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Background: The relationship between alcohol and pain is complex. Associations between pain and alcohol use disorder (AUD) vary by race, but the underlying biological basis is not understood. We examined the association of the kappa opioid receptor (KOR) with responses to the cold‐pressor test (CPT), before and after treatment with the opioid antagonist naltrexone, among individuals with AUD who self‐identified as Black or White. Methods: Thirty‐seven individuals (12 Black, 24 White, and 1 Multiracial) with AUD participated in two CPTs, separated by 1 week during which they received naltrexone 100 mg daily. During each CPT, pain reporting threshold (PRT), average pain increase rate (APIR), relative pain recovery (RPR), and alcohol craving were recorded. KOR availability was measured using [11C]‐LY2795050 positron emission tomography (PET) prior to treatment with naltrexone. Results: Black participants reported higher PRT and APIR than White participants during the CPT before, but not after, naltrexone treatment. Among Black participants, KOR availability was positively associated with PRT and APIR before, but not after naltrexone. Greater KOR availability was associated with faster RPR for White, but not Black, participants. The CPT induced more alcohol craving in Black than White participants, particularly in individuals with low KOR availability, an effect that was not attenuated by naltrexone. Conclusions: KOR involvement and naltrexone effects on responses to the CPT were different between Black and White participants. These preliminary findings suggest that further exploration of the differences in the opioid system and pain among Black and White individuals with AUD and their relationship with naltrexone's effects is warranted. [ABSTRACT FROM AUTHOR]

Objective: Recent studies have examined the factor structure and associated correlates of three neurofunctional domains, executive function, incentive salience, and negative emotionality in the development and maintenance of alcohol use disorders in clinical samples. The current study sought to replicate and extend prior work by testing this 3‐factor model, utilizing both exact and similar phenotypic measures, as well as novel measures, in a non–treatment‐seeking sample. Methods: Self‐report measures of alcohol addiction, impulsivity, behavior, and exposure to early‐life stress were collected as part of baseline assessments for alcohol imaging and pharmacotherapy studies in 335 individuals. Confirmatory factor analysis (CFA) was used to examine model structure and fit. A multiple indicators, multiple causes (MIMIC) model identified predictors of latent factors identified by CFA. Results: Results supported an intercorrelated model with three factors: executive function, incentive salience, and emotionality. All factors were associated with current AUD, and incentive salience was uniquely associated with past 30‐day drinking frequency. MIMIC results identified multiple significant predictors of these latent factors, including history of alcohol use disorder, positive family history of alcohol dependence, earlier age of first drink, and a history of childhood emotional abuse and physical neglect. Conclusions: Our results support an intercorrelated 3‐factor model of neurofunctional domains in alcohol use models, consistent with published findings. Because childhood physical neglect was a significant predictor of all latent factors, these results also highlight the significant negative impact of childhood neglect on later addiction development. [ABSTRACT FROM AUTHOR]

Ordinal data (eg, "low," "medium," "high"; graded response on a Likert scale) with an additional "don't know" category are frequently encountered in the medical, social, and behavioral science literature. The handling of a "don't know" option presents unique challenges as it often "destroys" the ordinal nature of the data. Commonly, nominal models are employed which ignore the partial ordering and have a complicated interpretation, especially in situations with repeatedly measured outcomes. We propose two‐part models that easily accommodate longitudinal partially ordered (semiordinal) data. The most easily interpretable formulation consists of a random effect logistic submodel for "don't know" vs all the other categories combined, and a random effect ordinal submodel for the ordered categories. Correlated random effects account for statistical dependence within individual. An extension allowing for nonproportionality of odds for the predictor effects in the ordinal submodel is also considered. Maximum likelihood estimation is performed using adaptive Gaussian quadrature in SAS PROC NLMIXED. A simulation study is performed to evaluate the performance of the estimation algorithm in terms of bias and efficiency, and to compare the results of joint and separate models of the two parts, and of proportional and nonproportional model formulations. The methods are motivated and illustrated on a dataset from a study of adolescents' perceptions of nicotine strength of JUUL e‐cigarettes. Using the proposed approach we show that adolescents perceive 5% nicotine content as relatively low, a misconception more pronounced among past month nonusers than among past month users of JUUL e‐cigarettes. [ABSTRACT FROM AUTHOR]

