine patch alone. METHODS: Twenty-two non-alcohol dependent heavy drinking smokers completed the double-blind cross-over, placebo-controlled study (21 mg nicotine patch + nicotine or placebo nasal spray). Six hours after 21 mg nicotine patch application, subjective and physiological responses to a priming drink (0.3 g/kg) were assessed, followed by two 1-hr alcohol self-administration periods, with possible consumption of up to 4 drinks per period (each 0.15 g/kg). Nasal spray (1 mg [active] or 0 mg [placebo] per dose) was administered 10 min prior to the priming dose and each self-administration period. RESULTS: Active nasal spray did not increase serum nicotine levels, compared with placebo administration. The number of drinks consumed did not differ by the nasal spray conditions. However, positive subjective responses to the priming drink were lower in the active nasal spray condition than the placebo nasal spray condition. During the self-administration period, urge to drink was also lower in the active spray condition than the placebo condition. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Augmenting the nicotine patch with nicotine nasal spray attenuated positive subjective alcohol response and craving and suggests that future studies should investigate whether these findings translate to a clinical setting.

Nicotine deprivation and trait impulsivity affect smokers' performance on cognitive tasks of inhibition and attention.

Increased nicotine deprivation and impulsivity have been associated with relapse but the degree to which they together influence cognitive processing has not been explored. We examined the effects of increasing levels of nicotine deprivation on cognitive processing, and assessed the relationship of trait impulsivity with these effects in daily smokers (n=30). Using a within-subject design with three deprivation conditions (nondeprived, 5-hr, 17-hr), volunteers completed the Conners' Continuous Performance Task-II and the Cued Go/No-Go Task. Trait impulsivity was assessed at intake with the Barratt Impulsiveness Scale (Patton et al., 1995). Mixed-model regression analyses revealed deprivation slowed reaction time, increased errors, increased variability in responding, and increased failures of inhibitory control. Performance at 17 hours of deprivation was most likely to be affected. Significant deprivation and impulsivity interactions indicated impulsiveness was negatively correlated with deprivation-associated performance decrements. Less impulsive smokers were more affected by deprivation, demonstrating greater impairment. Research is needed to understand mechanisms by which impulsivity confers greater risk for relapse. Our results suggest deprivation may not increase relapse risk among impulsive smokers by increasing impairment of cognitive processing.

Effects of alcohol on simulated driving and perceived driving impairment in binge drinkers.

BACKGROUND: Binge drinking (heavy episodic alcohol use) is associated with high rates of impaired driving and myriad alcohol-related accidents. However, the underlying reasons for the heightened accident risk in this demographic group are not known. This research examined acute alcohol effects on simulated driving performance and subjective ratings of intoxication and driving ability in binge and nonbinge drinkers. METHODS: Young social drinking college students (24 binge drinkers and 16 nonbinge drinkers) participated in this study. Participants attended a session during which they received a moderate dose of alcohol (0.65 g/kg) and a session during which they received a placebo. A simulated driving task measured participants' driving performance in response to each dose. Subjective responses to each dose were also assessed, including ratings of sedation, stimulation, and driving ability. RESULTS: The acute dose of alcohol impaired multiple aspects of driving performance in both binge and nonbinge drinkers. Under alcohol, all participants had greater difficulty in maintaining their lane position, maintaining the appropriate speed and made multiple driving errors compared to placebo performance. By contrast, compared with nonbinge drinkers, binge drinkers reported feeling less sedated by the alcohol and reported having a greater ability to drive following the acute dose of alcohol. CONCLUSIONS: Reduced subjective intoxication and perceived driving impairment in binge drinkers may account for the greater accident risk in this demographic group. Binge drinkers may lack the internal sedation cue that helps them accurately assess that they are not able to effectively drive a vehicle after drinking.

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 drinker's 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.

Young adult non-daily smokers: patterns of alcohol and cigarette use.

