Naltrexone has been extensively studied for the treatment of alcohol use disorder. However, less is known about the effects of naltrexone on smoking outcomes in the context of alcohol use among East Asian individuals who have been suggested to differ in response to alcohol and to naltrexone. The present study is a secondary analysis that used a double-blind placebo-controlled design (n = 31) to examine the (a) effects of alcohol on basal craving for cigarettes, (b) effects of naltrexone on cigarette craving and alcohol craving during alcohol administration, and (c) relationship between craving for alcohol and cigarettes. Heavy drinking smokers of East Asian descent completed two counterbalanced intravenous alcohol administration sessions, one after taking naltrexone (50 mg) for five days and one after taking a placebo for five days. Self-reported subjective craving for cigarettes and for alcohol was recorded during each experimental session. Craving for cigarettes and alcohol increased significantly throughout the intravenous alcohol administration. A significant breath alcohol concentration (BrAC) × Medication interaction revealed that naltrexone blunted cigarette craving during alcohol administration, compared to placebo. Naltrexone significantly reduced craving for alcohol during alcohol administration in this group of heavy drinking smokers. Alcohol craving significantly predicted cigarette craving, however this effect did not vary across rising alcohol administration or by medication. These findings demonstrate that naltrexone reduces the urge to smoke and to drink during alcohol administration. Clinical studies are needed to further ascertain whether naltrexone may be of benefit to this distinct subgroup of heavy drinking smokers. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
The corticotropin-releasing hormone type I receptor (CRHR1) gene has been implicated in the liability for neuropsychiatric disorders, particularly under conditions of stress. On the basis of the hypothesized effects of CRHR1 variation on stress reactivity, measures of adulthood traumatic stress exposure were analyzed for their interaction with CRHR1 haplotypes and single-nucleotide polymorphisms (SNPs) in predicting the risk for alcoholism. Phenotypic data on 2533 non-related Caucasian individuals (1167 alcoholics and 1366 controls) were culled from the publically available Study of Addiction: Genetics and Environment genome-wide association study. Genotypes were available for 19 tag SNPs. Logistic regression models examined the interaction between CRHR1 haplotypes/SNPs and adulthood traumatic stress exposure in predicting alcoholism risk. Two haplotype blocks spanned CRHR1. Haplotype analyses identified one haplotype in the proximal block 1 (P = 0.029) and two haplotypes in the distal block 2 (P = 0.026, 0.042) that showed nominally significant (corrected P < 0.025) genotype × traumatic stress interactive effects on the likelihood of developing alcoholism. The block 1 haplotype effect was driven by SNPs rs110402 (P = 0.019) and rs242924 (P = 0.019). In block 2, rs17689966 (P = 0.018) showed significant and rs173365 (P = 0.026) showed nominally significant, gene × environment (G × E) effects on alcoholism status. This study extends the literature on the interplay between CRHR1 variation and alcoholism, in the context of exposure to traumatic stress. These findings are consistent with the hypothesized role of the extra hypothalamic corticotropin-releasing factor system dysregulation in the initiation and maintenance of alcoholism. Molecular and experimental studies are needed to more fully understand the mechanisms of risk and protection conferred by genetic variation at the identified loci.
Background: Preclinical studies demonstrate that chronic and heavy alcohol use facilitates neuroadaptations that perpetuate addiction-like behaviors. In clinical studies, it is unclear whether the extent of heavy alcohol use over the lifetime contributes to alcohol use disorder (AUD) severity over and above current alcohol use patterns (i.e. last 30 days to 3-months). Such information may improve our understanding of the phenomenology of AUD.Objectives: The purpose of this study was to examine lifetime heavy drinking years in relation to a clinical assessment of AUD.Methods: Participants, who were non-treatment-seeking and engaged in heavy drinking (n = 140; 50% male), completed an interview-based assessment of lifetime regular and heavy drinking years along with a battery of measures indexing alcohol use and problems, drinking motives, and depression and anxiety symptomatology.Results: Lifetime heavy drinking years was positively associated with lifetime regular drinking years, current alcohol use, alcohol problems, tonic alcohol craving, drinking for the enhancing effects of alcohol, and drinking to cope (r's = .21-.58). Adjusting for lifetime regular drinking years and current alcohol use, lifetime heavy drinking years predicted higher scores on the Alcohol Use Disorder Identification Test (AUDIT; B = .382; SE = .123). A multivariate logistic regression found that lifetime heavy drinking years predicted greater odds of more severe AUD over and above current alcohol use (OR = 1.147).Conclusion: Our findings suggest that lifetime heavy drinking years are a clinically meaningful indicator of AUD severity that is not redundant with current alcohol use measures.
Given the significant cost of alcohol use disorder (AUD), identifying risk factors for alcohol seeking represents a research priority. Prominent addiction theories emphasize the role of motivation in the alcohol seeking process, which has largely been studied using preclinical models. In order to bridge the gap between preclinical and clinical studies, this study examined predictors of motivation for alcohol self-administration using a novel paradigm. Heavy drinkers (n = 67) completed an alcohol infusion consisting of an alcohol challenge (target breath alcohol = 60 mg%) and a progressive-ratio alcohol self-administration paradigm (maximum breath alcohol 120 mg%; ratio requirements range = 20-3 139 response). Growth curve modeling was used to predict breath alcohol trajectories during alcohol self-administration. K-means clustering was used to identify motivated (n = 41) and unmotivated (n = 26) self-administration trajectories. The data were analyzed using two approaches: a theory-driven test of a-priori predictors and a data-driven, machine learning model. In both approaches, steeper delay discounting, indicating a preference for smaller, sooner rewards, predicted motivated alcohol seeking. The data-driven approach further identified phasic alcohol craving as a predictor of motivated alcohol self-administration. Additional application of this model to AUD translational science and treatment development appear warranted.
Background: Alcohol use disorder (AUD) and its associated consequences remain significant public health concerns. Given that AUD represents a spectrum of severity, treatment options represent a continuum of care, ranging from single-session brief interventions to more intensive, prolonged, and specialized treatment modalities. Objective: This qualitative literature review seeks to describe the best practices for AUD by placing a particular emphasis on identifying those practices which have received the most empirical support. Method: This review summarizes psychological and pharmacological intervention options for AUD treatment, with a focus on the relapse prevention phase of recovery. Psychological and pharmacological treatments are summarized in terms of the empirical evidence favoring each approach and the level of AUD severity for which they are most indicated. Scientific significance: One of the broad assertions from this review is that while AUD is highly prevalent, seeking treatment for AUD is not. There are a myriad of behavioral and pharmacological treatments that have shown compelling evidence of efficacy for the treatment of AUD. In the behavioral treatment literature, cognitive behavioral therapy has received the most consistent support. Opioid antagonism (via naltrexone) has been the most widely studied pharmacotherapy and has produced moderate effect sizes. While none of the treatments reviewed herein represents a so-called silver bullet for AUD, they each have the potential to significantly improve the odds of recovery. Precision medicine, or the identification of best treatment matches for individual patients, looms as an important overarching goal for the field, although specific matches are not yet sufficiently reliable in their empirical evidence to warrant clinical dissemination.
