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Background The primary goals in conducting clinical trials of treatments for alcohol use disorders ( AUDs) are to identify efficacious treatments and determine which treatments are most efficacious for which patients. Accurate reporting of study design features and results is imperative to enable readers of research reports to evaluate to what extent a study has achieved these goals. Guidance on quality of clinical trial reporting has evolved substantially over the past 2 decades, primarily through the publication and widespread adoption of the Consolidated Standards of Reporting Trials statement. However, there is room to improve the adoption of those standards in reporting the design and findings of treatment trials for AUD. Methods This paper provides a narrative review of guidance on reporting quality in AUD treatment trials. Results Despite improvements in the reporting of results of treatment trials for AUD over the past 2 decades, many published reports provide insufficient information on design or methods. Conclusions The reporting of alcohol treatment trial design, analysis, and results requires improvement in 4 primary areas: (i) trial registration, (ii) procedures for recruitment and retention, (iii) procedures for randomization and intervention design considerations, and (iv) statistical methods used to assess treatment efficacy. Improvements in these areas and the adoption of reporting standards by authors, reviewers, and editors are critical to an accurate assessment of the reliability and validity of treatment effects. Continued developments in this area are needed to move AUD treatment research forward via systematic reviews and meta-analyses that maximize the utility of completed studies. [ABSTRACT FROM AUTHOR]

Background Over the past 60 years, the view that 'alcoholism' is a disease for which the only acceptable goal of treatment is abstinence has given way to the recognition that alcohol use disorders ( AUDs) occur on a continuum of severity, for which a variety of treatment options are appropriate. However, because the available treatments for AUDs are not effective for everyone, more research is needed to develop novel and more efficacious treatments to address the range of AUD severity in diverse populations. Here we offer recommendations for the design and analysis of alcohol treatment trials, with a specific focus on the careful conduct of randomized clinical trials of medications and nonpharmacological interventions for AUDs. Methods This paper provides a narrative review of the quality of published clinical trials and recommendations for the optimal design and analysis of treatment trials for AUDs. Results Despite considerable improvements in the design of alcohol clinical trials over the past 2 decades, many studies of AUD treatments have used faulty design features and statistical methods that are known to produce biased estimates of treatment efficacy. Conclusions The published statistical and methodological literatures provide clear guidance on methods to improve clinical trial design and analysis. Consistent use of state-of-the-art design features and analytic approaches will enhance the internal and external validity of treatment trials for AUDs across the spectrum of severity. The ultimate result of this attention to methodological rigor is that better treatment options will be identified for patients with an AUD. [ABSTRACT FROM AUTHOR]

Background: In a previous study, ondansetron, a serotonin 5‐HT3 receptor antagonist, reduced drinking intensity (drinks/drinking day [DPDD]) among European‐ancestry (EA) participants with moderate‐to‐severe alcohol use disorder (AUD) and variants in genes encoding the serotonin transporter (SLC6A4) and 5‐HT3A (HTR3A), and 5‐HT3B (HTR3B) receptors. We tested whether (1) ondansetron reduces DPDD among individuals of either European or African ancestry (AA), and (2) that reductions in DPDD are greatest among ondansetron‐treated individuals with population‐specific combinations of genotypes at SLC6A4, HTR3A, and HTR3B. Methods: In this 16‐week, double‐blind, placebo‐controlled, parallel‐group clinical trial, adults with AUD were randomized to receive low‐dose oral ondansetron (0.33 mg twice daily) or placebo stratified by "responsive" versus "nonresponsive" genotype defined using population‐specific genotypes at the three genetic loci. Generalized estimating equation regression models and a modified intent‐to‐treat analysis were used to compare the treatment groups on the primary outcome—DPDD—and two secondary outcomes—heavy drinking days per week [HDD] and drinks per day [DPD] across the 16 weeks of treatment. Results: Of 296 prospective participants screened, 95 (58 EA and 37 AA) were randomized and received at least one dose of study medication. In the modified intent‐to‐treat analysis, the ondansetron group averaged 0.40 more DPDD (p = 0.51), 1.35 times as many HDD (p = 0.16), and 1.06 times as many DPD (p = 0.59) as the placebo group. There were no significant interactions with genotype. There were no study‐related serious adverse events (AEs) and similar proportions of participants in the two treatment groups experienced AEs across organ systems. Conclusions: We found no evidence that low‐dose oral ondansetron is beneficial in the treatment of AUD, irrespective of genotype, thus failing to confirm prior study findings. However, the study was underpowered to identify medication by genotype interactions. [ABSTRACT FROM AUTHOR]

