Converging action of alcohol consumption and cannabinoid receptor activation on adult hippocampal neurogenesis

Alcoholism is characterized by successive periods of abstinence and relapse, resulting from long-lasting changes in various circuits of the central nervous system.

Accumulating evidence points to the endocannabinoid system as one of the most relevant biochemical systems mediating alcohol addiction. The endocannabinoid system regulates adult neurogenesis, a form of long-lasting adult plasticity that occurs in a few areas of the brain, including the dentate gyrus. Because exposure to psychotropic drugs regulates adult neurogenesis, it is possible that neurogenesis might be implicated in the pathophysiology, and hence treatment, of neurobiological illnesses related to drugs of abuse.

Here, we investigated the sensitivity of adult hippocampal neurogenesis to alcohol and the cannabinoid receptor agonist WIN 55,212-2 (WIN). Specifically, we analysed the potential link between alcohol relapse, cannabinoid receptor activation, and adult neurogenesis.

Adult rats were exposed to subchronic alcohol binge intoxication and received the cannabinoid receptor agonist WIN. Another group of rats were subjected to an alcohol operant self-administration task. Half of these latter animals had continuous access to alcohol, while the other half were subjected to alcohol deprivation, with or without WIN administration.

WIN treatment, when administered during alcohol deprivation, resulted in the greatest increase in alcohol consumption during relapse. Together, forced alcohol binge intoxication and WIN administration dramatically reduced hippocampal neurogenesis. Furthermore, adult neurogenesis inversely correlated with voluntary consumption of alcohol.

These findings suggest that adult hippocampal neurogenesis is a key factor involved in drug abuse and that it may provide a new strategy for the treatment of alcohol addiction and dependence.

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Request Reprint E-Mail: pmlledo@pasteur.fr
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Alcohol and food: making the public health connections

UK policy must address the links between alcohol and food in order to maximise the effectiveness of public health responses and enable people to make better informed choices about eating and drinking.

We urgently need to move away from seeing alcohol as a means to achieve inebriation to regarding itas an accompaniment to food with both being consumed in moderation.

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Portman Group

The following extract gives some insight into the context in which the Portman Group was established.

"In 1989, a new public relations alliance was formed by the UK's leading alcohol companies. Instrumental in setting the ball rolling was (Lord) John Wakeham, a Tory peer and then chairman of the Ministerial Group on Alcohol Issues. According to Anthony Hurse, civil servant at the Department of Health: "Lord Wakeham made it clear to the alcohol industry that he would like the industry's collaboration. He spoke to Peter Mitchell Director of Strategic Affairs at Guinness who agreed he'd do what he could. As a consequence of Wakeham's suggestions, the UK's seven leading alcohol companies including Whitbread, Bass and Seagram, launched a new PR organisation from the headquarters of Guinness plc in London's Portman Square" ^[1].

The Portman Group's publicly stated aim is "to promote sensible drinking" However, according to Professor Nick Heather, former Director of the Newcastle Centre for Alcohol and Drug Studies, the Group's real agenda is rather different: "The attempt to distance alcohol as a drug from other kinds of drug and to give it a good face is the main activity of groups like the Portman Group." ^[2]

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Nick Heather on controlled drinking and the relationship to harm reduction

Nick distinguishes between harm reduction and harm elimination. He describes the way in which views of harm reduction in the USA have ‘muddied the waters’ in relation to the goal of controlled drinking. Nick says that the controlled drinking goal in the alcohol field may have been watered down more recently by the influence of the concept of harm reduction from the illicit drugs field.

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Nick Heather explores harmful choices and explains Hyperbolic Discounting

Nick references George Ainslie’s work on ‘pico-economics’ and ‘breakdown of will’. He explains the idea of hyperbolic discounting and how this related to addiction. He also explores the concepts of resolutions and preferences and how these relate to our understanding of addiction.

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Nick Heather on Motivational Interviewing pre-comittment and Ulysses

Nick talks about the theory of how people resist temptation by findings ways of increasing the value later, larger rewards relative to earlier, smaller rewards, as described in the work of Jon Elster and George Ainslie..

