Neuronal nicotinic acetylcholine receptors as pharmacotherapeutic targets for the treatment of alcohol use disorders

Alcohol use disorders (AUDs) are complex and developing effective treatments will require the combination of novel medications and cognitive behavioral therapy approaches. Epidemiological studies have shown there is a high correlation between alcohol consumption and tobacco use, and the prevalence of smoking in alcoholics is as high as 80% compared to about 30% for the general population. Both preclinical and clinical data provide evidence that nicotine administration increases alcohol intake and nonspecific nicotinic receptor antagonists reduce alcohol-mediated behaviors. As nicotine interacts specifically with the neuronal nicotinic acetylcholine receptor (nAChR) system, this suggests that nAChRs play an important role in the behavioral effects of alcohol. In this review, we discuss the importance of nAChRs for the treatment of AUDs and argue that the use of FDA approved nAChR ligands, such as varenicline and mecamylamine, approved as smoking cessation aids may prove to be valuable treatments for AUDs. We also address the importance of combining effective medications with behavioral therapy for the treatment of alcohol dependent individuals.

Early life stress, nicotinic acetylcholine receptors and alcohol use disorders

Stress is a major driving force in alcohol use disorders (AUDs). It influences how much one consumes, craving intensity and whether an abstinent individual will return to harmful alcohol consumption. We are most vulnerable to the effects of stress during early development, and exposure to multiple traumatic early life events dramatically increases the risk for AUDs. However, not everyone exposed to early life stress will develop an AUD. The mechanisms determining whether an individual’s brain adapts and becomes resilient to the effects of stress or succumbs and is unable to cope with stress remain elusive. Emerging evidence suggests that neuroplastic changes in the nucleus accumbens (NAc) following early life stress underlie the development of AUDs. This review discusses the impact of early life stress on NAc structure and function, how these changes affect cholinergic signaling within the mesolimbic reward pathway and the role nicotinic acetylcholine receptors (nAChRs) play in this process. Understanding the neural pathways and mechanism determining stress resilience or susceptibility will improve our ability to identify individuals susceptible to developing AUDs, formulate cognitive interventions to prevent AUDs in susceptible individuals and to elucidate and enhance potential therapeutic targets, such as the nAChRs, for those struggling to overcome an AUD.

Factor structure and validity of the Alcohol Use Disorders Identification Test (AUDIT) in a sample of mentally disordered offenders

Investigations of the factor structure of the Alcohol Use Disorders Identification Test (AUDIT) have produced conflicting results. The current study assessed the factor structure of the AUDIT for a group of Mentally Disordered Offenders (MDOs) and examined the pattern of scoring in specific subgroups. The sample comprised 2005 MDOs who completed a battery of tests including the AUDIT. Confirmatory factor analyses revealed that a two-factor solution – alcohol consumption and alcohol-related consequences – provided the best data fit for AUDIT scores. A three-factor solution provided an equally good fit, but the second and third factors were highly correlated and a measure of parsimony also favoured the two-factor solution. This study provides useful information on the factor structure of the AUDIT amongst a large MDO population, while also highlighting the difficulties associated with the presence of people with mental health problems in the criminal justice system.

Association of adolescent symptoms of depression and anxiety with alcohol use disorders in young adulthood : findings from the Victorian Adolescent Health Cohort Study

Objective: To examine the association of adolescent depression and anxiety symptoms with alcohol abuse or dependence in young adulthood.

Design, setting and participants: Cohort study of the health and wellbeing of adolescents and young adults in Victoria, assessed at 8 waves (periods) of data collection, from age 14 to 24 years, between 1992 and 2003. Young people who participated in the cohort study at least once during the six adolescent assessment points (conducted 6 months apart, from age 14 to 17 years), at least once during young adulthood and who were alive at Wave 8 (n = 1758).

Main outcome measure: Alcohol abuse or dependence assessed using the alcohol and substance abuse modules of the Composite International Diagnostic Interview at age 24 years.

Results: Adolescents with moderate to high levels of depression and anxiety symptoms (measured by the revised Clinical Interview Schedule) had an increased risk of alcohol abuse or dependence in young adulthood, compared with young adults with low levels of adolescent depression and anxiety symptoms, after adjusting for potential confounding factors. Risk was higher for those with symptoms at more than two adolescent assessment points (odds ratio [OR] 1.9; 95% CI, 1.7–2.0) and for those with symptoms at one or two assessment points (OR 1.3; 95% CI, 1.2–1.4), compared with those with no above-threshold symptoms in adolescence.

