No Safety in Binge Drinking Numbers: Data Show That Most Bingers are Not Alone in Drinking, Consequences

06/06/2008

DENVER, June 6 /PRNewswire-USNewswire/ -- New research strongly suggests that binge drinking often occurs in settings that dramatically increase the risk of injury to bingers and others, a disturbing finding considering that binge drinking accounts for approximately half of the 75,000 alcohol-attributable deaths in the United States every year and opens the door to a host of dangerous risk behaviors.

According to Centers for Disease Control and Prevention (CDC) epidemiologist Timothy Naimi, M.D., M.P.H., who presented his data during the Conference of State and Territorial Epidemiologists national conference this week in Denver, almost half of all binge drinking occurs in public places. Two-thirds of the time, beer is the beverage of choice among binge drinkers, and it is readily available, even to underage drinkers.

Dr. Naimi's findings are from a CDC study that examined data from 14,150 respondents to the Behavioral Risk Factor Surveillance Survey Binge Drinking Module during 2003 and 2004. The results confirm that binge drinking can have serious consequences.

"Overall, 12 percent of binge drinkers reported driving during or soon after binge drinking," Dr. Naimi says, "meaning they were risking injury or death not only for themselves but also their passengers, other drivers and pedestrians."

The study found that 42 percent of those who drove after binge drinking were coming from a bar or club, and that 20 percent of those binge drinking at bars and clubs subsequently operated a motor vehicle. On average, they consumed more than eight drinks during their most recent binge bout. In addition, many binge drinkers were not old enough to legally purchase alcohol. However, 20 percent of underage respondents reported being able to buy their own alcohol at a store, bar, or restaurant.

While there are a number of effective policies to reduce excessive drinking, Dr. Naimi concludes that current prevention efforts are "grossly inadequate." He says research supports the aggressive implementation of effective evidence-based strategies to reduce binge drinking, such as increased alcohol taxes and enhanced enforcement of minimum legal drinking age laws. The research also points to the need to continue or step up surveillance of the context in which binge drinking occurs.
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Recent trends in risky alcohol consumption and related harm among young people in Victoria, Australia
Australian and New Zealand Journal of Public Health 32 (3) , 266–271


To examine recent trends in the proportion of young people who drink at risky levels and the rate of alcohol-related harms experienced by young people in Victoria, Australia.

The study uses published data from a series of surveys that ask questions relating to alcohol consumption to ascertain whether the proportion of young people drinking at risky levels has increased over the time period in which data are available. Alcohol-caused hospital admissions and emergency department presentations for young people are also examined over recent years to assess trends in alcohol-related harms.

The survey data shows mixed results, with no clear trend in the rate of risky drinking among young people. The harms data suggests that rates of alcohol-related harm, particularly acute intoxication, have increased dramatically over recent years.

The relationship between survey-derived estimates of alcohol consumption and rates of alcohol-related harms is not as clear-cut as expected, and raise concerns about the sensitivity of population surveys in detecting changes in harmful drinking patterns.

The current increasing trends in alcohol-related harms for young people in Victoria suggest the need for immediate public health interventions.

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Request Reprint E-Mail: michaell@turningpoint.org.au
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Alcohol craving reduced by drugs

Monday, 9 June 2008

Twin research projects have offered both present and future hope to people suffering from alcohol addiction.

US researchers say that epilepsy drug topiramate boosts general health as well as cutting the craving for drink.

A UK specialist said the potential side-effects of topiramate still merited caution.

A separate project showed that a single injection of a protein into the brains of rats almost immediately stopped them wanting alcohol.
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Alcoholic Energy Drinks: A Risky Mix
By JOHN CLOUD

Friday, May. 30, 2008

If you've never heard of alcoholic energy drinks, you're almost certainly over 25. Sold in tall, narrow cans, they carry teen-friendly names such as Sparks, Tilt and Joose. Like other flavored malt beverages — Mike's Hard Lemonade, for one, or Champale ("the malt liquor you serve like champagne") from back in the '60s — alcoholic energy drinks contain a lot of sugar and flavoring. The difference is that this new generation of malt beverages also contains stimulants. A typical can has about as much caffeine as a venti cup of Starbucks, along with additives like guarana and ginseng that can rev the central nervous system.

That's what has public-health and law-enforcement officials worried. Though flavored malt beverages make up less than 2% of alcohol servings in the U.S., alcohol-policy experts have long worried that many of those servings are consumed by minors who have no palate (yet) for real beer. The new alcoholic energy drinks have a further pull on the youth market: the promise that you can get drunk but still party all night because of the caffeine. Quite drunk: Joose, for instance, has the color and approximate flavor of strawberry soda, but it's 9% alcohol, compared with 5% for a typical can of Budweiser.
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News Release - The Gallo Center awarded prestigious grant from the NIAAA
29 May 2008

The Gallo Center recently was awarded a prestigious five-year specialized Center Grant from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). This multi-component project will be directed by Dr. Robert O. Messing, Associate Director of the Gallo Center. This is the largest competitive grant the Center has received in its 28 year history. The NIAAA currently funds 7 specialized research centers through their center grant program. Most of these centers are located at major research universities. The Gallo Center is the only NIAAA center located at an independent research institute.

The Gallo Center Grant research project has two major themes:

• To study novel proteins to determine whether they or the signaling pathways in which they participate contain potential drug targets for treating alcohol use disorders.

• To investigate whether the genes that encode these proteins are associated with risk of alcoholism in humans.

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Collection of Articles and Publications by William White

William L. White is a senior research consultant at Chestnut Health Systems/Lighthouse Institute and past board chair of Recovery Communities United. He has a Master's degree in Addiction Studies and 35 years of experience in the addictions field. He has authored or coauthored more than 275 articles and monographs and thirteen books. In 2003, he received the 2003 National Association of Addiction Treatment Providers’ Michael Q. Ford Journalism Award.

