A randomized trial for hazardous drinking and smoking cessation for callers to a quitline.

Objective: This study evaluated whether tobacco quitline telephone coaches can be trained to counsel hazardous-drinking smokers to improve smoking cessation success and to limit or abstain from alcohol use.

Method: Smokers (N = 1,948) who called the New York State Smokers' Quitline and reported hazardous drinking (exceeding sex-specific weekly limits [14 drinks for men, 7 drinks for women] or meeting/exceeding daily drinking limits [5 drinks for men, 4 drinks for women] at least once in the past year) were randomized to receive either brief motivational counseling to limit or abstain from alcohol plus an alcohol reduction booklet added to standard care (Alcohol + Tobacco Counseling; ATC), or only smoking cessation counseling plus a smoking cessation booklet added to standard care (Tobacco-Only Counseling; TOC).

Results: Acceptable coach adherence was achieved.

In with the old and out with the new? A comparison of the old and new binge drinking standards.

Background: There is consistent evidence that the binge drinking standard of 5+ drinks per drinking occasion for men (4+ for women) is associated with risk for negative consequences. Yet, many have questioned the adequacy of this measure as an index of intoxication (e.g.

Predictors of abstinence from heavy drinking during treatment in COMBINE and external validation in PREDICT.

Background: The goal of the current study was to use tree-based methods (Zhang and Singer, 2010, Recursive Partitioning and Applications, 2nd ed. Springer, New York) to identify predictors of abstinence from heavy drinking in COMBINE (Anton et al. JAMA 2006; 295:2003), the largest study of pharmacotherapy for alcoholism in the United States to date, and to validate these results in PREDICT (Mann et al.

Non-invasive bioluminescence imaging of β-cell function in obese-hyperglycemic [ob/ob] mice.

Background: Type 2 diabetes results from failure of the β-cells to compensate for increased insulin demand due to abnormal levels of metabolic factors. The ob/ob(lep-/-) mouse has been extensively studied as an animal model of type 2 diabetes. Previous studies have shown a correlation between β-cell function and bioluminescent imaging in lean genetically engineered mice.

A randomized, double-blind, placebo-controlled pilot study of naltrexone to counteract antipsychotic-associated weight gain: proof of concept.

Patients with schizophrenia experience higher rates of obesity as well as related morbidity and mortality than the general population does. Women with schizophrenia are at particular risk for antipsychotic-associated weight gain, obesity, and related medical disorders such as diabetes and cardiovascular disease. Given preclinical studies revealing the role of the endogenous opioid systems in human appetite and the potential of antipsychotic medications to interfere with this system, we hypothesized that opioid antagonists may be beneficial in arresting antipsychotic-associated weight gain and promoting further weight loss in women with schizophrenia.

What happens when people discontinue taking medications? Lessons from COMBINE.

Aims: We use intensive longitudinal data methods to illuminate processes affecting patients' drinking in relation to the discontinuation of medications within an alcohol treatment study. Although previous work has focused on broad measures of medication adherence, we focus on dynamic changes in drinking both before and after patients discontinue.

Design: We conducted secondary data analyses using the COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) study, focused on participants who discontinued medications prior to the planned end of treatment.

A new look at risk-taking: using a translational approach to examine risk-taking behavior on the balloon analogue risk task.

Models of risk-taking typically assume that the variability of outcomes is important in the likelihood of making a risky choice. In an animal model of the Balloon Analogue Risk Task (BART), within-session variability, or the coefficient of variability (CV), was found to be a novel predictor of behavior (Jentsch et al., 2010).

Discovery of MK-3168: A PET Tracer for Imaging Brain Fatty Acid Amide Hydrolase.

We report herein the discovery of a fatty acid amide hydrolase (FAAH) positron emission tomography (PET) tracer. Starting from a pyrazole lead, medicinal chemistry efforts directed toward reducing lipophilicity led to the synthesis of a series of imidazole analogues. Compound 6 was chosen for further profiling due to its appropriate physical chemical properties and excellent FAAH inhibition potency across species.

Psychometrically improved, abbreviated versions of three classic measures of impulsivity and self-control.

Self-reported impulsivity confers risk factor for substance abuse. However, the psychometric properties of many self-report impulsivity measures have been questioned, thereby undermining the interpretability of study findings using these measures. To better understand these measurement limitations and to suggest a path to assessing self-reported impulsivity with greater psychometric stability, we conducted a comprehensive psychometric evaluation of the Barratt Impulsiveness Scale-11 (BIS-11), the Behavioral Inhibition and Activation Scales (BIS/BAS), and the Brief Self-Control Scale (BSCS) using data from 1,449 individuals who participated in substance use research.

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.

Is eye gaze direction always determined without intent?

It is widely assumed that processing of gaze direction occurs "automatically," in the sense that it is reflexive (unfolds in the absence of intention). We assessed this view in a task in which participants saw a schematic face in which the eyes were gazing left or right, along with a second directional target (an arrow in Experiment 1; a directional word in Experiment 2). The eyes and other directional target were sometimes congruent and other times incongruent.

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.

Predictors of pretreatment commitment to abstinence: results from the COMBINE study.

Objective: Patients entering treatment for alcohol problems do not have uniform treatment goals, and a pretreatment drinking goal has a significant impact on treatment outcome. The objective of this study was to understand better how an array of individual characteristics, including factors that affect treatment, are related to treatment goals before beginning alcohol treatment in the COMBINE (Combining Medications and Behavioral Interventions) Study.

Method: Participants were alcohol-dependent individuals (N = 1,156; 357 women) recruited at 11 outpatient academic alcoholism-treatment clinics across the United States to participate in a randomized, double-blind, placebo-controlled trial that combined behavioral intervention with acamprosate and/or naltrexone.