Background: The serotonin transporter (SERT) mRNA was previously reported to be a quantitative and pathophysiology‐based biomarker of heavy drinking in 5HTTLPR:LL genotype‐carriers treated with ondansetron. Here, we validated the potential use of SERT mRNA for quantitative prediction of recent alcohol consumption (in the absence of treatment) and compared it with the known biomarkers ethyl glucuronide (EtG) and ethyl sulfate (EtS). Methods: Binge drinking men and women of European ancestry aged 21 to 65 years were enrolled in a 12‐day, in‐patient, randomized, double‐blind, crossover study, where they were administered three beverage doses (placebo, 0.5 g/kg [0.4 g/kg] ethanol, and 1 g/kg [0.9 g/kg] ethanol for men [women]) individually in three 4‐day periods (experiments), separated by minimum 7‐day washout period. Diet, sleep, and physical activity were controlled throughout the inpatient experiments. Twenty‐nine participants were randomized to receive beverage doses counterbalancing the sequence of treatment and gender within subgroups stratified by SERT genotypes 5HTTLPR:LL+rs25531:AA (LALA) versus 5HTTLPR:LS/SS. Peripheral venous blood was collected daily for (1) quantification of SERT mRNA (the primary outcome measure) using qRT‐PCR and (2) plasma EtG and EtS levels using tandem mass‐spectrometry. Results: The association between administered beverage dose and SERT mRNA from completers of at least one 4‐day experiment (N = 18) assessed by a linear mixed model was not statistically significant. Significant positive associations were found with beverage dose and plasma EtG, EtS and EtG/EtS ratio (β = 5.8, SE = 1.2, p < 0.0001; β = 1.3, SE = 0.6, p = 0.023; and β = 3.0, SE = 0.7, p < 0.0001, respectively; the C‐statistics for discriminating outcomes were 0.97, 0.8, and 0.92, respectively). Additionally, we observed a sequence effect with a greater placebo effect on SERT mRNA when it was administered during the first experiment (p = 0.0009), but not on EtG/EtS measures. Conclusion: The findings do not validate the use of SERT as a biomarker of heavy drinking. Larger and more innovative studies addressing the effects of placebo, race, gender, and response to treatment with serotonergic agents are needed to fully assess the utility of SERT as a biomarker of heavy and binge drinking. [ABSTRACT FROM AUTHOR]

Background: Excessive alcohol use is a leading cause of global morbidity and premature mortality. This study evaluated the effectiveness of two types of nurse‐delivered interventions to reduce excessive alcohol consumption among screened participants using the alcohol use disorders identification test (AUDIT) in the workplace. Methods: A randomized controlled trial involving AUDIT‐positive employees of five Japan‐based companies was conducted. A total of 351 participants were randomized into groups that received a patient information leaflet (PIL), 5 min of brief advice, or 15 min of brief advice and counseling. Outcomes (weekly alcohol consumption and drinking and binge drinking frequency in the previous 30 days) were evaluated at 6 and 12‐month follow‐up. Results: The follow‐up rates were 96.3% (n = 338) and 94.9% (n = 333) at 6 and 12 months, respectively. At 6 months, the mean change in weekly alcohol consumption was −38.1 g (−1.64 US fluid oz/week) in the 15‐min brief advice and counseling group, which differed significantly from the PIL group. The reduction in the advice and counseling group persisted at 12‐month follow‐up but was no longer significantly different from the PIL group. There was no significant change in alcohol consumption observed in the 5‐min brief advice group. Improvement in drinking and binge drinking frequency was observed in all three groups. Conclusions: Nurse‐delivered 15‐min brief advice and counseling was effective over a 6‐month period in reducing alcohol consumption in a workplace setting. This finding suggests that the implementation of workplace screening and brief intervention could play a useful role in preventing the burden of harmful alcohol use. [ABSTRACT FROM AUTHOR]