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Nick Heather: Alcohol is not an ordinary commodity

Nick says we demonise illicit drugs use to irrational levels but equally we underestimate the harmful effects of alcohol.

He goes on the discuss ways of reducing alcohol-related harm by pricing. Controlling the alcohol industry and reducing health inequalities.

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Nick Heather on 'Choice, Behavioural Economics and Addiction

Nick describes the background of a conference he convened with Rudy Vuchinich on behavioural economics and its relevance to addiction, and the book that arose from this conference.

He also talks about Alcoholics Anonymous and how its benefits could be applied to secular mutual-aid groups.

He then references the work of Keith Humphreys on self-help groups.

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Brief motivational feedback for college students and adolescents: a harm reduction approach

Alcohol consumption and its attendant problems are prevalent among adolescents and young adult college students. Harm reduction has been found efficacious with heavy drinking adolescents and college students. These harm reduction approaches do not demand abstinence and are designed to meet the individual where he or she is in the change process. The authors present a case illustration of a harm reduction intervention, the Brief Alcohol Screening and Intervention for College Students (BASICS), with a heavy-drinking female college student experiencing significant problems as a result of her drinking. BASICS is conducted in a motivational interviewing style and includes cognitive-behavioral skills training and personalized feedback. Read Full Abstract Request Reprint E-Mail: ursulawhiteside@gmail.com _________________________________________________

Adolescents alcohol-use and economic conditions: a multilevel analysis of data from a period with big economic changes

This paper examines how the unemployment rate is related to adolescent alcohol use and experience of binge drinking during a time period characterized by big societal changes.

The results show that the unemployment rate is negatively associated with adolescents’ alcohol use and the experience of binge drinking. When the unemployment rate increases, more adolescents do not drink at all. Regular drinking (twice per month or more) is, on the other hand, unrelated to the unemployment rate.

Examining gender-differences in the relationship, it is shown that the results are driven by behavior in girls, whereas drinking among boys does not show any significant relationship with changes in the unemployment rate.

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Request Reprint E-Mail: mikael.svensson@oru.se
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Challenging the “Inoffensiveness” of Regular Cannabis Use by Its Associations with Other Current Risky Substance Use—A Census of 20-Year-Old Swiss Men

3,537 men enrolling in 2007 for mandatory army recruitment procedures were assessed for the co-occurrence of risky licit substance use among risky cannabis users.

Risky cannabis use was defined as at least twice weekly; risky alcohol use as 6+ drinks more than once/monthly, or more than 20 drinks per week; and risky tobacco use as daily smoking.

Ninety-five percent of all risky cannabis users reported other risky use. They began using cannabis earlier than did non-risky users, but age of onset was unrelated to other risky substance use.

A pressing public health issue among cannabis users stems from risky licit substance use warranting preventive efforts within this age group.

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Alcohol, Other Drugs, and Health: Current Evidence

Current Issue: November–December 2009

Interventions and Assessments

• New Cocaine Vaccine Is Safe but Has Limited Efficacy
• Efficacy of Brief Intervention for Heavy Drinking in Hospitalized Patients Questionable
• Single-Question Alcohol Screen Detects Unhealthy Alcohol Use in a Primary Care Setting
• Methadone Treatment Documentation in the Medical Record: Implications for Patient Safety
• Brief Intervention for Hospitalized Patients with Problematic Prescription Drug Use: No Long-lasting Effects
• Prison-Initiated Methadone Maintenance Improves Postrelease Treatment Outcomes
• Abstinence Rates with Office-Based Buprenorphine Treatment Differ by Retention and Insurance Status

Health Outcomes

• Diverted Methadone and Buprenorphine Primarily Used to Prevent Withdrawal or to Stop Using Heroin
• Does Alcohol Use Affect Driving Performance in Patients with Obstructive Sleep Apnea?
• Methadone Contributes to Bone and Dental Disease: Fact or Fiction?
• Adults with Prescription-Opioid Dependence Engage in High Rates of HIV Risk Behaviors
• Inverse Association between Alcohol Consumption and Mortality May Differ by Ethnicity
• Does Folate Intake Modify the Association between Alcohol and Breast Cancer Risk?
• The Impact of Neighborhood Alcohol Outlet Density on Alcohol-related Health Outcomes

