Subjective Effects Of Alcohol Research Articles

An inpatient human laboratory study assessing the safety and tolerability, pharmacokinetics, and biobehavioral effect of GET 73 when co-administered with alcohol in individuals with alcohol use disorder.

Previous work suggests that GET 73, a novel compound with putative activity on the metabotropic glutamate receptor subtype 5 (mGluR5), may represent a novel pharmacological treatment for alcohol use disorder (AUD). In this study, we investigated the safety, tolerability, pharmacokinetics, and biobehavioral effects of GET 73, when co-administered with alcohol, in individuals with alcohol dependence (AD). This was an inpatient, cross-over, randomized, double-blind, placebo-controlled, human laboratory study with non-treatment-seeking, alcohol-dependent individuals. The study used a within-subject design, with two counterbalanced stages, during which participants received GET 73 and then placebo, or vice versa. During each stage, participants underwent an alcohol interaction session and, on a separate day, an alcohol cue reactivity, followed by an alcohol self-administration session. Safety outcomes of GET 73 were excellent with no serious adverse events, nor adverse events of severe grade. The co-administration of alcohol and GET 73 did not affect the pharmacokinetics of GET 73 or alcohol. GET 73, compared to placebo, did not affect the alcohol-related stimulation effects, but increased the subjective sedative effects of alcohol. GET 73 did not affect alcohol cue-induced craving, or alcohol self-administration in the laboratory. The study confirms the safety and tolerability of GET 73 when co-administered with alcohol. Although, under this experimental condition, we did not detect an effect on alcohol craving and consumption in the laboratory, additional studies should be conducted administering GET 73 for an extended period in an outpatient setting.

The effect of alcohol on mood among males drinking with a platonic friend.

Despite the social nature of most drinking experiences, prior work has largely failed to incorporate social context into the study of alcohol's effects on emotion. The present study provides an initial test of the effect of alcohol on mood among platonic friends drinking together in a non-stress setting. We hypothesized that subjects would report more positive postdrink mood after consuming alcohol than after consuming a nonalcoholic control beverage. Dyads of platonic male friends (n=36; 55.55% White, 38.88% Asian, 5.55% Black) attended two laboratory-based experimental sessions, wherein their drink conditions (alcohol vs. no alcohol control) were randomized by dyad and counter-balanced across sessions. They reported their mood before and after consuming their beverages together, using the Positive and Negative Affect Schedule and an 8-item mood measure. As hypothesized, alcohol enhanced positive mood ( =0.26, p<0.01). Although in the expected direction, the effect of alcohol on negative mood was not significant ( =-0.12, p=0.17). Post hoc analyses revealed that alcohol yielded greater increases in both stimulation ( , p=0.00) and sedation ( , p=0.00) as compared to the control condition. This study highlights the positive mood-enhancing and broader subjective effects of alcohol when drinking with a platonic friend and encourages further consideration of friendship contexts in the examination of alcohol's effects when developing models of the etiology of alcohol use disorder.

Sex differences in the acute pharmacological and subjective effects of smoked cannabis combined with alcohol in young adults.

Objective: The prevalence of co-use of alcohol and cannabis is increasing, particularly among young adults. Sex differences in the effects of alcohol alone and cannabis alone have been observed in animals and humans. However, sex differences in the acute pharmacological effects of cannabis combined with alcohol have not yet been studied. In young adults, aged 19-29 years, we aimed to examine sex differences following an intoxicating dose of alcohol (target 0.08% breath alcohol content) combined with a moderate dose of cannabis (12.5% Δ⁹-tetrahydrocannabinol; THC) using an ad libitum smoking procedure. Method: Using a within-subjects design, 28 regular cannabis users (16 males; 12 females) received in random order: (a) placebo alcohol and placebo cannabis, (b) active alcohol and placebo cannabis, (c) placebo alcohol and active cannabis, and (d) active alcohol and active cannabis. Blood samples for THC were collected and measures of vital signs, subjective drug effects, and cognition were collected. Results: In the alcohol-cannabis combined condition, females smoked significantly less of the cannabis cigarette compared to males (p < .001), although both sexes smoked similar amounts in the other conditions. There was minimal evidence that females and males differed in THC blood concentrations, vitals, subjective effects, or cognitive measures. Conclusions: In the alcohol-cannabis combined condition, females experienced the same acute pharmacological and subjective effects of alcohol and cannabis as males, after smoking less cannabis, which has potential implications for informing education and policy. Further research is warranted on sex differences in cannabis pharmacology, as well as the combined effects of alcohol and cannabis. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Alcohol subjective responses in heavy drinkers: Measuring acute effects in the natural environment versus the controlled laboratory setting

