Aims

To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.

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Saturday, February 4, 2012

Impact of Different Reference Period Definitions in the Quantification of Alcohol Consumption: Results from a Nationwide STEPS Survey in Mozambique



To compare the estimates of alcohol consumption in Mozambique obtained with different reference period definitions. This is a critical methodological aspect when measuring alcohol consumption and its impact is likely to vary across settings.

A nationally representative sample of 3264 Mozambicans aged 25–64 years was evaluated in a community-based cross-sectional study conducted between September and November 2005. Face-to-face interviews were conducted following the World Health Organization-Stepwise approach to Surveillance methodology. The amount of alcohol consumed was estimated among current drinkers, using the previous week (1W) and the 12 months (12M) prior to the data collection as the reference.

Among drinkers, the prevalence of consumption of >14 drinks/week was higher in men (12M: 18.6 vs. 7.8%; 1W: 16.3 vs. 6.1%), although the prevalence of excessive weekly intake (>7 drinks for women and >14 drinks for men) was higher among women (12M: 25.9 vs. 18.6%; 1W: 18.1 vs. 16.3%). The concordance between the reported intakes according to the reference period was low (κ = 0.25).

In this setting where alcohol consumption is a male-dominated behaviour, among drinkers the prevalence of gender-defined excessive amounts was higher in women. The concordance between different recall periods was low and this needs to be taken into account when comparing results from different studies.




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Request Reprint E-Mail: nlunet@med.up.pt

Gene-Selective Histone H3 Acetylation in the Absence of Increase in Global Histone Acetylation in Liver of Rats Chronically Fed Alcohol



The aim of this study was to determine the effect of chronic ethanol feeding on acetylation of histone H3 at lysine 9 (H3-Lys9) at promoter and coding regions of genes for class I alcohol dehydrogenase (ADH I), inducible nitric oxide synthase (iNOS), Bax, p21, c-met and hepatocyte growth factor in the rat liver.

Rats were fed ethanol-containing liquid diet (5%, w/v) for 1–4 weeks. The global level of acetylation of H3-Lys9 in the liver was examined by western blot analysis. The levels of mRNA for various genes were measured by real-time reverse transcriptase-polymerase chain reaction. The association of acetylated histone H3-Lys9 with the different regions of genes was monitored by chromatin immunoprecipitation assay.

Chronic ethanol treatment increased mRNA expression of genes for iNOS, c-jun and ADH 1. Chronic ethanol treatment did not cause increase in global acetylation of H3-Lys9, but significantly increased the association of acetylated histone H3-Lys9 in the ADH I gene, both in promoter and in coding regions. In contrast, chronic ethanol treatment did not significantly increase the association of acetylated histone H3-Lys9 with iNOS and c-jun genes.

Chronic ethanol exposure increased the gene-selective association of acetylated H3
Font size-Lys9 in the absence of global histone acetylation. Thus, not all genes expressed by ethanol are linked to transcription via histone H3 acetylation at Lys9.



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Request Reprint E-Mail: shuklasd@missouri.edu

Breath Alcohol Elimination Rate and Widmark Factor Derived from Breath Alcohol Concentration in Chinese and Indians in Singapore




To determine the breath alcohol elimination rate (AER) and Widmark factor derived from the maximum breath alcohol concentration (rpeak BrAC) in Chinese and Indians in Singapore, and to evaluate the contribution of genetic and non-genetic factors to variability of AER and rpeak BrAC.

A total of 180 subjects ingested a Vodka–orange juice mixture, together with a standardized meal and underwent a series of BrAC measurements.

Significant inter-ethnic differences in AER and rpeak BrAC were observed in females and males, respectively. Alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase (ALDH2) genotypes were identified as significant predictors for AER among males, accounting for 8.5% (P = 0.048) and 23.4% (P < 0.001) of the variance, respectively. ADH1B genotype was identified as a significant predictor for rpeak BrAC among males, accounting for 17.1% of the variance (P = 0.001). In females, however, none of the genotypes were found to be significant predictors for breath AER, and rpeak BrAC.

ALDH2 and/or ADH1B genotypes in males, but not in females, appear to contribute, albeit modestly, to variability in AER and rpeak BrAC. The median AER in Chinese males, Indian males, Chinese females and Indian females is 6.6 μg dl−1 h−1 [99% confidence interval (CI), 5.6–7.5 μg dl−1 h−1], 6.2 μg dl−1 h−1 (99% CI, 5.5–7.0 μg dl−1 h−1), 8.6 μg dl−1 h−1 (99% CI, 7.4–9.7 μg dl−1 h−1) and 7.4 μg dl−1 h−1 (99% CI, 6.2–8.4 μg dl−1 h−1), respectively. The median rpeak BrAC in Chinese males, Indian males, Chinese females and Indian females is 0.0229 (99% CI, 0.0216–0.0268), 0.0209 (99% CI, 0.0190–0.0237), 0.0214 (99% CI, 0.0185–0.0254) and 0.0199 (99% CI, 0.0187–0.0227), respectively.




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Request Reprint E-Mail: edmund_jd_lee@nuhs.edu.sg

Friday, February 3, 2012

'Tackling alcohol misuse: Should abstinence be our preferred approach?' British Liver Trust call for public health action on alcohol


The British Liver Trust have released a new report outlining the need for a comprehensive approach to tackling alcohol misuse. It warns against a "one size fits all approach for treatment" for a range of problem drinkers "each of whom will need tailored approach with the interventions and appropriate treatment goals."