Background: Progression through the stages of change is a proposed mechanism underlying the effects of treatment for alcohol use disorder (AUD). However, examining stages of change as a mechanism of treatment effects requires that the measure be invariant across patient subgroups, treatment conditions, and time. In this study, we examined measurement invariance of the University of Rhode Island Change Assessment Scale (URICA) in Project MATCH using an exploratory structural equation modeling (ESEM) approach. Methods: We conducted a secondary analysis of data from Project MATCH (N = 1726; Mage = 40.2, SD = 10.9; 75.7% male; 80% non‐Hispanic white), a multisite randomized clinical trial that tested three AUD treatments: Motivational Enhancement Therapy, Cognitive‐Behavioral Therapy, or Twelve‐Step Facilitation. Participants completed the 24‐item URICA for assessing the stages of change in relation to drinking at baseline and post‐treatment (3 months after baseline). Results: A 4‐factor ESEM provided a good fit to the data and a better fit to the data than a conventional 4‐factor confirmatory factor analysis model. Further, the URICA demonstrated scalar invariance across each patient subgroup at baseline (sex, ethnicity, marital status, education, and parental history of AUD) and treatment condition at follow‐up. However, the URICA was not longitudinally invariant as the metric model resulted in a significant decrement in model fit. Conclusions: Measurement invariance of the URICA over time was not supported. Longitudinally invariant measures of the stages of change are needed to test the proposal that progression through the stages explains treatment effects. [ABSTRACT FROM AUTHOR]

Background: Despite advances in the development of pharmacotherapy for alcohol use disorder (AUD), there remains a need for medications that can be administered to actively drinking outpatients to promote a reduction in harmful alcohol consumption. The primary aim of this pilot study was to determine whether high‐dose gabapentin (3600 mg/daily) is more effective than placebo in reducing harmful alcohol consumption in outpatients with AUD. Methods: Forty patients (27 men) who met DSM‐IV‐TR criteria for alcohol dependence and reporting at least 4 heavy drinking days (HDD) per week were recruited at a single site. Participants were actively drinking at study entry and received double‐blind gabapentin (3600 mg/day; n = 19) or placebo (n = 20) for 8 weeks. Study medication was titrated over 5 days and administered in three divided doses (1200 mg three times per day). The proportion of HDD (primary outcome) and percent days abstinent (PDA; secondary outcome) were analyzed using generalized longitudinal mixed models with the predictors being study arm, week, study arm by week interaction, and corresponding baseline drinking measure. Results: There was a significant interaction between study arm and week for the proportion of HDD per week, F (7, 215) = 3.33, p = 0.002. There was also a significant interaction between study arm and week for PDA per week, F (7, 215) = 3.11, p = 0.004. The overall retention rate was 67.5% with no significant difference in time‐to‐dropout between treatment groups. There were no serious adverse events. No participants were removed from the trial due to the development of moderate‐to‐severe alcohol withdrawal (CIWA‐Ar ≥ 13). Conclusions: Gabapentin treatment rapidly titrated to a dosage of 3600 mg/day is associated with a reduction in the proportion of HDD per week and an increase in PDA per week in actively drinking outpatients with AUD. High‐dose gabapentin is potentially a feasible approach to treating AUD and deserving of further study. [ABSTRACT FROM AUTHOR]

