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The COVID-19 pandemic has resulted in pronounced changes for college students, including shifts in living situations and engagement in virtual environments. Although college drinking decreased at the onset of the pandemic, a nuanced understanding of pandemic-related changes in drinking contexts and the risks conferred by each context on alcohol use and related consequences have yet to be assessed.Secondary data analyses were conducted on screening data from a large parent clinical trial assessing a college student drinking intervention (N = 1669). Participants across six cohorts (from Spring 2020 to Summer 2021) reported on the frequency of drinking in each context (i.e., outside the home, home alone, home with others in-person, and home with others virtually), typical amount of drinking, and seven alcohol-related consequence subscales.Descriptive statistics and negative binomial regressions indicated that the proportion and frequency of drinking at home virtually with others decreased, while drinking outside the home increased from Spring 2020 to Summer 2021. Limited differences were observed in the proportion or frequency of individuals drinking at home alone or at home with others in-person. Negative binomial and logistic regressions indicated that the frequency of drinking outside the home was most consistently associated with more alcohol-related consequences (i.e., six of the seven subscales). However, drinking at home was not without risks; drinking home alone was associated with abuse/dependence, personal, social, hangover, and social media consequences; drinking home with others virtually was associated with abuse/dependence and social consequences; drinking home with others in-person was associated with drunk texting/dialing.The proportion and frequency of drinking in certain contexts changed during the COVID-19 pandemic, although drinking outside the home represented the highest risk drinking context across the pandemic. Future prevention and intervention efforts may benefit from considering approaches specific to different drinking contexts.

The anterior insular cortex (AIC), a prominent salience network node, integrates interoceptive information and emotional states into decision making. While AIC activation during delay discounting (DD) in alcohol use disorder (AUD) has been previously reported, the associations between AIC activation, impulsive choice, alcohol consumption, and connectivity remain unknown. We therefore tested AIC brain responses during DD in heavy drinkers and their association with DD performance, alcohol drinking, and task-based connectivity.Twenty-nine heavy drinkers (12 females; mean (SD) age=31.5 ± 6.1 years; mean (SD)=40.8 ± 23.4 drinks/week) completed a DD task during functional MRI. Regions activated during DD decision making were tested for correlation with DD behavior and alcohol drinking. Psychophysiological interaction (PPI) models assessed the task-dependent functional connectivity (FC) of activation during choice.Delay discounting choice activated bilateral anterior insular cortex, anterior cingulate cortex, and left precentral gyrus. Right dorsal (d) AIC activation during choice negatively correlated withdiscounting of delayed rewards and alcohol consumption. PPI analysis revealed FC of the right dAIC to both the anterior and posterior cingulate cortices-key nodes in the midline default mode network.Greater dAIC involvement in intertemporal choice may confer more adaptive behavior (lower impulsivity and alcohol consumption). Moreover, salience network processes governing discounting may require midline default mode (precuneus/posterior cingulate cortex) recruitment. These findings supporta key adaptive role for right dAIC in decision making involving future rewards and risky drinking.

The possibility of residual impairment of cognitive performance after multiday drinking sessions is particularly important given the potential for the deleterious effects of fatigue and hangover. This pilot study aimed to devise a methodology to compare sober performance on driving-relevant attentional tasks at the end of a 4-day music festival with performance at varying levels of the breath-alcohol curve.Fifty-two participants completed selective and sustained attention tasks at a breath alcohol concentration (BrAC) of 0.00%, 0.05%, and 0.08% following acute dosing in a controlled laboratory setting. A subset of participants (n = 13) were then tested at the conclusion of a 4-day music festival at 0.00% BrAC, with task performance compared with laboratory results.During the laboratory phase, sustained attention was poorer at the 0.05% ascending timepoint only (compared to 0.00% BrAC). During the festival phase, participants made a greater number of errors on the selective attention task predeparture than at 0.00% and 0.05% BrAC in the laboratory. Sustained attention performance was poorer while intoxicated in the laboratory.Our findings suggest that the absence of blood alcohol acutely may not be indicative of unimpaired cognitive performance and that other factors related to multiday drinking may produce driving-related attentional deficits. The findings reinforce the need to measure attentional performance in real-world drinking contexts despite the methodological complexities of doing so. A larger study is warranted to replicate the findings and should include attentional measures that either are more sensitive to the effects of acute alcohol intoxication than those in our study or are based on a driving simulator.

Day drinking, or drinking during the daytime, is a term used colloquially in the media and among college students based on anecdotal evidence. Drinking at tailgate parties, generally thought to be a type of day drinking, tends to be particularly heavy and to achieve levels comparable to drinking on holidays and special occasions. The objective of this study was to assess how many and how often students day drink and whether day drinking days (i.e., days drinking began before 4:00 p.m.) were associated with heavy drinking, legal intoxication, negative alcohol-related consequences, and three risky substance use behaviors.We conducted a longitudinal daily diary study of college students who were followed for their first seven semesters of college. The analytic sample includes 7,633 drinking days nested with 619 student drinkers. We used logistic and Poisson multilevel models to test associations between day drinking days and substance use outcomes and negative consequences.Approximately 50% of drinkers drank durinng the day at least once, and day drinking occurred on 9% of drinking days. Greek organization participants reported significantly more day drinking days than non-participants. Day drinking days were characterized by heavy drinking as evidenced by strong, positive associations between day drinking and drinking to heavy episodic drinking (HED) and high-intensity drinking (HID) thresholds on a given day. In contrast, students were less likely to reach legal intoxication and experienced fewer negative alcohol-related consequences on day drinking days than days on which drinking began in the evening or nighttime. Students who reported day drinking more often throughout the study also reported having more days of drinking at the HED and HID thresholds and playing drinking games and mixed alcohol with energy drinks more frequently.Day drinking was common among this sample of college students. Findings suggest that day drinking days may be characterized by heavy drinking and may be a behavior most typically engaged in by heavy drinkers, including members of Greek organizations.

Background Alcohol intoxication produces ataxia by affecting the cerebellum, which coordinates movements. Fragile X mental retardation (FMR) protein is a complex regulator of RNA and synaptic plasticity implicated in fragile X-associated tremor/ataxia syndrome, which features ataxia and increased Fmr1 mRNA expression resulting from epigenetic dysregulation of FMRP. We recently demonstrated that acute ethanol-induced ataxia is associated with increased cerebellar Fmr1 gene expression via histone modifications in rats, but it is unknown whether similar behavioral and molecular changes occur following chronic ethanol exposure. Here, we investigated the effects of chronic ethanol exposure on ataxia and epigenetically regulated changes in Fmr1 expression in the cerebellum. Methods Male adult Sprague-Dawley rats were trained on the accelerating rotarod and then fed with chronic ethanol or a control Lieber-DeCarli diet while undergoing periodic behavioral testing for ataxia during ethanol exposure and withdrawal. Cerebellar tissues were analyzed for expression of the Fmr1 gene and its targets using a real-time quantitative polymerase chain reaction assay. The epigenetic regulation of Fmr1 was also investigated using a chromatin immunoprecipitation assay. Results Ataxic behavior measured by the accelerating rotarod behavioral test developed during chronic ethanol treatment and persisted at both the 8-h and 24-h withdrawal time points compared to control diet-fed rats. In addition, chronic ethanol treatment resulted in up-regulated expression of Fmr1 mRNA and increased activating epigenetic marks H3K27 acetylation and H3K4 trimethylation at 2 sites within the Fmr1 promoter. Finally, measurement of the expression of relevant FMRP mRNA targets in the cerebellum showed that chronic ethanol up-regulated cAMP response element binding (CREB) Creb1, Psd95, Grm5, and Grin2b mRNA expression without altering Grin2a, Eaa1, or histone acetyltransferases CREB binding protein (Cbp) or p300 mRNA transcripts. Conclusions These results suggest that epigenetic regulation of Fmr1 and subsequent FMRP regulation of target mRNA transcripts constitute neuroadaptations in the cerebellum that may underlie the persistence of ataxic behavior during chronic ethanol exposure and withdrawal.

Background The preference for immediate rewards and high sensation seeking are both potent risk factors for alcohol use disorder (AUD), but how they interact during intoxication is poorly understood. To model decision making linked to AUD risk, we tested heavy drinkers for impulsive choice (delay discounting with alcohol:money or money:money) and behavioral sensation seeking using a novel odor choice task. Laboratory tasks measured actual behavior with real contingencies. Our goals were to determine, in heavy drinkers, (i) alcohol's effects on delay discounting, and (ii) how AUD risk factors relate to delay discounting, and (iii) how delay discounting with alcohol choices compares with strictly monetary choices. Methods Thirty-five heavy drinkers (≥2 binges per month; age = 22.8 ± 2.2; 20 male; 5.8 ± 2.3 drinks/drinking day) performed cross-commodity discounting (CCD) of immediate alcohol vs. delayed money, a monetary delay discounting (DD), and behavioral sensation-seeking tasks. CCD and DD were performed while sober and during controlled alcohol infusion targeting 0.08 g/dl. The behavioral sensation-seeking task presented binary choices of odorants varying in intensity and novelty, and the risk of exposure to a malodorant. Results CCD and DD behaviors were highly correlated across conditions, mean r = 0.64. Alcohol increased delayed reward preference in DD, p = 0.001, but did not alter mean CCD, p > 0.16. However, alcohol-induced changes in CCD correlated with behavioral sensation seeking, such that higher sensation seekers' immediate alcohol preference increased when intoxicated, p = 0.042; self-reported sensation seeking was uncorrelated, ps > 0.08. Behavioral sensation seeking also correlated with "want" alcohol following a priming dose targeting 0.035 g/dl, p = 0.021. CCD and DD did not correlate with self-reported drinking problems or other personality risk traits. Conclusions Alcohol increased impulsive alcohol choice in high sensation seekers, suggesting an interaction that may underlie impaired control of drinking, at least in a subset of heavy drinkers-consistent with models highlighting high novelty/sensation-seeking AUD subtypes. Discounting behavior overall appears to be a generalized process, and relatively stable across methods, repeated testing, and intoxication. These findings further support the utility of behavioral tasks in uncovering key behavioral phenotypes in AUD.