Binge drinking and non-daily cigarette smoking are behaviors that are both problematic and prevalent in young adults. Although the relationship between drinking and daily smoking has been well categorized, the intersection between drinking and smoking in non-daily smokers has not been heavily researched. Past 30-day and within-episode patterns of alcohol and cigarette use were collected in young adult non-daily smokers (N=40). Results demonstrated that 79% of smoking occurred on drinking days. Alcohol use was significantly greater on smoking days with the result that drinking to risky binge levels was more likely to occur on a smoking day. Smoking typically occurred after a certain level of alcohol pre-load (2.87 drinks). Together these results confirm that young adult non-daily smokers often concurrently use alcohol and cigarettes. Research is needed to identify possible mechanisms underlying the association between binge drinking and cigarette use in this vulnerable population.

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 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 driver's sensitivity to the impairing effects of alcohol.

Effects of varenicline on alcohol cue reactivity in heavy drinkers.

RATIONALE: Clinical trials and human laboratory studies have established that varenicline can reduce rates of alcohol use among heavy drinkers. Less is known about the mechanisms by which varenicline has this effect on drinking behavior. Reactivity to alcohol cues is often cited as the primary cause of relapse among those being treated for alcohol use disorder, and several front-line treatments for alcohol use disorder work, at least in part, by minimizing cue-induced alcohol craving. OBJECTIVE: The current double-blind, placebo-controlled human laboratory study tested the effects of varenicline on alcohol cue reactivity in a group of heavy-drinking adult smokers and nonsmokers. METHODS: As part of a larger series of sequential human laboratory experiments testing the effects of varenicline on drinking outcomes, participants were assigned (between-participant) to receive either active varenicline (2 mg/day) or placebo. Following a titration period, participants (n = 77) attended a laboratory session during which they were exposed to alcohol and neutral cues using a standard cue reactivity paradigm. RESULTS: Alcohol cue exposure increased craving for alcohol in both medication groups. However, participants receiving varenicline showed a smaller increase in alcohol craving compared to participants receiving placebo. The medication effect did not differ between smokers and nonsmokers. Among smokers, alcohol cue exposure also increased tobacco craving. Varenicline did not attenuate this effect. CONCLUSIONS: Results support the use of varenicline for reducing alcohol use in heavy drinkers and identify a potential mechanism by which varenicline reduces drinking. Varenicline continues to show promise as a pharmacological treatment for alcohol use disorder.

Transfer of learning to compensate for impairment by alcohol and visual degradation.

RATIONALE: Past research on social drinkers shows that prior experience performing a task in a visually degraded environment results in the reduction of alcohol-induced impairment. It is possible that task experience under alcohol might similarly carry over to reduce impairment from visual degradation. OBJECTIVES: The purpose of this study was to test the symmetry of the transfer of learning between two distinct sources of impairment, visual degradation and alcohol. MATERIALS AND METHODS: Psychomotor impairment was measured by a pursuit rotor tracking task. Forty two participants were randomly assigned to one of six treatment groups. Two groups were tested under alcohol after having prior task experience performing with or without visual degradation. Two groups were tested under visual degradation after having prior task experience performing under active (0.65 g/kg) or inactive (placebo) doses of alcohol. The remaining two groups served as controls that tested the learning effects of repeating each active treatment. RESULTS: Clear evidence for asymmetrical transfer of learning was observed. Prior task experience with visual degradation reduced the impairing effects of alcohol. By contrast, prior task experience under alcohol had no effect on impairment produced by visual degradation. CONCLUSIONS: Evidence for differential transfer of learning to compensate for alcohol- and visual-degradation-induced impairment is of practical interest, given that the two disturbances commonly co-occur outside the laboratory. Reasons for the asymmetry are unclear, and likely involve differences in mechanisms by which each treatment impairs psychomotor function.

Social drinkers underestimate the additive impairing effects of alcohol and visual degradation on behavioral functioning.

RATIONALE: Studies have shown that social drinkers are poor estimators of alcohol-induced impairment. Underestimates of blood alcohol concentration and other indices of intoxication are associated with decisions to perform risky behaviors, such as operating a motor vehicle. It is possible that self-evaluations of impaired functioning under alcohol might be particularly compromised in the presence of other sources of impairment. A common source of impairment that co-occurs with alcohol is visual degradation. OBJECTIVES: The present study compared actual and self-evaluated impairment in response to four conditions (0.65 g/kg alcohol, degradation of task-relevant stimuli, alcohol plus visual degradation, and no-treatment control) to determine whether social drinkers would perceive an increase in impairment from the combined treatments. METHODS: Actual psychomotor impairment was measured in 16 social drinkers (eight men) by a pursuit rotor task and their self-evaluations of this impairment were obtained on a rating scale. RESULTS: Alcohol and visual degradation impaired participants' actual performance to a similar degree and, in combination, the impairing effects were additive. Participants' self-evaluation ratings showed that they underestimated the additive impairment produced by the combination of alcohol and visual degradation. CONCLUSIONS: The findings suggest that social drinkers might be unable to appreciate an increase in behavioral impairment when alcohol is consumed in the context of another impairing influence.