Background: Computer‐based delivery of cognitive behavioral therapy (CBT) may be a less costly approach to increase dissemination and implementation of evidence‐based treatments for alcohol use disorder (AUD). However, comprehensive evaluations of costs, cost‐effectiveness, and cost–benefit of computer‐delivered interventions are rare. Methods: This study used data from a completed randomized clinical trial to evaluate the cost‐effectiveness and cost–benefit of a computer‐based version of CBT (CBT4CBT) for AUD. Sixty‐three participants were randomized to receive one of the following treatments at an outpatient treatment facility and attended at least one session: (1) treatment as usual (TAU), (2) CBT4CBT plus treatment as usual (CBT4CBT+TAU), or (3) CBT4CBT plus brief monitoring. Results: Median protocol treatment costs per participant differed significantly between conditions, Kruskal‐Wallis H(2) = 8.40, p = 0.02, such that CBT4CBT+TAU and CBT4CBT+monitoring each cost significantly more per participant than TAU. However, when nonprotocol treatment costs were included, total treatment costs per participant did not differ significantly between conditions. Median incremental cost‐effective ratios (ICERs) revealed that CBT4CBT+TAU was more costly and more effective than TAU. It cost $35.08 to add CBT4CBT to TAU to produce a reduction of one additional drinking day per month between baseline and the end of the 8‐week treatment protocol: CBT4CBT+monitoring cost $33.70 less to produce a reduction of one additional drinking day per month because CBT4CBT+monitoring was less costly than TAU and more effective at treatment termination, though not significantly so. Net benefit analyses suggested that costs of treatment, regardless of condition, did not offset monthly costs related to healthcare utilization, criminal justice involvement, and employment disruption between baseline and 6‐month follow‐up. Benefit–cost ratios were similar for each condition. Conclusions: Results of this pilot economic evaluation suggest that an 8‐week course of CBT4CBT may be a cost‐effective addition and potential alternative to standard outpatient treatment for AUD. Additional research is needed to generate conclusions about the cost–benefit of providing CBT4CBT to treatment‐seeking individuals participating in standard outpatient treatment. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorders (AUDs) are associated with altered regulation of physiological processes in the brain. Acetate, a metabolite of ethanol, has been implicated in several processes that are disrupted in AUDs including transcriptional regulation, metabolism, inflammation, and neurotransmission. To further understand the effects of acetate on brain function in AUDs, we investigated the effects of acetate on cerebral blood flow (CBF), systemic inflammatory cytokines, and behavior in AUD. Methods: Sixteen participants with AUD were recruited from a nonmedical, clinically managed detoxification center. Each participant received acetate and placebo in a randomly assigned order of infusion and underwent 3T MR scanning using quantitative pseudo‐continuous arterial spin labeling. Participants and the study team were blinded to the infusion. CBF values (ml/100 g/min) extracted from thalamus were compared between placebo and acetate using a mixed effect linear regression model accounting for infusion order. Voxel‐wise CBF comparisons were set at threshold of p < 0.05 cluster‐corrected for multiple comparisons, voxel‐level p < 0.0001. Plasma cytokine levels and behavior were also assessed between infusions. Results: Fifteen men and 1 woman were enrolled with Alcohol Use Disorders Identification Test (AUDIT) scores between 13 and 38 with a mean of 28.3 ± 9.1. Compared to placebo, acetate administration increased CBF in the thalamus bilaterally (Left: 51.2 vs. 68.8, p < 0.001; Right: 53.7 vs. 69.6, p = 0.001), as well as the cerebellum, brainstem, and cortex. Older age and higher AUDIT scores were associated with increases in acetate‐induced thalamic blood flow. Cytokine levels and behavioral measures did not differ between placebo and acetate infusions. Conclusions: This pilot study in AUD suggests that during the first week of abstinence from alcohol, the brain's response to acetate differs by brain region and this response may be associated with the severity of alcohol dependence. [ABSTRACT FROM AUTHOR]

