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ObjectiveA pressing tobacco policy concern is how to help smokers who have little interest in quitting cigarettes, a group that often suffers severe health consequences. By switching from cigarettes to e-cigarettes, they could obtain nicotine, potentially with less harm. We examined if policy-relevant attributes of cigarettes/e-cigarettes might encourage these smokers to switch to e-cigarettes.MethodsAn online survey and discrete choice experiment on a nationally-representative sample of adult smokers in the US who reported low interest in quitting (n=2000). We modelled preference heterogeneity using a latent class, latent variable model. We simulated policies that could encourage switching to e-cigarettes.ResultsParticipants formed two latent classes: (1) those with very strong preferences for their own cigarettes; and (2) those whose choices were more responsive to policies. The latter group’s choices were only somewhat responsive to menthol cigarette bans and taxes; the former group’s choices were unresponsive.ConclusionsThe policies studied seem unlikely to encourage harm reduction for individuals with little interest in quitting smoking.

Heterogeneity in the clinical presentation of SARS-CoV-2 infection and COVID-19 progression underscores the urgent need to identify individual-level susceptibility factors that affect infection vulnerability and disease severity. Tobacco product use is a potential susceptibility factor. In this Personal View, we provide an overview of the findings of peer-reviewed, published studies relating tobacco product use to SARS-CoV-2 infection and COVID-19 outcomes, with most studies focusing on cigarette smoking in adults. Findings pertaining to the effects of tobacco product use on the incidence of SARS-CoV-2 infection are inconsistent. However, evidence supports a role for cigarette smoking in increasing the risk of poor COVID-19 outcomes, including hospital admission, progression in disease severity, and COVID-19-related mortality. We discuss the potential effects of tobacco use behaviour on SARS-CoV-2 transmission and infection, and highlight the pathophysiological changes associated with cigarette smoking that could promote SARS-CoV-2 infection and increased disease severity. We consider the biological mechanisms by which nicotine and other tobacco product constituents might affect immune and inflammatory responses to SARS-CoV-2 infection. Finally, we identify current knowledge gaps and suggest priorities for research to address acute and post-acute health outcomes of COVID-19 during and after the pandemic.

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. 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. 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. 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. This study explored associations between kappa opioid receptor levels and aspects of the response to pain via the cold‐pressor task (CPT) in Blacks and Whites with alcohol use disorder (AUD) before and after naltrexone. Differences between black and white participants in response to the CPT, their associations with KOR, and the effect of naltrexone thereon were discovered. Our preliminary observations highlight the need for further investigation into the possible need for individualized treatments of pain and AUD by opiates.

The efficacy of naltrexone to treat alcohol use disorder (AUD) is modest. A better understanding of the neurobiology underlying naltrexone effects could optimize treatments. We evaluated the occupancy of the kappa opioid receptor (KOR) by naltrexone measured with [11C]-LY2795050 positron emission tomography (PET) as a predictor of response to naltrexone. Response to naltrexone was defined as the difference in craving and the difference between the number of drinks consumed during an alcohol drinking paradigm (ADP) before and after 1 week of supervised 100 mg daily oral naltrexone. Forty-four (14 F) nontreatment seeking heavy drinkers meeting criteria for AUD were enrolled. Participants drank 47 ± 16 drinks per week and were balanced in family history of alcoholism (FH, 26 positive). High KOR occupancy (92 ± 1%) was achieved. Occupancy was negatively associated with number of years drinking (YOD) in FH positive, but not FH negative, participants (t3,42= 4.00, p= 0.0003). Higher KOR occupancy by naltrexone was associated with higher alcohol craving during the ADP (F1,81= 4.88, p= 0.030). The reduction in drinking after naltrexone was negatively associated with KOR occupancy, with significant effects of FH status (t1,43= −2.08, p= 0.044). A logistic regression model including KOR occupancy, YOD, and FH variables achieved an 84% prediction accuracy for ≥50% reduction in drinking. These results confirm that naltrexone binds at the KOR site and suggest that KOR occupancy by naltrexone may be related to clinical response. Based on our results, we propose that differential affinities for the mu and KOR could explain why lower doses of naltrexone can have greater clinical efficacy.

