Common Genetic Contributions to Alcohol and Cannabis Use and Dependence Symptomatology

Background: Despite mounting evidence that use of and dependence on alcohol and cannabis are influenced by heritable factors, the extent to which heritable influences on these phenotypes overlap across the 2 substances has only rarely been explored. In the current study, we quantified cross‐substance overlap in sources of variance and estimated the degree to which within‐substance associations between use and dependence measures are attributable to common genetic and environmental factors for alcohol and cannabis. Methods: The sample was comprised of 6,257 individuals (2,761 complete twin pairs and 735 singletons) from the Australian Twin Registry, aged 24 to 36 years. Alcohol and cannabis use histories were collected via telephone diagnostic interviews and used to derive an alcohol consumption factor, a frequency measure for cannabis use, and DSM‐IV alcohol and cannabis dependence symptom counts. Standard genetic analyses were conducted to produce a quadrivariate model that provided estimates of overlap in genetic and environmental influences across the 4 phenotypes. Results: Over 60% of variance in alcohol consumption, cannabis use, and cannabis dependence symptoms, and just under 50% of variance in alcohol dependence (AD) symptoms were attributable to genetic sources. Shared environmental factors did not contribute significantly to the 4 phenotypes. Nearly complete overlap in heritable influences was observed for within‐substance measures of use and dependence symptoms. Genetic correlations across substances were 0.68 and 0.62 for use and dependence symptoms, respectively. Conclusions: Common heritable influences were evident for alcohol and cannabis use and for AD and cannabis dependence symptomatology, but findings indicate that substance‐specific influences account for the majority of the genetic variance in the cannabis use and dependence phenotypes. By contrast, the substantial correlations between alcohol use and AD symptoms and between cannabis use and cannabis dependence symptoms suggest that measures of heaviness of use capture much of the same genetic liability to alcohol‐ and cannabis‐related problems as dependence symptomatology.     

Alcohol Effects on Mood, Equilibrium, and Simulated Driving

BACKGROUND: The effects of alcohol on simple versus complex psychomotor performance were compared in 18 adults. METHODS: Subjects received ethanol doses of 0.0, 0.5, and 0.8 g/kg in a randomized, double-blind, within-subject design. Forty minutes after finishing their drinking, the subjects completed a 60-min battery of tests that included: 1) a sensory organization posturography test (EquiTest); 2) latency to apply the brake after appearance of a barrier in a driving simulator (brake reaction time); 3) visual analog subjective-effects scales (VAS); 4) the Profile of Mood States (POMS); 5) critical flicker fusion (CFF); and 6) choice reaction time (CRT). RESULTS: Alcohol dose dependently reduced composite equilibrium scores and increased brake reaction time. On the CRT task, total reaction time was significantly increased after the high dose but not the low dose. Alcohol dose dependently increased VAS "dizzy," "high," and "drug effect" ratings. The POMS and CFF were not significantly affected by alcohol. CONCLUSIONS: These data suggest that an ethanol dose that neither influences certain mood states nor impairs simple psychomotor task performance nonetheless may impair equilibrium and complex psychomotor tasks (e.g., driving).     

Implications of Cannabis Use and Heavy Alcohol Use on HIV Drug Risk Behaviors in Russian Heroin Users

Cannabis and heavy alcohol use potentially increase HIV transmission by increasing risky drug behaviors. We studied 404 subjects entering treatment for heroin dependence, in St. Petersburg, Russia. We used the HIV Risk Assessment Battery (RAB) drug subscale to measure risky drug behavior. Although all heavy alcohol users had risky drug behaviors, their drug RAB scores did not differ from non-heavy alcohol users in unadjusted or adjusted analyses. Cannabis use was significantly associated with drug RAB scores in unadjusted analyses (mean difference 1.7 points) and analyses adjusted for age, sex, and employment (mean difference 1.3 points). When also adjusting for stimulant use, the impact of cannabis use was attenuated and no longer statistically significant (mean difference 1.1 points). Because of the central role of risky drug behaviors in the Russian HIV epidemic, it is important to understand how the use of multiple substances, including cannabis and alcohol, impacts risky drug behaviors.     

Effects of Alcohol on Performance on a Distraction Task During Simulated Driving

Background:  Prior studies report that accidents involving intoxicated drivers are more likely to occur during performance of secondary tasks. We studied this phenomenon, using a dual-task paradigm, involving performance of a visual oddball (VO) task while driving in an alcohol challenge paradigm. Previous functional MRI (fMRI) studies of the VO task have shown activation in the anterior cingulate, hippocampus, and prefrontal cortex. Thus, we predicted dose-dependent decreases in activation of these areas during VO performance.
Methods:  Forty healthy social drinkers were administered 3 different doses of alcohol, individually tailored to their gender and weight. Participants performed a VO task while operating a virtual reality driving simulator in a 3T fMRI scanner.
Results:  Analysis showed a dose-dependent linear decrease in Blood Oxygen Level Dependent activation during task performance, primarily in hippocampus, anterior cingulate, and dorsolateral prefrontal areas, with the least activation occurring during the high dose. Behavioral analysis showed a dose-dependent linear increase in reaction time, with no effects associated with either correct hits or false alarms. In all dose conditions, driving speed decreased significantly after a VO stimulus. However, at the high dose this decrease was significantly less. Passenger-side line crossings significantly increased at the high dose.
Conclusions:  These results suggest that driving impairment during secondary task performance may be associated with alcohol-related effects on the above brain regions, which are involved with attentional processing/decision-making. Drivers with high blood alcohol concentrations may be less able to orient or detect novel or sudden stimuli during driving.     