• Newsletter Articles
• Publications
• Materials from Recovery Symposium: Philadelphia, PA, May 2, 2008

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Improvement of Physical Health and Quality of Life of Alcohol-Dependent Individuals With Topiramate Treatment
Arch Intern Med. 2008;168(11):1188-1199.


Topiramate can improve drinking outcomes via a hypothesized mechanism of facilitating -aminobutyric acid function and inhibiting glutaminergic pathways in the corticomesolimbic system. We sought to determine whether topiramate's antidrinking effects are bolstered by improvements in physical and psychosocial well-being.

In a 17-site, 14-week, double-blind, randomized controlled trial, we compared the effects of topiramate (up to 300 mg/d) vs placebo on physical health, obsessional thoughts and compulsions about using alcohol, and psychosocial well-being among 371 alcohol-dependent subjects who received weekly adherence enhancement therapy.

Topiramate was more efficacious than placebo in reducing body mass index (calculated as weight in kilograms divided by height in meters squared) (mean difference, 1.08; 95% confidence interval [CI], 0.81-1.34; P < .001), all liver enzyme levels (P < .01 for all comparisons), plasma cholesterol level (mean difference, 13.30 mg/dL; 95% CI, 5.09-21.44 mg/dL; P = .002), and systolic (mean difference, 9.70 mm Hg; 95% CI, 6.81-12.60 mm Hg; P < .001) and diastolic (mean difference, 6.74 mm Hg; 95% CI, 4.57-8.90 mm Hg; P < .001) blood pressure to about prehypertension levels—effects that might lower the risk of fatty liver degeneration and cirrhosis as well as cardiovascular disease.

Topiramate compared with placebo significantly (P < .05 for all comparisons) decreased obsessional thoughts and compulsions about using alcohol, increased subjects' psychosocial well-being, and improved some aspects of quality of life, thereby diminishing the risk of relapse and longer-term negative outcomes. Paresthesia, taste perversion, anorexia, and difficulty with concentration were reported more frequently for topiramate than for placebo.

Topiramate appears to be generally effective at improving the drinking outcomes and physical and psychosocial well-being of alcoholic subjects.

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Request Reprint E-Mail: bj4x@virginia.edu

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Wine on French Web caught in Legal Web

June 9, 2008

Lingering uncertainty continues to exist whether or not wine ads on the Internet are legal in France and this perceived neo prohibitionist policy is angering wine professionals in Bordeaux, reports AFP.

In February this year, Heineken was forced to close its French website as the judge in the case filed against it by an anti-alcohol group ruled that since Internet was not on a 1991 list of approved media for alcohol publicity, web-based wine, beer and any alcohol ads were illegal.
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Italy starts seizing cars from drunk drivers

Wed Jun 4, 2008

ROME (Reuters Life!) - Italy has begun confiscating the cars of people driving under the effect of drugs or alcohol in the latest attempt to lower one of western Europe's highest rates of road casualties.

Two drivers in their early 20s, a woman under the influence of alcohol and a man who had smoked a cannabis joint, have had their cars seized in northern Italy since the legislation came into effect at the end of last month.

The new legislation states that any driver who tests positive for any illegal drug or has blood alcohol levels exceeding set limits can have their car confiscated, as well as toughening fines and jail sentences.
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Swedish alcohol monopoly down the hatch

Published: 6 Jun 08

Mark Majzner looks at how two landmark EU decisions have affected the alcohol retail trade in Sweden.

It is one year since Systembolaget lost its complete monopoly on alcohol sales to consumers. The June 5th 2007 Rosengren decision by the EU Court of Justice legalized our right to import wine from other EU countries using a freight transport service.

It took Klas Rosengren and crusading lawyer Ulf Stigare seven years to win the right for Swedish consumers to choose where and how they buy alcohol within the EU. One year on and a lot has changed but it is not widely understood exactly what.

Systembolaget retains its retail store monopoly, but as it sells less than 50% of all alcohol consumed in Sweden, it is no longer a true monopoly. Swedes can now shop online, order a case of wine and have it home delivered. A few e-commerce companies such as mine have started offering a range of mid to high priced wines and quality of service that far surpasses Systembolaget’s.
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The Relationship Between Alcohol Dependence and Periodontal Disease

Journal of Periodontology 2008, Vol. 79, No. 6, Pages 993-998


The aim of this study was to evaluate the relationship between alcohol dependence and periodontal disease.

A cross-sectional study of 49 alcoholic and 49 non-alcoholic men was conducted at Philippe Pinel Institute, Rio de Janeiro, Brazil. Subjects were screened for alcohol dependence using the CAGE (cut-down, annoyed, guilty, eye-opener) questionnaire and the criteria of the International Statistical Classification of Diseases, 10th Revision. Sociodemographic data and periodontal clinical parameters, such as visible plaque, bleeding on probing, probing depth (PD), and clinical attachment level (CAL), were collected. Groups were controlled for smoking. Intergroup comparisons of sociodemographic data and mean percentage of clinical parameters were analyzed by the χ² and Mann-Whitney tests. The independent effect of alcohol dependence on CAL and PD was assessed by multiple linear regression analysis, adjusting for the effects of plaque, age, income, education, and living conditions.

A significant linear relationship was found between alcohol dependence and mean CAL (P ≤0.013) and mean PD (P ≤0.001).

Alcohol dependence may be associated with an increased severity of CAL and PD.

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Drinking themselves sick ... boozing teens crowd hospitals

Date: June 10 2008

Leo Shanahan Canberra

YOUNG Australians are drinking themselves sick in unprecedented numbers, with new research showing a surge in hospital admissions for alcohol-related conditions since 1999.

In findings that will add to public alarm about teenage drinking, researchers have found that many more youths are ending up in hospital due to alcohol abuse than previous studies might have suggested.

The latest study, published in the Australian and New Zealand Journal of Public Health, used data from Victorian hospital emergency rooms and compared it with other research that relied on people reporting how much they drink.