Background: In‐laboratory drinking sessions that allow direct assessment of drinking and craving are an emerging method for testing novel pharmacotherapy compounds and behavioral interventions for alcohol use disorders. Despite wide implementation, limited evidence supports the concordance between drinking in the laboratory and in a natural setting. This study examined the relationship between self‐reports of drinking prior to and drinking and craving during an alcohol drinking paradigm (ADP). Methods: Participants were adult heavy drinkers (N = 64) who participated in a pharmacotherapy study. Participants completed self‐report alcohol assessments and a baseline ADP session prior to any medication administration. Alcohol craving was assessed during priming and ad lib ADP phases. Outcomes were the associations of total drinks consumed in‐laboratory and summary drinking measures for the 30 days prior to the ADP and reports of maximum drinks (past year and lifetime). Additional outcomes were the association of self‐reported drinking and alcohol craving during the ADP and the concordance between self‐report and ADP World Health Organization (WHO) drinking classifications. Results: Number of drinking days, average drinks per drinking occasion, and lifetime and past‐year maximum drinks were all related to drinking in the laboratory. Heavy drinking days were not related to drinking in the laboratory but were associated with ADP craving. Alcohol craving was also associated with other measures of self‐reported drinking. There was also a significant association between WHO drinking risk classification and in‐laboratory drinking. Conclusions: The observed relationships between self‐reported drinking and drinking in‐laboratory across drinking indices suggest that in‐laboratory alcohol consumption may reflect participants' real‐world alcohol consumption, supporting the value of laboratory‐based drinking paradigms. The demonstrated relationship with self‐reported drinking and ADP alcohol craving further supports the value of such paradigms to model key drinking predictors. These results provide support for the validity of laboratory‐based paradigms to accurately reflect participants' recent drinking levels. [ABSTRACT FROM AUTHOR]

Background and Aims: To estimate progression to polytobacco use (PTU) over 1 year among a sample of US youth. Design Prospective survey with two waves 1 year apart: wave 1 (2013–14) and wave 2 (2014–15). We conducted latent transition analysis (LTA) to identify latent class transitions and examine socio‐demographic predictors of transition types. Setting: United States. Participants: A total of 11, 996 people who were aged 12–17 years at wave 1. Measurements Publicly available data were used from the Population Assessment of Tobacco and Health (PATH) study, a nationally representative sample of US civilian, non‐institutionalized population aged 12 years and older. Tobacco use status was assessed and classified in terms of: never use, non‐current (not in the past 30 days) and current (past 30‐day) use of cigarettes, cigars, e‐cigarettes, hookah and smokeless tobacco. Other nicotine products were excluded because rates of use were either too low to model (e.g. pipe) or the product was not assessed in the PATH youth sample (e.g. nicotine replacement products). Findings We identified three distinct patterns: class 1, non‐use (wave 1 prevalence = 86%; wave 2 prevalence = 78%); class 2, ever use of cigarettes and e‐cigarettes (wave 1 prevalence = 11%; wave 2 prevalence = 14%); and class 3, current PTU (wave 1 prevalence = 4%; wave 2 prevalence = 7%). Probability of progression from non‐use to ever use of cigarettes and e‐cigarettes was 0.06 and ever use of cigarettes and e‐cigarettes to current PTU was 0.32. Non‐users were more likely to transition to ever use of cigarettes and e‐cigarettes if they were older (versus younger), white (versus non‐white) or if their parental education level was high school or less (versus more than high school); and ever users of cigarettes and e‐cigarettes to current PTU if they were older, male or white. Conclusions: US youth who had previously tried e‐cigarettes and cigarettes at wave 1 (2013–14) had a 32% chance of transitioning to current use of two or more tobacco products within 1 year. [ABSTRACT FROM AUTHOR]