Substance Abuse Problems,Psychiatric Symptoms,and Post-Treatment Status in MCMI Psychopathology Subgroups of Cocaine Dependent Males

This study involved cluster analysis of Millon Clinical Multiaxial Inventory-II (MCMI-II) records of 304 cocaine dependent males and examined differences among personality-based clusters in medical, legal, employment, drug, alcohol, family, and psychiatric problem severity at treatment intake and in outcome status during the 12 months after completion of residential drug treatment. A hierarchical cluster analysis (Ward's method) was used to identify 4 cluster subgroups: antisocial, subclinical, neurotic, and high psychopathology. MANOVA revealed that membership in Neurotic and High Psychopathology Cluster subgroups was linked with more severe family and psychiatric problems at treatment intake than found in the Subclinical Cluster Subgroup (all ps <. 05). The High Psychopathology Cluster Subgroup also had more severe drug problems at intake than did the Subclinical Subgroup (p <. 05). Logistic regression analysis revealed that membership in the High Psychopathology Subgroup predicted relapse/loss to follow-up status after controlling for age, education, ethnicity, treatment program attended, and pretreatment cocaine use frequency (X² = 21.25, df = 3, p <. 001).     

Probability and Predictors of Transition from Abuse to Dependence on Alcohol,Cannabis, and Cocaine: Results from the National Epidemiologic Survey on Alcohol and Related Conditions

Background: Little is known about the transition from substance abuse to substance dependence. Objectives: This study aims to estimate the cumulative probability of developing dependence and to identify predictors of transition to dependence among individuals with lifetime alcohol, cannabis, or cocaine abuse. Methods: Analyses were done for the subsample of individuals with lifetime alcohol abuse (n = 7802), cannabis abuse (n = 2832), or cocaine abuse (n = 815) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Estimated projections of the cumulative probability of transitioning from abuse to dependence were obtained by the standard actuarial method. Discrete-time survival analyses with time-varying covariates were implemented to identify predictors of transition to dependence. Results: Lifetime cumulative probability estimates indicated that 26.6% of individuals with alcohol abuse, 9.4% of individuals with cannabis abuse, and 15.6% of individuals with cocaine abuse transition from abuse to dependence at some point in their lives. Half of the transitions of alcohol, cannabis, and cocaine dependence occurred approximately 3.16, 1.83, and 1.42 years after abuse onset, respectively. Several sociodemographic, psychopathological, and substance use-related variables predicted transition from abuse to dependence for all of the substances assessed. Conclusion: The majority of individuals with abuse do not transition to dependence. Lifetime cumulative probability of transition from abuse to dependence was highest for alcohol, followed by cocaine and lastly cannabis. Time from onset of abuse to dependence was shorter for cocaine, followed by cannabis and alcohol. Although some predictors of transition were common across substances, other predictors were specific for certain substances.     

Toward an Alcohol Treatment Model: A Comparison of Treated and Untreated Respondents with DSM-IV Alcohol Use Disorders in the General Population

The purpose of this study was to compare characteristics of person with alcohol use disorders who sought alcohol treatment with those who did not using data from a nationally representative sample of the United States. Applying an organizing framework from the larger literature on service utilization, a logistic regression analysis was conducted to examine the interaction among factors influencing treatment. The results identified unemployment status and lower educational level as barriers to alcohol treatment, but the impact of these factors differed depending on whether the respondent had previous experience with alcohol treatment. The major findings of this study are discussed in terms of consumer satisfaction, minimizing barriers to alcohol treatment services, and the need to examine individual determinants of alcohol treatment within the larger context of organizational and sociopolitical factors.     

Epidemiology of Alcohol Abuse and Dependence in Rural Chinese Men

Background:  Several national and regional epidemiological studies in China have reported increases in the prevalence of alcohol use disorders over the past 3 decades.
Methods:  This cross-sectional study conducted in 2007 identified 11,884 male subjects aged 18 to 60 years using multi-stage randomized cluster sampling methods in 2 rural communities in China and interviewed 9,866 of them. Current and lifetime alcohol use disorders were assessed with a semi-structured diagnostic interview.
Results:  The age-standardized prevalence of current (lifetime) alcohol abuse and alcohol dependence in Hunan were 1.8% (4.8%) and 4.7% (8.6%) respectively, and those in Henan were 7.6% (11.8%) and 8.7% (10.8%). Higher age (55 to 60) and lower education were risk factors for alcohol dependence in Hunan while middle age (35 to 44), currently married, and higher education and higher income were risk factors in Henan.
Conclusions:  Alcohol abuse and dependence are no longer uncommon disorders among rural men in China. Unlike most western reports, alcohol dependence shows higher prevalence than abuse. There are significant differences in the prevalence of alcohol use disorders and the socio-demographic profile of affected individuals in the 2 different regions of the country.     