The emergency room data showed that between 1999-2000 and 2005-06, there were "rapid increases in alcohol presentation rates" in people aged between 16 and 24. Their symptoms included alcohol dependence, mental and behavioural disorder due to alcohol, alcohol poisoning, alcoholic gastritis and alcoholic liver cirrhosis.

The most alarming increases occurred among women aged 18 to 24, with admissions more than doubling to 14.6 per 10,000 people, from about six per 10,000.
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VAMP8 is the v-SNARE that mediates basolateral exocytosis in a mouse model of alcoholic pancreatitis
J. Clin. Invest. Published June 5, 2008



In rodents and humans, alcohol exposure has been shown to predispose the pancreas to cholinergic or viral induction of pancreatitis.

We previously developed a rodent model in which exposure to an ethanol (EtOH) diet, followed by carbachol (Cch) stimulation, redirects exocytosis from the apical to the basolateral plasma membrane of acinar cells, resulting in ectopic zymogen enzyme activation and pancreatitis. This redirection of exocytosis involves a soluble NSF attachment receptor (SNARE) complex consisting of syntaxin-4 and synapse-associated protein of 23 kDa (SNAP-23).

Here, we investigated the role of the zymogen granule (ZG) SNARE vesicle-associated membrane protein 8 (VAMP8) in mediating basolateral exocytosis. In WT mice, in vitro EtOH exposure or EtOH diet reduced Cch-stimulated amylase release by redirecting apical exocytosis to the basolateral membrane, leading to alcoholic pancreatitis. Further reduction of zymogen secretion, caused by blockade of both apical and basolateral exocytosis and resulting in a more mild induction of alcoholic pancreatitis, was observed in Vamp8^–/– mice in response to these treatments. In addition, although ZGs accumulated in Vamp8^–/– acinar cells, ZG-ZG fusions were reduced compared with those in WT acinar cells, as visualized by electron microscopy. This reduction in ZG fusion may account for reduced efficiency of apical exocytosis in Vamp8^–/– acini.

These findings indicate that VAMP8 is the ZG-SNARE that mediates basolateral exocytosis in alcoholic pancreatitis and that VAMP8 is critical for ZG-ZG homotypic fusion.

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Control and sale of alcoholic beverages
Monday, June 9, 2008

Fiscal year ending March 31, 2007

Beer remains the alcoholic drink of choice for Canadians in terms of both volume and dollar value, but its dominance continues to decline as consumers turn more to wine.

Canada's beer and liquor stores and agencies sold more than $18.0 billion worth of alcoholic beverages during the fiscal year ending March 31, 2007, up 4.9% from the year before. This was the fastest rate of growth in sales since 2003.

This advance reflects, in part, the 1.4% increase in the population aged 15 and over as well as a 0.9% average increase in alcoholic beverage prices during this period.

In litres of absolute alcohol, the volume of sales of alcoholic beverages increased 3.1% to 218.7 million litres.

Market shares for the three alcoholic beverage types have changed substantially during the past decade. In 1997, beer accounted for 52% of dollar sales, spirits 27% and wine 21%. By 2007, beer had declined to 47% and spirits had slipped to 25%, while wine had captured 28% of the market.

In volume terms, wine sales significantly outpaced the growth of beer and spirit sales between 2005/2006 and 2006/2007.

Alcoholic beverage sales on a per capita basis, for Canadians aged 15 and over, amounted to $667 in 2006/2007, up $22 from the previous year.
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Alcohol-attentional bias and motivational structure as independent predictors of social drinkers’ alcohol consumption
Drug and Alcohol Dependence Article in Press, Corrected Proof 27 May 2008


Prior studies aimed at explaining cognitive–motivational reasons for drinking have focused on either cognitive or motivational factors, but not on both.

This study examined the ability of both alcohol-attentional bias and motivational structure to predict alcohol consumption.

Participants were university students (N = 87) who completed a battery of tests, including the Personal Concerns Inventory (a measure of adaptive and maladaptive motivation), an alcohol Stroop test (a measure of alcohol-attentional bias), and an alcohol-use inventory.

Regression, moderation, and mediation analyses showed that (a) maladaptive motivation and alcohol-attentional bias were positive predictors of alcohol consumption after participants’ age, gender, and executive cognitive functioning had been controlled, and (b) maladaptive motivation and alcohol-attentional bias independently predicted alcohol consumption.

The implications of the results for both theory and practice are discussed.


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Request Reprint E-Mail: J.S.Fadardi@bangor.ac.uk __________________________________________________________________

Ministers meet to tackle problem premises
Monday, June 09, 2008

Ministers met with senior local authority and police officials this week to discuss further use of powers to tackle premises selling irresponsibly. In a press release from the Department for Culture, Media and Sport details of some of the key measures to control problem premises were given. These include discussions on the use of a new 'yellow card, red card' system designed to get sharper on premises breaching conditions as well as encouraging authorities to make the best use of of local knowledge.
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Alcoholism: protein expression profiles in a human hippocampal model
Expert Review of Proteomics, Volume 5, Number 2, April 2008 , pp. 321-331(11)


It is well known that chronic, excessive consumption of alcohol can cause brain damage/structural changes in the regions important for neurocognitive function. Some of the damages are permanent, while others are reversible. Molecular mechanisms underlying alcohol-induced and/or -related brain damage are largely unknown, although it is generally believed that three factors (ethanol, nutritious and hepatic factors) play important roles.

Recently, we have been employing a high-throughput proteomics technology to investigate several alcohol-sensitive brain regions from uncomplicated and hepatic cirrhosis-complicated alcoholics to understand the mechanisms of alcohol effects on the CNS at the level of protein expression.

The changes of protein expression profiles in the hippocampus of alcoholic subjects were firstly demonstrated using 2D gel electrophoresis-based proteomics. Protein expression profiles identified in the hippocampus of alcoholic subjects were significantly different from those previously identified by our group in other brain regions of the same alcoholic cases, possibly indicating that these different brain regions react differently to chronic alcohol ingestion at the level of protein expression.