Download 'Reducing alcohol harm: recovery and informed choice for those with alcohol related health problems'

A supporting commentary piece by Andrew Langford, Chief Executive of the British Liver Trust also appeared in the Guardian. > > > > Read More

News Release - NIH study uncovers probable mechanism underlying resveratrol activity



Findings may settle scientific debate surrounding this chemical found in red wine and other foods

National Institutes of Health researchers and their colleagues have identified how resveratrol, a naturally occurring chemical found in red wine and other plant products, may confer its health benefits. The authors present evidence that resveratrol does not directly activate sirtuin 1, a protein associated with aging. Rather, the authors found that resveratrol inhibits certain types of proteins known as phosphodiesterases (PDEs), enzymes that help regulate cell energy.

These findings may help settle the debate regarding resveratrol's biochemistry and pave the way for resveratrol-based medicines. The chemical has received significant interest from pharmaceutical companies for its potential to combat diabetes, inflammation, and cancer. The study appears in the Feb. 3 issue of Cell. > > > > Read More

Current Issue: November–December 2011


Interventions & Assessments

  • Buprenorphine-Naloxone Works for Prescription Opioid Dependence As Long As It Is Maintained
  • Ongoing Primary and Specialty Care Is Associated with Improved Substance Use Outcomes
  • Patients Who Receive Opioids for Chronic Pain Are Inadequately Managed
  • Accuracy of “Last Occasion” Self-Reported Drinking in Young Adults
  • Does Mailed Feedback Decrease Risky Drinking After an Emergency Department Visit?
  • Buprenorphine Treatment Is Not Associated with Significant Impairment of Driving Ability

Health Outcomes

  • “Moderate” Drinking Is a Risk Factor for Breast Cancer
  • Association between Open-Angle Glaucoma and Cocaine Use
  • Heavier Alcohol Consumption Linked to Colorectal Cancer
  • Heavy Beer Consumption Is a Risk Factor for Gastric Cancer
  • Regular Moderate Alcohol Intake Associated with “Successful Aging” in Women
  • Unhealthy Alcohol Use Is Associated with Unhealthy Eating Patterns

HIV and HCV

  • A Multidisciplinary Approach to Hepatitis-C Treatment Reduced Viral Load and Increased Abstinence in Patients with Co-Occurring Alcohol Dependence
  • A New Piece of the Harm Reduction Puzzle? Directly Observed Antiretroviral Therapy for HIV-infected Opioid-Dependent Individuals
  • Factors Associated with Substance-Abuse Treatment Utilization among Patients Living with HIV/AIDS Who Use Alcohol and Other Drugs

Slide Presentations

  • Update on Alcohol, Other Drugs, and Health
  • Journal Club


Read Full Newsletter

Critique 069: Little effect of binge drinking on heart disease or mortality among moderate drinkers in Denmark



Skov-Ettrup LS, Eliasen M, Ekholm O, Grønbaek M, Tolstrup JS. Binge drinking, drinking frequency, and risk of ischaemic heart disease: A population-based cohort study. Scandinavian Journal of Public Health 2011;39:880–887.

Comments on study: This appears to be a well-done population–based study with good follow up and excellent ascertainment of outcomes: IHD and all-cause mortality. This was made possible by the unique civil registry number allocated to each Danish citizen at birth. This number is used in any sort of business with the authorities such as tax, social security, and health, and a social security card with the number must be presented with any contact with the national health system – a failsafe method of securing exact follow-up of all diagnoses or death.

The assessments of alcohol were based on consumption in the week prior to the examination, and binge drinking was defined as more than 5 drinks/occasion. Given that the assessment was from only one week, data were not available to judge whether or not binge-drinking episodes occurred rarely or regularly.

Data were available on the usual covariates related to IHD: smoking, education, physical activity, BMI, and self-reported hypertension and diabetes. There was a strong correlation between binge drinking and the total amount of alcohol consumed, but the authors controlled for total alcohol intake when comparing binge and non-binge drinkers.

When comparing outcomes in binge vs. non-binge drinkers, the analyses were restricted to subjects in the “light-to-moderate” categories. Here, there were no significant differences noted between subjects who binged and those who did not. In all comparisons, the relative risk of IHD and all-cause mortality was higher for non-drinkers than for all categories of drinkers.

When relating frequency of drinking (the number of days of the week when subjects consumed alcohol) to IHD and total mortality, all subjects (not just the light-to-moderate drinkers) were included. Here, again, there were no significant differences in outcomes comparing people consuming alcohol on 1-2, 3-4, 5-6, or 7 days/week (although , once again, the highest risk was always among the non-drinkers). These results differ from those of Mukamal et al1 and Tolstrup et al,2 studies showing that frequency of consumption was a key determinant of health outcomes.

Thus, these findings do not show differences in effects of binge vs. non-binge drinking in terms of IHD or mortality. Further, the study does not show a significant effect according to the number of days per week that subjects consumed alcohol. As one reviewer stated: “The present paper suggests that, within the group of persons following sensible drinking limits of weekly amount of alcohol intake, there does not appear to be adverse effects on the heart when not following the recommendation to avoid having more than five drinks on a single occasion.”

Specific comments on the results of the present study: As a Forum reviewer commented: “The sensible drinking limits of up to 21 drinks/week for men or up to 14 drinks/week for women (1 drink = 12 grams of alcohol) proposed by the Danish National Board of Health are well known in Denmark. It is estimated that, overall, 20% of the population over 16 years of age drink in excess of the proposed drinking limits.3 However, by limiting the study of the effect of binge drinking to subjects who follow the weekly drinking limits (83.7% of the male and 90.4% of the female participants), you have restricted the analysis of binge drinking effects to a population of genuine moderate drinkers.” If binge drinking among all drinkers were evaluated, the results may well have been different.