Slide Presentations

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

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Age-period-cohort modelling of alcohol volume and heavy drinking days in the US National Alcohol Surveys: Divergence in younger and older adult trends

The decomposition of trends in alcohol volume and heavy drinking days into age, period, cohort and demographic effects offers an important perspective on the dynamics of change in alcohol use patterns in the US.

Trend analyses show that while mean values of drinking measures have continued to decline for those aged 26 and older, there has been a substantial increase in both alcohol volume and 5+ days among those aged 18 to 25. Age-period-cohort models indicate a potential positive cohort effect among those born after 1975. However, an alternative interpretation of an age-cohort interaction where drinking falls off more steeply in the late twenties than was the case in the oldest surveys cannot be ruled out. For women only, the 1956–60 birth cohort appears to drink more heavily than those born just before or after. Models also indicate the importance of income, ethnicity, education and marital status in determining these alcohol measures.

Increased heavy drinking among young adults in recent surveys presents a significant challenge for alcohol policy and may indicate a sustained increase in future US alcohol consumption.

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PROOF-OF-CONCEPT HUMAN LABORATORY STUDY FOR PROTRACTED ABSTINENCE IN ALCOHOL DEPENDENCE: EFFECTS OF GABAPENTIN

There is a need for safe medications that can effectively support recovery by treating symptoms of protracted abstinence in alcoholics that may precipitate relapse e.g., craving and disturbances in sleep and mood.

This proof-of-concept study reports on the effectiveness of gabapentin 1200 mg for attenuating these symptoms in a non treatment-seeking sample of cue-reactive, alcohol-dependent individuals.

Subjects were 33 paid volunteers with current DSM-IV alcohol dependence and a strength of craving rating 1σ or greater for alcohol than water cues. Subjects were randomly assigned to gabapentin or placebo for 1-week and then participated in a within-subjects trial where each was exposed to standardized sets of pleasant, neutral, and unpleasant visual stimuli followed by alcohol or water cues.

We found a significant attenuating effect of gabapentin (vs. placebo) on several measures of subjective craving for alcohol as well as for affectively-evoked craving. Gabapentin was also found to significantly improve several measures of sleep quality. Side effects were minimal, and gabapentin effects were not found to resemble any major classes of abused drugs.

Results suggest that gabapentin may be effective for treating the protracted abstinence phase in alcohol dependence and, hence, that a randomized clinical trial would be an appropriate next step.

The study also suggests the value of cue reactivity studies as proof-of-concept screens for potential anti relapse drugs.

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Estimating risk of alcohol dependence using alcohol screening scores

Brief alcohol counseling interventions can reduce alcohol consumption and related morbidity among non-dependent risky drinkers, but more intensive alcohol treatment is recommended for persons with alcohol dependence.

This study evaluated whether scores on common alcohol screening tests could identify patients likely to have current alcohol dependence so that more appropriate follow-up assessment and/or intervention could be offered.

Based on the prevalence of past-year alcohol dependence in this sample (men: 12.2%; women: 5.8%), zones of the AUDIT and AUDIT-C identified wide variability in the post-screening risk of alcohol dependence in men and women, even among those who screened positive for alcohol misuse.

Among men, AUDIT zones 5–10, 11–14 and 15–40 were associated with post-screening probabilities of past-year alcohol dependence ranging from 18 to 87%, and AUDIT-C zones 5–6, 7–9 and 10–12 were associated with probabilities ranging from 22 to 75%.

Among women, AUDIT zones 3–4, 5–8, 9–12 and 13–40 were associated with post-screening probabilities of past-year alcohol dependence ranging from 6 to 94%, and AUDIT-C zones 3, 4–6, 7–9 and 10–12 were associated with probabilities ranging from 9 to 88%.

