Effects of galantamine on smoking behavior and cognitive performance in treatment-seeking smokers prior to a quit attempt.

OBJECTIVE: Drugs that enhance cholinergic transmission have demonstrated promise treating addictive disorders. Galantamine, an acetylcholinesterase inhibitor, may reduce cigarette smoking in otherwise healthy treatment-seeking smokers. METHODS: The current study is a double-blind, placebo-controlled, study that randomized daily smokers (n = 60) to receive one of two doses of galantamine extended release (8 or 16 mg/day), or a placebo treatment. Participants completed a smoking choice task as well as study measures and cognitive tasks in the laboratory and daily life using ecological momentary assessment. Analysis focused on smoking behavior and satisfaction, cognitive performance, and decision to smoke prior to a quit attempt. RESULTS: Linear mixed models demonstrated that, compared with placebo, both doses of galantamine reduced smoking in a laboratory choice task (p = 0.006) and decreased urine cotinine levels, but not self-reported cigarettes, during the pre-quit period (p = 0.007). Treatment had minimal effect on smoking satisfaction or cognitive performance. CONCLUSIONS: The results suggest that galantamine reduces nicotine intake but it is unlikely that galantamine improves cognitive performance in otherwise healthy, treatment-seeking smokers. Larger randomized clinical trials can determine if galantamine adjunctive to addiction treatment can improve smoking treatment outcomes.

Inhalation of Alcohol Vapor: Measurement and Implications.

Decades of alcohol research have established the health risks and pharmacodynamic profile of oral alcohol consumption. Despite isolated periods of public health concern, comparatively less research has evaluated exposure to alcohol vapor. Inhaled alcohol initially bypasses first-pass metabolism and rapidly reaches the arterial circulation and the brain, suggesting that this route of administration may be associated with pharmacological effects that increase the risk of addiction. However, detailed reviews assessing the possible effects of inhaled alcohol in humans are lacking. A comprehensive, systematic literature review was conducted using Google Scholar and PubMed to examine manuscripts studying exposure to inhaled alcohol and measurement of biomarkers (biochemical or functional) associated with alcohol consumption in human participants. Twenty-one publications reported on alcohol inhalation. Fourteen studies examined inhalation of alcohol vapor associated with occupational exposure (e.g., hand sanitizer) in a variety of settings (e.g., naturalistic, laboratory). Six publications measured inhalation of alcohol in a controlled laboratory chamber, and 1 evaluated direct inhalation of an e-cigarette with ethanol-containing "e-liquid." Some studies have reported that inhalation of alcohol vapor results in measurable biomarkers of acute alcohol exposure, most notably ethyl glucuronide. Despite the lack of significantly elevated blood alcohol concentrations, the behavioral consequences and subjective effects associated with repeated use of devices capable of delivering alcohol vapor are yet to be determined. No studies have focused on vulnerable populations, such as adolescents or individuals with alcohol use disorder, who may be most at risk of problems associated with alcohol inhalation.

Momentary Associations Between Reported Craving and Valuing Health in Daily Smokers.

INTRODUCTION: Research suggests that a blunted response to nondrug rewards, especially under conditions associated with strong cigarette cravings, is associated with reduced abstinence motivation in daily smokers. One limitation of previous studies is that they have largely focused on monetary rewards as broad representative of nondrug rewards. It remains unclear whether craving dampens responses to more abstract nondrug rewards, such as personal values. Personal values often have a positive valence and are frequently assumed to remain stable across time and situations. However, there may be time-varying and contextual influences on smokers' appraisal of values in daily life. Characterizing fluctuations in value importance in relation to relapse precipitants (eg, craving) may inform interventions that leverage personal values as motivation for cessation. METHODS: Daily smokers (n = 18) completed ecological momentary assessment surveys measuring the importance of specific personal values and smoking-related variables during 8 days of monetarily reinforced cigarette abstinence. We hypothesized that value ratings would demonstrate adequate within-person heterogeneity for multilevel modeling and that within-person fluctuations in craving would be negatively related to valuing personal health. RESULTS: All values demonstrated adequate within-person variability for multilevel modeling. Within-person craving was negatively related to health valuation (p = .012) and a cross-level interaction (p > .0001) suggested this effect is stronger for individuals who report greater overall craving. CONCLUSIONS: Greater craving is associated with decreased importance of personal health in the moment, particularly for those with high average levels of craving. Timely interventions that bolster importance of health during moments of elevated craving can potentially improve cessation outcomes. IMPLICATIONS: This study builds on research highlighting the positive influence of personal values in motivating behavior change. Values are an often used, but poorly studied, construct that has considerable utility in smoking cessation. Valuing personal health is frequently reported as a primary motivator for a quit attempt. Inasmuch as personal health is a distal nondrug reward used to motivate smoking abstinence, naturalistic evaluation of health importance, and motivators for continued smoking (ie, craving) could inform the timing and content of smoking treatment. This study is among the first to evaluate momentary assessment of personal values and craving within daily life.