BACKGROUND: The Monkey Alcohol and Tissue Research Resource (MATRR) is a repository and analytics platform for detailed data derived from well-documented Non-Human Primate (NHP) alcohol self-administration studies. This macaque model has demonstrated categorical drinking norms reflective of human drinking populations, resulting in consumption pattern classifications of Very Heavy Drinking (VHD), Heavy Drinking (HD), Binge Drinking (BD), and Low Drinking (LD) individuals. Here we expand on previous findings that suggest ethanol drinking patterns during initial drinking to intoxication can reliably predict future drinking category assignment. METHODS: The classification strategy uses a machine learning approach to examine an extensive set of daily drinking attributes during 90 sessions of induction across seven cohorts of five to eight monkeys for a total of 50 animals. A Random Forest classifier is employed to accurately predict categorical drinking after 12 months of self-administration. RESULTS: Predictive outcome accuracy is approximately 78% when classes are aggregated into two groups, "LD and BD" and "HD and VHD". A subsequent two-step classification model distinguishes individual LD and BD categories with 90% accuracy and between HD and VHD categories with 95% accuracy. Average four-category classification accuracy is 74%, and provides putative distinguishing behavioral characteristics between groupings. CONCLUSION: We demonstrate that data derived from the induction phase of this ethanol self-administration protocol has significant predictive power for future ethanol consumption patterns. Importantly, numerous predictive factors are longitudinal, measuring the change of drinking patterns through three stages of induction. Factors during induction that predict future heavy drinkers include being younger at the time of first intoxication and developing a shorter latency to first ethanol drink. Overall, this analysis identifies predictive characteristics in future very heavy drinkers that optimize intoxication, such as having increasingly fewer bouts with more drinks. This analysis also identifies characteristic avoidance of intoxicating topographies in future low drinkers, such as increasing number of bouts and waiting longer before the first ethanol drink. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved. Language: en

BACKGROUND. Driving under the influence (DUI) programs are a unique setting to reduce disparities in treatment access to those who may not otherwise access treatment. Providing evidence-based therapy in these programs may help prevent DUI recidivism. METHODS. We conducted a randomized clinical trial of 312 participants enrolled in one of three DUI programs in California. Participants were 21 and older with a first-time DUI offense who screened positive for at-risk drinking in the past year. Participants were randomly assigned to a 12-session manualized cognitive behavioral therapy (CBT) or usual care (UC) group, and then surveyed 4- and 10-months later. We conducted intent-to-treat analyses to test the hypothesis that participants receiving CBT would report reduced impaired driving, alcohol consumption (drinks per week, abstinence, and binge drinking), and alcohol-related negative consequences. We also explored whether race/ethnicity and gender moderated CBT findings. RESULTS. Participants were 72.3% male, 51.7% Hispanic, with an average age of 33.2 (SD = 12.4). Relative to UC, participants receiving CBT had lower odds of driving after drinking at the 4-month and 10-month follow-ups compared to participants receiving UC (odds ratio (OR)=0.37, p=0.032, and OR=0.29, p=0.065, respectively). This intervention effect was more pronounced for females at 10-month follow-up. The remaining four outcomes did not significantly differ between UC versus CBT at 4- and 10-month follow-ups. Participants in both UC and CBT reported significant within-group reductions in two of five outcomes, binge drinking and alcohol-related consequences, at 10-month follow-up (p

BACKGROUND Erythrocyte mean corpuscular volume (MCV) has been used for decades as a biomarker of chronic alcohol abuse and in the treatment of alcohol dependence. More recently, it has also been adopted to investigate the fitness of subjects to hold the driving license to prevent traffic accidents. So far, however, the studies on the association of MCV with an increased risk of alcohol-associated car accidents are extremely scarce, if not totally absent. To the best of our knowledge, the present work is the first specifically aimed at studying a plausible association between elevated MCV and crash accidents correlated with alcohol abuse. METHODS A total of 6,244 drivers involved in traffic accidents underwent mandatory laboratory analyses including blood alcohol concentration (BAC) determination and MCV analysis. BAC and MCV determinations were performed by headspace gas chromatography and complete blood count, respectively. RESULTS The chi-square test evaluating the proportions of subjects with elevated MCVs (>95 fl) yielded a highly significant result (χ2 = 68.0; p 0.5 g/l). However, when considering only drivers showing BACs in the range of 0.51 to 1.5 g/l, the frequencies of elevated MCV values are fairly comparable (χ2 = 0.062, p = 0.80). In contrast, limiting the evaluation to BACs > 1.5 g/l, the frequency of elevated MCVs raised to 19.1% (χ2 = 58.9, p value

BACKGROUND: Bystander training programs aim to encourage third-party witnesses to intervene in high-risk sexual situations; however, these programs rarely focus on training bystanders to effectively intervene when intoxicated. This is not surprising due to the limited evidence on the proximal effects of alcohol on bystander intervention for sexual aggression. To this end, the aim of the present study was to test the effects of men’s self-reported intent to help strangers and acute alcohol intoxication on the likelihood and speed of sexual aggression intervention. METHODS: Participants were 74 men who completed a measure of intent to help (Session 1) and were randomly assigned to consume alcohol or a no-alcohol control beverage (Session 2). Next, they engaged in a novel laboratory paradigm in which they and four confederates (two men, two women) watched a female confederate, who reported a strong dislike of sexual content in the media, view a sexually explicit film which they could stop at any time. Bystander intervention was operationalized as whether and how quickly participants stopped the film. RESULTS: Findings indicated that (1) intent to help strangers predicted faster sexual aggression intervention, and (2) intent to help strangers predicted a higher likelihood and faster rate of sexual aggression intervention among sober, but not intoxicated, men. This latter finding suggests that among men who endorsed a high willingness to intervene in sexual aggression, alcohol intoxication decreased intervention behavior. CONCLUSIONS: Results demonstrate that alcohol functions as a barrier to intervention for men who would otherwise intervene. Findings are interpreted using an integrative framework for intoxicated sexual aggression intervention and highlight the need for bystander training programs to incorporate alcohol interventions to reduce heavy drinking and psychoeducation to train bystander how to intervene when intoxicated.

Background This study tested a moderated-mediational model whereby dimensions of impulsivity (i.e., negative urgency, positive urgency, sensation seeking, lack of premeditation, and lack of perseverance) differentially predict perpetration of physical intimate partner aggression through problematic drinking in intoxicated and non-intoxicated heavy drinkers. Methods Participants were 249 heavy drinkers (148 men and 101 women) with a recent history of psychological and/or physical intimate partner aggression perpetration toward their current partner recruited from two metropolitan U.S. cities. Participants completed questionnaires that assessed impulsivity and problematic drinking, consumed an alcohol or no-alcohol control beverage, and completed a shock-based aggression task in which they were ostensibly provoked by their intimate partner Results Results indicated an indirect effect of urgency on intimate partner aggression through problematic drinking that was significantly more positive in intoxicated individuals Conclusions These findings implicate a tendency to act rashly in response to emotions as the specific dimension of impulsivity associated with problematic drinking, which in turn exacerbates risk for intimate partner aggression perpetration. Results also suggest acute effects of alcohol are key in facilitating this mechanism. This article is protected by copyright. All rights reserved.

Background Young adult use of alcohol mixed with energy drinks (AmEDs) has been linked with elevated risks for a constellation of problem behaviors. These risks may be conditioned by expectancies regarding the effects of caffeine in conjunction with alcohol consumption. The aim of this study was to describe the construction and psychometric evaluation of the Intoxication-Related AmED Expectancies Scale (AmED_EXPI), 15 self-report items measuring beliefs about how the experience of AmED intoxication differs from the experience of noncaffeinated alcohol (NCA) intoxication. Methods Scale development and testing were conducted using data from a U.S. national sample of 3,105 adolescents and emerging adults aged 13-25. Exploratory and confirmatory factor analyses were conducted to evaluate the factor structure and establish factor invariance across gender, age, and prior experience with AmED use. Cross-sectional and longitudinal analyses examining correlates of AmED use were used to assess construct and predictive validity. Results In confirmatory factor analyses, fit indices for the hypothesized four-factor structure (i.e., Intoxication Management [IM], Alertness [AL], Sociability [SO], and Jitters [JT]) revealed a moderately good fit to the data. Together, these factors accounted for 75.3% of total variance. The factor structure was stable across male/female, teen/young adult, and AmED experience/no experience subgroups. The resultant unit-weighted subscales showed strong internal consistency and satisfactory convergent validity. Baseline scores on the IM, SO, and JT subscales predicted changes in AmED use over a subsequent three-month period. Conclusions The AmED_EXPI appears to be a reliable and valid tool for measuring expectancies about the effects of caffeine during alcohol intoxication. This article is protected by copyright. All rights reserved.