Background: While the opiate antagonist, naltrexone, is approved for treating alcohol use disorder (AUD), not everyone who receives the medication benefits from it. This study evaluated whether the OPRM1 SNP rs1799971 interacts with the dopamine transporter gene DAT1/SLC6A3 VNTR rs28363170 or the catechol‐O‐methyltransferase (COMT) gene SNP rs4680 in predicting naltrexone response. Methods: Individuals who met DSM‐IV alcohol dependence were randomly assigned to naltrexone (50 mg/d) or placebo based on their OPRM1 genotype (75 G‐allele carriers and 77 A‐allele homozygotes) and also genotyped for DAT1 VNTR (9 vs. 10 repeats) or COMT SNP (val/val vs. met carriers). Heavy drinking days (%HDD) were evaluated over 16 weeks and at the end of treatment. Effect sizes (d) for naltrexone response were calculated based on genotypes. Results: Naltrexone, relative to placebo, significantly reduced %HDD among OPRM1 G carriers who also had DAT1 10/10 (p = 0.021, d = 0.72) or COMT val/val genotypes (p = 0.05, d = 0.80), and to a lesser degree in those OPRM1 A homozygotes who were also DAT1 9‐repeat carriers (p = 0.09, d = 0.70) or COMT met carriers (p = 0.03, d = 0.63). All other genotype combinations showed no differential response to naltrexone. Diarrhea/abdominal pain was more prominent in OPRM1 A homozygotes who were also DAT 9 or COMT met carriers. Conclusions: These results suggest that individuals with AUD with a more opioid‐responsive genotype (OPRM1 G carriers) respond better to naltrexone if they have genotypes indicating normal/less dopamine tone (DAT1 10,10 or COMT val,val), while those with a less responsive opioid‐responsive genotype (OPRM1 A homozygotes) respond better to naltrexone if they have genotypes indicating greater dopamine tone (DAT1 9‐repeat or COMT met carriers). These results could lead to more personalized AUD treatments. [ABSTRACT FROM AUTHOR]

Aims: Information provided on glass labels may be an effective method to reduce alcohol consumption. The aim of this study was to assess the impact of glass labels conveying unit information and a health warning in reducing ad libitum alcohol consumption. Methods: A cluster‐randomized experimental study was conducted to measure the efficacy of a labeled glass in reducing alcohol consumption in a semi naturalistic bar laboratory setting, in a sample of 81 pairs (n = 162) of UK young adult drinkers. Pairs were randomized to receive two 340‐ml glasses of beer or wine: labeled or plain (control). Alcohol consumption was assessed in an ad libitum drinking period, and urge to drink was measured at baseline and postdrinking period. Focus groups (n = 2) were conducted, and thematic analysis was used to gain an insight into the acceptability and the perceived effectiveness of the glasses. Results: Mean unit consumption was 1.62 (SD ± 0.83) units in the labeled glass condition and 1.69 (SD ± 0.82) units in the non labeled glass condition. There were no significant effects of the labeled glasses on ad libitum alcohol consumption (95% CI −0.25 to 0.37, p = 0.35), despite participants (85%) noticing the information. Qualitative analysis of focus groups indicated that although participants perceived the glasses as a useful tool for increasing awareness of units and guidelines, they were viewed as limited in their potential to change drinking behavior due to the unappealing design of the glass and a view that unit guidelines were not relevant to drinking patterns or contexts. Conclusions: Labeled glasses did not change alcohol consumption in the current study, potentially due to ineffectiveness of this type of message in a young adult population. The information on the glasses was attended to, highlighting that glasses could be a feasible tool for providing information. [ABSTRACT FROM AUTHOR]

Background: It is widely accepted that the therapeutic alliance (TA) is a mediator of psychotherapy effects, but evidence is sparse that the TA is an actual mechanism of behavior change. The purpose of this study was to provide the first systematic evidence regarding the TA as a mechanism of change in the treatment of alcohol use disorder (AUD). Methods: Participants were 155 adult men and women presenting for individual outpatient treatment of AUD. Each was randomly assigned to 1 of 6 experienced therapists, who did or did not receive over 3 study phases postsession participant feedback on his/her ratings of the TA. All participants received a 12‐session version of cognitive behavioral therapy for AUD. Participants rated the TA by use of the California Psychotherapy Alliance Scale (CALPAS) and reported their daily alcohol consumption between sessions and for 1 year posttreatment by use of the timeline followback interview. Multilevel statistical models that partitioned within‐ and between‐participant effects and between‐therapist effects were run to test the effects of feedback condition on the alliance and alcohol use, and the effects of the alliance on alcohol use. Results: The study's main hypotheses that feedback causes an enhanced therapeutic alliance and that the alliance is associated with better alcohol use outcomes were not supported. Conclusions: Several methodological and substantive reasons for the pattern of findings are suggested, as well as directions for future research that would advance study of the TA as a mechanism of change in psychotherapy and in studying therapist effects on outcomes in general. This study highlights the importance of several factors that might be incorporated in research designs to study the therapeutic alliance as a mechanism of alcohol use disorder treatment‐related changes in alcohol use and related outcomes. [ABSTRACT FROM AUTHOR]