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. 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 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. 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.

E-cigarettes are the most-used nicotine product among adolescents, but limited psychometrically-sound, e-cigarette-relevant measures exist for adolescents. We examined psychometric properties of the Self-Report Habit Index (SRHI) for assessing adolescents’ habitual e-cigarette use.

IntroductionRestricting available e-cigarette flavours to only tobacco and menthol may reduce appeal among youth; it is unknown how flavour restrictions impact adults using e-cigarettes to quit smoking cigarettes.MethodsOnline US survey data were collected in summer 2021 from 857 adults who reported using e-cigarettes in a recent attempt to quit smoking. Survey items assessed e-cigarette flavours used during their quit attempt, whether e-cigarette flavour bans restricted access to flavours they like, and what impact the restrictions had on e-cigarette behaviour. Multivariable logistic regression models were used to examine the associations of flavour bans with success quitting smoking for 1 month or longer.Results30.2% (N=259) reported restricted access to e-cigarette flavours they like. During their quit attempt, 64.9% (N=168) used tobacco or menthol-flavoured e-cigarettes, and 90.7% (N=235) used another flavour that could be affected by restrictions, most commonly fruit, mint, and candy/dessert. Responses to flavour restrictions included switching devices to continue using preferred flavours (39.4%), using the same device only with available flavours (35.9%), buying preferred flavours elsewhere (eg, online) (19.3%), making flavours (3.5%) and ‘other’ (eg, no longer using e-cigarettes) (1.9%). The odds of quitting smoking for 1 month or longer were not significantly different between those experiencing flavour restrictions (vs not), preferring tobacco/menthol (vs restricted) flavour, or switching flavours in response to the bans (vs finding another way to obtain restricted flavours) (p>0.11).ConclusionExperiencing e-cigarette flavour restrictions was not associated with success quitting smoking among adults using e-cigarettes to try to quit.

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). 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. 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. 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.

IntroductionMenthol 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.Methods29 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). Repeated-measures analyses examined within-person changes in smoking behaviour when participants were switched from smoking their usual brand menthol cigarettes to a matched-brand non-menthol cigarette for 2 weeks to model a potential ban of menthol cigarettes.ResultsParticipants smoked significantly fewer non-menthol (vs menthol) cigarettes per day (mean decrease=2.2 cigarettes, SD=3.2, p<0.001), confirmed by significant reductions in urine cotinine levels (p=0.013). After switching to non-menthol cigarettes, participants had significantly lower nicotine dependence scores (reduced by >18%, p<0.001) and greater increases in quitting motivation and confidence (rated 1–10) (motivation: mean increase=2.1, SD=2.8, p<0.001; confidence: mean increase=1.3, SD=3.3, p=0.04). Exploratory analyses indicated significant interactions by race (p=0.004); Black smokers had greater reductions in cigarettes per day (mean decrease=3.5 cigarettes, SD=2.8) versus non-Black smokers (mean decrease=0.2, SD=2.6).ConclusionsBanning menthol as a characterising flavour in cigarettes may decrease smoking and reduce the addictive potential of cigarettes among current smokers. Results provide additional support for tobacco regulatory policies banning menthol flavour in an effort to improve public health.Trial registrationNCT03075839.

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. 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. 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. 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. This study provides insight into the synergistic effects of impulsivity‐related traits and family history of alcohol use disorder (FHP) on alcohol outcomes. We found partial support for our hypothesis suggesting traits reflecting deficits in self‐control interacted with FHP to increase risk for alcohol problems. Specifically, we found a stronger association between Barratt Impulsiveness (BIS) poor self‐regulation and impulse control alcohol‐related consequences (displayed) and interpersonal alcohol‐related consequences among FHP. These findings suggest prevention efforts should consider the compounding effects of poor self‐regulation and FHP. The shaded regions in the figure represent confidence intervals.