Background A functional polymorphism within the μ-opioid receptor (OPRM1) gene, rs1799971 (A118G), previously has been associated with measures of alcohol use and sensitivity to its effects, but findings have been inconclusive. A recent study suggested that a second nearby variant within OPRM1, rs3778150, is robustly associated with heroin dependence and fully explained a smaller observed association with rs1799971. Given evidence that the rs3778150-C allele is associated with decreased OPRM1 expression levels in the human brain, the current study sought to test the hypothesis that rs3778150 represents a causal variant within OPRM1 that increases risk for a variety of alcohol use phenotypes. Methods Participants with genotype and phenotype data from a larger experimental study (N = 152) were assessed on measures of subjective response to alcohol and alcohol use. Measures included (i) the Self-Rating of the Effects of Alcohol and the Alcohol Sensitivity Questionnaire, (ii) the Biphasic Alcohol Effects Scale (BAES) and ratings of subjective intoxication, and (iii) average number of drinks per week in the past month. Results Compared to rs3778150-T homozygous individuals, carriers of the rs3778150-C allele exhibited significantly lower retrospective self-report levels of alcohol sensitivity. Carriers of the rs3778150-C allele also exhibited lower levels of BAES alcohol-related stimulation during an alcohol challenge and reported higher levels of drinking in the last 30 days. With the exception of lower levels of BAES alcohol-related sedation, the rs1799971 variant did not show consistent significant association with any of the alcohol phenotypes in the presence of rs3778150. Conclusions Results suggest that rs3778150 may be causally related to alcohol use phenotypes, and could potentially account for previously observed associations of rs1799971 with substance use phenotypes. Future studies may investigate potential causal relations among genetic variants in OPRM1, subjective response to alcohol, and drinking phenotypes to further delineate the effects of rs3778150.

BACKGROUND: Vehicle alcohol ignition interlocks reduce alcohol-impaired driving recidivism while installed, but recidivism reduction does not continue after removal. It has been suggested that integrating alcohol use disorder (AUD) treatment with interlock programs might extend the effectiveness of interlocks in reducing recidivism beyond their removal. This study evaluated the first implementation of a Florida policy mandating AUD treatment for driving under the influence (DUI) offenders on interlocks. Treatment was required when the offender accumulated 3 violations (defined as 2 "lockouts" within 4 hours; a lockout occurs when the device prevents a drinking driver from starting the vehicle). METHODS: Cox regression was used to compare alcohol-impaired driving recidivism during the 48 months following the interlock removal between 2 groups: (i) 640 multiple DUI offenders who received AUD treatment while interlocks were installed; and (ii) 806 matched offenders not mandated to treatment while interlocks were installed. RESULTS: The ignition interlock plus treatment group experienced 32% lower recidivism, 95% confidence interval [9, 49], following the removal of the interlock during the 12 to 48 months in which they were compared with the nontreatment group. We estimated that this decline in recidivism would have prevented 41 rearrests, 13 crashes, and almost 9 injuries in crashes involving the 640 treated offenders over the period following interlock removal. CONCLUSIONS: This study provides strong support for the inclusion of AUD treatment for offenders in interlock programs based on the number of times they are "locked out." The offenders required to attend treatment demonstrated a one-third lower DUI recidivism following their time on the interlock compared to similar untreated offenders.Copyright © 2016 by the Research Society on Alcoholism. Language: en

Background Using a social transmission of food preference paradigm in rats, we previously demonstrated that ethanol (EtOH) exposure during adolescence, as either an observer (interaction with an intoxicated conspecific) or demonstrator (intragastric infusion with EtOH), altered the reflexive odor-mediated responses to the drug. The 2 modes of exposure were equivalent in the magnitude of their effects. Human adolescents, however, are likely to experience the drug in a social setting as both an EtOH observer and demonstrator. That is, both interacting with an intoxicated peer and experiencing EtOH's postingestive consequences in conjunction with hematogenic olfaction. Therefore, we tested whether combined adolescent exposure as both an observer and demonstrator differed from either form of individual experience. Methods Beginning on postnatal day (P) 29, naive rats received EtOH or water exposures in a social interaction paradigm as either an observer, a demonstrator, or combined experience (where each animal in the interaction was, itself, an observer and demonstrator). Exposures occurred 4 times, once every 48 hours. On P37, the reflexive behavioral response to EtOH odor was tested, using whole-body plethysmography. Results The odor-mediated responses of adolescent EtOH observers, demonstrators, and combined exposure animals all significantly differed from controls. Compared to controls, however, the magnitude of the behavioral effect was greatest in the combined exposure animals. Moreover, combined exposure as both an EtOH observer and demonstrator significantly differed from either form of individual EtOH experience. Conclusions EtOH's component chemosensory qualities are known to be central contributors to its acceptance and increases in the acceptability of EtOH's odor, resulting from a social transmission experience, are predictive of enhanced EtOH avidity in adolescence. Our findings demonstrate that combined exposure as an observer and demonstrator, within a socially relevant framework, may represent a higher risk scenario for increased EtOH avidity in adolescence (and by extension adult persistence) as compared to the individual effects of direct ingestion or social experience with the drug.

The genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) are associated with the risk of alcoholism and upper aerodigestive tract cancer in alcoholics. Salivary ethanol (sEtOH) levels are well correlated with blood EtOH levels.To study the effects of ADH1B and ALDH2 genotypes on the alcohol elimination rate (AER) and salivary acetaldehyde (sAcH) levels, we measured the sEtOH and sAcH levels twice at a 1-hour intervals in 99 intoxicated Japanese alcoholic men who had stopped drinking for 4 or more hours.The initial sEtOH levels did not differ between the ADH1B*2 group (n = 50) and the ADH1B*1/*1 group (n = 49) (median: 0.617 vs. 0.762 mg/ml). The salivary AER (sAER) increased as the sEtOH levels increased (p 0.0001). After stratification according to the sEtOH levels (0.4, 0.4 to 0.99, and ≥1.00 mg/ml), the median sAER of the ADH1B*2 group was 0.075, 0.188, and 0.228 mg/ml/h, respectively, and that of the ADH1B*1/*1 group was 0.037, 0.115, and 0.233 mg/ml/h, respectively. The sAER of the ADH1B*2 group was faster than that of the ADH1B*1/*1 group overall (p = 0.001) and when the sEtOH category was 0.4 to 0.99 mg/ml (p 0.0001). The ADH1B genotype and the sEtOH levels had an interaction effect on the sAER (p = 0.036). A multiple linear regression analysis with a stepwise procedure selected the ADH1B*2 allele (p = 0.004) and the sEtOH levels (p 0.0001) as positive predictors of sAER. The sAER did not differ according to the ALDH2 genotype. The sAcH levels were higher than the blood AcH levels reported in alcoholics, probably because of AcH production by oral microorganisms. The sAcH of the ALDH2*1/*2 group (n = 18) was higher than that of the ALDH2*1/*1 group (n = 81) overall (p = 0.0008) and when the corresponding sEtOH category was ≥1.00 mg/ml (median: 3.195 vs. 1.776 μg/ml, p = 0.009). A multiple linear regression analysis selected the ALDH2*1/*2 and the sEtOH levels as positive predictors of the sAcH levels (p 0.0001).The enhanced AER in ADH1B*2 carriers and the increased sAcH levels in ALDH2*1/*2 carriers among intoxicated alcoholics provide possible mechanisms explaining how each genetic polymorphism affects the risk of alcoholism and upper aerodigestive tract cancer.

BACKGROUND: Early onset drinking is associated with later heavy drinking and related consequences. Early drinking onset and binge drinking are also independently associated with blackouts, which are periods of amnesia for events during a drinking episode. The objective of this study was to examine how early onset drinking relates to changes in the frequency of experiencing blackouts across 3 years controlling for year-specific binge drinking. METHODS: Participants (N = 1,145; 67.9% female) from a 6-year, longitudinal study are included in these analyses. Measures of self-reported age at drinking onset included ages at first drink, first high, and first drunk, which were used to create a latent early onset drinking factor. Frequency of binge drinking and blackouts were assessed annually during Years 4 to 6. RESULTS: Overall, 69.2% of participants reported experiencing blackouts. After controlling for year-specific binge drinking, a growth curve model indicated that early onset drinkers reported more frequent blackouts at Year 4. There were, however, no significant effects of acceleration or deceleration in the frequency of blackouts across the 3 years. Early onset drinkers continued to experience more frequent blackouts compared with those who initiated alcohol use later, despite decreases in binge drinking over time. CONCLUSIONS: Early onset drinkers reported more frequent blackouts across all 3 years, indicating that early alcohol initiation predisposes those individuals to continue to experience more frequent blackouts, despite a decrease in their binge drinking. This may be due to various factors, such as altered hippocampal development and functioning resulting from early alcohol exposure. Language: en