In the present analyses, a very high percentage of the “light-to-moderate drinkers” reported binge drinking: up to 61% of men in the 14-21 drinks/week category and 35% of the women in the 7-14 drinks/week category. The median number of drinks on a binge was 9 for men and 7 for women. Despite reporting binge drinking, the overall average intake of the subjects in these analyses remained in the light-to-moderate category. Hence, although they reported binge drinking on at least one occasion in the preceding week, they were not overall heavy drinkers.

As one reviewer commented, “The combination of moderate drinking with occasional parties with intake of >5 drinks is a normal pattern of drinking in Denmark. It is assumed that many were in the habit of sharing some bottles of wine with friends on a Saturday evening and then drink very little during work days, while others prefer the daily glass of wine or beer with their meals. However, they would be very similar in other choices of lifestyle.” While the type of beverage consumed was not reported in this paper, a reviewer comments: “Based on data from earlier reports from the Danish National Cohort Study. you would expect that most of the female participants are wine drinkers and that many of the moderate male consumers also prefer wine.” Previous studies from Copenhagen have shown better health outcomes for wine drinkers than for consumers of other beverages.4 In this study, non-drinkers tended to have lower levels of education than the moderate drinkers, as has been found commonly in other studies. > > > > Read More

Alcohol Use Disorders Identification Test (AUDIT) scores are elevated in antipsychotic-induced hyperprolactinaemia


Hyperprolactinaemia in antipsychotic treated patients with schizophrenia is a consequence of D2 receptor (DRD2) blockade. Alcohol use disorder is commonly comorbid with schizophrenia and low availability of striatal DRD2 may predispose individuals to alcohol use.

In this pilot study we investigated whether hyperprolactinaemia secondary to pharmacological DRD2 blockade was associated with alcohol use disorder in 219 (178 males and 41 females) patients with schizophrenia.

Serum prolactin determinations were made in patients diagnosed with schizophrenia and maintained on antipsychotic agents. Clinical assessment included demographics, family history and administration of the AUDIT (Alcohol Use Disorders Identification Test).

Higher AUDIT scores were associated with prolactin-raising antipsychotic medication (
n = 106) compared with prolactin-sparing medication (n = 113). Risperidone (n = 63) treated patients had higher AUDIT scores and prolactin levels than those on other atypical antipsychotics (n = 113). Across the entire sample, patients with a prolactin greater than 800 mIU/L had higher AUDIT scores and were more likely to exceed the cut-off score for harmful and hazardous alcohol use.

These differences were not explained by potential confounds related to clinical features and demographics, comorbidity or medication side-effects. These data suggest that by lowering dosage, or switching to another antipsychotic agent, the risk for alcohol use disorder in those with schizophrenia may be reduced.

This hypothesis requires testing using a prospective methodology.




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Request Reprint E-Mail: bruce_lawford@health.qld.gov.au

Pharmacokinetics and central nervous system effects of the novel dopamine D3 receptor antagonist GSK598809 and intravenous alcohol infusion at pseudo-


GSK598809 is a novel selective dopamine D3 receptor antagonist, currently in development for the treatment of substance abuse and addiction.

In a blinded, randomized, placebo-controlled study, effects of single oral doses of 175 mg GSK598809 were evaluated in healthy volunteers. Pharmacokinetics, central nervous system (CNS) effects and potential for interactions with alcohol were evaluated, using an alcohol infusion paradigm and analysis of eye movements, adaptive tracking, visual analogue scales, body sway, serum prolactin and verbal visual learning test.

Adverse effects of GSK598809 included headache, dizziness and somnolence. Plasma concentration of GSK598809 was maximal 2–3 hours postdose and decreased with a half-life of roughly 20 hours. CNS effects were limited to prolactin elevation and decreased adaptive tracking. Co-administration of GSK598809 and alcohol did not affect alcohol pharmacokinetics, but caused a 9% decrease of
Cmax and a 15% increase of AUC of GSK598809. CNS effects of co-administration were mainly additive, except a small supra-additive increase in saccadic reaction time and decrease in delayed word recall.

In conclusion, GSK598809 causes elevation of serum prolactin and a small decrease in adaptive tracking performance. After co-administration with alcohol, effects of GSK598809 are mainly additive and the combination is well tolerated in healthy volunteers.




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Request Reprint E-Mail: etbeek@chdr.nl

Thursday, February 2, 2012

Model-based appraisal of alcohol minimum pricing and off-licensed trade discount bans in Scotland using the Sheffield Alcohol Policy Model (v.2)




In 2009, ScHARR developed an adaptation of the Sheffield Alcohol Policy Model for the population of Scotland. The findings of this original modelling work were published in September 2009 (Purshouse et al, 2009b). A first update using more up to date evidence was published in April 2010 (Meng et al, 2010). Since this time, a series of more recent datasets have become available. These include:
  • New adult consumption data from the Scottish Health Survey (SHeS) is available for 2010 (the data in the previous model relates to 2008).
  • New purchase data from the Living Costs and Food Survey (LCF), previously known as the Expenditure and Food Survey (EFS) is available for 2006 to 2009 (the data in the previous model relates to 2001/2 to 2005/6).
  • The Scottish Government has also procured market research data on the 2010 price distribution of off-trade alcohol (in terms of ethanol content) in Scotland from The Nielsen Company.
  • New mortality data is available for 2010.
  • New person specific hospitalisation data is available for 2009/10.
  • Police recorded crime statistics and the Scottish Crime and Justice Survey (SCJS) data is available for 2009/10.
  • The Labour Force Survey data is available for 2010.
The requirement of this research project was to update the previous Scotland model with the new data to provide revised estimates of the effects of current proposals for minimum pricing and prohibition of off-trade discounting. The technical details of the methodology have not been changed. Therefore the methods section (Chapter 2) of the original published report has not been reproduced in full. > > > > Read More