Glutamate and opioid systems play important roles in alcohol drinking behaviors. We examined if combined treatment with the NMDA antagonist memantine and the opioid antagonist naltrexone, when compared with naltrexone alone, would have a greater influence on alcohol drinking behaviors. Fifty-six, non-treatment-seeking heavy drinkers, with alcohol dependence and a positive family history (FHP) of alcoholism, participated in a randomized, double-blind, crossover trial, including two 6–8 days treatment periods, separated by a 6-day washout, and 3 alcohol drinking paradigm (ADP) sessions. After the first baseline (BAS) ADP1 session, participants were randomized to receive either naltrexone (NTX; 50 mg/day) + placebo memantine, or NTX (50 mg/day) + memantine (MEM; 20 mg/day), during the first treatment period, following which they completed ADP2. After a 6-day washout, participants were crossed over to the treatment they did not receive during the first treatment period, following which they completed ADP3. During each ADP, participants received a priming drink of alcohol followed by 3 1-hour, self-administration periods during which they had ad-lib access to 12 drinks. Individually, both NTX and NTX + MEM, when compared to BAS ADP1, significantly reduced the number of drinks consumed (p’s < 0.001) and craving (p’s < 0.001). When comparing NTX + MEM vs. NTX on number of drinks consumed, there was a significant treatment* sequence interaction (p= 0.004). Specifically, when NTX + MEM followed NTX alone, NTX + MEM resulted in a further reduction in drinking (mean: −1.94; 95% CI: −2.6, −0.8, p= 0.0005). However, when NTX alone followed NTX + MEM, NTX alone did not lead to further reduction in drinking (mean: 0.59; 95% CI: −0.67, 1.43, p= 0.47). Similar patterns were observed for alcohol craving; specifically, a significant reduction in craving was observed when NTX + MEM followed NTX alone (p= 0.009), but craving reduction was maintained when NTX + MEM was followed by NTX alone. Neither treatment condition significantly influenced alcohol-induced stimulation or sedation. Memantine (at a dose of 20 mg/day) enhances the efficacy of naltrexone (50 mg/day) in reducing alcohol drinking and craving among FHP drinkers with beneficial effects that appear to carryover after discontinuation of memantine treatment.

Rates of certain tobacco products have decreased over the past decade, but nicotine use disorder is still prevalent among adolescents. New trends in tobacco use, such as in the use of electronic cigarettes, are creating alarm. This article reviews nicotine addiction and measurement in adolescents, along with potential health risks and comorbidities. Various psychosocial and pharmacologic interventions are reviewed along with novel interventions that show promise for reducing tobacco use in this vulnerable population.

Purpose: Evaluate the feasibility and preliminary efficacy of implementing evidence-based tobacco treatment at the workplace for service industry employees.Design: Randomized trial using 6 paired worksites (3 test and 3 delayed intervention control sites).Setting: US Northeast city.Participants: Employees were recruited from university food service settings.Intervention: Comprehensive smoking treatment was provided at the workplace including individual counseling, free pharmacotherapy (dual nicotine replacement therapy or varenicline), and 5 weeks of contingency management that reinforced abstinence or reductions in smoking to encourage progress toward quitting.Measures: Primary measures included a smoking status survey administered at the end of treatment at the test sites and before treatment began at the delayed intervention control sites.Analysis: Analyses compared rates of quit attempts and successful abstinence for at least 24 hours between the test and delayed intervention control sites.Results: Twenty-five employees were enrolled in treatment. The majority were single (12/25), black (16/25), and reported their educational attainment as high school or less (18/25). Employees in the test (vs delayed intervention control) sites reported higher rates of quit attempts (66.7% vs 12.5%, P= .02) and success quitting for at least 24 hours (53.3% vs 12.5%, P= .08). Participants rated the treatment as very helpful overall.Conclusion: Findings support the feasibility and efficacy of providing workplace-based smoking cessation services and may inform strategies to increase access to treatment.