Identified changes of protein expression associated with astrocyte and oxidative stress may indicate the possibility that increased levels of CNS ammonia and reactive oxygen species induced by alcoholic mild hepatic damage/dysfunction could cause selective damage in astrocytes of the hippocampus.

Although our data did not demonstrate any evidence of direct alcohol effects to induce the alteration of protein expression in association with brain damage, high-throughput neuroproteomics approaches have proved to have the potential to dissect the mechanisms of complex brain disorders.

Proteomics studies on human hippocampus, an important region for neurocognitive function and psychiatric illnesses (e.g., Alzheimer's disease, alcoholism and schizophrenia) are still sparse, and further investigation is warranted to understand the underlying mechanisms.

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Request Reprint E-Mail: haruka.matsuda@imb.me-h.ne.jp
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Prognostic Value of Serum Selenium Levels in Alcoholics
Biological Trace Element Research Online First 03 June 2008


In alcoholics, exposure of Kupffer cells to intestinal-borne Gram-negative bacteria increases free radical release, which may, in turn, enhance cytokine secretion, creating a positive feedback loop, which contributes to liver inflammation.

Impaired antioxidant mechanisms further aggravates this scenario. Some trace elements, such as selenium, are main cofactors of antioxidant enzymes. Some authors have found low Se levels in alcoholics in relation either with undernutrition, liver dysfunction, or intensity of alcoholism, but in general, Se supplementation has no effect on survival.

In this study we measured serum Se in 16 controls and 76 alcoholics, 34 of them cirrhotics, 68 of whom were followed up for a median period of 38 months; 17 died during this period. Se levels were lower in patients than in controls and were related to prothrombin activity and nutritional status, more closely to this last parameter (stepwise logistic regression analysis). Patients who died showed lower Se values than those who survived. Se values over the median were associated with better survival, assessed by Kaplan–Meier curves and log-rank test. However, in multivariate analysis (Cox regression model), prothrombin activity displaced serum Se as a prognostic factor.

We conclude that serum Se levels are low in alcoholics; these low values depend more heavily on impaired nutrition but also on liver dysfunction; although low Se levels were associated with a higher mortality, prothrombin activity displaced serum Se when survival was assessed using Cox’s regression model.

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Pregnancy-related changes in tobacco, alcohol and cannabis use reported by antenatal patients at two public hospitals in South Australia
The Australian and New Zealand Journal of Obstetrics and GynaecologyVolume 48 Issue 3 Page 248-254, June 2008

Australian substance use data do not demonstrate pregnancy-related changes or distinguish between pregnant and lactating women.

To determine such changes by antenatal patients at two South Australian public hospitals accounting for 35% of the state's births.

In 2005–2006, all first visit antenatal women at the two hospitals were asked by clinic staff to complete an anonymous, self-administered questionnaire prompting details of substance use, current and previous (while not pregnant or lactating).

Questionnaires were returned by 748 women, 34.4% of 2173 eligible in the study period. Women reported use at significantly lower rates than before pregnancy. Tobacco was most used in pregnancy (18.5%), followed by alcohol (11.8%) and cannabis (4.5%), with negligible use of other illicit substances. There was no significant difference in substance use related to trimester. Women with previous pregnancy losses were significantly more likely to use tobacco and alcohol. Younger women were more likely to use tobacco and cannabis, with no age-related differences in alcohol consumption. First pregnancy was the only factor independently associated with the likelihood of ceasing substance use when pregnant, but only in relation to alcohol.

Women were less likely to use all substances when pregnant, and health-care providers should reinforce and support these decisions. The use of cannabis and alcohol while pregnant was below expectations. Reported tobacco use was concordant with existing data and confirms that the risk of smoking in pregnancy remains a message difficult to communicate in the context of chronic nicotine dependence.

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Request Reprint E-Mail: libby.hotham@unisa.edu.au

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Pregnancy characteristics of women giving birth to children with fetal alcohol syndrome in Far North Queensland
The Australian and New Zealand Journal of Obstetrics and GynaecologyVolume 48 Issue 3 Page 240-247, June 2008

Fetal alcohol syndrome (FAS) has been identified as a major cause of impairment to normal physical and intellectual development among Indigenous children in Far North Queensland; however, little is known of the pregnancy characteristics of mothers of those children diagnosed with FAS or of interventions that might assist in lowering the prevalence of the syndrome.

Mothers of cases were older, of higher parity, smoked more cigarettes, attended fewer antenatal visits and experienced more antenatal and delivery complications than mothers of controls. The average gestational age at booking was not statistically significant between the two groups.

There was a significant difference between the two groups in self-reported alcohol consumption both before and during pregnancy and in numbers of women who decreased alcohol consumption once the diagnosis of pregnancy was known to them.

There is the potential to identify prospectively women presenting for antenatal care who are heavy drinkers and risk FAS in their infants, using the self-reported information about alcohol intake already being collected by our service; such women may then be offered specific interventions to try to reduce alcohol consumption in pregnancy.

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Request Reprint E-Mail: caroline.decosta@jcu.edu.au

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Alcohol and pregnancy: The pivotal role of the obstetrician
The Australian and New Zealand Journal of Obstetrics and Gynaecology
Volume 48 Issue 3 Page 236-239, June 2008

New draft alcohol guidelines for Australia state that, for pregnant women and women planning pregnancy, ‘no drinking is the safest option’.

One of the best known adverse effects of alcohol exposure on the fetus is the fetal alcohol syndrome. Others include alcohol-related birth defects, alcohol-related neurodevelopmental disorders and increased risks of miscarriage, stillbirth, intrauterine growth restriction, preterm birth and low birthweight. Over half of Australian women consume alcohol during pregnancy.

Obstetricians have a pivotal role in advising women of the effects of alcohol on the fetus and reducing fetal exposure.