Wednesday, February 1, 2012

The effects of TPA023, a GABAAα2,3 subtype-selective partial agonist, on essential tremor in comparison to alcohol


Essential tremor (ET) is a relatively frequent neurological disorder that responds in some patients to gamma-aminobutyric acid A (GABAA) agonists such as the benzodiazepines. Partial subtype-selective GABAA agonists may have an improved side effect profile compared to non-selective GABAA agonists. However, it is unknown which GABAA subtypes are involved in the therapeutic effects of benzodiazepines in ET.

The effects of 2 mg TPA023, a GABA
A α2,3 subtype-selective partial agonist, on ET were compared to the effects of a stable alcohol level (0.6 g/L) and placebo in nine patients with ET. Tremor evaluation included laboratory accelerometry and a performance-based scale. Additional measurements were performed to evaluate other effects on the central nervous system (CNS).

Alcohol significantly diminished tremor symptoms in the postural and kinetic condition, as assessed by laboratory accelerometry, but the performance-based rating scale was unaffected.

Tremor was also reduced after TPA023 treatment in the kinetic condition, albeit not significantly. Additionally, TPA023 decreased saccadic peak velocity, while alcohol decreased subjective feelings of alertness.

This study showed that alcohol reduced maximum tremor power, as assessed by laboratory accelerometry, unlike TPA023, which decreased tremor symptoms to some extent but not significantly.

This study showed that treatment with an α2,3 subunit-selective GABA
A partial agonist was less effective than a stable level of alcohol in reducing ET symptoms.

These results provide no support for a therapeutic role of TPA023 in the suppression of ET symptoms.



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Request Reprint E-Mail: rzoethout@chdr.nl

A [11C]Ro15 4513 PET study suggests that alcohol dependence in man is associated with reduced α5 benzodiazepine receptors in limbic regions



Preclinical evidence suggests the α5 subtype of the GABA-benzodiazepine receptor is involved in some of the actions of alcohol and in memory. The positron emission tomography (PET) tracer, [11C]Ro15 4513 shows relative selectivity in labelling the α5 subtype over the other GABA-benzodiazepine receptor subtypes in limbic regions of the brain.

We used this tracer to investigate the distribution of α5 subtype availability in human alcohol dependence and its relationship to clinical variables. Abstinent (>6 weeks) alcohol-dependent men and healthy male controls underwent an [
11C]Ro15 4513 PET scan. We report [11C]Ro15 4513 brain uptake for 8 alcohol-dependent men and 11 healthy controls.

We found a significant reduction in [
11C]Ro15 4513 binding in the nucleus accumbens, parahippocampal gyri, right hippocampus and amygdala in the alcohol-dependent compared with the healthy control group.

Levels of [
11C]Ro15 4513 binding in both hippocampi were significantly and positively associated with performance on a delayed verbal memory task in the alcohol-dependent but not the control group. We speculate that the reduced limbic [11C]Ro15 4513 binding seen here results from the effects of alcohol, though we cannot currently distinguish whether they are compensatory in nature or evidence of brain toxicity.



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Request Reprint E-Mail: anne.lingford-hughes@ic.ac.uk

Effects of acute alcohol intoxication on automated processing: evidence from the double-step paradigm



Reflexive and voluntary levels of processing have been studied extensively with respect to possible impairments due to alcohol intoxication.

This study examined alcohol effects at the ‘automated’ level of processing essential to many complex visual processing tasks (e.g., reading, visual search) that involve ongoing modifications or reprogramming of well-practiced routines.

Data from 30 participants (16 male) were collected in two counterbalanced sessions (alcohol vs. no-alcohol control; mean breath alcohol concentration = 68 mg/dL vs. 0 mg/dL). Eye movements were recorded during a double-step task where 75% of trials involved two target stimuli in rapid succession (inter-stimulus interval [ISI] = 40, 70, or 100 ms) so that they could elicit two distinct saccades or eye movements (double steps). On 25% of trials a single target appeared.

Results indicated that saccade latencies were longer under alcohol. In addition, the proportion of single-step responses and the mean saccade amplitude (length) of primary saccades decreased significantly with increasing ISI.

The key novel finding, however, was that the reprogramming time needed to cancel the first saccade and adjust saccade amplitude was extended significantly by alcohol. The additional time made available by prolonged latencies due to alcohol was not utilized by the saccade programming system to decrease the number of two-step responses.

These results represent the first demonstration of specific alcohol-induced programming deficits at the automated level of oculomotor processing.




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Request Reprint E-Mail: vorstius@psy.fsu.edu

Effects of acute alcohol consumption on the perception of eye gaze direction



Alcohol consumption is associated with increases in aggressive behaviour, but the mechanisms underlying this relationship are poorly understood. One mechanism by which alcohol consumption may influence behaviour is via alterations in the processing of social cues such as gaze.