Background: Web‐based alcohol screenings and brief interventions have been shown to be effective methods for changing drinking behavior. This study evaluated the efficacy of the online‐based Brief Empowerment Program for Alcohol‐Use Monitor (on‐BEAM), a brief intervention applying personalized normative feedback (PNF) and components of motivational interviewing (MI) techniques. Methods: A community‐based, double‐blind, parallel‐group randomized controlled trial with individual randomization was conducted in Korea (registered at Clinical Research Information Service—KCT0003050). An e‐mail about participating in a survey on drinking behavior was sent to 5,684 individuals, aged 20 to 40, that were registered as part of a research panel. Male and female participants with AUDIT‐C scores of ≥4 and ≥3, respectively, were randomly assigned to either an intervention (received a drinking behavior assessment and the results with normative feedback) or control group (assessment and results without normative feedback). To evaluate the effects of the intervention with 2 sessions over the course of a month, a follow‐up assessment was performed online 4 weeks after completion of the intervention. The main outcome was the number of standard drinks consumed during the past week measured using the timeline followback method. The rate ratios (RRs) were calculated to test the effects of the intervention. Results: In total, 1,496 participants were randomized and 93% of them followed up. The intervention group reported consuming less alcohol during the past week (RR = 0.13; p = 0.012) than the control group. Additionally, the intervention group had fewer binge drinkers (RR = 0.69; p < 0.001) and a lower AUDIT‐C score (RR = 0.59; p = 0.009) than the control group. Conclusions: The web‐based intervention, on‐BEAM, which applies PNF and MI components related to high‐risk drinking reduced the amount of alcohol consumption in our study population. Further research is needed to determine the duration of on‐BEAM's effects and evaluate its effectiveness in the real world. [ABSTRACT FROM AUTHOR]

Background: Mindfulness‐based relapse prevention (MBRP) and transcranial direct current stimulation (tDCS) have independently shown benefits for treating alcohol use disorder (AUD). Recent work suggests tDCS may enhance mindfulness. The combination of MBRP and tDCS may provide synergistic benefits and may target both behavioral and neurobiological dysfunctions in AUD. The goal of this double‐blind sham‐controlled randomized trial was to examine the efficacy of a rolling group MBRP treatment combined with tDCS among individuals interested in reducing their drinking. Methods: Individuals who were interested in reducing their alcohol use (n = 84; 40.5% female; mean age = 52.3; 98.9% with current AUD) were randomized to receive active (2.0 milliamps) or sham (0.0 milliamps) anodal tDCS (5 cm × 3 cm electrode) of the right inferior frontal gyrus with the 5 cm × 3 cm cathodal electrode applied to the left upper arm, combined with 8 weeks of outpatient MBRP rolling group treatment. Assessments were conducted at baseline, posttreatment, and 2 months following treatment. The primary outcome was drinks per drinking day, and secondary outcomes were percent heavy drinking days, self‐reported craving, alcohol cue reactivity in an alcohol cue task, and response inhibition in a stop signal reaction time task. Results: Results indicated significant reductions in drinks per drinking day over time, B(SE) = −0.535 (0.16), p = 0.001, and a significant dose effect for number of groups attended, B(SE) = −0.259 (0.11), p = 0.01. There were also significant effects of time and dose for number of groups attended on secondary outcomes of percent heavy drinking days and alcohol cue reactivity. There were no effects of active versus sham tDCS on primary or secondary outcomes. Conclusions: Findings from the current study provide initial support for the effectiveness of rolling group MBRP as an outpatient treatment for drinking reduction. The current study did not find additive effects of this tDCS protocol in enhancing MBRP among individuals with drinking reduction goals. [ABSTRACT FROM AUTHOR]