Opioid receptors are implicated in alcoholism, other addictions, withdrawal, and depression, and are considered potential pharmacological targets for treatment. Our goal in the present study was to compare the availability of kappa opioid receptors (KOR) between an alcohol-dependent cohort (AD) and a healthy control cohort (HC). Sixty-four participants—36 AD and 28 HC—underwent PET scans with [11C]LY2795050, a selective kappa antagonist tracer. Partial-volume correction was applied to all PET data to correct for atrophy. Volume of distribution (VT) of the tracer was estimated regionally as a measure of KOR availability. VTvalues of AD versus HC were compared for 15 defined ROIs. Multivariate analysis showed a main effect of group on VTacross these 15 ROIs. Post hoc tests showed that AD had significantly lower VTand thus a lower KOR availability than HC in amygdala and pallidum (corrected for multiple comparisons). Exploratory analysis of change in VTwith age was conducted; VTwas not found to vary significantly with age in any region. Our findings of lower VTin AD versus HC in multiple regions are in contrast to findings in the mu and delta opioid receptor systems of higher VTin AD versus HC. Although age-related decline in receptors has previously been observed in the mu opioid receptor system, we found that KOR availability does not change with age.

Black people are disproportionately burdened by tobacco-related diseases and are less successful at cigarette cessation with current treatments. We know little about the effectiveness of e-cigarettes as a smoking cessation method compared to currently approved methods in Black adults who smoke. Many Black adults report experiencing racial discrimination in health care, but if discrimination is related to utilization of smoking cessation aids including e-cigarettes and success with smoking cessation in this population is unclear. Therefore, this exploratory study aimed to understand how negative experiences and racial discrimination in health care influence use of e-cigarettes for cigarette cessation and success with cigarette cessation among Black adults.

ABSTRACTBackground:Adolescent smoking is a major public health concern, and current treatments are only somewhat effective in promoting abstinence. One way to improve treatments is to identify psychosocial characteristics that impede cessation, allowing development of targeted treatments. This study examined the influence of 2 such characteristics, life event stressors and coping, on initiation of cessation treatment and end-of-treatment abstinence status. Methods:One hundred five adolescent smokers were eligible to participate in a validated contingency management (CM) and cognitive-behavioral (CBT) cessation treatment; of those, 72 completed at least 1 treatment session. Data included sociodemographic characteristics, questionnaires assessing past-year life events and coping behavior use, and abstinence status at the end of the 4-week treatment. Logistic regression was used to predict treatment initiation and abstinence status, with life event stressor number, coping, or their interaction as predictors. Results:Higher levels of cognitive and peer support coping predicted treatment initiation, whereas life events were unrelated. End-of-treatment abstinence was predicted by higher numbers of life events and greater use of avoidant coping. The interaction of helpless coping and life events also predicted abstinence, with greater increases in helpless coping as total life events rose in abstinent but not nonabstinent participants. Finally, greater use of behavioral coping predicted abstinence in participants exposed to only CM treatment, whereas lesser use of behavioral coping predicted abstinence in participants receiving combined CM/CBT treatment. Conclusions:Exposure to life event stressors may promote cessation by forcing use of self-control resources prior to the quit attempt, which may strengthen such resources. Techniques that improve self-control resources may improve cessation outcome, and prevention programs may want to emphasize behavioral coping to improve rates of treatment initiation.