Conclusions: Adolescents with depression and anxiety symptoms are at increased risk for alcohol use disorders into young adulthood. They warrant vigilance from primary care providers in relation to alcohol use well into adulthood.

Development and Implementation of a structured intervention for alcohol use disorders for telephone helpline services

A six-session intervention for harmful alcohol use was piloted via a 24-hour alcohol and other drug (AOD) helpline, assessing feasibility of telephone-delivered treatment. The intervention, involving practice elements from Motivational Interviewing, Cognitive-Behavioral Therapy, and node-link mapping, was evaluated using a case file audit (n = 30) and a structured telephone interview one month after the last session (n = 22). Average scores on the Alcohol Use Disorder Identification Test (AUDIT) dropped by more than 50%, and there were significant reductions in psychological distress. Results suggest that, even among dependent drinkers, a telephone intervention offers effective and efficient treatment for those unable or unwilling to access face-to-face treatment.

Alcohol use disorders in patients with obsessive-compulsive disorder: The importance of appropriate dual-diagnosis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Utilização do alcohol use disorders identification test (Audit) para identificação do consumo de álcool entre estudantes do ensino médio

Alcohol is one of the drugs most widely used among teenagers. Just recently, studies have been developed regarding the screening of use of alcohol by this population. This work aimed to investigate the use of AUDIT as a method for screening and evaluation of alcohol consumption among High School students. The sample was composed by 1227 students from two public schools, who answered to the Alcohol Use Disorders Identification Test (AUDIT) and informed their socioeconomic level, religion, and occurrence of relationship problems caused by drunkenness of family members. Using an 8 cut-off point, AUDIT has identified 17.8% of students with risk drinking. These results have revealed that AUDIT is easy to be applied and well accepted by the students. It was also evident the importance of this instrument in the follow-up programs of prevention and intervention of alcoholic beverages use.

Association between craving and attention deficit/hyperactivity disorder symptoms among patients with alcohol use disorders

Adult Alcohol Use Disorders (AUD) patients with Attention Deficit/Hyperactivity Disorder (ADHD) symptoms may suffer more from craving than patients who only have AUD. However, craving may be even more strongly related to withdrawal and psychiatric symptoms; therefore, the association between craving and ADHD may be misinterpreted. The purpose of this study is to examine the association between craving and ADHD symptoms among AUD patients in more detail.

Prescription procedures in medication for relapse prevention after inpatient treatment for alcohol use disorders in Switzerland

In randomized controlled trials with high internal validity, pharmacotherapy using acamprosate, naltrexone, and, to a somewhat lesser extent, disulfiram has proved effective in preventing relapse in patients with alcohol use disorders (AUD). There remains, however, a paucity of studies with sufficient external validity in which the effectiveness of pharmacotherapy in clinical practice is investigated. This study aimed to make a contribution to close this gap in research.

Predictors of attempted suicide among Swiss patients with alcohol-use disorders

Objective: Suicide attempts are common in patients being treated for alcohol-use disorders (AUDs). However, clinical assessment of suicide risk is difficult. In this Swiss multisite study, we propose a decision tree to facilitate identification of profiles of AUD patients at high risk for suicidal behavior. Method: In this retrospective study, we used a sample of 700 patients (243 female), attending 1 of 12 treatment programs for AUDs in the German-speaking part of Switzerland. Sixty-nine patients who reported a suicide attempt in the 3 months before the index treatment were compared using risk factors with 631 patients without a suicide attempt. Receiver operating characteristic (ROC) analyses were used to identify patients at risk of having had a suicide attempt in the previous 3 months. Results: Consistent with previous empirical findings in AUD patients, a prior history of attempted suicide and severe symptoms of depression and aggression considerably increased the risk of a suicide attempt and, in combination, raised the likelihood of a prior suicide attempt to 52%. In addition, one third of AUD patients who had a history of suicide attempts and previous inpatient psychiatric treatment, or who were male and had previous inpatient psychiatric treatment, also reported a suicide attempt. Conclusions: The empirically supported decision tree helps to identify profiles of suicidal AUD patients in Switzerland and supplements clinicians' judgments in making triage decisions for suicide management.