We investigated the effects of acute alcohol consumption on the perception of gaze, using a task in which participants determined whether a stimulus face was looking towards or away from them. Gaze direction varied across trials, allowing calculation of a threshold at which participants considered gaze to switch from direct to averted. Target faces varied in both sex and attractiveness. Thirty social drinkers attended three randomized experimental sessions. At each session, participants consumed 0.0, 0.2 or 0.4 g/kg alcohol, and completed the gaze perception task.

A significant three-way interaction involving target sex, participant sex and alcohol dose indicated that alcohol increased the cone of gaze for females viewing male targets (i.e. females were biased towards making a direct gaze judgement), but decreased the cone of gaze for males viewing male targets.

Our data indicate that alcohol consumption influences gaze perception, but that these effects vary across sex of both stimulus and rater. These effects may have important implications for alcohol-related violence.

Effects of acute alcohol consumption on alcohol-related cognitive biases in light and heavy drinkers are task-dependent


We investigated (1) the effects of alcohol on cognitive biases for alcohol-related cues, (2) the effects of drinking status on alcohol-related cognitive biases and (3) the similarity of any effects of alcohol across two measures of alcohol cognitive bias.

Healthy, heavy and light social alcohol users (
n = 72) were examined in a single-blind placebo-controlled design. Participants received 0.00 g/kg, 0.13 g/kg or 0.40 g/kg of alcohol in a between-subjects design and then completed both a modified Stroop task and a visual probe task.

Modified Stroop data indicated a main effect of cue type, which was qualified by drinking status, with heavier drinkers slower to respond to alcohol-related cues. Visual probe data, in contrast, indicated a significant interaction effect between validity (valid:
alcohol-related, invalid: neutral) and drink condition.

Participants receiving a moderate dose of alcohol (0.40 g/kg) were faster to respond to alcohol-related stimuli compared with participants receiving a low dose of alcohol or placebo.

These data indicate that the cognitive processes assayed by the visual probe and Stroop tasks may not be mediated by a common underlying mechanism.




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Request Reprint E-Mail: sally.adams@bristol.ac.uk

Alcohol stress response dampening: selective reduction of anxiety in the face of uncertain threat



Problematic alcohol use and stress response dampening (SRD) are intimately interconnected. Recent evidence suggests that alcohol produces selective SRD during uncertain but not certain threat.

We systematically varied shock probability in a novel task assessing alcohol SRD during low probable/uncertain threat, while holding temporal precision of threat constant. Intoxicated (0.08% target blood alcohol concentration) and placebo participants completed a cued shock threat task in which probability of shock administration at the offset of brief visual cues varied parametrically. High probability (100%) shock cues represented certain threat as used in earlier research, while lower probability (20% and 60%) shock cues provided novel uncertain threat conditions. Startle potentiation during cues and inter-trial intervals (ITIs) served as the measure of affective response.

General linear model analysis indicated that alcohol SRD magnitude increased monotonically as threat uncertainty increased. Alcohol SRD was significantly greater during 20% and 60% shock threat relative to 100% shock threat. Alcohol also significantly reduced startle potentiation during distal threat in shock-free ITIs. Alcohol SRD magnitude during distal/uncertain threat was meaningfully moderated by individual differences in negative affectivity and weekly alcohol consumption.

This work advances understanding of which properties of uncertainty are relevant to anxiety and anxiolytic effects of alcohol
.



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Request Reprint E-Mail: jjcurtin@wisc.edu

Acquisition, expression, and reinstatement of ethanol-induced conditioned place preference in mice: effects of exposure to stress and modulation by me


Nicotinic acetylcholine receptors mediate some of the rewarding and motivational effects of ethanol, including relapses. Relapses are common in drug addicts during abstinence when exposure to any stressor ensues. However, the role of nicotinic acetylcholine receptors in the ethanol- and stress-induced reinstatement of ethanol-induced conditioned place preference has not yet been explored.

Therefore, the present study investigated the influence of mecamylamine, a nicotinic acetylcholine receptors antagonist on acquisition, expression, and reinstatement of ethanol-induced conditioned place preference in adult male Swiss mice.

The results revealed that mecamylamine (0.1–10 µg/mouse, intracerebroventricularly) dose dependently prevented the development, expression, and reinstatement of ethanol-induced conditioned place preference. Further, acute treatment with mecamylamine blocked the restraint stress and forced swim stress-induced reinstatement of ethanol-induced conditioned place preference. All of these treatments had no influence on the locomotor activity.

Therefore, it is concluded that mecamylamine blocks the acquisition, expression and reinstatement of conditioned reinforcing effects of ethanol without
per se reinforcing or aversive influence. This ability of mecamylamine might be a potential advantage in the treatment of alcoholism.




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Request Reprint E-Mail: psbhutada@live.com

Alcohol selectively impairs negative self-relevant associations in young drinkers


The stress-dampening effects of alcohol have been attributed to ‘appraisal disruption’− decreased ability of stimuli to evoke threatening associations in memory. Appraisal disruption could apply to oneself as well as situational stimuli.

This question was investigated in undergraduate drinkers (
n = 90/Gender) with low or high anxiety sensitivity (AS; n = 90/AS Group), a trait linked with hyper-vigilance to threat. Subjects received alcohol (0.7 g/kg males; 0.63 g/kg females), placebo or soft drink and performed a speech about their appearance. Sequence of drink administration and speech advisory (threat) was manipulated between subjects: Threat before Drink, Threat after Drink, No-Threat Control. The Implicit Association Test measured self-relevant associations based upon time to classify positive and negative attribute words (e.g. Cute, Ugly) paired with self-relevant or non-self-relevant object words (e.g. Me, Them).