BACKGROUND: Sipping alcohol is common during early adolescence, but research has ignored the distinction between sipping and drinking whole alcohol beverages, conflating the 2, or else simply classifying "sippers" as abstainers. Research has not addressed whether sippers are different to drinkers, in relation to variables known to be associated with adolescent alcohol consumption, or considered whether sipping and drinking behaviors may have quite different associations. METHODS: Parent-child dyads (N = 1,823) were recruited in 3 states from Australian grade 7 classes. Multinomial logistic analyses compared adolescents who had only had a sip/taste of alcohol (sippers) with adolescents who had consumed at least a whole drink (drinkers) in the past 6 months. The multivariate model assessed a broad range of demographics, parenting practices, peer influences, and adolescent externalizing and internalizing behaviors, and controlled for school clustering. RESULTS: Compared to drinkers, sippers were less likely to come from 1-parent households (odds ratio [OR] = 0.59, 95% confidence interval [CI]: 0.35 to 0.98); less likely to come from low-socioeconomic status (SES) households (OR = 0.54, 95% CI: 0.31 to 0.94); more likely to come from families where parents provide stricter alcohol-specific rules (OR = 1.21, 95% CI: 1.11 to 1.32), stricter monitoring of the child's activities (OR = 1.10, 95% CI: 1.04 to 1.16), more consistent parenting practices (OR = 1.13, 95% CI: 1.05 to 1.23), and more positive family relationships (OR = 1.56, 95% CI: 1.02 to 2.43); and report having fewer substance-using peers (OR = 0.80, 95% CI: 0.70 to 0.91) and greater peer disapproval of any substance use (OR = 1.30, 95% CI: 1.19 to 1.42). After adjustment for confounders, the associations with household composition and SES were no longer significant, but the familial and peer associations remained significant in the multivariate analysis, χ(2) (40) = 1,493.06, p CONCLUSIONS: Sipping alcohol has different associations with known predictors of adolescent alcohol use than drinking whole beverages, and sipping may be a distinct or separable behavior. Future research should better define quantities of early consumption and assess the relationship between early sipping and drinking on long-term outcomes separately. Language: en

To control underage drinking in the United States, which has been associated with an estimated 5,000 deaths and 2.6 million injuries or other harm annually, each state has developed a unique set of laws. Previous research examining these laws' effectiveness has frequently focused on the laws' existence without considering variance in sanctions, enforcement, or exemptions.We scored 20 minimum legal drinking age 21 (MLDA-21) laws for their strengths and weaknesses based on (i) sanctions for violating the law, (ii) exceptions or exemptions affecting application, and (iii) provisions affecting the law or enforcement. We then replicated a 2009 study of the effects of 6 MLDA-21 laws in 3 different ways (using identical structural equation modeling): Study 1-8 additional years of data, no law strengths; Study 2-years from the original study, added law strengths; Study 3-additional years, law strengths, serving as an update of the 6 laws' effects.In all 3 studies-and the original study-keg registration laws were associated with both an unexpected significant increase (+11%, p0.001) in underage drinking-driver ratios and a notable 25% reduction in per capita beer consumption-opposing results that are difficult to explain. In Study 3, possession and purchase laws were associated with a significant decrease in underage drinking-driver fatal crash ratios (-4.9%, p0.001; -3.6%, p0.001, respectively). Similarly, zero tolerance and use and lose laws were associated with reductions in underage drinking-driver ratios (-2.8%, p0.001; -5.3%, p0.001, respectively).Including strengths and weaknesses of underage drinking laws is important when examining their effects on various outcomes as the model fit statistics indicated. We suggest that this will result in more accurate and more reliable estimates of the impact of the laws on various outcome measures.

Background: Ethanol exposure contributes to infectious complications in burn and trauma patients through a process known as “bacterial translocation.” Two major factors, 1) physical disruption of the intestinal mucosal barrier and 2) suppression of immune defense, explain this phenomenon. However, little information is available concerning the immune mechanisms of ethanol-induced bacterial translocation. In this study we investigated the effect of physiological concentrations of ethanol on immune function, especially on CXC-chemokine secretion, neutrophil migration, and barrier function in the small intestine Methods: A rat small intestinal intestinal cell line (IEC-18 cells) was exposed to 50–500 mM ethanol for 24 hr with or without IL-1β. Secretion of CXC chemokines (GRO/CINC-1 and MIP-2) was measured by ELISA assay, and barrier dysfunction was assessed by the apical-to-basolateral flux of HRP-dextran. Neutrophil transmigration was assessed by enzyme histochemistry (AS-D chloroesterase staining) Results: Exposure to ethanol concentrations of 200mM and over increased GRO/CINC-1 secretion, and MIP-2 secretion increased at 500 mM. Administration of ethanol in combination with IL-1β had no additive effect on the release of GRO/CINC-1 and MIP-2. Exposure of IEC-18 monolayers to ethanol resulted in a dose-dependent increase in peameability but IL-1β had no effect on barrier function. Ethanol had no effect on neutrophil migration in enzyme histochemistry analysis Conclusions: The above observations suggest that ethanol induced physical disruption of the intestine but not neutrophil transmigration is the main cause of the bacterial translocation that leads to bacteremia and endotoxemia in alcoholics.

BACKGROUND: Alcohol-related driving accidents and fatalities occur most frequently at nighttime and at dawn, that is, a mesopic lighting condition in which visual processing depends on both rod and cone photoreceptors. The temporal functions of the rod and cone pathways are critical for driving in this lighting condition. However, how alcohol influences the temporal functions in the rod and cone pathways at mesopic light levels is inconclusive. To address this, this study investigated whether an acute intoxicating dose of alcohol impairs rod- and/or cone-mediated critical fusion frequency (CFF; the lowest frequency of which an intermittent or flickering light stimulus is perceived as steady). METHODS: In Experiment I, we measured the CFFs for 3 types of visual stimuli (rod stimulus alone, cone stimulus alone, and the mixture of both stimuli types), under 3 illuminant light levels (dim illuminance: 2 Td; low illuminance: 20 Td; and medium illuminance: 80 Td) in moderate-heavy social drinkers before and after they consumed an intoxicating dose of alcohol (0.8 g/kg) compared with a placebo beverage. In Experiment II, we examined whether the illuminance level (dark vs. light) of the visual area surrounding the test stimuli alters alcohol's effect on the temporal processing of rods and cones. RESULTS: The results showed that compared with placebo, alcohol significantly reduced CFFs of all stimulus types at all illuminance levels. Furthermore, alcohol intoxication produced a larger impairment on rod-pathway-mediated CFFs under light versus dark surround. CONCLUSIONS: These results indicate that alcohol intake slows down rod and cone-pathway-mediated temporal processing. Further research may elucidate whether this effect may play a role in alcohol-related injury and accidents, which often occur under low-light conditions. Language: en

BACKGROUND: It is principally the area of enforcement that offers the greatest opportunity for reducing alcohol-impaired driving in the near future. How much of a reduction in drinking and driving would be achieved by how much improvement in enforcement intensity? METHODS: We developed logistic regression models to explore how enforcement intensity (6 different measures) related to the prevalence of weekend nighttime drivers in the 2007 National Roadside Survey who had been drinking (blood alcohol concentration [BAC] ≥ 0.00 g/dl), who had BACs ≥ 0.05 g/dl, and who were driving with an illegal BAC ≥ 0.08 g/dl. RESULTS: Drivers on the roads in our sample of 30 communities who were exposed to fewer than 228 traffic stops per 10,000 population aged 18 and older had 2.4 times the odds of being BAC positive, 3.6 times the odds of driving with a BAC ≥ 0.05, and 3.8 times the odds of driving with a BAC ≥ 0.08 compared to those drivers on the roads in communities with more than 1,275 traffic stops per 10,000 population. Drivers on the roads in communities with fewer than 3.7 driving under the influence (DUI) arrests per 10,000 population had 2.7 times the odds of BAC-positive drivers on the roads compared to communities with the highest intensity of DUI arrest activity (>38 DUI arrests per 10,000 population). CONCLUSIONS: The number of traffic stops and DUI arrests per capita were significantly associated with the odds of drinking and driving on the roads in these communities. This might reflect traffic enforcement visibility. The findings in this study may help law enforcement agencies around the country adjust their traffic enforcement intensity to reduce impaired driving in their community. Language: en

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., a blood alcohol concentration [BAC] of 0.08 g%). In response to these concerns, a National Institute on Alcohol Abuse and Alcoholism task force recommended adding a time qualifier of 2 hours to this criterion. Although conceptually appealing, there has been little effort to determine whether this new measure better captures drinking that leads to negative consequences. METHODS: This study examined the new binge standard (2-hour period) and old binge standard (no time qualifier) in relation to frequency of drinking to an estimated BAC of 0.08 g% and the experience of negative drinking consequences. These relations were examined within both a social drinking sample of adults (N = 200) and a sample of heavy-drinking young adults (N = 168) participating in a randomized clinical trial for drinking reduction. RESULTS: Contrary to the purpose of adding a time qualifier, the new binge measure was not more strongly correlated with drinking to an estimated BAC of 0.08 g% relative to the old binge measure. In addition, when both measures were entered simultaneously into a regression model, only the old binge measure accounted for significant variance in negative drinking consequences. CONCLUSIONS: These empirically based results suggest that the original binge standard without a time qualifier may be preferable to the 2-hour standard as a marker for risk. The findings also suggest that further efforts are needed to identify a brief measure that effectively captures drinking to intoxication and related risk for negative consequences. Language: en