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ABSTRACT.Background:The study examined in adolescents how alcohol-drinking frequency relates to gambling-related attitudes and behaviors and perceptions of both problem-gambling prevention strategies and adult (including parental) behaviors/attitudes. Methods:A survey assessing alcohol, gambling, and health and functioning measures in 1609 high school students. Students were stratified into low-frequency/nondrinking and high-frequency-drinking groups, and into low-risk and at-risk/problematic gambling groups. Results:High-frequency drinking was associated with at-risk/problematic gambling (χ2(1,N= 1842) = 49.22, P< .0001). High-frequency-drinking versus low-frequency/nondrinking adolescents exhibited more permissive attitudes towards gambling (e.g., less likely to report multiple problem-gambling prevention efforts to be important). At-risk problematic gamblers exhibited more severe drinking patterns and greater likelihood of acknowledging parental approval of drinking (χ2(1, N= 1842) = 31.58, P< .0001). Problem-gambling severity was more strongly related to gambling with adults among high-frequency-drinking adolescents (odds ratio [OR] = 3.17, 95% confidence interval [95% CI] = [1.97, 5.09]) versus low-frequency/nondrinking (OR = 1.86, 95% CI = [0.61, 2.68]) adolescents (interaction OR = 1.78, 95% CI = [1.05, 3.02]). Conclusions:Interrelationships between problematic drinking and gambling in youth may relate to more permissive attitudes across these domains. Stronger links between at-risk/problem gambling and gambling with adults in the high-frequency-drinking group raises the possibility that interventions targeting adults may help mitigate youth gambling and drinking.

ABSTRACT.Background:This study sought to determine the relationship between the frequency of current marijuana and alcohol use and cigarette quit attempts in male and female adolescent smokers. Methods:Data from a cross-sectional survey of health behaviors in high-school-aged adolescents were analyzed. Current cigarette smokers (n= 804) who reported use of at least 1 cigarette in the past month were divided into those with and without a history of at least 1 quit attempt (a self-reported episode of trying to “stop smoking”). Logistic regression models were fit to describe the association between the frequency of marijuana/alcohol use and a history of cigarette quit attempts. Results:Among the total sample, higher-frequency marijuana use (more than 6 times in the past 30 days) and frequent binge drinking (more than 5 days of binge drinking in the past 30 days) decreased the odds of having a past cigarette quit attempt (higher-frequency marijuana: adjusted odds ratio [AOR] = 0.56, 95% confidence interval [CI] = 0.36–0.86; frequent binge drinking: AOR = 0.49, 95% CI = 0.29–0.83). A significant gender interaction was observed for the relationship between higher-frequency marijuana use and a history of cigarette quit attempts (P= .03), with decreased odds in boys (AOR = 0.41, 95% CI = 0.22–0.77) but not in girls (AOR = 0.71, 95% CI = 0.37–1.33). Conclusions:Adolescent smokers who report higher-frequency marijuana use or frequent binge drinking have a decreased likelihood of a history of a cigarette quit attempt. The gender-related association between higher-frequency marijuana use and a history of quit attempts suggests that boys with greater substance use may need particularly intensive support to initiate quit attempts.

Introduction: Smokers with depressive and alcohol use disorders report more severe tobacco abstinence effects (e.g., tobacco withdrawal and craving, mood and sleep disturbance), but less is known about abstinence effects among smokers with subclinical features of these disorders.Aims: The time-course and severity of acute abstinence effects were evaluated in smokers with and without subclinical depressive symptoms (DEP) and with and without subclinical alcohol consumption (ALC). Methods: Participants (N= 106) received smoking cessation counselling and were contingently compensated for biochemically-verified smoking abstinence. Abstinence effects were assessed pre-quit and daily for eight days post-quit.Results/Findings: Seventy-four participants (70%) achieved eight-day continuous smoking abstinence. Generalised estimating equations revealed that time and DEP group significantly interacted to predict change in Wisconsin Smoking Withdrawal Scale (WSWS) Anxiety (Wald = 21.18, p< .01) and Questionnaire of Smoking Urges Relief from Negative Affect (Wald = 20.12, p< .01) subscale scores. Time and ALC group significantly interacted to predict change in Profile of Mood States (POMS) Fatigue subscale score (Wald = 19.78, p< .01). Compared to non-DEP smokers, DEP smokers reported higher mean post-quit scores on several measures of abstinence effects, including WSWS Sadness and POMS Total; however, pre-quit differences between DEP groups may have confounded post-quit differences.Conclusions: Smokers with subclinical depressive symptoms endorsed high levels of abstinence effects, but it was unclear if these were related to the absence of tobacco. Smokers with subclinical alcohol consumption did not endorse high levels of abstinence effects but abstinence-related fatigue took longer to improve.

