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Preclinical and clinical work suggests that mifepristone may be a viable treatment for alcohol use disorder (AUD). This was a Phase 1/2, outpatient, cross‐over, randomized, double‐blind, placebo‐controlled trial with non‐treatment‐seeking individuals with AUD (N = 32). We assessed safety, alcohol craving and consumption, after 1‐week mifepristone 600 mg/day administration, in a human laboratory study comprised of a single oral yohimbine administration (32.4 mg), a cue‐reactivity procedure and alcohol self‐administration. Safety was monitored by adverse events and hemodynamic parameters, alcohol craving by alcohol craving questionnaire and cue‐induced saliva output. During the alcohol self‐administration, we assessed alcohol pharmacokinetics, subjective effects and consumption. Outcomes were assessed using Generalized Estimating Equations and mediation analysis. Mild‐moderate adverse events were reported in both conditions. There was no statistically significant difference between mifepristone and placebo in alcohol pharmacokinetics and subjective effects. Furthermore, blood pressure increased only in the placebo condition after the stress‐induced laboratory procedures. Mifepristone, compared to placebo, significantly reduced alcohol craving and increased cortisol levels. Mifepristone‐induced cortisol increase was not a mediator of alcohol craving. Mifepristone, compared to placebo, did not reduce alcohol consumption in the laboratory or in a naturalistic setting. This study successfully translated a developed preclinical procedure to a human laboratory study, confirming the safety of mifepristone in people with AUD and providing evidence to its role in reducing alcohol craving under stress procedures. The lack of effects on alcohol drinking may be related to the selection of non‐treatment seekers and suggests future treatment‐oriented trials should investigate mifepristone in people with AUD. [ABSTRACT FROM AUTHOR]

Objective: Primary outcomes from the COMBINE Study indicated support for naltrexone (Revia) on measures of abstinence and time to heavy drinking; however, effect sizes were modest. The delineation of individual difference variables that qualify these results could aid efforts to target treatment approaches appropriately. Laboratory and clinical studies have found greater effectiveness of naltrexone among men and those with familial alcoholism. The present study used multilevel modeling to investigate family history of alcoholism (FHA) based on first-degree relatives and gender as moderators of naltrexone's effects on three drinking outcomes: percentage of days abstinent, drinks per drinking day, and percentage of heavy drinking days. Method: Data were drawn from the COMBINE public data set and included the subsample of participants (n = 603) randomized to receive active medication or placebo plus medical management. Results: We observed a main effect of FHA on drinks per drinking day (B = 2.01, SE = .91, p = .03) such that greater FHA was associated with greater alcohol use per drinking occasion. No other main effects of FHA were observed on drinking outcomes. A significant Naltrexone x Time interaction was observed for percentage of heavy drinking days (B = -1.61, SE = .69, p = .02), consistent with the previously published COMBINE results. No significant Naltrexone x FHA interactions were observed for any of the three outcomes. Gender did not modify these results. Conclusions: Taken together, these results indicate an effect of FHA on drinking behavior but do not support FHA among first-degree relatives as a moderator of naltrexone's efficacy in this sample. (J. Stud. Alcohol Drugs, 72, 135-140, 2011), THE IDENTIFICATION OF EFFECTIVE pharmacotherapies for treating alcohol use disorders remains an important research imperative. The opiate antagonist naltrexone (Revia) has garnered support as a treatment option for alcohol dependence. [...]

Polymorphisms of the [mu]-opioid receptor (OPRM1) and dopamine D4 receptor (DRD4) genes are associated with subjective responses to alcohol and urge to drink under laboratory conditions. This study examined these associations in the natural environment using ecological momentary assessment. Participants were non-treatment-seeking heavy drinkers (n = 112, 52% female, 61% alcohol dependent) who enrolled in a study of naltrexone effects on craving and drinking in the natural environment. Data were culled from 5 consecutive days of drinking reports prior to medication randomization. Analyses revealed that, alter drinking, carriers of the Asp40 allele of the OPRM1 gene reported higher overall levels of vigor and lower levels negative mood, as compared to homozygotes for the Asn40 variant. Carriers of the long allele (i.e., [greater than or equal to] 7 tandem repeats) of the DRD4 endorsed greater urge to drink than homozygotes for the short allele. Effects of OPRMI and DRD4 variable-number-of-tandem-repeats genotypes appear to be alcohol dose-dependent. Specifically, carriers of the DRD4-L allele reported slight decreases in urge to drink at higher levels of estimated blood alcohol concentration (eBAC), and Asp40 carriers reported decreases in vigor and increases in negative mood as eBAC rose, as compared to carriers of the major allele for each gene. Self-reported vigor and urge to drink were positively associated with alcohol consumption within the same drinking episode. This study extends findings on subjective intoxication, urge to drink, and their genetic bases from controlled laboratory to naturalistic settings. Keywords: OPRM1, DRD4, urge to drink, alcohol, EMA DOI: 10.1037/a0017550

A behavioral economic approach to alcohol use disorders (AUDs) emphasizes both individual and environmental determinants of alcohol use. The current study examined individual differences in alcohol demand (i.e., motivation for alcohol under escalating conditions of price) and delayed reward discounting (i.e., preference for immediate small rewards compared to delayed larger rewards) in 61 heavy drinkers (62% with an AUD). In addition, based on theoretical accounts that emphasize the role of craving in reward valuation and preferences for immediate rewards, craving for alcohol was also examined in relation to these behavioral economic variables and the alcohol-related variables. Intensity of alcohol demand and delayed reward discounting were significantly associated with AUD symptoms, but not with quantitative measures of alcohol use, and were also moderately correlated with each other. Likewise, craving was significantly associated with AUD symptoms, but not with alcohol use, and was also significantly correlated with both intensity of demand and delayed reward discounting. These findings further emphasize the relevance of behavioral economic indices of motivation to AUDs and the potential importance of craving for alcohol in this relationship. Keywords: alcohol, behavioral economics, discounting, demand, craving DOI: 10.1037/a0017513

A study investigates if topiramate is a safe and effective treatment for alcohol dependence. Results show that topiramate is significantly efficacious in treating alcohol dependence.