BACKGROUND: Binge drinking during adolescence is common and may predict increased drinking in young adulthood and enhanced risk of alcohol dependence. Variation in level of response to the hedonic and adverse effects of alcohol is in part an inherited factor that may also influence its use, abuse, and dependence. This study investigated, in young adults, whether an association could be demonstrated between variation in self-reported responses to alcohol and a history of binge drinking during adolescence. METHODS: Young adult (18 to 30 years, n = 790) Native Americans and Mexican Americans were recruited from the community and completed a structured diagnostic interview. Response to alcohol was indexed using the expectation version of the Subjective High Assessment Scale (SHAS-E). An adolescent history of regular binge drinking was defined as drinking 5 or more drinks for boys and 4 or more drinks for girls per drinking occasion at least once a month during their highest drinking period prior to the age of 18. RESULTS: An adolescent history of regular binge drinking was found to be associated with a lower level of self-reported responses to the negative aspects of alcohol intoxication (feeling terrible) as well as to the overall level of intoxication, but not to the positive impressions of intoxication (feeling great) on the SHAS-E. A history of regular adolescent binge drinking was also correlated with less feelings of the "terrible" and "total" effects of alcohol, as indexed by the SHAS-E, in a linear regression model that included several diagnostic and demographic variables such as a history of conduct disorder and current levels of drinking. CONCLUSIONS: These data suggest that a history of adolescent binge drinking is associated with a reduction in the self-reported level of intoxication in young adulthood, a factor that could theoretically lead to increased risk of alcohol dependence. Language: en

Background Evidence has emerged demonstrating that ethanol (EtOH) influences cytokine expression within the central nervous system, although most studies have examined long-term exposure. Thus, the cytokine response to an acute EtOH challenge was investigated, in order to characterize profiles of cytokine changes following acute exposure. Methods Rats pups were injected intraperitoneally (i.p.) with 2-g/kg EtOH, and IL-1 mRNA and protein were assessed 0, 60, 120, 180, and 240 minutes post injection (Experiment 1). In Experiments 2 to 5, the expression of several cytokines was examined in adult male rats during acute intoxication (3 hours after 4-g/kg EtOH), as well as withdrawal (18 hours post injection), after i.p. or intragastric (i.g.) EtOH administration. Results Early in ontogeny, acute EtOH significantly decreased brain IL-1 mRNA and protein. Subsequently, when adult rats were examined, significant and temporally dynamic alterations in central and peripheral cytokines were observed following acute i.p. EtOH exposure (4 g/kg). Although cytokine- and region-dependent central IL-6 expression was generally increased and tumor necrosis factor alpha decreased during intoxication, IL-1 expression exhibited increases during withdrawal. In the periphery, acute i.p. EtOH elevated expression of all cytokines, with the response growing in magnitude as the time post injection increased. Following acute i.g. EtOH (4 g/kg), intoxication-related increases in IL-6 expression were again observed in the paraventricular nucleus of the hypothalamus (PVN), although to a lesser extent. Long-term, voluntary, intermittent EtOH consumption resulted in tolerance to the effects of an i.g. EtOH challenge (4 g/kg) on PVN IL-6 expression, whereas these same elevations in IL-6 expression were still seen in the amygdala in rats with a history of moderate EtOH intake. Treatment with minocycline did not significantly attenuate i.p. or i.g. EtOH-induced changes in central cytokine expression. Conclusions Together, these studies provide a foundation for understanding fluctuations in central and peripheral cytokines following acute EtOH as potential contributors to the constellation of neural and behavioral alterations observed during EtOH intoxication and withdrawal.

Background Initial sensitivity to ethanol (EtOH) and the capacity to develop acute functional tolerance (AFT) to its adverse effects may influence the amount of alcohol consumed and may also predict future alcohol use patterns. The current study assessed sensitivity and AFT to the ataxic and hypnotic effects of EtOH in the first replicate of mice (HDID-1) selectively bred for high blood EtOH concentrations (BECs) following limited access to EtOH in the Drinking in the Dark (DID) paradigm. Methods Naive male and female HDID-1 and HS/Npt mice from the progenitor stock were evaluated in 3 separate experiments. In Experiments 1 and 2, EtOH-induced ataxia was assessed using the static dowel task. In Experiment 3, EtOH-induced hypnosis was assessed by using modified restraint tubes to measure the loss of righting reflex (LORR). Results HDID-1 mice exhibited reduced initial sensitivity to both EtOH-induced ataxia (p

BACKGROUND: Alcohol consumption is influenced by heritable factors. The genetic influence on usual high-density drinking, including alcohol intoxication and hangover, is unknown. We aim to estimate the heritability of usual high-density drinking. METHODS: A total of 13,511 male twins in this cross-sectional study were included from the National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry. Data on the frequency of alcohol intoxication and alcohol hangover over the past year, that is, usual high-density drinking (phenotypes), were collected through a self-administered questionnaire when twins were middle-aged in 1972. Structural equation modeling was used to estimate the variance components of phenotypes. RESULTS: The mean of the frequency of usual high-density drinking in the entire twin population was 0.16 times per month for intoxication and 0.18 times per month for hangover. The heritability of usual alcohol intoxication was 50.7% (95% confidence interval [CI] 46.2 to 55.0) before and 49.9% (95% CI 45.3 to 54.2) after the body mass index (BMI) adjustment. The heritability of usual hangover was 55.4% (95% CI 51.2 to 58.6) before and 54.8% (95% CI 50.6 to 58.8) after adjustment for BMI. Unshared environmental factors between co-twins explained the remaining variance in alcohol intoxication and in hangover. CONCLUSIONS: Both genetic and unshared environmental factors have important influences on usual alcohol intoxication and hangover. These findings are important in understanding the occurrence of and developing interventions for usual high-density drinking. Language: en

BACKGROUND: It has been argued that consuming alcohol mixed with energy drinks (AmED) causes a subjective underestimation of intoxication and an increased level of risk-taking behavior. To date, however, there is mixed support for AmED-induced reductions in perceived intoxication, and no objective assessment of risk-taking following AmED consumption. Consequently, the present study aimed to determine the effect of alcohol and energy drink (ED) consumption on subjective measures of intoxication and objective measures of risk-taking. METHODS: Using a placebo-controlled, single-blind, cross-over design, participants (n = 28) attended 4 sessions in which they were administered, in counterbalanced order: 0.5 g/kg alcohol, 3.57 ml/kg ED, AmED, and a placebo beverage. Participants completed the Biphasic Alcohol Effects Scale and a Subjective Effects Scale at baseline and 30 and 125 minutes postbeverage administration; risk-taking was measured using the Balloon Analogue Risk Task (BART). RESULTS: Participants reported greater subjective intoxication, impairment, and sedation after active relative to placebo alcohol consumption, with no interactive AmED effects. However, a significant moderate magnitude increase in stimulation ratings was observed in the AmED relative to alcohol, ED, and placebo conditions. There was no independent effect of alcohol, or interactive effect with ED, on the BART. A significant, yet small magnitude, increase in risk-taking was evident in active relative to placebo ED conditions. CONCLUSIONS: The interactive effect of AmED appears restricted to perceived stimulation, with alcohol-induced increases in subjective intoxication occurring regardless of presence or absence of ED. Engagement in risk-taking behavior was only increased by ED consumption; however, this effect was only of small magnitude; at these doses, alcohol consumption, with or without EDs, did not affect risk-taking. Further research assessing the dose-dependent effects of AmED on objectively measured risk-taking behavior could clarify whether the ED effect increases with higher doses and whether an interactive effect is observed with higher alcohol doses. Language: en

A low level of response (i.e., a low LR) to alcohol is a genetically influenced phenotype that predicts later alcoholism. While the low LR reflects, at least in part, a low brain response to alcohol, the physiological underpinnings of the low LR have only recently been addressed.Forty-nine drinking but not yet alcoholic matched pairs of 18- to 25-year-old subjects (N = 98; 53% women) with low and high LRs as established in separate alcohol challenges were evaluated in 2 event-related functional magnetic resonance imaging (fMRI) sessions (placebo and approximately 0.7 ml/kg of alcohol) while performing a validated stop signal task. The high and low LR groups had identical blood alcohol levels during the alcohol session.Significant high versus low LR group and LR group × condition effects were observed in blood oxygen level-dependent (BOLD) signal during error and inhibitory processing, despite similar LR group performance on the task. In most clusters with significant (corrected p0.05, clusters1,344 μl) LR group × alcohol/placebo condition interactions, the low LR group demonstrated relatively less, whereas the high LR group demonstrated more, error and inhibition-related activation after alcohol compared with placebo.This is one of the first fMRI studies to demonstrate significant differences between healthy groups with different risks of a future life-threatening disorder. The results may suggest a brain mechanism that contributes to how a low LR might enhance the risk of future heavy drinking and alcohol dependence.

The differentiator model predicts that individuals with a positive family history of alcoholism (FHA) or heavy alcohol consumers will feel more sensitive to the effects of alcohol on the ascending phase of the blood alcohol content while feeling less sedated on the descending phase. This study tested whether subjective perceptions are sensitive to the slope of breath alcohol concentration (BrAC) and whether that sensitivity is associated with an FHA and/or recent drinking history (RDH).Family-history-positive (FHP, n = 27) and family-history-negative (FHN, n = 27) young adult nondependent drinkers were infused intravenously with alcohol in 2 sessions separated by 1 week. After 20 minutes, one session had an ascending BrAC (+3.0 mg%/min), while the other session had a descending BrAC (-1 mg%/min). The BrAC for both sessions at this point was approximately 60 mg%, referred to as the crossover point. Subjective perceptions of intoxication, high, stimulated, and sedation were sampled frequently and then interpolated to the crossover point. Within-subject differences between ascending and descending responses were examined for associations with FHA and/or RDH.Recent moderate drinkers reported increased perceptions of feeling intoxicated (p0.023) and high (p0.023) on the ascending slope compared with the descending slope. In contrast, recent light drinkers felt more intoxicated and high on the descending slope.Subjective perceptions in young adult social drinkers depend on the slope of the BrAC when examined in association with RDH. These results support the differentiator model hypothesis concerning the ascending slope and suggest that moderate alcohol consumers could be at risk for increased alcohol consumption because they feel more intoxicated and high on the ascending slope. Subjects did not feel less sedated on the descending slope, contrary to the differentiator model but replicating several previous studies.