Background Aspects of impulsivity have been implicated in the development, or maintenance, of alcohol use disorder ( AUD). The brain dopamine system is implicated in both reward processing/memory (typically subcortical) and in brain inhibitory control mechanisms (typically cortical). Using a validated clinical laboratory paradigm, the dopamine/serotonin 'stabilizing' drug, aripiprazole was evaluated in non-treatment-seeking AUD individuals based on their level of impulsivity/self-control. Methods Ninety-nine individuals (77% male; mean age 27; 7.5 drinks per day; 83% heavy drinking days) meeting DSM- IV criteria for alcohol dependence were randomized to aripiprazole ( N = 47 evaluable) or placebo ( N = 48 evaluable) based on their Barratt Impulsiveness Scale ( BIS-11) score (above or below 68). Aripiprazole, or similar placebo, was titrated to 15 mg over 8 days. Drinking was recorded over 6 days under natural conditions. On Day 8, after 1 day of required abstinence, individuals participated in a bar laboratory paradigm that included a priming drink (breath alcohol concentration [ BAC] target 0.02 to 0.03 g/dl) and free-choice consumption of up to 8 drinks (max BAC 0.1 g/dl) in exchange for a 'bar credit' of $2 per drink (max $16). End points were drinks per day under natural conditions and drinks consumed in the bar laboratory after the priming drink. Results There was no significant main effect of aripiprazole or interaction with BIS-11 score during the natural drinking period. However, there was a main effect of aripiprazole on bar laboratory drinking ( p = 0.04) and aripiprazole reduced the total number of drinks consumed more among individuals with low self-control ( p = 0.034) and increased latency to consume those drinks ( p = 0.045) more among those with high impulsivity. Relative to placebo, aripiprazole caused more side effects and increased alcohol-induced sedation, but neither significantly influenced its interaction with impulsivity/self-control scores on drinking. Conclusions This paradigm forced a choice between immediate drinking reward and delayed monetary reward. In those with high impulsivity and/or low self-control, aripiprazole shifts the balance away from immediate drinking toward a later reward. Medications targeting cortical dopamine/serotonin balance might show clinical benefit of reduced drinking, among individuals with impulsivity/low self-control. [ABSTRACT FROM AUTHOR]

Background Reducing the nicotine content in cigarettes could improve public health by reducing smoking and toxicant exposure, but may also have unintended consequences on alcohol use. The primary objective of this study was to examine the effect of reducing the nicotine content in cigarettes on alcohol outcomes. The secondary aim was to examine whether the effects of these cigarettes on alcohol outcomes were mediated by changes in nicotine exposure, smoking behavior, or withdrawal. Methods Between June 2013 and July 2014, we conducted a 7-arm, double-blind, randomized clinical trial at 10 U. S.-based sites. Daily smokers not currently interested in quitting ( n = 839) were assigned to equally sized groups to smoke for 6 weeks cigarettes containing either normal nicotine content ( NNC; 15.8 mg/g, 9 mg tar), moderate nicotine content (5.2 mg/g nicotine, 9 mg tar), or very low nicotine content ( VLNC; 0.4 to 2.4 mg/g, 9 to 13 mg tar). This investigation focused on a subsample of current drinkers ( n = 403). Each reduced nicotine content cigarette condition was compared to the NNC control condition with respect to trajectories over the 6-week period of average daily alcohol use and occurrence of binge drinking. Moderating variables were considered. Mediation analyses tested potential explanatory processes including changes in nicotine exposure, cigarettes per day, and withdrawal. Results Over time, reduced nicotine exposure and smoking rate mediated effects of VLNC cigarette use on reduced alcohol use. There was no evidence of compensatory drinking in response to nicotine reduction or nicotine withdrawal, even among subgroups expected to be at greater risk (e.g., relatively heavier drinkers, highly nicotine-dependent individuals). Conclusions The findings suggest that compensatory drinking is unlikely to occur in response to switching to VLNC cigarettes. In contrast, reducing the nicotine content of cigarettes may reduce alcohol use (clinicalTrials.gov number, NCT01681875). [ABSTRACT FROM AUTHOR]