Are bad drivers more impaired by alcohol? Sober driving precision predicts impairment from alcohol in a simulated driving task.

The contribution of driver experience to risk for alcohol-related crashes is based on the tacit assumption that driver experience contributes to driver skill which could mediate the impairing effects of alcohol on driving performance. Surprisingly, few studies of alcohol effects on simulated driving performance have examined the role of driver skill as a mediator of the intensity of alcohol impairment. The present study examined the degree to which individual differences in driving skill mediated the intensity of impairment produced by a moderate dose of alcohol in a group of young adult drivers. Twenty-eight participants were familiarized with a simulated driving road test. After determining their baseline skill level, participants' driving performance was re-tested under either an active dose of alcohol (0.65 g/kg) or a placebo. Results showed that alcohol reduced driving precision, as evident by the increased within-lane deviation observed under the drug. Moreover, those individuals with poorer baseline skill levels showed the greater impairments in response to alcohol. The results highlight the importance of understanding interactions between driver skill level and the effects of alcohol and possibly other drugs.

Does co-morbid depression alter the inverse relationship between obesity and substance use disorders?

BACKGROUND: Substance use disorders and obesity are often inversely related to one another, hypothetically due to competition over shared neurobiological reward circuitry. However, obesity and substance use disorders share common risk factors, such as other psychiatric disorders. It is unknown whether the inverse relationship between obesity and substance use disorders continues to exist in the presence of shared risk factors. METHODS: For the current study, we examined the associations between major depression, alcohol and drug use disorders, and overweight/obesity status in a nationally representative sample of U.S. adults (n=40,715). RESULTS: Our findings demonstrated that adults with major depression were more likely to be obese, whereas adults with alcohol or drug use disorders were less likely to be obese. However, the inverse relationship between substance use and obesity continued to exist in adults with co-morbid depression. Adults with depression disorders co-morbid with alcohol (Relative Risk [RR]=0.63, 95% CI=0.47-0.84) or drug (RR=0.54, 95% CI=0.36-0.81) use disorders were less likely to be obese vs normal weight. CONCLUSIONS: Our findings provide support for the proposal that excess food consumption and excess drug use appear to compete over shared neurobiology even when the motivation to self-medicate with either food or substances might be elevated.

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.

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.

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.

Alcohol expectancy increases positive responses to cigarettes in young, escalating smokers.

RATIONALE: A large proportion of smokers consolidate their smoking patterns during young adulthood, and it is possible that the high rates of drinking found in this age group may facilitate the transition from nondaily to daily cigarette use. OBJECTIVE: The primary aim of this study was to examine how alcohol alters the subjective effects of smoking in heavy-drinking young adults (age 21-25) who are still at an experimental stage of smoking but show recent increases in their smoking behavior. METHODS: Using a within-subject design, we examined whether alcohol or the expectation of receiving alcohol increased either subjective responses to smoking or the amount smoked. Subjects participated in three sessions, in which they received alcohol (0.08 g/dL targeted blood alcohol level), a taste-masked placebo presented as alcohol, or a mixer beverage not presented as alcohol. Measures included positive and negative subjective reactivity (e.g., satisfaction, nausea, craving relief, and enjoyment of airway sensations) associated with smoking a single cigarette and subsequent ad lib smoking behavior. RESULTS: Both conditions in which the subjects expected to receive alcohol increased positive effects of smoking (satisfaction, calm, and taste), compared to the mixer beverage. Alcohol, compared to the placebo and mixer beverages, decreased negative effects (nausea) associated with smoking a cigarette and increased subsequent smoking. CONCLUSIONS: This initial study has implications for understanding how alcohol and the expectation of alcohol improves the experience of smoking in nondaily smokers who are still at an experimental stage of smoking.

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.

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.

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.