Neurobiological mechanisms for the regulation of mammalian sleep-wake behavior: reinterpretation of historical evidence and inclusion of contemporary cellular and molecular evidence.

At its most basic level, the function of mammalian sleep can be described as a restorative process of the brain and body; recently, however, progressive research has revealed a host of vital functions to which sleep is essential. Although many excellent reviews on sleep behavior have been published, none have incorporated contemporary studies examining the molecular mechanisms that govern the various stages of sleep. Utilizing a holistic approach, this review is focused on the basic mechanisms involved in the transition from wakefulness, initiation of sleep and the subsequent generation of slow-wave sleep and rapid eye movement (REM) sleep. Additionally, using recent molecular studies and experimental evidence that provides a direct link to sleep as a behavior, we have developed a new model, the cellular-molecular-network model, explaining the mechanisms responsible for regulating REM sleep. By analyzing the fundamental neurobiological mechanisms responsible for the generation and maintenance of sleep-wake behavior in mammals, we intend to provide a broader understanding of our present knowledge in the field of sleep research.

The relationship between anxiety and sleep-wake behavior after stressor exposure in the rat.

Disturbed sleep is a common subjective complaint among individuals diagnosed with anxiety disorders. In rodents, sleep is often recorded after exposure to various foot-shock paradigms designed to induce an anxiety state. Although differences in sleep-wake architecture are noted, the relationship to specific level of anxiety is often assumed or absent. Utilizing the elevated plus-maze (EPM) after exposure to escapable shock (ES), inescapable shock (IS) or fear conditioning (FC), resulting differences in sleep architecture were compared to an objective measure of anxiety. Male Wistar rats were implanted with EEG, EMG and hippocampal theta electrodes to record sleep-wake behavior. After recovery and recording of baseline sleep, rats were exposed to one of five manipulations: ES, IS, FC or control (CES or CIS; utilizing either chamber with no shock exposure). Shortly after experimental manipulation, the EPM was employed to quantify traditional and ethological measures of anxiety and polygraphic signs of sleep-wake behavior were recorded continuously for 6 h. Although no significance was observed in EPM measurements across groups, profound differences in sleep architecture were present. Individual correlation analysis revealed no differences in anxiety level and total percentage of time spent in sleep-wake states. These results indicate that differences in sleep architecture after foot-shock exposure may not be simply due to increased anxiety. Rather, individual anxiety may be exacerbated by disrupted sleep. To fully understand the relationship between anxiety and sleep-wake behavior, a more objective analysis of anxiety after stressor exposure is mandated.

Kudzu root extract does not perturb the sleep/wake cycle of moderate drinkers.

OBJECTIVES: According to ancient Chinese medicine, kudzu root has been used as an ingredient to treat alcohol intoxication for centuries. Kudzu root extract is effective at reducing alcohol intake in animals and in humans, both in a natural-settings laboratory environment and on an outpatient basis. In dependent populations, withdrawal from alcohol is associated with disturbed sleep. These disturbances to the quantity and quality of sleep likely impact relapse to drinking. Many medications used to treat alcohol dependence also affect sleep. Therefore, as a possible treatment for alcohol dependence, the impact of kudzu root extract on the sleep/wake cycle is an important aspect of its effectiveness. DESIGN: This double-blind, placebo-controlled, crossover trial tested the effects of kudzu root extract on the sleep/wake cycles of moderate drinkers. RESULTS: Kudzu extract had no effect on any of the sleep parameters measured, including sleep efficiency, sleep latency, total time asleep per night, number of waking episodes, time awake per episode, number of moving minutes, number of sleep episodes, time asleep per episode, and number of immobile minutes. CONCLUSIONS: These data suggest that the administration of kudzu root extract does not disturb sleep/wake cycles of moderate drinkers, and as such its utility as an adjunct treatment for alcohol dependence remains free of any potential side-effects on sleep.