AUDIT or AUDIT-C scores could be used to estimate the probability of past-year alcohol dependence among patients who screen positive for alcohol misuse and inform clinical decision-making.

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Request Reprint E-Mail: Anna.Rubinsky@va.gov

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Association of SOD2, a Mitochondrial Antioxidant Enzyme, with Gray Matter Volume Shrinkage in Alcoholics

Chronic alcoholism leads to gray matter shrinkage and induces the formation of superoxide anions (O₂⁻) that can cause neuronal cell death. The mitochondrial superoxide dismutase 2 (SOD2) enzyme is critical in the metabolism of superoxide. An Ala16Val polymorphism putatively affects SOD2 enzyme activity in vivo.

Brain volumes of 76 treatment-seeking alcohol-dependent individuals were measured with a 1.5T MRI. Intracranial tissue margins were manually outlined on coronal sections. Gray matter, white matter, sulcal, and ventricular CSF volumes were estimated using intensity-based K-means clustering. Ala16Val (rs4880) and a second haplotype tagging SNP, rs10370, were genotyped. The q-value package was used to correct for multiple comparisons.

In the alcoholics, cerebrospinal fluid and intra-cranial volumes showed significant differences across the six diplotype categories. The homozygous Ala16-containing diplotype rs10370TT-rs4880GG was associated with lowest gray matter ratio (greater shrinkage; p=0.005). Presence of one or two copies of the low activity Ala16 allele was a risk factor for lower gray matter volume in alcoholics below the median alcohol consumption (p=0.03) but not in alcoholics above this level. White matter ratio was associated with sex (p=0.002) and lifetime total alcohol consumption (p=0.01) but not with diplotypes.

In this exploratory analysis, a putative functional missense variant of SOD2 appears to influence gray matter loss in alcoholics. This may be due to impaired clearance of reactive oxygen species formed as a result of alcohol exposure.

The risk/protective effect was observed in alcoholics with lower levels of lifetime alcohol consumption. Highest levels of exposure may overwhelm the protective action of the SOD2 enzyme.

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Request Reprint E-Mail: srivastavav@mail.nih.gov
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Too much of the hard stuff: what alcohol costs the NHS

Consumption of alcohol in the UK has increased by 19 per cent over the last three decades and is now higher than in any other European country. Recent reports indicate that 10.5 million adults in England drink above sensible limits and around 1.1 million have a level of alcohol addiction. Alcohol is the third leading cause of disease burden in developed countries and, as a result, the cost of providing alcohol-related services is escalating. The burden on the NHS will be unsustainable if this continues.

This Briefing, produced with the Royal College of Physicians, outlines the extent of the problem and gives examples of where the NHS is managing problem drinkers effectively and efficiently. The NHS Confederation visited hospitals between August and November 2009 and gathered evidence from members to gain an understanding of the extent of the burden and the ways in which hospitals can improve their services.

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News Release - NIH Opportunity Network to Expand Basic Behavioral and Social Sciences Research

National Institutes of Health (NIH) Director Francis Collins, M.D., Ph.D., today announced the launch of the Basic Behavioral and Social Science Opportunity Network (OppNet), a trans-NIH initiative to expand the agency’s funding of basic behavioral and social sciences research (b-BSSR).

The b-BSSR field studies mechanisms and processes that influence behavior at the individual, group, community and population level. Research results lead to new approaches for reducing risky behaviors and improving the adoption of healthy practices. . . . . .

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Russia fixes minimum vodka price

Russia introduced on Friday a minimum price of vodka in an effort to fight counterfeit alcohol production in the country.

From January 1, any 0.5l vodka bottle selling at below 89 rubles (almost $3) will be outlawed. The price ban is one of the first government steps toward regulating the domestic alcohol market.

First Deputy Prime Minister Viktor Zubkov said earlier other measures in the sphere would be accomplished by July 1, 2010. Theses include the licensing of alcohol supplies, the introduction of a unified excise duty on alcohol, and tougher responsibility for the production and marketing of fake vodka.
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