Background: Extensive research indicates that having a positive family history of alcohol use disorder (FHP) and impulsivity are 2 risk factors for problem drinking. To our knowledge, no study has investigated which facets of impulsivity interact with family history to increase risk for problem drinking. The goal of this study was to: (i) examine whether FHP individuals with higher levels of impulsivity are more likely to engage in problematic drinking, and (ii) identify which facets of impulsivity interact with FHP to increase risk for problems. Methods: The data consisted of a combined sample of 757 participants (50% female, 73% White, mean age = 32.85, SD = 11.31) drawn from the Transdisciplinary Tobacco Use Research Center and the Center for the Translational Neuroscience of Alcohol. Analyses of covariance and cumulative logistic regression models investigated the association of family history and impulsivity‐related traits with drinking quantity, frequency, and alcohol‐related problems. Models were adjusted for age, sex, race, ethnic group, education level, and data source. Results: Significant interactions between impulsivity and family history were found for measures of alcohol‐related problems. Specifically, there was a stronger positive association of Barratt Impulsiveness Scale (BIS) poor self‐regulation with interpersonal, F(1, 504) = 6.27, p = 0.01, and impulse control alcohol‐related problems, F(1, 504) = 6.00, p = 0.01, among FHP compared to FHN individuals. Main effects of family history and impulsivity on alcohol quantity and frequency of use and problems were also found. Conclusions: These findings suggest that having both a family history of AUD and high BIS poor self‐regulation is more strongly associated with alcohol‐related consequences in the interpersonal and impulse control domains. Given the heterogeneity of impulsivity, these findings highlight the need for additional research to examine which facets of impulsivity are associated with which alcohol outcomes to narrow phenotypic risk for alcohol misuse. [ABSTRACT FROM AUTHOR]

This pilot study evaluated the optimal format of cognitive behavioral therapy (CBT) to combine with contingency management (CM) in a four-week, high school-based smoking cessation program. Thirty-four adolescent smokers received a standard weekly version of CBT or a frequent brief behavioral intervention. Results indicate a trend toward a higher seven-day point prevalence end-of-treatment abstinence rate and percent days abstinent during treatment in the CBT condition. In addition, significantly more participants in the CBT group completed treatment. These preliminary results suggest that when combined with CM, the standard weekly format of CBT is more acceptable to adolescent smokers. [ABSTRACT FROM AUTHOR]

Background The objective of this study was to determine the effects of the N-methyl- d-aspartate ( NMDA) receptor antagonist, memantine (0, 20, 40 mg/d), upon alcohol drinking and craving in heavy drinkers with or without a family history ( FH) of alcoholism, and to explore the modulatory influence of the presence of impulsivity on these outcomes. Methods Ninety-two, nontreatment-seeking, heavy drinkers received memantine or placebo for 8 days. On the eighth day, they received a priming dose of alcohol followed by a 3-hour period of alcohol access. Results Memantine at a dose of 20 mg reduced alcohol craving but did not influence alcohol drinking. No effects of FH were observed. In participants with higher baseline levels of impulsivity, 40 mg of memantine reduced alcohol craving but increased alcohol drinking and alcohol-induced stimulation. Conclusions NMDA receptor signaling may play divergent roles in mediating alcohol cue-induced craving and alcohol drinking in heavy drinkers. The potential efficacy of memantine as monotherapy for alcohol use disorders may be limited by its tendency to disinhibit drinking in some individuals. [ABSTRACT FROM AUTHOR]

Background Quickly progressing from initiating alcohol use to drinking to intoxication recently was identified as a novel risk factor for hazardous drinking in college students (ME Morean et al. [2012] Alcohol Clin Exp Res, 36, 1991-1999). The current study evaluated the risk associated with age of onset ( AO) and delay to first intoxication (Delay) in a high school sample. Methods Adolescent drinkers ( N = 295, age 16.29 [1.14], 55.3% female, 80.3% Caucasian, AO = 13.51 [2.29] years, Delay = 0.80 [1.43] years) completed an anonymous survey about their substance use in February of 2010. Self-report questions assessed AO and age of first intoxication (AI) (i.e., 'How old were you the first time you tried alcohol/got drunk?') and past-month alcohol use/binge drinking (i.e., How often did you drink alcohol/drink ≥5 drinks?). Results Bivariate correlations indicated that AO was positively correlated with AI and inversely correlated with Delay, the frequency of any drinking, and the frequency of binge drinking. When considered alone, Delay was not significantly correlated with either alcohol use outcome. In contrast, hierarchical regression analyses indicated that when considered in concert, an earlier AO and a shorter Delay were each associated with heavier drinking (any drinking adjusted R2 = 0.08; binge drinking R2 = 0.06, p-values <0.001) beyond demographic characteristics. Two-way interactions among study variables were nonsignificant, suggesting that AO and Delay conferred risk similarly by racial/ethnic status, gender, and grade in high school. Conclusions When considered simultaneously, both an early AO and a quick progression to drinking to intoxication appear to be important determinants of high school student drinking. In addition to continuing efforts to postpone AO, efforts designed to delay intoxication may modulate alcohol-related risk associated with early drinking. [ABSTRACT FROM AUTHOR]