To examine how factors such as pubertal status, sensation-seeking, and impulsivity are related to substance use (cigarettes, alcohol, and marijuana) in high school students and examine these associations by gender.

Marijuana use in adolescents is associated with many adverse outcomes, including neurobiological and health consequences. Despite this, little is known about gender differences in the correlates of adolescent marijuana use. This study attempted to fill this gap by examining gender differences in the correlates of lifetime and past 30-day marijuana use. Data from a cross-sectional statewide survey of adolescent risk behavior participation in Connecticut were analyzed using 2and hierarchical logistic regression methodologies to examine the demographic, psychosocial, and risk behavior correlates of adolescent marijuana use. Gender-by-trait interactions were tested with hierarchical logistic regression. Of the 4523 participants (51.8% females, 75.8% white), 40.4% endorsed lifetime marijuana use and 24.5% endorsed past 30-day marijuana use. Risk behavior participation, particularly other substance use, had the most robust associations with lifetime and past 30-day adolescent marijuana use; participation in extracurricular activities seemed protective. Gender interactions were observed for African American, Asian, or other race and participation in extracurricular activities; in these 3 cases, males had a greater likelihood of use. They were also observed for having a job (lifetime use only), with females having elevated odds, and past 30-day cigarette smoking (past 30-day use only), with males having elevated odds. Finally, there was preliminary evidence of a faster transition from initiation of marijuana use to regular use in females, when compared with males. These results indicate important gender differences in the correlates of marijuana use in adolescents, and these findings may facilitate the development of gender-informed prevention and early intervention programs for adolescent marijuana use.

This study attempted to evaluate whether impulsive sensation seeking mediated the relationship between parental alcohol problems and offspring alcohol and tobacco use.

This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim, Germany, in October 2004. This symposium explored the potential role of hypothalamic‐pituitary‐adrenal (HPA) axis dysregulation upon relapse. HPA axis stimulation induces the release of the glucocorticoid cortisol, a compound with profound effects upon behavior and emotion. Altered stress‐responses of the HPA axis in abstinent alcohol‐dependent subjects, therefore, may influence their affective and behavioral regulation, thus impacting their potential for relapse. Bryon Adinoff began the symposium with a review of HPA axis dysfunction in alcohol‐dependent subjects, including recent studies from his lab demonstrating an attenuated glucocorticoid response to both endogenous and exogenous stimulation in one‐month abstinent men. Klaus Junghanns presented his work demonstrating that a blunted ACTH or cortisol response to subjective stressors (social stressor or alcohol exposure) is predictive of a return to early drinking. The final two presenters examined the interaction between naltrexone and HPA responsiveness in alcohol‐dependent or at‐risk subjects, as naltrexone induces an increase in ACTH and cortisol. Falk Kiefer discussed the relationship between basal HPA axis responsivity and clinical outcome following treatment with naltrexone or acamprosate. Plasma ACTH significantly decreased over the course of the study in the medication groups, but not the placebo group. Lower basal concentrations of ACTH and cortisol were associated with quicker relapse in the placebo group only. Suchitra Krishnan‐Sarin described her preliminary work, in which family‐history positive (FH+) and family history negative (FH‐) subjects were administered naltrexone, followed by an assessment of alcohol‐induced craving. The cortisol response to alcohol was significantly and inversely related to craving in the FH+, but not the FH‐, subjects. Alterations in HPA axis responsivity may therefore have a negative impact upon clinical outcome in alcohol‐dependent subjects, and disinhibition of the axis with medication may have therapeutic potential.