Background It has been known that ADH1B*2 allele has a protective effect against the development of alcohol dependence. However, the protection mechanism is still unknown. We investigated whether ADH1B gene polymorphism affects ethanol (EtOH) metabolism. Methods In a parent study, we conducted a randomized crossover trials on 24 healthy male subjects who were selected by genotyping: 12 with ALDH2*1/*1 (active form) and 12 with ALDH2*1/*2 (inactive form). In the present study, the 24 subjects were reclassified into 2 groups of 11 with ADH1B*1/*2 and 13 with ADH1B*2/*2 according to the ADH1B genotypes. Each subject was administered 1 of 3 doses of EtOH (0.25, 0.5, 0.75 g/kg) or a placebo in 4 trials. After the administration of alcohol, blood EtOH and acetaldehyde concentrations were measured 9 times over 4 hours. Results In the case of EtOH, the area under the concentration-time curve from 0 to 4 hours ( AUC0-4) and the peak blood concentration of EtOH ( Cmax) in subjects with ADH1B*2/*2 were significantly higher than those in subjects with ADH1B*1/*2 at all 3 dosages before stratifying by ALDH2 genotype. However, after stratifying by ALDH2 genotype, a statistically significant difference between ADH1B*2/*2 and ADH1B*1/*2 was found only at the 0.5 g/kg dosage regardless of ALDH2 genotype. In the case of acetaldehyde, the AUC0-4 and Cmax of acetaldehyde of ADH1B*2/*2 after administration of 0.25 g/kg alcohol and the AUC0-4 of acetaldehyde of ADH1B*2/*2 at 0.5 g/kg were significantly higher than corresponding values of ADH1B*1/*2 only in the group of ALDH2*1/*2. Conclusions Our findings indicate that the blood EtOH concentrations of ADH1B*2/*2 group are higher than those of ADH1B*1/*2 group regardless of ALDH2 genotype, and the blood acetaldehyde concentrations of ADH1B*2/*2 are also higher than those of ADH1B*1/*2 only in the ALDH2*1/*2 group. To our knowledge, this is the first report to demonstrate the association of ADH1B*2 allele with blood EtOH and acetaldehyde levels in humans, and these results suggest that higher blood EtOH and acetaldehyde concentrations in ADH1B*2/*2 may constitute the mechanism of protection against alcoholism by ADH1B*2/*2. [ABSTRACT FROM AUTHOR]

Background: Brief interventions have the potential to reduce heavy drinking in young adults who present to the emergency department (ED), but require time and resources rarely available. Text-messaging (TM) may provide an effective way to collect drinking data from young adults after ED discharge as well as to provide immediate feedback and ongoing support for behavior change. The feasibility of screening young adults in the ED, recruiting them for a TM-based interventional trial, collecting weekly drinking data through TM, and the variance in drinking outcomes remains unknown. Methods: Young adults in 3 urban EDs ( n = 45; aged 18 to 24 years, 54% women) identified as hazardous drinkers by the Alcohol Use Disorders Identification Test-Consumption score were randomly assigned to weekly TM-based feedback with goal setting (Intervention), weekly TM-based drinking assessments without feedback (Assessment), or control. Participants in the Intervention group who reported ≥5 (for men) and ≥4 (for women) maximum drinks during any one 24-hour period were asked whether they would set a goal to reduce their drinking the following week. We describe the interaction with TM and goal setting. We also describe the heavy drinking days (HDDs), drinks per drinking day (DPDD) using timeline follow-back procedure at baseline and 3 months. Results: We screened 109 young adults over 157 hours across 24 unique days and 52 (48%; 95% CI 38 to 50) screened positive for hazardous drinking. Of these, 45 (87%; 95% CI 74 to 94) met inclusion criteria, were enrolled and randomized, and 6 (13%; 95% CI 5 to 27) did not complete 3-month web-based follow-up; 88% (95% CI 84 to 91) of weekly TM-based drinking assessments were answered, with 77% (95% CI 58 to 90) of participants responding to all 12 weeks. Agreeing to set a goal was associated with a repeat HDD 36% (95% CI 17 to 55) of the time compared with 63% (95% CI 44 to 81) when not willing to set a goal. At 3 months, participants that were exposed to the TM-based intervention had 3.4 (SD 5.4) fewer HDDs in the last month and 2.1 (SD 1.5) fewer DPDD when compared to baseline. Conclusions: TM can be used to assess drinking in young adults and can deliver brief interventions to young adults discharged from the ED. TM-based interventions have the potential to reduce heavy drinking among young adults but larger studies are needed to establish efficacy. [ABSTRACT FROM AUTHOR]