Sex differences exist in tobacco smoking behaviors. Nicotine, the primary addictive ingredient in tobacco smoke, indirectly affects γ-amino butyric acid (GABA) function. Previous studies reported sex-by-smoking interactions in brain GABA levels. The goal of the present study was to evaluate if there is a sex-by-smoking interaction at the GABA(A)-benzodiazepine receptors (GABA(A)-BZRs), as well as relationships between GABA(A)-BZR availability and behavioral variables before and after 1 week of smoking cessation. Twenty-six women (8 non-smokers, age 36.0 ± 13.4 years; 19 smokers, age 34.6 ± 8.9 years) and 25 men (8 non-smokers, age 37.9 ± 13.8 years; 17 smokers, 34.1 ± 12.4 years) were imaged using [123I]iomazenil and single-photon emission computed tomography. Smokers were imaged at baseline 7 hours after the last cigarette. A significantly great number of men were able to abstain from smoking for 1 week (P = 0.003). There were no significant differences in nicotine dependence and cigarette craving, mood or pain sensitivity between male and female smokers. There was a significant effect of gender across all brain regions (frontal, parietal, anterior cingulate, temporal and occipital cortices, and cerebellum; P < 0.05), with all women (smokers and non-smokers combined) having a higher GABA(A)-BZR availability than all men. There was a negative correlation between GABA(A)-BZR availability and craving (P ≤ 0.02) and pain sensitivity (P = 0.04) in female smokers but not male smokers. This study provides further evidence of a sex-specific regulation of GABA(A)-BZR availability in humans and demonstrates the potential for GABA(A)-BZRs to mediate tobacco smoking craving and pain symptoms differentially in female and male smokers. [ABSTRACT FROM AUTHOR]

ABSTRACT Sex differences exist in tobacco smoking behaviors. Nicotine, the primary addictive ingredient in tobacco smoke, indirectly affects γ-amino butyric acid (GABA) function. Previous studies reported sex-by-smoking interactions in brain GABA levels. The goal of the present study was to evaluate if there is a sex-by-smoking interaction at the GABAA-benzodiazepine receptors (GABAA-BZRs), as well as relationships between GABAA-BZR availability and behavioral variables before and after 1 week of smoking cessation. Twenty-six women (8 non-smokers, age 36.0 ± 13.4 years; 19 smokers, age 34.6 ± 8.9 years) and 25 men (8 non-smokers, age 37.9 ± 13.8 years; 17 smokers, 34.1 ± 12.4 years) were imaged using [123I]iomazenil and single-photon emission computed tomography. Smokers were imaged at baseline 7 hours after the last cigarette. A significantly great number of men were able to abstain from smoking for 1 week ( P = 0.003). There were no significant differences in nicotine dependence and cigarette craving, mood or pain sensitivity between male and female smokers. There was a significant effect of gender across all brain regions (frontal, parietal, anterior cingulate, temporal and occipital cortices, and cerebellum; P < 0.05), with all women (smokers and non-smokers combined) having a higher GABAA-BZR availability than all men. There was a negative correlation between GABAA-BZR availability and craving ( P ≤ 0.02) and pain sensitivity ( P = 0.04) in female smokers but not male smokers. This study provides further evidence of a sex-specific regulation of GABAA-BZR availability in humans and demonstrates the potential for GABAA-BZRs to mediate tobacco smoking craving and pain symptoms differentially in female and male smokers. [ABSTRACT FROM AUTHOR]

Background: Adolescence is a critical developmental period when tobacco use is initiated and progression to regular smoking occurs. Another growing concern is the mounting evidence of ethnic/racial disparities in the smoking rates and adverse health consequences related to smoking. To reduce ethnic/racial disparities in smoking behaviors, understanding the protective influences against smoking behaviors among minority adolescents is important. Therefore, we examined the role of ethnic pride and parental disapproval of smoking on a wide range of smoking behaviors in ethnic/racial minority and White adolescents attending a suburban high school in Connecticut. Methods: A total of 870 adolescents (ethnic/racial minority: n= 202) completed questions on susceptibility to smoking, ever trying a cigarette, smoking at least one cigarette daily in the past 30 days, as well as parental disapproval of smoking and ethnic pride in a school-wide survey. Results: Logistic regression analyses indicated that perceived parental disapproval of adolescent smoking and ethnic pride were associated with susceptibility to smoking, ever trying a cigarette, and daily smoking differently for minority and White adolescents. For White youth, high parental disapproval of smoking was protective against all three smoking behaviors whereas ethnic pride was not. For minority youth, the combined protective effect of higher ethnic pride and higher parental disapproval of smoking was protective against all smoking behaviors. Conclusion: The protective role of parental disapproval of smoking and ethnic pride on smoking behaviors may inform culturally sensitive smoking interventions aimed at diverse, multi-ethnic youth, and future studies are needed to examine this. (Am J Addict 2012;21:424-434) [ABSTRACT FROM AUTHOR]