Nicotine and other constituents of tobacco smoke elevate dopamine (DA) and serotonin (5‐HT) levels in brain and may cause homeostatic adaptations in DA and 5‐HT transporters. Since sex steroids alter DA and 5‐HT transporter expression, the effects of smoking on DA and 5‐HT transporter availability may differ between sexes. In the present study, DA and 5‐HT transporter availabilities were quantitated using single photon emission computed tomography (SPECT) imaging approximately 22 h after bolus administration of [123I]β‐CIT, an analog of cocaine which labels DA and 5‐HT transporters. Forty‐two subjects including 21 pairs of age‐, race‐, and gender‐matched healthy smokers and nonsmokers (12 female and 9 male pairs) were imaged. Regional uptake was assessed by the outcome measures, V3″, which is the ratio of specific (i.e., ROI‐cerebellar activity) to nondisplaceable (cerebellar) activity, and V3, the ratio of specific to free plasma parent. Overall, striatal and diencephalic [123I]β‐CIT uptake was not altered by smoking, whereas brainstem [123I]β‐CIT uptake was modestly higher (10%) in smokers vs. nonsmokers. When subgrouped by sex, regardless of smoking status, [123I]β‐CIT uptake was higher in the striatum (10%), diencephalon (15%), and brainstem (15%) in females vs. males. The sex*smoking interaction was not significant in the striatum, diencephalon, or brainstem, despite the observation of 20% higher brainstem [123I]β‐CIT uptake in male smokers vs. nonsmokers and less than a 5% difference between female smokers and nonsmokers. The results demonstrate higher DA and 5‐HT transporter availability in females vs. males and no overall effect of smoking with the exception of a modest elevation in brainstem 5‐HT transporters in male smokers. Although these findings are preliminary and need validation with a more selective 5‐HT transporter radiotracer, the results suggest that brainstem 5‐HT transporters may be regulated by smoking in a sex‐specific manner. Synapse 41:275–284, 2001. © 2001 Wiley‐Liss, Inc.

Naltrexone, an opiate antagonist, is well tolerated by most alcoholic patients; however, a subset reports significant nausea that can limit the effectiveness of this therapy. The goal of this study was to identify risk factors for naltrexone-precipitated nausea to assist in the development of management strategies to maximize the overall effectiveness of naltrexone. On the basis of the hypothesis that alterations in the endogenous opioid system occur with repeated stimulation of endogenous opioids by alcohol, the authors predicted that the recency and intensity of alcohol use would be related to the risk of naltrexone-induced nausea. One hundred twenty alcohol-dependent subjects participated in an open-label trial of naltrexone. After 5 to 30 days of abstinence, subjects received an initial naltrexone dose of 25 mg followed by a dose of 50 mg daily thereafter for 10 weeks. New-onset adverse effects were rated mild, moderate, or severe after 1 week of naltrexone. Logistic regression analyses were used to predict moderate to severe nausea during the first week of therapy from pretreatment patient characteristics. Moderate to severe nausea was reported by 18 subjects (15%) and was linked to poorer medication compliance and heavier drinking during treatment. Risk of nausea was significantly predicted by age, gender, intensity of drinking, duration of abstinence, and the interaction of abstinence duration and intensity of drinking. At shorter durations of abstinence, lighter drinkers were more likely to experience nausea than heavier drinkers. However, the risk of nausea declined with longer periods of abstinence, particularly for lighter drinkers. Younger age and female gender were associated with higher rates of nausea. These results support the hypothesis that recency and intensity of alcohol use are related to opiate antagonist-precipitated nausea and suggest that long-term alcohol use may result in alterations in the endogenous opioid system. Potential strategies to minimize the risk of nausea in vulnerable individuals are discussed.

This review focuses on the relationship between alcohol dependence and neuropsychiatric and neurocognitive disorders, with an emphasis on the implication of these findings for treatment.In addition, recent reports related to the effects of alcohol on neurotransmitters and neuroregulatory hormones are briefly reviewed. Curr Opin Psychiatry 11:253-257.