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Request Reprint E-Mail: elizabe2@chw.edu.au
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Alcohol exposure during the first two trimesters-equivalent alters the development of corpus callosum projection neurons in the rat
Alcohol Volume 42, Issue 4, June 2008, Pages 285-293


Children exposed prenatally to alcohol can display a variety of neural deficits, including an altered development of the corpus callosum (CC), the largest interhemispheric axon pathway in the brain. Furthermore, these children show functional abnormalities that are related to brain regions with significant numbers of CC connections. Little is known about how alcohol imparts influence on CC development, but one possible mechanism is by affecting the corpus callosum projection neurons (CCpn) directly.

The purpose of this study was to quantify the effects of prenatal alcohol exposure on the number, size, and distribution of CCpn within the visual cortex. The visual cortex was selected specifically due to the many vision-related deficits noted in fetal alcohol exposed children and because the critical role of the CC in visual cortex development is well documented.

Sprague–Dawley rat pups received one of four alcohol dosages during gestational days (G) 1–20, or reared as nutritional or untreated control animals. Each litter was categorized according to the peak blood alcohol concentration experienced. Pups were removed from each litter on days equivalent to G29, G36, G43, and G50, for histology and measurement. Callosal axons were labeled retrogradely to their CCpn using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) and the CCpn were then examined using confocal laser scanning microscopy.

Differences between alcohol-exposed and control animals were observed in CCpn cell body size, number, and location with the cortex. This was particularly true of animals exposed to high doses of alcohol. In addition, some trends of CCpn development were found to be unchanged as a result of prenatal alcohol exposure.

The results demonstrate clear differences in the development of CCpn in the visual cortex between alcohol-exposed and control animals and suggest that this development is particularly affected in those animals exposed to high doses of alcohol.

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Request Reprint E-Mail: aelberger@utmem.edu
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Alcohol consumption and cerebral blood flow among older adults
Alcohol Volume 42, Issue 4, June 2008, Pages 269-275



A substantial epidemiological literature now supports the existence of a J or U-shaped association between alcohol consumption and a broad range cardiovascular health outcomes including stroke.

Although it is well documented that alcoholics exhibit both global and regional cerebral hypoperfusion in the sober state, little is known regarding the effects of a broader range of alcohol consumption on cerebral blood flow (CBF).

The present study employed positron emission tomography with H₂¹⁵O to assess quantitative global and regional CBF in 86 participants (51 men and 35 women; mean age 60.1) as a function of self-reported weekly alcohol consumption (none, <1,>15 drinks per week).

Analyses controlling for age, gender, and vascular health (carotid intima-media thickness) revealed that, relative to the weighted population mean, global CBF was greater in the lightest alcohol consumption group (<1>15 per week). Effects did not vary across regions of interest.

This report is the first to describe an inverted J-shaped relationship between alcohol consumption and CBF in the absence of stroke.

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Request Reprint E-Mail: christieic@upmc.edu
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Children's hedonic responses to the odors of alcoholic beverages: A window to emotions
Alcohol Volume 42, Issue 4, June 2008, Pages 249-260



The present study of 145 children and their mothers aimed to determine whether children's responses to the odors of alcoholic beverages were related to their mothers' reasons for drinking.

Mothers completed a series of questionnaires to describe the emotional context in which they drink and whether they use alcohol to “escape” by changing their state of mind and reducing feelings of dysphoria. Children participated in two age-appropriate tasks that focused on the most salient psychological attribute of an odor, its perceived hedonic valence.

To this aim, we determined children's liking, reaction times, and identification of individual odors including beer and whiskey in Task 1, and their preference for beer relative to odors that differed in hedonic valence in Task 2.

The type of task and behavioral measure revealed different aspects of children's responses, to alcohol odors. In Task 1, verbally identifying an odor was a more difficult task than deciding whether they liked the odor. Although there were few group differences in liking for individual odors, children of Escape drinkers took significantly longer to determine whether they liked the odors. In Task 2, children of Escape drinkers preferred beer less often, particularly when it was compared with less pleasant odors. They preferred coffee to beer odors and, if their mothers did not smoke cigarettes, preferred the odors of cigarette smoke and pyridine to beer. These children experienced the odor of alcohol more frequently and in the context of mood disturbed mothers who felt guilty and worried about their drinking.

Whether children who associate the odor of alcohol with such emotional contexts display a trajectory toward or against using alcohol to escape remains unknown.

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Request Reprint E-Mail: mennella@monell.org,
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Effects of Chronic Ethanol Feeding on Murine Dendritic Cell Numbers, Turnover Rate, and Dendropoiesis
Alcoholism: Clinical and Experimental Research OnlineEarly Articles 06 June 2008

Chronic alcoholics have increased susceptibility to and severity of infection, which are likely to be a result of impaired immune defense mechanisms. The contribution of dendritic cells (DC) to these immune defense changes is not well understood. Alterations in DC numbers, dendropoiesis, and lifespan have not been specifically studied in vivo in chronic ethanol (EtOH) exposure models. As DC play an essential role in initiating immune responses, alterations in these DC characteristics would help explain changes observed in adaptive immune responses.

The percentage and absolute numbers of DC were decreased in spleen and increased in thymus beginning as early as 4 weeks of EtOH feeding. In addition, the overall cellularity of spleen and thymus were altered by this regimen. However, chronic EtOH consumption did not adversely affect DC precursor numbers, differentiation abilities, or turnover rates.

Decreased splenic DC numbers observed following chronic murine EtOH consumption are not because of altered DC precursor numbers or differentiation, nor increased DC turnover rate. Similarly, increased thymic DC numbers are not the result of alterations in DC precursor differentiation or turnover rate. Compartment size plays a role in determining splenic and thymic DC numbers following chronic EtOH feeding. EtOH-induced alterations in total DC numbers provide several mechanisms to partially explain why chronic alcoholics have increased susceptibility to infections.