Endocannabinoid Signaling in the Central Amygdala and Bed Nucleus of the Stria Terminalis: Implications for the Pathophysiology and Treatment of Alcohol Use Disorder

High rates of relapse are a chronic and debilitating obstacle to effective treatment of alcohol use disorder (AUD); however, no effective treatments are available to treat symptoms induced by protracted abstinence. In the first part of this 2‐part review series, we examine the literature supporting the effects of alcohol exposure within the extended amygdala (EA) neural circuitry. In Part 2, we focus on a potential way to combat negative affect associated with AUD, by exploring the therapeutic potential of the endogenous cannabinoid (eCB) system. The eCB system is a potent modulator of neural activity in the brain, and its ability to mitigate stress and negative affect has long been an area of interest for developing novel therapeutics. This review details the recent advances in our understanding of eCB signaling in 2 key regions of the EA, the central nucleus of the amygdala and the bed nucleus of the stria terminalis (BNST), and their role in regulating negative affect. Despite an established role for EA eCB signaling in reducing negative affect, few studies have examined the potential for eCB‐based therapies to treat AUD‐associated negative affect. In this review, we present an overview of studies focusing on eCB signaling in EA and cannabinoid modulation on EA synaptic activity. We further discuss studies suggesting dysregulation of eCB signaling in models of AUD and propose that pharmacological augmentation of eCB could be a novel approach to treat aspects of AUD. Lastly, future directions are proposed to advance our understanding of the relationship between AUD‐associated negative affect and the EA eCB system that could yield new pharmacotherapies targeting negative affective symptoms associated with AUD.     

ICD-10 and Proposed DSM-IV Harmful Use of Alcohol/ Alcohol Abuse and Dependence, United States 1988: A Nosological Comparison

The purpose of this study was to compare ICD-10 and the proposed DSM-IV (options 1 and 2) diagnostic criteria for harmful use/abuse and dependence in a representative sample of the United States general population. Harmful use/abuse and dependence categories were contrasted in terms of prevalence and overlap. The prevalences of DSM-IV diagnoses of alcohol abuse and dependence combined were much greater than those for the corresponding ICD-10 diagnoses. Disaggregation of the harmful use/abuse and dependence diagnoses showed that the major discrepancy between the classification systems resided between harmful use and abuse categories. The prevalence of the harmful use of alcohol was nearly nonexistent in this general population sample. Reasons for this and other discrepancies are discussed in terms of the hypothesized severity of the harmful use criteria, differences in the number of diagnostic criteria and the content of the ICD-10 and DSM-IV dependence categories, the relationship between the harmful use/abuse and dependence categories, and the impact of the duration criterion.     

Processes and Outcomes of Substance Abuse Treatment Between Two Programs for Clients Insured Under Managed Care

The purpose of this research (N = 160) was to describe and compare substance abuse treatment in two programs under managed care: one residential (RT) and one outpatient (OP). Clients in both settings improved significantly from before to after treatment in relation to substance use and quality of life. However, intensity of treatment (hours of care/week) was much greater in RT and days of sobriety were significantly higher after treatment in RT than in OP (p = .04). Intensity was negatively related to incidents of substance use during treatment (SUdT), which predicted substance use after treatment; SUdT averaged. 2 for RT, and 1.6 for OP (p = .0001). Importantly, treatment was completed by 74 patients (over 90%) from RT, with 8 dropping out, and 53 (almost 70%) of those in OP completed treatment while 25 dropped out. Intensity, as seen in the RT program, rather than duration, was more effective in substance use reduction and treatment completion.     

DSM-III-R and Proposed DSM-IV Alcohol Abuse and Dependence, United States 1988: A Nosological Comparison

The purpose of the present study was to compare DSM-III-R and the proposed DSM-IV (options 1 and 2) diagnostic criteria for alcohol abuse and dependence in a representative sample of the United States general population. Alcohol abuse and dependence diagnostic categories were contrasted in terms of prevalence and overlap. The prevalences of DSM-III-R and DSM-IV diagnoses of alcohol abuse and dependence combined were remarkably similar. However, disaggregation of abuse and dependence diagnoses showed that there were major discrepancies between the classification systems. Reasons for these discrepancies are discussed in terms of differences in the number of diagnostic criteria and the content of the DSM-III-R and DSM-IV abuse and dependence categories, the requirement for physiological dependence in DSM-IV classifications, the relationship between the abuse and dependence categories, and the impact of the duration criteria.