Individual differences in subjective response to alcohol, as measured by laboratory-based alcohol challenge, have been identified as a candidate phenotypic risk factor for the development of alcohol-use disorders (AUDs). Two models have been developed to explain the role of subjective response to alcohol, but predictions from the 2 models are contradictory, and theoretical consensus is lacking.This investigation used a meta-analytic approach to review the accumulated evidence from alcohol-challenge studies of subjective response as a risk factor. Data from 32 independent samples (total N = 1,314) were aggregated to produce quantitative estimates of the effects of risk-group status (i.e., positive family history of AUDs or heavier alcohol consumption) on subjective response.As predicted by the Low Level of Response Model (LLRM), family history-positive groups experienced reduced overall subjective response relative to family history-negative groups. This effect was most evident among men, with family history-positive men responding more than half a standard deviation less than family history-negative men. In contrast, consistent with the Differentiator Model (DM), heavier drinkers of both genders responded 0.4 standard deviations less on measures of sedation than did the lighter drinkers but nearly half a standard deviation more on measures of stimulation, with the stimulation difference appearing most prominent on the ascending limb of the blood alcohol concentration curve.The accumulated results from 3 decades of family history comparisons provide considerable support for the LLRM. In contrast, results from typical consumption comparisons were largely consistent with predictions of the DM. The LLRM and DM may describe 2 distinct sets of phenotypic risk, with importantly different etiologies and predictions for the development of AUDs.

Previous laboratory research on alcohol absorption has found that substitution of artificially sweetened alcohol mixers for sucrose-based mixers has a marked effect on the rate of gastric emptying, resulting in elevated blood alcohol concentrations. Studies conducted in natural drinking settings, such as bars, have indicated that caffeine ingestion while drinking is associated with higher levels of intoxication. To our knowledge, research has not examined the effects of alcohol mixers that contain both an artificial sweetener and caffeine, that is, diet cola. Therefore, we assessed the event-specific association between diet cola consumption and alcohol intoxication in bar patrons. We sought to determine whether putative increases in blood alcohol, produced by accelerated gastric emptying following diet cola consumption, as identified in the laboratory, also appear in a natural setting associated with impaired driving.We conducted a secondary analysis of data from 2 nighttime field studies that collected anonymous information from 413 randomly selected bar patrons in 2008 and 2010. Data sets were merged and recoded to distinguish between energy drink, regular cola, diet cola, and noncaffeinated alcohol mixers.Caffeinated alcohol mixers were consumed by 33.9% of the patrons. Cola-caffeinated mixed drinks were much more popular than those mixed with energy drinks. A large majority of regular cola-caffeinated mixed drink consumers were men (75%), whereas diet cola-caffeinated mixed drink consumers were more likely to be women (57%). After adjusting for the number of drinks consumed and other potential confounders, number of diet cola mixed drinks had a significant association with patron intoxication (β = 0.233, p0.0001). Number of drinks mixed with regular (sucrose-sweetened) cola and energy drinks did not have significant associations with intoxication (p0.05).Caffeine's effect on intoxication may be most pronounced when mixers are artificially sweetened, that is, lack sucrose which slows the rate of gastric emptying of alcohol. Risks associated with on-premise drinking may be reduced by greater attention given to types of mixers, particularly diet colas.

Heavy drinking is one of the leading causes of morbidity and mortality in young men. Brief motivational intervention (BMI) has shown promising results for young people, but has never been tested in young men in the community who volunteered to receive an intervention.We evaluated the effectiveness of BMI in reducing alcohol use among heavy episodic users and in maintaining low-risk drinking among nonheavy episodic users. Participants were French-speaking young men attending the mandatory Swiss army conscription process. They were offered the opportunity to receive a 20-minute BMI, and those interested were randomized into an intervention group (BMI immediately) or into a control group (BMI after the 6-month follow-up assessment, in a waiting list design). Analyses were conducted separately for heavy and nonheavy episodic users (separated using baseline heavy episodic use frequency) as the hypotheses tested were different between both groups (primary vs. secondary prevention intervention).From a pool of 6,085 young men invited to receive BMI, 727 (11.9%) showed up and 572 were included in the study (after exclusions related to organizational aspects of the conscription process). Among nonheavy episodic users, there was a protective effect of BMI on weekly alcohol use (p0.05). Among heavy episodic users, there were no significant effects of BMI.About 12% of young men were interested in addressing their drinking within the BMI framework, suggesting that there is some need for easily accessible alcohol intervention. The present intervention did have a preventive effect among low-risk young drinkers in helping them maintain their patterns of alcohol use. An explanation for the lack of effectiveness among heavy episodic users might be that those individuals interested in BMI had patterns of more severe alcohol use, thereby making change more difficult.

The Hangover Symptoms Scale (HSS) assesses the frequency of 13 symptoms experienced after drinking in the past year. Cross-sectional analyses in college drinkers showed preliminary evidence for the validity of the HSS (Slutske et al., 2003). The current investigation extended this work by examining the construct validity of the HSS in an ecological momentary assessment investigation.Frequent drinkers (N = 404) carried electronic diaries to track their daily experiences over 3 weeks. Each morning, the diary assessed prior-night drinking behaviors, the presence of current hangover, and intensity of current headache and nausea.Adjusting for sex and body mass, the HSS significantly predicted diary endorsement of hangover (OR = 2.11, 95% CI = 1.78 to 2.49, p0.001). Participants who endorsed the HSS headache and nausea items were especially likely to report the elevations of corresponding symptoms in diary records made the morning after drinking. HSS scores incrementally predicted hangover when the number of drinks consumed in the episode was covaried but did not moderate the relationship between the number of drinks and diary hangover reports.The HSS appears to be a valid tool for hangover research. Higher HSS scores identify individuals who complain of "real world" hangovers and who may be especially likely to display particular symptoms after a night of drinking. Past hangovers predicted future hangovers, suggesting hangovers do not necessarily discourage or inhibit future drinking, at least across the several-week time interval studied here. There is a need to develop and evaluate complementary measures that can more directly index individual differences in hangover susceptibility in survey designs.

Heavy drinking and smoking during pregnancy are known to have a negative impact on the unborn child. However, the impact of low-to-moderate alcohol consumption and binge drinking has been debated recently. The aim of this study was to examine the relationship of moderate prenatal drinking and binge drinking with birthweight, being small for gestational age (SGA) at birth, preterm birth, and neonatal asphyxia.Moderate alcohol drinking, binge drinking, and several possible confounders were assessed in 1,258 pregnant women; information on neonatal health was obtained at birth.Results indicate that 30.8% of the women drank at low levels (2 glasses/wk), 7.9% drank moderately (2 to 4 glasses/wk), and 0.9% showed higher levels of drinking (5 glasses/wk); 4.7% reported binge drinking (defined as 3 glasses/occasion). 6.4% of the children were SGA (10th percentile of birthweight adjusted for gestational age), 4.6% were preterm (37th week of gestation), and 13.0% showed asphyxia (arterial cord pH7.10 and/or arterial cord lactate6.35 mmol and/or Apgar score7 at 5 minutes). When controlling for maternal age, citizenship, occupational status, parity, smoking, use of prescription/over-the-counter drugs, illicit drug use, and child gender moderate drinking was related to lower birthweight (p0.01), and moderate drinking and binge drinking were associated with neonatal asphyxia at trend level (p = 0.06 and p = 0.09). Moderate drinking and binge drinking were not related to length of gestation.In contrast to recent reviews in the field, our results assume that moderate drinking and binge drinking are risk factors for neonatal health.

Level of response (LR) to alcohol has been shown to be associated with the risk of developing alcohol dependence and can be measured using the self-rating of the effects of alcohol (SRE) questionnaire. This study examined the heritability of the SRE-measured LR and the relationship between LR and recent alcohol drinking history (RDH) in a predominantly African American nonalcohol-dependent population.This was a sibling study of 101 social drinkers aged 21 to 35 years recruited from the Washington, DC metropolitan area. Participants were administered the SRE to assess LR and the timeline followback (TLFB) to assess RDH. The indices of SRE used were total SRE score (SRTT), early drinking SRE score (SRED), regular drinking SRE score (SRRD), and heavy drinking SRE score (SRHD). Pearson's product-moment correlation and linear regression were used to analyze SRE indices and RDH variables (quantity and drinks per drinking occasion). Heritability analysis was conducted using Sequential Oligogenic Linkage Analysis Routines (SOLAR) software with SRE indices as traits of interest.There was a significant relationship between SRE and RDH measures. Drinks per drinking day, maximum drinks, and quantity of drinks were significantly associated with SRTT, SRHD, and SRRD (all p0.05). SRTT showed significant heritability (h(2) = 0.67, p = 0.025), however, the SRE subindices (SRED, SRRD, SRHD) were not significantly heritable. Analysis performed in the subset consisting of only African Americans (n = 86) showed similar trends.LR, as measured by the SRE, is associated with RDH. The high level of heritability of the SRE total score suggests that genetics accounts for a significant proportion of the variation in the LR to alcohol in social drinkers.