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Request Reprint E-Mail: annette-schlueter@uiowa.edu

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Alcohol Sensitizes Cerebral Responses to the Odors of Alcoholic Drinks: An fMRI Study
Alcoholism: Clinical and Experimental Research OnlineEarly Articles 06 June 2008

Small, priming doses of alcohol enhance desire to drink, and thus play a role in the loss of control of alcohol consumption. Using functional magnetic resonance imaging (fMRI), we previously showed that alcoholic drink odors (AO; subjects’ drinks of choice) induce greater nucleus accumbens (NAc) activity than non-appetitive odors (NApO; grass, leather) in subjects at risk for alcoholism.

Here we hypothesized that priming exposure to alcohol would enhance responses to AO in the NAc and orbitofrontal cortex in comparison to NApO (grass, leather) and to the appetitive control odors (ApCO) of chocolate and grape.

Alcohol infusion enhanced the contrast between AO and NApO in the NAc, and in orbitofrontal, medial frontal, and precuneus/posterior cingulate regions. The contrast between AO and appetitive control odors (ApCO; chocolate and grape) was similarly larger in the orbital, medial frontal, precuneus, and posterior cingulate/retrosplenial areas, with the most robust finding being a potentiated response in the posterior cingulate/retrosplenial area. The orbital region is similar to an area previously shown to manifest satiety-related decreases in activity induced by food cues.

The results suggest that priming exposure to alcohol renders a limbic network more responsive to alcohol cues, potentially enhancing desire to drink.

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Request Reprint E-Mail: dkareken@iupui.edu

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Acamprosate: Recent Findings and Future Research Directions
Alcoholism: Clinical and Experimental Research OnlineEarly Articles 06 June 2008

This article explores the mechanisms of action and the potential responder profile of acamprosate, a compound efficacious in relapse prevention of alcoholism. New evidence at the molecular and cellular level suggests that acamprosate attenuates hyper-glutamatergic states that occur during early abstinence and involves iono (NMDA)- and metabotrotropic (mGluR5) glutamate receptors along with augmented intracellular calcium release and electrophysiological changes.

Thus mutant mice with enhanced glutamate levels exhibit higher alcohol consumption than wild type mice and respond better to acamprosate, demonstrating that acamprosate acts mainly on a hyper-glutamatergic system. This mode of action further suggests that acamprosate exhibits neuroprotective properties. In rats, cue-induced reinstatement behavior is significantly reduced by acamprosate treatment whereas cue-induced craving responses in alcohol-dependent patients seem not to be affected by this treatment.

An ongoing study ("Project Predict") defines specific responder profiles for an individualized use of acamprosate and naltrexone. Neurophysiological as well as psychometric data are used to define 2 groups of patients: "reward cravers" and "relief cravers". While naltrexone should work better in the first group, acamprosate is hypothesized to be efficacious in the latter where withdrawal associated and/or cue induced hyper-glutamatergic states are thought to trigger relapse.

Further research should target the definition of subgroups applying endophenotypic approaches, e.g. by detecting a hyperglutamatergic syndrome using MR spectroscopy.

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Request Reprint E-Mail: sucht@zi-mannheim.de
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Proton Magnetic Resonance Spectroscopy in Alcohol Use Disorders: A Potential New Endophenotype?
Alcoholism: Clinical and Experimental Research OnlineEarly Articles 06 June 2008

Current effort is directed at defining new classification schemes for alcohol use disorders (AUD) based on genetic/biological, physiological, and behavioral endophenotypes.

We describe briefly findings of in vivo brain proton magnetic resonance spectroscopy (¹H MRS) studies in AUD and propose that they be further explored and expanded regarding their value as a potential endophenotype for AUD.

In vivo ¹H MRS, as part of the emerging field of "imaging genomics," may provide readily accessible, objective, functionally significant and region-specific neurobiological measures that successfully link genotypes to neurocognition and to psychiatric symptomatology in relatively small patient cohorts. We discuss several functional gene variants that may affect specific ¹H MRS-detectable metabolites and provide recent data from our own work that supports the view of genetic effects on metabolite measures.

MRS-genetics research will not only offer clues to the functional significance and downstream effects of genetic differences in AUD, but, via monitoring and/or predicting the efficacy of pharmacological and behavioral interventions as a function of genotype, has the potential to influence future clinical management of AUD.

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Request Reprint E-Mail: Dieter.Meyerhoff@ucsf.edu

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A Placebo-Controlled Randomized Clinical Trial of Naltrexone in the Context of Different Levels of Psychosocial Intervention
Alcoholism: Clinical and Experimental Research OnlineEarly Articles 06 June 2008

Naltrexone is approved for the treatment of alcohol dependence when used in conjunction with a psychosocial intervention. This study was undertaken to examine the impact of 3 types of psychosocial treatment combined with either naltrexone or placebo treatment on alcohol dependency over 24 weeks of treatment: (1) Cognitive-Behavioral Therapy (CBT) + medication clinic, (2) BRENDA (an intervention promoting pharmacotherapy) + medication clinic, and (3) a medication clinic model with limited therapeutic content.

There was a modest main treatment effect for the psychosocial condition favoring those subjects randomized to CBT. Intent-to-treat analyses suggested that there was no overall efficacy of naltrexone and no medication by psychosocial intervention interaction. There was a relatively low level of medication adherence (50% adhered) across conditions, and this was associated with poor outcome.

Results from this 24-week treatment study demonstrate the importance of the psychosocial component in the treatment of alcohol dependence. Moreover, results demonstrate a substantial association between medication adherence and treatment outcomes. The findings suggest that further research is needed to determine the appropriate use of pharmacotherapy in maximizing treatment response.