Alcohol selectively slowed negative self-relevant decisions, regardless of other factors. Relative fluency of negative versus positive decisions (
D) correlated inversely with state anxiety and systolic blood pressure immediately before speech performance, and correlated directly with severity of alcohol problems.

These findings are consistent with the Appraisal Disruption hypothesis. Preferential impairment of negative self-relevant associations may decrease perceived vulnerability under alcohol and increase risk for alcohol problems in young drinkers.




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Request Reprint E-Mail: martin_zack@camh.net

Popular intoxicants: what lessons can be learned from the last 40 years of alcohol and cannabis regulation



In this paper we discuss the relative physical, psychological and social harms of the two most frequently used intoxicant drugs in the UK, namely cannabis and alcohol.

Over the past 40 years, the use of both drugs has risen significantly with differential consequences.

It is argued that increased policing of cannabis use under the current drug classification system will lead to increased criminalization of young people, but is unlikely to significantly reduce the rates of schizophrenia and psychosis.

In comparison, increases in alcohol drinking are related to significant increases in liver cirrhosis hospital admissions and mortality, at a time when mortality rates from other major causes are on the decline.

A recent expert-led comparison of the health and social harms to the user and to others caused by the most commonly used drugs in the UK showed alcohol to be more than twice as harmful as cannabis to users, and five times as harmful as cannabis to others.

The findings underline the need for a coherent, evidence-based drugs policy that enables individuals to make informed decisions about the consequences of their drug use.



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Request Reprint E-Mail: D.Nutt@imperial.ac.uk

Tuesday, January 31, 2012

Effects of 0.4g/kg alcohol on attentional bias and alcohol-seeking behaviour in heavy and moderate social drinkers


Alcohol intoxication is known to influence attentional biases for alcohol-related cues and alcohol-seeking behaviour. It is unknown if heavier drinkers are more or less sensitive to these effects of alcohol, or whether the effects of alcohol on attentional bias are associated with subsequent alcohol-seeking behaviour.

In the present study, 55 social drinkers were administered either 0.4 g/kg alcohol or placebo in a repeated measures, double-blind experimental design. Participants completed a visual probe task with eye movement monitoring (to measure attentional bias) and a bogus taste test (to measure alcohol-seeking) in both alcohol and placebo sessions.

Heavy drinkers showed an attentional bias for alcohol cues that was unaffected by alcohol, whereas in moderate drinkers attentional bias was present after alcohol administration, but was absent after placebo.

All participants voluntarily consumed more beer during the taste test after administration of alcohol compared with placebo.

The effects of alcohol on attentional bias were unrelated to the effects of alcohol on beer consumption.

Results are consistent with the development of tolerance, rather than sensitization, to the acute effects of alcohol on attentional biases in heavy drinkers.

However, alcohol-induced increases in attentional bias were not related to the effects of alcohol on the motivation to drink.




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Request Reprint E-Mail: mfield@liverpool.ac.uk

Substitution therapy for alcoholism: time for a reappraisal?



A number of compounds already in use as medications for various indications substitute for ethanol at clinically relevant brain pathways, in particular, at gamma-aminobutyric acid (GABA) receptors.

Nevertheless, although substitute medications have been recognized for heroin and tobacco dependence, patients with alcohol dependence are rarely offered an analogous approach.

Benzodiazepines may have paradoxical effects, and abuse and dependence are known. Baclofen (GABA
B agonist) has not been associated with dependence or misuse and has been effective in several trials in preventing relapse, although research is required to establish the optimal dosing regimen. GABA-ergic anticonvulsants, helpful in treating withdrawal, have yet to emerge as effective in relapse prevention. Clomethiazole and sodium oxybate, the latter having been shown to be effective in relapse prevention, have incurred a reputation for dependence and abuse. However, data have emerged showing that the risk of abuse of sodium oxybate is lower than many clinicians had foreseen.

For a condition where existing therapies are only effective in a proportion of patients, and which has high morbidity and mortality, the time now seems right for reappraising the use of substitute prescribing for alcohol dependence.



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Request Reprint E-Mail: jonathan.chick@gmail.com