Isoflavone administration in the form of a purified extract from the herbal medication kudzu root has been shown to reduce, but not eliminate, alcohol consumption in alcohol-abusing and alcohol-dependent men. The precise mechanism of this action is unknown, but 1 possible explanation for these results is that the isoflavones in kudzu might actually increase the intensity or duration of alcohol's effects and thus delay the desire for subsequent drinks. This study was designed to test this hypothesis.Twelve (12) healthy adult men and women (27.5 ± 1.89 years old) who consumed moderate amounts of alcohol (7.8 ± 0.63 drinks/wk) participated in a double-blinded, placebo-controlled crossover study in which they were treated with either kudzu extract (total isoflavone dose of 750 mg/d) or matched placebo for 9 days. On days 8 and 9, participants received an acute challenge of ethyl alcohol (either 0.35 or 0.7 g/kg alcohol). During the challenges, the following measures were collected: subjective effects, psychomotor (body sway), cognitive performance (vigilance/reaction time), physiological measures (heart rate and skin temperature), and plasma ethanol concentration.Alcohol resulted in a dose-related alteration in subjective measures of intoxication, impairment of stance stability, and vigilance/reaction time. Kudzu extract did not alter participants' subjective responses to the alcohol challenge or to alcohol's effects on stance stability or vigilance/reaction time. However, individuals treated with kudzu extract experienced a slightly more rapid rise in plasma ethanol levels, but only after the 0.7 g/kg dose. This transient effect during the first 30 minutes of the ascending plasma alcohol curve lasted only 10-15 minutes; there were no differences in peak plasma alcohol levels or alcohol elimination kinetics. Additionally, kudzu pretreatment enhanced the effects of the 0.7 g/kg dose of alcohol on heart rate and skin temperature.These data suggest that individuals who drink alcohol while being treated with kudzu extract experience no adverse consequences, and furthermore the reported reductions in alcohol intake after kudzu extract treatment are not related to an alteration in alcohol's subjective or psychomotor effects.

Alcohol addiction develops through a series of stages, and mechanistic studies are needed to understand the transition from initial drug use to sustained controlled alcohol consumption followed by abuse and physical dependence. The focus of this study was to examine the effects of voluntary alcohol consumption on brain gene expression profiles using a mouse model of binge drinking. The main goal was to identify alcohol-responsive genes and functional categories after a single episode of drinking to intoxication.We used a modification of a "Drinking In the Dark" (DID) procedure (Rhodes et al., 2005) that allows mice to experience physiologically relevant amounts of alcohol in a non-stressful environment and also allows for detection of alcohol-sensitive molecular changes in a dose-dependent manner. C57BL/6J male mice were exposed to either 20% ethanol solution or water (single bottle) starting 3 hours after lights off for 4 hours and brains were harvested immediately after the drinking session. cDNA microarrays were used to assess the effects of voluntary drinking on global gene expression in 6 brain regions. We employed three statistical approaches to analyze microarray data.A commonly used approach that applies a strict statistical threshold identified the eight top statistically significant genes whose expression was significantly correlated with blood ethanol concentration (BEC) in one of the brain regions. We then used a systems network approach to examine brain region-specific transcriptomes and identify modules of co-expressed (correlated) genes. In each brain region, we identified alcohol-responsive modules, i.e., modules significantly enriched for genes whose expression was correlated with BEC. A functional over-representation analysis was then applied to examine the organizing principles of alcohol-responsive modules. Genes were clustered into modules according to their roles in different physiological processes, functional groups, and cell types, including blood circulation, signal transduction, cell-cell communication, and striatal neurons. Finally, a meta-analysis across all brain regions suggested a global role of increasing alcohol dose in coordination of brain blood circulation and reaction of astrocytes.This study showed that acute drinking resulted in small but consistent changes in brain gene expression which occurred in a dose-dependent manner. We identified both general and region-specific changes, some of which represent adaptive changes in response to increasing alcohol dose, which may play a role in alcohol-related behaviours, such as tolerance and consumption. Our systems approach allowed us to estimate the functional values of individual genes in the context of their genetic networks and formulate new refined hypotheses. An integrative analysis including other alcohol studies suggested several top candidates for functional validation, including Mt2, Gstm1, Scn4b, Prkcz, and Park7.

Individual differences in subjective alcohol intoxication, as measured by laboratory-based alcohol challenge, have been identified as a phenotypic risk factor for alcohol use disorders. Further, recent evidence indicates that subjective alcohol response is also associated with event-level physiological consequences among college students, including blackouts and hangovers.The current investigation tested predictors of and outcomes associated with subjective intoxication in the natural drinking environment. In a preliminary laboratory alcohol-challenge study (n = 53), we developed a brief measure of subjective alcohol intoxication for use in event-level research. Participating students in the principal study (n = 1,867; 63% women; 54% Caucasian) completed 30 days of Web-based self-monitoring in each of the 4 college years.In the principal study, generalized estimating equation analyses revealed that both lighter drinking and a family history of alcohol problems predicted greater subjective intoxication after accounting for estimated blood alcohol concentration (eBAC). Moreover, greater subjective intoxication during a given drinking episode was associated with negative alcohol-related consequences, illicit drug use, and unsafe sex, and at higher eBACs, was associated with aggression, sex, and property crime. Students who on average experienced greater subjective intoxication were also more likely to experience negative consequences and engage in illicit drug use, sex, unsafe sex, and aggression.These findings suggest that both within-person variability and between-person individual differences in subjective intoxication may be risk factors for adverse drinking outcomes at the event level. Intervention efforts aimed at reducing problems associated with collegiate drinking may benefit from consideration both of who experiences greater subjective intoxication and of the situations in which they are more likely to do so.

To our knowledge, no research has assessed whether young male victims and perpetrators of barroom aggression differ in terms of their drinking patterns and predisposing characteristics. This study assessed the extent that frequent heavy episodic drinking (HED) and bar-going, trait aggression, and hypermasculinity were differentially associated with victimization versus perpetration for aggression occurring among young adult men in the setting of the public drinking establishment.A random sample of 2,500 male students attending a local university and a local community college was invited to participate in an online survey. Participants were asked the number of times in the past 12 months they had experienced an incident of aggression at a bar in which (a) someone was physically aggressive toward them and (b) they were physically aggressive toward another person. Responses were coded as (i) any perpetration of aggression, (ii) victim only, (iii) no aggression. A composite variable of HED (5 or more drinks per occasion) and bar-going frequency was computed: (i) both HED and bar ≥ twice a month, (ii) only HED ≥ twice a month, (iii) only bar ≥ twice a month, and (iv) bothtwice a month. Standard measures of trait aggression and hypermasculinity were used.Multivariate multinomial logistic regression analyses revealed that a combination of both frequent HED and frequent bar-going was associated with both perpetration and victimization at a bar (compared to no aggression). Trait aggression and hypermasculinity were associated with perpetration but not with victimization. Logistic regression analyses directly comparing perpetrators with victims indicated that perpetrators were more likely to both drink heavily and go to bars frequently and were more likely to have high levels of trait aggression and hypermasculinity.While HED is an important target for prevention programming, additional efforts should be directed toward addressing the combination of frequent HED and frequent bar-going as well as underlying aggressive personalities and masculinity concerns among young men.

Energy drinks are highly caffeinated beverages that are increasingly consumed by young adults. Prior research has established associations between energy drink use and heavier drinking and alcohol-related problems among college students. This study investigated the extent to which energy drink use might pose additional risk for alcohol dependence over and above that from known risk factors.Data were collected via personal interview from 1,097 fourth-year college students sampled from 1 large public university as part of an ongoing longitudinal study. Alcohol dependence was assessed according to DSM-IV criteria.After adjustment for the sampling design, 51.3%(wt) of students were classified as "low-frequency" energy drink users (1 to 51 days in the past year) and 10.1%(wt) as "high-frequency" users (≥52 days). Typical caffeine consumption varied widely depending on the brand consumed. Compared to the low-frequency group, high-frequency users drank alcohol more frequently (141.6 vs. 103.1 days) and in higher quantities (6.15 vs. 4.64 drinks/typical drinking day). High-frequency users were at significantly greater risk for alcohol dependence relative to both nonusers (AOR = 2.40, 95% CI = 1.27 to 4.56, p = 0.007) and low-frequency users (AOR = 1.86, 95% CI = 1.10, 3.14, p = 0.020), even after holding constant demographics, typical alcohol consumption, fraternity/sorority involvement, depressive symptoms, parental history of alcohol/drug problems, and childhood conduct problems. Low-frequency energy drink users did not differ from nonusers on their risk for alcohol dependence.Weekly or daily energy drink consumption is strongly associated with alcohol dependence. Further research is warranted to understand the possible mechanisms underlying this association. College students who frequently consume energy drinks represent an important target population for alcohol prevention.

