Acute alcohol consumption alters the peripheral cytokines IL-8 and TNF-α.

Background: Acute alcohol consumption triggers release of cytokines, which are immune signaling molecules. Dysregulated cytokine levels are associated with impaired immune function, and peripheral cytokine levels may communicate with the brain to propagate drinking-related behaviors. This exploratory study aims to characterize the peripheral cytokine response to an alcohol challenge in a well-controlled laboratory setting.

Evaluating the effect of switching to non-menthol cigarettes among current menthol smokers: an empirical study of a potential ban of characterising menthol flavour in cigarettes.

Introduction: Menthol cigarette use remains a serious public health problem, prompting the consideration of tobacco regulatory efforts to ban menthol cigarettes. The current study uses a novel empirical design to model the potential effects of a ban of menthol cigarettes on smoking behaviour among current menthol smokers.

Methods: 29 non-treatment-seeking adults who smoked menthol cigarettes were recruited in Connecticut in 2017-2018 (n=15 female; n=17 Black, n=10 White, n=5 Hispanic).

Modulation of "Protective" Nicotine Perception and Use Profile by Flavorants: Preliminary Findings in E-cigarettes.

Introduction: Characterizing flavors are widely available in e-cigarettes and motivate initiation and continued use. Flavors may enhance appeal and facilitate development of addiction to tobacco products through modulation of tobacco products' reinforcing or aversive actions. Palatable flavors (eg, fruit) may increase appeal through primary reinforcing properties.

Acute effects of inhaled menthol on the rewarding effects of intravenous nicotine in smokers.

Objective: This double-blind, placebo controlled study examined whether menthol inhaled from an electronic cigarette (e-cigarette) would change subjective and withdrawal alleviating effects of intravenous nicotine in young adult smokers.

Methods: A total of 32 menthol-preferring smokers and 25 non-menthol-preferring smokers participated in the study that consisted of a random sequence of three different inhaled menthol conditions (0.0%, 0.

Plasma Menthol Glucuronide as a Biomarker of Acute Menthol Inhalation.

Objectives: Menthol is often added to cigarettes and e-cigarette solutions for its cooling and anti-irritant effects, and may contribute to development of nicotine dependence, particularly in vulnerable populations such as adolescents, and among African Americans. Menthol is rapidly metabolized to menthol glucuronide (MG) with little or no unconjugated menthol measurable in venous blood. Human challenge studies of the effects of inhaled menthol, and of its interactions with nicotine, would benefit from a quantitative measure of acute menthol exposure.

Effect of Varenicline Combined With Medical Management on Alcohol Use Disorder With Comorbid Cigarette Smoking: A Randomized Clinical Trial.

Importance: Individuals with alcohol use disorder have high rates of cigarette smoking. Varenicline tartrate, an approved treatment for smoking cessation, may reduce both drinking and smoking.

Objectives: To test the efficacy of varenicline with medical management for patients with alcohol use disorder and comorbid smoking seeking alcohol treatment, and to evaluate the secondary effects on smoking abstinence.

Impact of E-cigarettes on Smoking and Related Outcomes in Veteran Smokers With Psychiatric Comorbidity.

Objective: Compared to the general U.S. population, smokers with comorbid psychiatric and/or substance use disorders have lower quit rates after evidence-based treatments and disproportionately high smoking-related deaths.

Studying the interactive effects of menthol and nicotine among youth: An examination using e-cigarettes.

Background: Tobacco products containing menthol are widely used by youth. We used e-cigarettes to conduct an experimental evaluation of the independent and interactive effects of menthol and nicotine among youth.

Procedures: Pilot chemosensory experiments with fourteen e-cigarette users identified low (barely perceptible, 0.

Menthol disrupts nicotine's psychostimulant properties in an age and sex-dependent manner in C57BL/6J mice.