Alcohol News - 5/2012



Irish Times (Ireland) - Minimum alcohol price across island planned to tackle abuse
HEALTH AUTHORITIES on both sides of the Border are planning to introduce a minimum price for alcohol on the island in an effort to combat alcohol abuse.
Read more
Wall Street Journal (USA) - Stricter Thinking on Alcohol During Pregnancy
In the sixth to 12th week of pregnancy, a fetus's bones, brain and central nervous system are forming. Buds blossom into arms and legs, and internal organs start to function. A face with eyelids, lips and other features appears.
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Huffington Post (USA) - Illinois Alcohol Abuse: Midwest 'Binge Drinking Belt,' By The Numbers
Data released Monday shows that some of the highest rates of binge drinking in the nation can be found in the Midwest -- specifically in Illinois.
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BBC News (UK) - Alcohol deaths increase slightly
Alcohol related deaths in the UK have increased slightly between 2009 and 2010, according to official figures. The number of deaths linked to drinking has gone from 8,664 to 8,790 - a rise of 126.
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BBC News (Ireland) - New plans for all-Ireland minimum alcohol price
Health authorities have decided upon a cross-border strategy on a minimum price for alcohol. The proposals were outlined at the first formal North/South conference on alcohol misuse, held in Armagh on Thursday.
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Scotsman (Scotland) - Scots alcohol-related deaths double during last 30 years
THE number of alcohol-related deaths in Scotland has more than doubled in the past three decades, latest figures show.
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PRWeb - Is Alcohol a Bigger Threat to Male Sexual Health than Smoking?
Men who drink what is considered to be above the normal amount of alcohol on a weekly basis are at higher risk of developing erection problems than those who smoke and do not drink as regularly, reports QuitFullStop.
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Irish Times (Ireland) - Ban on selling alcohol in shops urged
A BAN on the sale of alcohol in supermarkets and garages should be considered by Government, a new report on alcohol and drugs has said.
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The Canberra Times (Australia) - Alcohol incidents 'double' on Aust Day
Heavy drinking is the Australian way for many, and Australia Day is the day more young people are involved in harmful alcohol-related incidents, such as assaults and car accidents, than on any other public holiday, research has found.
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Medscape (USA) - Prevalence of HIV Risk Behaviors Between Binge Drinkers and Non-binge Drinkers Aged 18- to 64-Years in US, 2008
Using data from the 2008 Behavioral Risk Factor Surveillance System on 281,303 adults aged 18–64 years in the United States, we examined the relationship between HIV risk behaviors and binge drinking of alcoholic beverages and the frequency of binge drinking among a subgroup of 41,073 respondents who were acknowledged binge drinkers (bingers), based on reported drinking behavior in the year preceding survey.
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Mayo Advertiser (Ireland) - Oireachtas alcohol report will tackle drink problem – O’Mahony
Fine Gael Mayo TD, John O’Mahony, has said that the report on alcohol and drug misuse published by the Oireachtas Joint Committee on Health and Children, “provides a blueprint on how we can tackle our national drink problem”.
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Irish Times (UK) - UK and Republic top European binge-drinking list
SOME 80 per cent of drinking takes place around a meal table in Italy, Spain and France, while in Britain and Ireland 80 per cent of drinking happens away from the meal table, the first North-South conference on alcohol heard yesterday.
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The Guardian (Poland) - Polish stereotypes: hard-drinking Catholic zealots? Nie!
These stereotypes of Poles are true but only partly. Poles drink average amounts of alcohol, they are Catholic but not really bothered by what the church says, and they dislike Jews just slightly more than the average European.
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RAPSI (Russia) - Lawsuit against watchdog to register Russian Alcohol brand to be heard Jan. 31
A commercial court will start reconsidering on January 31 the Russian Alcohol (Russky Alkogol) distributor's lawsuit disputing the patent watchdog's refusal to register the Russian Alcohol trademark, the court told the Russian Legal Information Agency (RAPSI/rapsinews.com) on Monday.
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dailyRx (Netherlands) - Binge Drinking Linked to Explicit Thoughts
Widely accepted patterns of alcohol consumption suggest that both explicit and implicit behaviors influence the way people drink. A recent research study debunked that frame of thought. A study done by scientific investigators in the Netherlands implies that our social thoughts, such as excitement to see friends or anticipation to meet someone new, encourage excess alcohol consumption.
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Irish Times (France/Ireland) - French law on breath test kits to affect Irish tourists
THOUSANDS OF Irish tourists who will take their car with them to France this summer will face fines unless they are carrying a breathalyser with them in their vehicle.
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Alcohol Concern urges action on minimum pricing ahead of new national alcohol strategy



Alcohol Concern are calling on the public to urge MPs to push for minimum pricing ahead of the forthcoming national alcohol strategy. Alcohol Concern state:

The next few weeks will be our last chance to influence the shape of the alcohol strategy, which will shape public policy on reducing alcohol harm for years to come. We must act now to counteract the lobbying power of the drinks industry and major retailers.

The Prime Minister has come out in support of minimum pricing, but the Secretary of State for Health has not- this is the moment when we need MPs to call for minimum pricing and help ensure that it becomes government policy.

Up until now, the government has relied largely on voluntary measures by the drinks industry to reduce consumption. Given that the turnover and profitability of the drinks industry is entirely reliant on maintaining or increasing alcohol consumption, there is a clear conflict of interest involved in this approach. > > > > Read More

Monday, January 30, 2012

Acute alcohol intoxication impairs top–down regulation of stroop incongruity as revealed by blood oxygen level-dependent functional magnetic resonance



Functional neuroanatomy of executive functions has been delineated in a large number of neuroimaging studies using conflict-inducing tasks. The neural basis of alcohol's effects on cognitive control is poorly understood despite the evidence of impaired ability to evaluate competing demands and to inhibit maladaptive responses.

To investigate the effects of moderate intoxication, healthy social drinkers participated in both alcohol (0.60 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions while being scanned using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI).

A modified four-color Stroop task combined reading and color naming and used manual responses. Twenty subjects (10 women) were instructed to press a button corresponding to the font color except when a word was written in gray in which case they had to respond to the meaning of the word.

Alcohol increased reaction times and a tendency to make more errors on incongruent trials. Behavioral indices of alcohol-induced premature responding correlated with the current drinking levels and impulsivity traits, suggesting an interaction between alcohol effects and personality predispositions.

A distributed frontoparietal cortical network was activated by incongruity. However, moderate alcohol inebriation selectively attenuated anterior cingulate cortex (ACC) activation during both high-conflict trials and erroneous responses, indicating vulnerability of the regulative function subserved by the ACC.

By disrupting top–down, strategic processing, alcohol may interfere with goal-directed behavior, resulting in poor self control.

The present results support models proposing that alcohol-induced prefrontal impairments diminish inhibitory control and are modulated by dispositional risk factors and levels of alcohol consumption
.