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Request Reprint E-Mail: oslin@mail.med.upenn.edu

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The Usefulness of Direct Ethanol Metabolites in Assessing Alcohol Intake in Nonintoxicated Male Patients in an Emergency Room Setting
Alcoholism: Clinical and Experimental Research Online Early Articles 06 June 2008

A major part of medical pathology in internal medicine is associated with chronic alcoholism. The aim of the current study was to investigate whether screening for Alcohol Use Disorders (AUD) can be improved through determination of direct ethanol metabolites compared to traditional biological state markers, the Alcohol Use Disorders Identification Test (AUDIT) and additional self-reports beyond the detection time period of a positive blood alcohol concentration (BAC).

A total of 74 blood alcohol negative male patients who presented at the emergency room with either thoracic or gastrointestinal complaints were included. Phosphatidylethanol (PEth) was determined in whole blood, and ethyl glucuronide (EtG) in serum and urine samples. Traditional biological state markers [carbohydrate deficient transferrin (%CDT), gamma glutamyl transpeptidase (GGT), mean corpuscular volume (MCV)] were determined. The AUDIT was obtained and furthermore, all patients completed an additional self-report of alcohol consumption. Patients were divided into two (2) groups: AUDIT scores <>

After assessment of the AUDIT, patients were allocated to one of the following groups: patients with AUDIT scores <>n = 52) and with AUDIT scores ≥ 8 (n = 22). Twenty-five percent of the patients with AUDIT scores below the cut-off (n = 13/52) were tested positive for both PEth and UEtG. Of the patients who declared to be sober during the past 12 months, 38.5% were tested positive for PEth and UEtG. PEth discriminated similarly as %CDT for AUDIT scores ≥ 8 (AUC: 0.672; 95%CI 0.524 to 0.821). Self-reports of alcohol consumption were unreliable.

Determination of direct ethanol metabolites such as PEth and UEtG provides additional evidence in screening for AUD in an ER setting. Determination of PEth might be considered complementary with or alternatively to %CDT.

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Request Reprint E-Mail: claudia.spies@charite.de

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Effects of Family History of Alcohol Use Disorders on Spatial Working Memory BOLD Response in Adolescents
Alcoholism: Clinical and Experimental Research OnlineEarly Articles 06 June 2008

A positive family history (FH) of alcohol use disorders (AUD) has been linked to increased risk for the development of AUD, and neurocognitive factors have been postulated as important underlying mechanisms of familial alcoholism transmission.

We used functional magnetic resonance imaging (fMRI) during a spatial working memory (SWM) and vigilance paradigm to investigate potential neurodevelopmental differences linked to familial density of AUD in 72 adolescents aged 12 to 14 years.

Youth with denser family histories of AUD showed less activation during a simple vigilance condition relative to SWM in cingulate and medial frontal gyri (β = 0.28, p = 0.03), and a trend for more relative activity during rest (β = −0.25, p = 0.07) in this cluster.

Youth with greater familial densities of AUD may be less successful at modulating activity of the default network, potentially indicating a greater propensity for task-independent thought or reduced inhibition of task-irrelevant processing. Failure to moderate activation of the default network may have implications for cognitive efficiency and goal directed behavior in youth with dense FH. Further, aberrant activation in cingulate regions may be linked to genetic variation in GABA receptor units, suggesting a useful endophenotype for risk associated with alcohol dependence.

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Request Reprint E-Mail: stapert@ucsd.edu

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Effects of Alcohol on Simulated Driving and Perceived Driving Impairment in Binge Drinkers
Alcoholism: Clinical and Experimental Research OnlineEarly Articles 06 June 2008

Binge drinking (heavy episodic alcohol use) is associated with high rates of impaired driving and myriad alcohol-related accidents. However, the underlying reasons for the heightened accident risk in this demographic group are not known. This research examined acute alcohol effects on simulated driving performance and subjective ratings of intoxication and driving ability in binge and nonbinge drinkers.

The acute dose of alcohol impaired multiple aspects of driving performance in both binge and nonbinge drinkers. Under alcohol, all participants had greater difficulty in maintaining their lane position, maintaining the appropriate speed and made multiple driving errors compared to placebo performance. By contrast, compared with nonbinge drinkers, binge drinkers reported feeling less sedated by the alcohol and reported having a greater ability to drive following the acute dose of alcohol.

Reduced subjective intoxication and perceived driving impairment in binge drinkers may account for the greater accident risk in this demographic group. Binge drinkers may lack the internal sedation cue that helps them accurately assess that they are not able to effectively drive a vehicle after drinking.

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Request Reprint E-Mail: cecile.marczinski@uky.edu

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Inhibition of the Activity of Excitatory Amino Acid Transporter 4 Expressed in Xenopus Oocytes After Chronic Exposure to Ethanol
Alcoholism: Clinical and Experimental Research OnlineEarly Articles 06 June 2008

The extracellular glutamate concentration is tightly controlled by excitatory amino acid transporters (EAATs). EAAT4 is the predominant EAAT in the cerebellar Purkinje cells. Purkinje cells play a critical role in motor coordination and may be an important target for ethanol to cause motor impairments.

We designed this study to determine the effects of chronic ethanol exposure on the activity of EAAT4 and evaluate the involvement of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) in these effects.

Ethanol dose- and time-dependently reduced EAAT4 activity. EAAT4 activity after a 96-hour exposure was significantly decreased compared to the control values at all concentrations tested (10 to 100 mM). Ethanol (50 mM) significantly decreased the Vmax (2.2 ± 0.2 μC for control vs. 1.6 ± 0.2 μC for ethanol, n = 18, p < 0.05) of EAAT4 for l-aspartate. Preincubation of ethanol-treated (50 mM for 96 hours) oocytes with phorbol-12-myrisate-13-acetate (100 nM for 10 minutes) abolished the ethanol-induced decrease in EAAT4 activity. While staurosporine (2 μM for 1 hour) or chelerythrine (100 μM for 1 hour) significantly decreased EAAT4 activity, no difference was observed in EAAT4 activity among the staurosporine, ethanol, or ethanol plus staurosporine groups. Similarly, EAAT4 activity did not differ among the chelerythrine, ethanol, or ethanol plus chelerythrine groups. Pretreatment of the oocytes with wortmannin (1 μM for 1 hour) also significantly decreased EAAT4 activity. However, no difference was observed in the wortmannin, ethanol, or ethanol plus wortmannin groups.