Menthol is a commonly used flavorant in tobacco and e-cigarettes, and could contribute to nicotine sensitivity. To understand how menthol could contribute to nicotine intake and addiction, it is important to determine whether specific mechanisms related to sex and age could underlie behavioral changes induced by menthol-laced nicotinic products. Using a validated paradigm of nicotine-dependent locomotor stimulation, adolescent and adult C57BL/6J mice of both sexes were exposed to nicotine, or nicotine laced with menthol, as their sole source of fluid, and psychostimulant effects were evaluated by recording home cage locomotor activity for ten days.

Biomarkers of exposure to new and emerging tobacco delivery products.

Accurate and reliable measurements of exposure to tobacco products are essential for identifying and confirming patterns of tobacco product use and for assessing their potential biological effects in both human populations and experimental systems. Due to the introduction of new tobacco-derived products and the development of novel ways to modify and use conventional tobacco products, precise and specific assessments of exposure to tobacco are now more important than ever. Biomarkers that were developed and validated to measure exposure to cigarettes are being evaluated to assess their use for measuring exposure to these new products.

Use of Electronic Cigarettes Leads to Significant Beta2-Nicotinic Acetylcholine Receptor Occupancy: Evidence From a PET Imaging Study.

Background: Electronic cigarettes (ECs) can influence nicotine addiction by delivering aerosolized nicotine. We investigated if nicotine from ECs is delivered to the brain β2*-nicotinic acetylcholine receptors (β2*-nAChR) and how this relates to the behavioral effects and nicotine delivery from cigarettes.

Methods: Seven nicotine users participated in positron emission tomography (PET) studies with (-)-[18F]Flubatine before and after nicotine challenge with 0, 8, and 36 mg/ml nicotine in a 3.

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.

The effects of alcohol-containing e-cigarettes on young adult smokers.

Background: The liquids (e-liquids) used in an electronic cigarette (e-cigarette) contain myriad chemicals without adequate human inhalation safety data. Furthermore, the absence of e-liquid labeling requirements poses a formidable challenge to understanding how e-liquid constituents may promote nicotine addiction and/or have independent or synergistic biological effects when combined with nicotine. Ethyl alcohol is such a constituent, but has received little scientific interest in this context.

Nicotine metabolite ratio (3-hydroxycotinine/cotinine) in plasma and urine by different analytical methods and laboratories: implications for clinical implementation.

Background: The highly genetically variable enzyme CYP2A6 metabolizes nicotine to cotinine (COT) and COT to trans-3'-hydroxycotinine (3HC). The nicotine metabolite ratio (NMR, 3HC/COT) is commonly used as a biomarker of CYP2A6 enzymatic activity, rate of nicotine metabolism, and total nicotine clearance; NMR is associated with numerous smoking phenotypes, including smoking cessation. Our objective was to investigate the impact of different measurement methods, at different sites, on plasma and urinary NMR measures from ad libitum smokers.

Acute alcohol consumption elevates serum bilirubin: an endogenous antioxidant.

Background: Moderate alcohol consumption has been associated with both negative and favorable effects on health. The mechanisms responsible for reported favorable effects remain unclear. Higher (not necessarily elevated) concentrations of serum bilirubin, an antioxidant, have also been associated with reduced risk of cardiovascular disease and all-cause mortality.

Smoking cessation is followed by increases in serum bilirubin, an endogenous antioxidant associated with lower risk of lung cancer and cardiovascular disease.

Introduction: Lower concentrations of serum bilirubin, an endogenous antioxidant, have been associated with risk of many smoking-related diseases, including lung cancer and cardiovascular disease, and current smokers are reported to have lower bilirubin levels than nonsmokers and past smokers. This study evaluates the effects of smoking cessation on bilirubin levels.

Methods: In a secondary analysis of a 6-week placebo-controlled trial of naltrexone for smoking cessation, indirect and total bilirubin concentrations were evaluated at baseline and following smoking cessation.

Ethyl glucuronide and ethyl sulfate assays in clinical trials, interpretation, and limitations: results of a dose ranging alcohol challenge study and 2 clinical trials.

Background: The ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS), are biomarkers of recent alcohol consumption that provide objective measures of abstinence. Our goals are to better understand the impact of cutoff concentration on test interpretation, the need for measuring both metabolites, and how best to integrate test results with self-reports in clinical trials.