This study assessed in Sardinian alcohol-preferring (sP) rats a procedure known to promote alcohol drinking and based on the intermittent (once every other day) access to 2 bottles containing alcohol (20%, v/v) and water, respectively (Wise, 1973).To this end, sP rats were exposed - under the 2-bottle choice regimen - to: (i) 10% (v/v) alcohol with continuous access (CA10%; i.e., the procedure under which sP rats had been selectively bred); (ii) 10% (v/v) alcohol with intermittent access (IA10%); (iii) 20% (v/v) alcohol with continuous access (CA20%); (iv) 20% (v/v) alcohol with intermittent access (IA20%; the "Wise" condition) (Experiment 1). Additional experiments assessed the influence of (i) adulteration with quinine of the alcohol solution (Experiment 2) and (ii) concurrent presentation of a saccharin solution (Experiment 3) on alcohol drinking under the CA10% and IA20% conditions. Finally, it was assessed whether alcohol drinking under the CA10% and IA20% conditions resulted in motor incoordination at the Rota-Rod task, as a possible sign of alcohol intoxication (Experiment 4).Daily alcohol intake markedly escalated in rats exposed to the IA20% condition, averaging 9.0 g/kg (in comparison with the average intake of 6.5 g/kg in the CA10% rat group). CA20% and IA10% rats displayed intermediate values of daily alcohol intake between those of CA10% and IA20% rats. Alcohol intake was virtually abolished by addition of quinine or by concurrent presentation of the saccharin solution in CA10% rats; conversely, alcohol intake in IA20% rats was only partially affected by gustatory aversion or concurrent presentation of an alternative reinforcer. Finally, alcohol intake in IA20%, but not in CA10%, rats resulted in clear motor-incoordinating effects.These data suggest that the "Wise" procedure is effective in inducing marked increases in alcohol intake in sP rats. These increases are associated with a reduced flexibility of alcohol drinking (suggesting the development of "behavioral" dependence) and produce signs of alcohol intoxication that are not detected when sP rats are exposed to the more conventional CA10% condition.

Significant evidence has accumulated to suggest an association between single-nucleotide polymorphisms (SNPs) in the GABRA2 gene and alcoholism. However, research has yet to show an association between these polymorphisms and the human brain's reward system function. In this study, we stratified subjects who had participated in an fMRI study of alcohol cue responses according to their genotype at a SNP in GABRA2 (rs279871) shown to be associated with alcohol dependence (Edenberg et al., 2004).Genotyping showed 13 subjects to be homozygous for the high-risk allele (AA), and 23 subjects to be heterozygous (AG). In fMRI, subjects were exposed to the aromas of their preferred alcoholic drink odors (AO), as well as to appetitive control odors (ApCO) under both alcohol intoxication and placebo control conditions.Homozygous AA subjects had a larger [AOApCO] response than did AG subjects in medial frontal cortical areas thought to code reward value. However, AG subjects had a larger [AOApCO] effect in the ventral tegmental area. Alcohol intoxication did not alter these group differences.These are the first data to suggest that GABRA2 genotype could affect the brain's responses to cues associated with alcohol.

Alcohol abuse is associated with an increased incidence and severity of pneumonia. In both the general population and individuals consuming excess alcohol, Streptococcus pneumoniae is the most frequent lung infection pathogen. Alcoholic patients with pneumonia frequently present with granulocytopenia, which is predictive of increased mortality. The mechanisms underlying this impaired granulopoietic response to pneumococcal pneumonia have yet to be elucidated.Acute alcohol intoxication was induced in mice 30 minutes before intrapulmonary infection with S. pneumoniae. Bone marrow, lung, and blood samples were collected. Bone marrow cells were also isolated from naïve mice and treated in vitro with plasma from mice infected with S. pneumoniae.Alcohol intoxication impaired the pneumococcal-induced increase in granulocyte recruitment into the alveolar space, decreased bacterial clearance from the lung, and increased mortality. Pneumococcal pneumonia significantly increased bone marrow lineage(-) c-Kit(+) Sca-1(+) (LKS) cell number and colony-forming unit-granulocytes and monocyte (CFU-GM) activity of these cells. Both enhanced proliferation of LKS cells and re-expression of Sca-1 surface protein on downstream progenitor cells bearing lineage(-) c-Kit(+) Sca-1(-) surface markers accounted for the expansion of marrow LSK cells during pneumonia. Alcohol intoxication impaired these 2 mechanisms of LKS cell population expansion and was associated with a relative granulocytopenia during pneumococcal lung infection.Alcohol inhibits the hematopoietic precursor cell response to pneumonia, which may serve as a mechanism underlying the granulocytopenia and impaired host defense in alcohol abusers with bacterial pneumonia.

Despite advances in our understanding of excessive alcohol-intake-related tissue injury and modernization of the management of septic patients, high morbidity and mortality caused by infectious diseases in alcohol abusers remain a prominent challenge. Our previous studies have shown that milk fat globule epidermal growth factor-factor VIII (MFG-E8), a protein required to opsonize apoptotic cells for phagocytosis, is protective in inflammation. However, it remains unknown whether MFG-E8 ameliorates sepsis-induced apoptosis and organ injury in alcohol-intoxicated rats. The purpose of this study was to determine whether recombinant murine MFG-E8 (rmMFG-E8) attenuates organ injury after acute alcohol exposure and subsequent sepsis.Acute alcohol intoxication was induced in male adult rats by a bolus injection of intravenous alcohol at 1.75 g/kg BW, followed by an intravenous infusion of 300 mg/kg BW/h of alcohol for 10 hours. Sepsis was induced at the end of 10-hour alcohol infusion by cecal ligation and puncture (CLP). rmMFG-E8 or vehicle (normal saline) was administered intravenously 3 times (i.e., at the beginning of alcohol injection, the beginning of CLP, and 10 hours post-CLP) at a dose of 20 microg/kg BW each. Blood and tissue samples were collected 20 hours after CLP in alcoholic animals for various measurements.Acute alcohol exposure per se did not affect the production of MFG-E8; however, it primed the animal and enhanced sepsis-induced MFG-E8 downregulation in the spleen. Administration of rmMFG-E8 reduces alcohol/sepsis-induced apoptosis in the spleen, lungs, and liver. In addition, administration of rmMFG-E8 after alcohol exposure and subsequent sepsis decreases circulating levels of TNF-alpha and interleukin-6 and attenuates organ injury.rmMFG-E8 attenuates sepsis-induced apoptosis and organ injury in alcohol-intoxicated rats.

We examined the extent to which driving under the influence (DUI) offenders delay reinstatement, the reasons for that delay, and the relationship of the delay to recidivism. Analyzed were the driving records of 40 million drivers (3 million convicted of DUI) from 7 of the largest states spanning 7 to 14 years. License suspension effectively reduces, but does not eliminate, impaired driving. Apparently, many feel they can avoid apprehension for unlicensed driving; the limited research to date suggests that up to 75% of convicted offenders continue to drive and up to 84% delay reinstatement for 3 or more years.ANOVA and regression procedures were used to determine the relationship of prior driving record and sentence length to the DUI offender's delay in reinstatement. Meta-analysis was used to summarize results across the 7 states and survival analysis to determine the effect of the delay on recidivism.Forty-two percent of first offenders and 55% of multiple offenders convicted for DUI delay reinstatement for more than a year. For a third of the offenders, there were no records of their having reinstated within 5 years of becoming eligible. Both factors-more than one prior offense and the length of suspension imposed-were related to delay in reinstatement. Offenders who delayed reinstatement were more likely to recidivate both while they delayed before reinstating and after they reinstated.DUI offenders who delay reinstatement after they become eligible are high-risk drivers. Offenders who reinstate, however, have lower recidivism rates than those who do not. This suggests that encouraging reinstatement but with continued controls, as some states have provided through laws requiring interlocks as a condition of reinstatement, may be effective if they do not motivate extended delays.

Conditioned reward is a classic measure of drug-induced brain changes in animal models of addiction. The process can be examined in humans using the Conditioned Pattern Preference (CPP) task, in which participants associate nonverbal cues with reward but demonstrate low awareness of this conditioning. Previously, we reported that alcohol intoxication does not affect CPP acquisition in humans, but our data indicated that prior drug use may impact conditioning scores.To test this possibility, the current study examined the relationship between self-reported alcohol use and preference conditioning in the CPP task. Working memory was assessed during conditioning by asking participants to count the cues that appeared at each location on a computer screen. Participants (69 female and 23 male undergraduate students) completed the Alcohol Use Disorders Identification Test (AUDIT) and the Rutgers Alcohol Problem Index (RAPI) as measures of hazardous drinking.Self-reported hazardous drinking was significantly correlated with preference conditioning in that individuals who scored higher on these scales exhibited an increased preference for the reward-paired cues. In contrast, hazardous drinking did not affect working memory errors on the CPP task.These findings support evidence that repeated drug use sensitizes neural pathways mediating conditioned reward and point to a neurocognitive disposition linking substance misuse and responses to reward-paired stimuli. The relationship between hazardous drinking and conditioned reward is independent of changes in cognitive function, such as working memory.

Recent animal and human studies indicate that the exposure to alcohol during early adolescence increases the risk for heavy alcohol use in response to stress. The purpose of this study was to examine whether this effect may be the consequence of a higher susceptibility to develop "drinking to cope" motives among early initiators.Data from 320 participants were collected as part of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study. Structured interviews at age 15 and 19 were used to assess age at first alcohol experience and drunkenness. The young adults completed questionnaires to obtain information about the occurrence of stressful life events during the past 4 years and current drinking habits. In addition, alcohol use under conditions of negative states was assessed with the Inventory of Drinking Situations.The probability of young adults' alcohol use in situations characterized by unpleasant emotions was significantly increased the earlier they had initiated the use of alcohol, even when controlling for current drinking habits and stressful life events. Similar results were obtained for the age at first drunkenness.The findings strengthen the hypothesis that alcohol experiences during early adolescence facilitate drinking to regulate negative affect as an adverse coping strategy which may represent the starting point of a vicious circle comprising drinking to relieve stress and increased stress as a consequence of drinking.