Association of alcohol craving and proximal outcomes of a residential treatment program for patients with alcohol use disorders

Background: Alcohol craving is an essential construct in research and treatment of alcohol use disorders (AUD). Craving is mostly investigated in association with concurrent variables or distal treatment outcomes at follow-up. Objectives: The aim of this study is to examine craving at admission and its relevance for essential proximal outcomes at discharge from AUD treatment such as positive alcohol expectancy, abstinent-related self-efficacy, and substance-related coping, as well as patients’ demographic and AUD characteristics. Methods: In total, 36 patients were recruited within an inpatient treatment AUD program. Results: An association between craving and positive alcohol expectancies at discharge was found in the regression model even when the respective expectancies, age, gender, and severity of alcohol dependence at admission were controlled for (F(2,29)1⁄432.71, p50.001). Craving explained 2.3% of the variance of change in positive alcohol expectancy. Conclusion: The results suggest a low predictive value of craving for positive alcohol expectancy. In addition, we found significant associations between the craving and the severity of AUD and alcohol consumption before admission. Future studies should include proximal outcomes related to treatment efficacy as well as distal outcomes.

Efficacy of motivational enhancement therapy on alcohol use disorders in patients with chronic hepatitis C: a randomized controlled trial

AIMS: To determine the efficacy of motivational enhancement therapy (MET) on alcohol use in patients with the hepatitis C virus (HCV) and an alcohol use disorder (AUD). DESIGN: Randomized, single-blind, controlled trial comparing MET to a control education condition with 6-month follow-up. SETTING: Patients were recruited from hepatitis clinics at the Minneapolis, Minnesota and Portland, Oregon Veterans Affairs Health Care Systems, USA. PARTICIPANTS AND INTERVENTION: Patients with HCV, an AUD and continued alcohol use (n = 139) were randomized to receive either MET (n = 70) or a control education condition (n = 69) over 3 months. MEASUREMENTS: Data were self-reported percentage of days abstinent from alcohol and number of standard alcohol drinks per week 6 months after randomization. FINDINGS: At baseline, subjects in MET had 34.98% days abstinent, which increased to 73.15% at 6 months compared to 34.63 and 59.49% for the control condition. Multi-level models examined changes in alcohol consumption between MET and control groups. Results showed a significant increase in percentage of days abstinent overall (F(1120.4)  = 28.04, P < 0.001) and a significant group × time effect (F(1119.9)  = 5.23, P = 0.024) with the MET group showing a greater increase in percentage of days abstinent at 6 months compared with the education control condition. There were no significant differences between groups for drinks per week. The effect size of the MET intervention was moderate (0.45) for percentage of days abstinent. CONCLUSION: Motivational enhancement therapy (MET) appears to increase the percentage of days abstinent in patients with chronic hepatitis C, alcohol use disorders and ongoing alcohol use. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Air Force web-based preventive health assessement alcohol screening effectiveness using the Alcohol Use Disorders Identification Tool (AUDIT)

Alcohol consumption has a long-standing tradition in the United States Air Force (USAF). From squadron bars to officers and enlisted clubs, alcohol has been used in social settings to increase morale and also as a way to help decrease the stress of military operations. Surveys have demonstrated that the USAF has more than double the percentage of heavy drinkers than the US population. More than one-third of the Air Force reports binge drinking in the last month while only six percent of the nation reports the same consumption pattern.^ However, alcohol has a significant harmful health effect if consumed in excess. As part of an overall prevention and treatment program aimed at curbing the harmful effects of alcohol consumption, the USAF uses the Alcohol Use Disorder Identification Test (AUDIT) to screen for high-risk alcohol consumption patterns before alcohol disorder and disability occur. All Air Force active-duty members are required to complete a yearly Preventive Health Assessment questionnaire. Various health topics are included in this questionnaire including nutrition, exercise, tobacco use, family history, mental health and alcohol use. While this questionnaire has been available in a web-based format for several years, mandatory use was not implemented until 2009.^ Although the AUDIT was selected due to its effectiveness in assessing high-risk alcohol consumption in other populations, its effectiveness in the Air Force population had not been studied previously. In order to assess the sensitivity, specificity, and positive predictive value of this screening tool, the Air Force Web-based Preventive Health Assessment alcohol screening results were compared to whether any alcohol-related diagnosis was made from January 1, 2009 to March 31, 2010.^ While the AUDIT has previously been shown to have a high sensitivity and specificity, the Air Force screening values were 27.9% and 93.0% respectively. Positive predictive value was only 4.9%. With the screening statistics found, less than one-third of those having an alcohol disorder will be found with this screening tool and only 1 out of 20 Airmen who require further evaluation actually have an alcohol-related diagnosis.^