Methods: Subjects (n = 18) were administered, 1 week apart, 3 alcohol doses calibrated to achieve blood concentrations of 20, 80, and 120 mg/dl, respectively.

Nicotine fails to attenuate ketamine-induced cognitive deficits and negative and positive symptoms in humans: implications for schizophrenia.

Background: The uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, ketamine, induces a range of symptoms resembling those seen in schizophrenia. Enhancement of nicotinic acetylcholine receptor (nAChR) function may have potential as a treatment for the cognitive deficits and negative symptoms of schizophrenia. Accordingly, we examined the modulatory effects of brain nAChR systems on NMDAR antagonist-induced effects.

Rapid nicotine clearance is associated with greater reward and heart rate increases from intravenous nicotine.

The ratio of nicotine metabolites (trans-3'-hydroxycotinine (3HC) to cotinine) correlates with nicotine clearance. In previous studies, high nicotine metabolite ratio (NMR) predicted poor outcomes for smoking cessation treatment with nicotine patch. The underlying mechanisms that associate NMR with treatment outcomes have not been fully elucidated.

Exploring the impact of gender and reproductive status on outcomes in a randomized clinical trial of naltrexone augmentation of nicotine patch.

In a series of exploratory analyses, we examined the roles of gender, reproductive status and negative affect on smoking abstinence in subjects participating in a large (n=385) 6-week randomized clinical trial (RCT) of nicotine patch therapy, with varying doses of oral naltrexone (0mg, 25mg, 50mg, 100mg) treatment. Negative affect was assessed daily during the first post-quit week via telephone interactive voice response (IVR). Weight and adverse events were recorded weekly.

Low-dose naltrexone augmentation of nicotine replacement for smoking cessation with reduced weight gain: a randomized trial.

Background: Fear of weight gain is a significant obstacle to smoking cessation, preventing some smokers from attempting to quit. Several previous studies of naltrexone yielded promising results for minimization of post-quit weight gain. Given these encouraging findings, we endeavored to test whether minimization of weight gain might translate to better quit outcomes for a population that is particularly concerned about gaining weight upon quitting.

Clinical (nonforensic) application of ethyl glucuronide measurement: are we ready?

Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are minor metabolites of ethanol. Multiple studies have documented that, depending upon the amount of alcohol consumed, they can be measured in biological fluids for hours to days after the parent compound can no longer be detected. Testing for the presence of EtG, in a manner analogous to urinary drug abuse screening, has largely been restricted to forensic and law enforcement situations.

Effect of cocaine use on methadone pharmacokinetics in humans.

Chronic cocaine use has been shown to significantly decrease buprenorphine concentrations in the blood with potential for adverse events and poor treatment response. In this study, we investigated whether a similar drug interaction occurred between cocaine and methadone. In a retrospective analysis, methadone pharmacokinetics were compared for those who were either regular cocaine users (N = 16) or with intermittent or no cocaine use (N = 23).

A double-blind, placebo-controlled, randomized clinical trial of oral selegiline hydrochloride for smoking cessation in nicotine-dependent cigarette smokers.

Aim: The primary aim of this study was to determine the safety and efficacy of the monoamine oxidase-B (MAO-B) inhibitor selegiline hydrochloride (SEL, l-Deprenyl; Eldepryl) as an aid for smoking cessation in cigarette smokers.

Methods: One hundred and one nicotine-dependent adult cigarette smokers without current psychiatric or substance use disorders participated in this 8-week randomized, double-blind, placebo-controlled trial. Participants received either SEL (5mg bid, n=51) or placebo (PLO, n=50), in combination with brief (<10 min) manualized smoking cessation counseling.

Contingency management for smoking cessation: enhancing feasibility through use of immunoassay test strips measuring cotinine.

Contingency management (CM) is a powerful behavioral intervention shown to reduce the use of a variety of substances including tobacco. Use of CM techniques for smoking cessation has been restricted by the use of multiple daily measurements of breath CO as the objective indicator to reinforce abstinence. Cotinine, with its longer half-life, may be a better marker.