Relationships between impulsivity and subjective response in an IV ethanol paradigm.

Rationale: Impulsivity and individual differences in subjective response to alcohol are risk factors for alcohol problems and possibly endophenotypes for alcohol dependence. Few prior studies have addressed relationships between the two constructs.

Objectives: To predict subjective responses to ethanol, we tested self-reported impulsiveness, ethanol dose condition (high dose, low dose, or placebo), and time (seven time points) along with interactions among these variables.

Predictors of Interest in an Alcohol Reduction Clinical Trial of Naltrexone among Undergraduates.

Background: We tested predictors of interest in a clinical trial of naltrexone plus counseling for heavy drinking reduction in young adults using a web survey. Respondents could indicate interest in the clinical trial at the conclusion of the survey.

Methods: A random sample of university students completed the survey ( = 584, 60% female).

"Quitting smoking will benefit your health": the evolution of clinician messaging to encourage tobacco cessation.

Illnesses that are caused by smoking remain as the world's leading cause of preventable death. Smoking and tobacco use constitute approximately 30% of all cancer-related deaths and nearly 90% of lung cancer-related deaths. Thus, improving smoking cessation interventions is crucial to reduce tobacco use and assist in minimizing the burden of cancer and other diseases in the United States.

Financial versus health motivation to quit smoking: a randomized field study.

Objective: Smoking is the most preventable cause of death, thus justifying efforts to effectively motivate quitting. We compared the effectiveness of financial versus health messages to motivate smoking cessation. Low-income individuals disproportionately smoke and, given their greater income constraints, we hypothesized that making financial costs of smoking more salient would encourage more smokers to try quitting.

Menthol cigarette use predicts treatment outcomes of weight-concerned smokers.

Background: Studies have shown that individuals who smoke menthol cigarettes are less likely to quit smoking and more likely to relapse during a quit attempt. The current study investigated menthol cigarette use as a potential predictor of smoking cessation outcomes in a sample of treatment-seeking smokers.

Methods: This is a secondary analysis of data from a randomized controlled trial of low-dose naltrexone augmentation of nicotine replacement designed to examine smoking cessation and postcessation weight gain in weight-concerned smokers.

Mediating role of stress reactivity in the effects of prenatal tobacco exposure on childhood mental health outcomes.

Introduction: Prenatal tobacco exposure, through maternal smoking during pregnancy, has been associated with adverse mental health outcomes in childhood. However, the mechanisms by which prenatal tobacco exposure compromises mental health later in life are unclear. We hypothesized that sensitized reactivity to stressful life events in early childhood mediates the effect of prenatal tobacco exposure on mental health outcomes in middle childhood, after accounting for earlier mental health outcomes.

In vivo quantification of calcitonin gene-related peptide receptor occupancy by telcagepant in rhesus monkey and human brain using the positron emission tomography tracer [11C]MK-4232.

Calcitonin gene-related peptide (CGRP) is a potent neuropeptide whose agonist interaction with the CGRP receptor (CGRP-R) in the periphery promotes vasodilation, neurogenic inflammation and trigeminovascular sensory activation. This process is implicated in the cause of migraine headaches, and CGRP-R antagonists in clinical development have proven effective in treating migraine-related pain in humans. CGRP-R is expressed on blood vessel smooth muscle and sensory trigeminal neurons and fibers in the periphery as well as in the central nervous system.

A human alcohol self-administration paradigm to model individual differences in impaired control over alcohol use.

We developed an alcohol self-administration paradigm to model individual differences in impaired control. The paradigm includes moderate drinking guidelines meant to model limits on alcohol consumption, which are typically exceeded by people with impaired control. Possible payment reductions provided a disincentive for excessive drinking.

Localization of CGRP receptor components, CGRP, and receptor binding sites in human and rhesus cerebellar cortex.

The cerebellum is classically considered to be mainly involved in motor processing, but studies have suggested several other functions, including pain processing. Calcitonin-gene-related peptide (CGRP) is a neuropeptide involved in migraine pathology, where there is elevated release of CGRP during migraine attacks and CGRP receptor antagonists have antimigraine efficacy. In the present study, we examined CGRP and CGRP receptor binding sites and protein expression in primate cerebellar cortex.

CBP Activity Mediates Effects of the Histone Deacetylase Inhibitor Butyrate on WNT Activity and Apoptosis in Colon Cancer Cells.

Mutations in the WNT/beta-catenin pathway are responsible for initiating the majority of colorectal cancers (CRCs). We have previously shown that hyperactivation of this signaling by histone deacetylase inhibitors (HDACis) such as butyrate, a fermentation product of dietary fiber, promotes CRC cell apoptosis. The extent of association between beta-catenin and the transcriptional coactivator CREB-binding protein (CBP) influences WNT/catenin signaling and, therefore, colonic cell physiology.

Reading aloud: does previous trial history modulate the joint effects of stimulus quality and word frequency?

No one would argue with the proposition that how we process events in the world is strongly affected by our experience. Nonetheless, recent experience (e.g.

Virtual medicinal chemistry: in silico pre-docking functional group transformation for discovery of novel inhibitors of botulinum toxin serotype A light chain.

A novel method for applying high-throughput docking to challenging metalloenzyme targets is described. The method utilizes information-based virtual transformation of library carboxylates to hydroxamic acids prior to docking, followed by compound acquisition, one-pot (two steps) chemical synthesis and in vitro screening. In two experiments targeting the botulinum neurotoxin serotype A metalloprotease light chain, hit rates of 32% and 18% were observed.