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Request Reprint E-Mail: xenia@ucsd.edu

Early-Onset Alcohol Dependence Increases the Acoustic Startle Reflex



Hyperreactivity and impaired sensory gating of the acoustic startle response in alcohol dependence has been suggested to reflect a residual effect of previous detoxifications, increasing the severity of subsequent withdrawal episodes. Previous studies on the acoustic startle only included early-onset alcohol-dependent patients. The observed abnormalities may therefore also be specific for this subtype of alcohol dependence. We investigated the acoustic startle response in alcohol-dependent patients and healthy controls and hypothesized that (i) early-onset alcohol-dependent patients show increased acoustic startle responses compared with late-onset alcohol-dependent patients and healthy controls, and (ii) the duration of alcohol dependence or the number of prior detoxifications would not explain the differences in the acoustic startle between early- and late-onset alcohol dependence.

The acoustic startle reflex was assessed in detoxified, male alcohol-dependent patients (N = 83) and age-matched healthy male controls (N = 86). Reflex eye blink responses to an auditory startle stimulus were measured by means of electromyographic recordings over the right orbicularis oculi muscle. Reflex amplitudes and levels of prepulse inhibition (PPI) were analyzed.

There was no association between number of previous withdrawals and the startle response or PPI. Early-onset alcohol-dependent patients showed higher acoustic startle amplitudes compared with late-onset alcohol-dependent patients and healthy controls [75/105 dB:F(2, 166) = 9.2, p < 0.001; 85/105 dB:F(2, 166) = 12.1, p < 0.001; 95 dB:F(2, 166) = 8.2, p < 0.001; 105 dB:F(2, 166) = 9.7, p < 0.001], and there were no differences in PPI.

Increased acoustic startle response in detoxified early-onset alcohol-dependent patients may reflect a trait marker specifically involved in early-onset alcohol dependence. The findings of the current study do not support the hypothesis that the increased startle response is a residual state marker.


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Request Reprint E-Mail: a.f.a.schellekens@psy.umcn.nl

Sunday, January 29, 2012

Anti-obesity effect of a standardised ethanol extract from Curcuma longa L. fermented with Aspergillus oryzae in ob/ob mice and primary mouse adipocyt



We examined the anti-obesity effect of fermented Curcuma longa L. (turmeric) standardised ethanol extract (FTE) in the C57BL/6J ob/ob mouse model. Mice were fed a chow diet containing FTE (0, 200, or 500 mg kg−1 body weight) for 9 weeks.

Supplementation with FTE significantly reduced body weight gain and retroperitoneal and epididymal adipose tissue weights compared to the ob/ob control group. Additionally, total cholesterol and triglyceride levels in serum and liver were significantly decreased in FTE-200 and FTE-500 groups when compared to those of the ob/ob control group, whereas the high-density lipoprotein-cholesterol level was significantly increased. The levels of serum adiponectin as well as mRNA expression of lipases, such as hormone sensitive lipase and adipose triglyceride lipase, were clearly increased. In primary adipocytes of C57BL/6J mice, FTE treatment caused a significant increase glycerol release and hormone sensitive lipase levels and decreased perilipin A levels.

These results suggest that supplementation of FTE has potent anti-obesity effects by controlling body weight, fat mass, serum lipids, and hepatic lipids. Moreover, FTE could be considered a potential resource for the treatment of obesity through its promotion of lipolysis via the protein kinase A pathway.


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Request Reprint E-Mail: jlee2007@khu.ac.kr

Podcast - Binge Drinking – Nationwide Problem, Local Solutions



This podcast is based on the January 2012 CDC Vital Signs report. One in six adults binge drinks about four times a month. It's a problem nationwide but community-based strategies, such as reducing access to alcohol and increasing the price, can prevent binge drinking. Created: 1/3/2012 by Centers for Disease Control and Prevention (CDC). Date Released: 1/3/2012. Series Name: CDC Vital Minute.

Listen to CDC Podcast


Making the Grade on College Drinking Prevention



In December 2011, the National Institute on Drug Abuse’s Monitoring the Future survey posted some fantastic news: Underage drinking by 8th, 10th, and 12th graders has reached historical lows. Among 12th graders, for example, past-month alcohol use dropped to 63.5 percent in 2010, down from a high of 74.8 percent in 1997. While this decrease is heartening, it also signals a need to step up our prevention game on college campuses. Underage college students drink often and excessively. How can we help maintain our progress in reducing underage drinking as today’s high school students enter college? How can we help current college students who drink make healthier choices?

Please join the Substance Abuse and Mental Health Services Administration (SAMHSA) on February 6, 2012, from 1:45 to 3:00 p.m. (EST), as it hosts Making the Grade on College Drinking Prevention, a live Webcast of a national 2012 Town Hall Meeting on underage drinking prevention. Dr. William DeJong, Boston University School of Public Health, will moderate a panel that will include Dr. Ralph W. Hingson, director of the National Institute on Alcohol Abuse and Alcoholism’s Division of Epidemiology and Prevention Research, and representatives from campus communities. The panel will discuss both challenges and successes in preventing alcohol use by college students, with a focus on proven environmental prevention approaches, and answer questions from a live audience and from people posting via the Web. For more details and login information, visit http://www.stopalcoholabuse.gov/townhallmeetings/resources/trainings/webcasts/making-the-grade/default.aspx. Follow us on Twitter @SAMHSAgov, #THM2012, for meeting highlights before, during, and after the event. > > > > Read More