In adults, different levels of gambling problem severity are differentially associated with measures of health and general functioning, gambling behaviors, and gambling-related motivations. Here we present data from a survey of 2,484 Connecticut high school students, and investigate the data stratifying by gambling problem severity based on DSM-IV criteria for pathological gambling. Problem/pathological gambling was associated with a range of negative functions; for example, poor academic performance, substance use, dysphoria/depression, and aggression. These findings suggest a need for improved interventions related to adolescent gambling and a need for additional research into the relationship (eg, mediating factors) between gambling and risk and protective behaviors. (Am J Addict 2011;20:495-508) [ABSTRACT FROM AUTHOR]

Many smokers experience subsyndromal anxiety symptoms while smoking and during acute abstinence, which may contribute to relapse. We hypothesized that cortical gamma aminobutyric acidA-benzodiazepine receptor (GABAA-BZR) availability in smokers and nonsmokers might be related to the expression of subsyndromal anxiety, depressive, and pain symptoms. Cortical GABAA-BZRs were imaged in 15 smokers (8 men and 7 women), and 15 healthy age and sex-matched nonsmokers, and 4 abstinent tobacco smokers (3 men; 1 woman) using [123I]iomazenil and single photon emission computed tomography (SPECT). Anxiety and depressive symptoms were measured using the Spielberger's State-Trait Anxiety Index (STAI) and the Center for Epidemiology Scale for Depressive Symptoms (CES-D). The cold pressor task was administered to assess pain tolerance and sensitivity. The relationship between cortical GABAA-BZR availability, smoking status, and subsyndromal depression and anxiety symptoms, as well as pain tolerance and sensitivity, were evaluated. Surprisingly, there were no statistically significant differences in overall GABAA-BZR availability between smokers and nonsmokers or between active and abstinent smokers; however, cortical GABAA-BZR availability negatively correlated with subsyndromal state anxiety symptoms in nonsmokers but not in smokers. In nonsmokers, the correlation was seen across many brain areas with state anxiety [parietal ( r = −0.47, P = 0.03), frontal ( r = −0.46, P = 0.03), anterior cingulate ( r = −0.47, P = 0.04), temporal ( r = −0.47, P = 0.03), occipital ( r = −0.43, P = 0.05) cortices, and cerebellum ( r = −0.46, P = 0.04)], trait anxiety [parietal ( r = −0.72, P = 0.02), frontal ( r = −0.72, P = 0.02), and occipital ( r = −0.65, P = 0.04) cortices] and depressive symptoms [parietal ( r = −0.68; P = 0.02), frontal ( r = −0.65; P = 0.03), anterior cingulate ( r = −0.61; P = 0.04), and temporal ( r = −0.66; P = 0.02) cortices]. The finding that a similar relationship between GABAA-BZR availability and anxiety symptoms was not observed in smokers suggests that there is a difference in GABAA-BZR function, but not number, in smokers. Thus, while subsyndromal anxiety and depressive symptoms in nonsmokers may be determined in part by GABAA-BZR availability, smoking disrupts this relationship. Aberrant regulation of GABAA-BZR function in vulnerable smokers may explain why some smokers experience subsyndromal anxiety and depression. Synapse 63:1089-1099, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Few studies have examined the smoking behaviors of problem gamblers. A high proportion of problem gamblers calling a gambling helpline reported daily tobacco smoking (43.1%). Problem gamblers reporting daily tobacco smoking more frequently acknowledged depression and suicidality secondary to gambling, gambling-related arrests, alcohol and drug use problems, mental health treatment, and problems with casino slot machine gambling. The findings substantiate the relationship in problem gamblers between tobacco smoking and psychiatric symptomatology, particularly other substance use problems. The high proportion of callers reporting daily tobacco smoking highlights the need for enhanced smoking cessation efforts in problem gamblers. [ABSTRACT FROM AUTHOR]