The results of this study suggest that chronic ethanol exposure decreases EAAT4 activity and that PKC and PI3K may be involved in these effects. These effects of ethanol on EAAT4 may cause an increase in peri-Purkinje cellular glutamate concentration, and may be involved in cerebellar dysfunction and motor impairment after chronic ethanol ingestion.

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Request Reprint E-Mail: anesing1@snu.ac.kr
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Development and Pilot Validation of Computer-Assisted Self-Infusion of Ethanol (CASE): A New Method to Study Alcohol Self-Administration in Humans
Alcoholism: Clinical and Experimental Research OnlineEarly Articles 06 June 2008

Human alcohol self-administration studies employing oral intake are subject to high variability of the resulting blood alcohol concentrations because of idiosyncrasies of gastrointestinal absorption kinetics among subjects. We sought to improve the subjects’ opportunity to control their brain alcohol exposure by computer-assisted i.v. self-administration.

Instead of drinking, subjects could request increments of their arterial blood alcohol concentration (aBAC) of precisely 7.5 mg% at any time they wanted by pressing a button, provided their aBAC would not exceed 100 mg%. The latency between pushing the button and reaching the new aBAC peak was preset to be 2.5 minutes on the first day and was randomly changed to 1.5 or 3.5 minutes on days 2 and 3 in a crossover design. The necessary rate and amount of alcohol infusion was calculated by the software about once every second. Nine healthy social drinkers (4 females/5 males; mean age 25.0 ± 4.0 year) participated in 3 sessions each. Outcome measures were mean and maximum observed aBAC, and the number of alcohol requests.

Maximum aBAC was 76.5 ± 26.3 mg% on average over all experiments. When grouping days 2 and 3 according to latency (1.5 vs. 3.5 minutes), maximum aBAC and the number of requests in the session were significantly higher with the faster rise and all 3 outcome measures were significantly correlated between days. No such correlations were found between the first and either of the following days.

These data suggest that CASE is practical and safe, and results in considerable alcohol exposure that can be manipulated with parameters chosen for the incremental exposure. Following 1 practice day, test–retest stability was good, suggesting a potential for use in scientific studies.

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Request Reprint E-Mail: ulrich.zimmermann@uniklinikum-dresden.de

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Differential Neural Response to Alcohol Priming and Alcohol Taste Cues Is Associated With DRD4 VNTR and OPRM1 Genotypes
Alcoholism: Clinical and Experimental Research OnlineEarly Articles 06 June 2008

Studies suggest that polymorphisms in the D4 dopamine receptor (DRD4) and opioid receptor, μ1 (OPRM1) genes are involved in differential response to the effects of alcohol and to alcohol cues. However, to date, the mechanisms that underlie these differences remain largely unknown.

The results indicated that DRD4 VNTR >7 repeat individuals (DRD4.L) had significantly greater response to alcohol cues in the orbitofrontal cortex, anterior cingulate gyrus, and striatum compared with individuals with <7>p <>

The DRD4 VNTR and OPRM1 A118G polymorphisms are associated with functional neural changes in mesocorticolimbic structures after exposure to alcohol cues. This provides evidence for the contributions of the DRD4 and OPRM1 genes in modulating neural activity in structures that are involved in the motivation to drink.

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Request Reprint E-Mail: ffilbey@mrn.org
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Trends in population drug use in New Zealand: findings from national household surveying of drug use in 1998, 2001, 2003, and 2006
Journal of the New Zealand Medical Association, 23-May-2008, Vo 121 No 1274

National household surveys of drug use were conducted in New Zealand in 1998, 2001, 2003,and 2006 using the same Computer Assisted Telephone Interview (CATI) methodology. The age ranges of the random digit dial (RDD) samples from each survey wave were truncated to those aged 15–45 years old. The respective sample sizes for each of the survey waves were: 5475 in 1998; 5504 in 2001, 3042 in 2003, and 1902 in 2006. Statistical comparisons were made between the 2006 survey wave and the three other survey waves for 13 different drug types.

A higher proportion of the sample had tried alcohol in their lifetimes in 2006 compared to 2003 (89.5% vs 83.7%, p<0.0001) and compared to 2001 (89.5% vs 86.4%, p=0.0038). A lower proportion had tried tobacco in 2006 compared to 2001 (57.6% vs 63.9%, p<0.0001) and compared to 1998 (57.6% vs 64.4%, p<0.0001). A lower proportion had used cannabis in the past 12 months in 2006 compared to 2001 (17.9% vs 20.3%, p=0.0448). A lower proportion had used amphetamine in the past year in 2006 than in 2001 (3.4% vs 5.0%, p=0.0085). A higher proportion of the sample had used ecstasy (MDMA) in the past year in 2006 compared to 1998 (3.9% vs 1.5%, p<0.0001).

There was an increase in the level of alcohol use by last year drinkers in 2006 compared to 1998 with an increase in the proportion of drinkers saying they were using ‘more’ alcohol and a decrease in those saying they were using ‘less’ alcohol. There was an increase in the level of amphetamine use by current amphetamine users in 2006 compared to 2003 with less users saying they had ‘stopped’ using the drug (12% vs 42%, p=0.0386).

The rise in the lifetime use and level of use of alcohol is consistent with the liberalisation of the alcohol environment in New Zealand. Conversely, the decline in the lifetime use of tobacco reflects stricter regulation and shifts in societal tolerance of smoking. The growing negative social connotations attached to smoking, as well the emergence of new synthetic stimulants, may have impacted negatively on levels of cannabis use. There has been some entrenchment of amphetamine use since a reported levelling off of its prevalence in 2003.

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Request Reprint E-Mail: c.wilkins@massey.ac.nz
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