For decades, laboratory alcohol challenges have been the "gold standard" for measuring individual differences in alcohol's subjective effects. However, these approaches are expensive and labor-intensive, making them impractical for large-scale use. This study examined the reliability and validity of a new high-resolution EMA (HR-EMA) ambulatory approach to assessing alcohol use and subjective responses in drinkers' natural environments. Participants were 83 young adult heavy social drinkers (58% male; mean±SD age=25.4±2.6years) who completed up to two smartphone-based, 3-h HR-EMA assessments of alcohol use and related subjective responses in their typical drinking environments. Reported alcohol consumption during the HR-EMA periods was used to calculate estimated blood alcohol concentration (eBAC). Subjective effects were measured using the Brief Biphasic Alcohol Effects Scale (B-BAES) and Drug Effects Questionnaire (DEQ). All participants also completed identical measures during a separate, 4 to 5-h laboratory session in which they received a 0.8g/kg alcohol challenge. Most natural environment drinking episodes (87%) met or exceeded the threshold for binge drinking (final mean eBAC=0.12g/dl). Associations between reported alcohol use and subjective responses on the B-BAES and DEQ were strongest earlier in the drinking events, with fair reliability of reported subjective effects across two HR-EMA episodes (intraclass correlation [ICC] range = 0.46-0.49). There was fair-to-good correspondence between HR-EMA- and laboratory-derived subjective responses (ICC range = 0.49-0.74), even after accounting for differences in alcohol consumption and drinking context. Reported stimulating and rewarding alcohol effects were higher in the ambulatory than laboratory setting, and vice versa for sedating effects. This study supports the reliability and validity of smartphone-based HR-EMA to measure alcohol use and subjective responses in heavy drinkers' natural environments. These findings lend support to the use of ambulatory HR-EMA as a measure of alcohol subjective responses in risky drinkers when a laboratory protocol is not practical, feasible, or safe.

Alcohol conditioned contexts enhance positive subjective alcohol effects and consumption

Associations between alcohol and the places it is consumed are important at all stages of alcohol abuse and addiction. However, it is not clear how the associations are formed in humans or how they influence drinking, and there are few effective strategies to prevent their pathological effects on alcohol use. We used a human laboratory model to study the effects of alcohol environments on alcohol consumption. Healthy regular binge drinkers completed conditioned place preference (CPP) with 0 vs. 80 mg/100 mL alcohol (Paired Group). Control participants (Unpaired Group) completed sessions without explicit alcohol-room pairings. After conditioning, participants completed alcohol self-administration in either the alcohol- or no alcohol-paired room. Paired group participants reported greater subjective stimulation and euphoria, and consumed more alcohol in the alcohol-paired room in comparison to the no alcohol-paired room, and controls tested in either room. Moreover, the strength of conditioning significantly predicted drinking; participants who exhibited the strongest CPP consumed the most alcohol in the alcohol-paired room. This is the first empirical evidence that laboratory-conditioned alcohol environments directly influence drinking. The results also confirm the viability of the model to examine the mechanisms by which alcohol environments stimulate drinking and to test strategies to counteract their influence on behavior.

Contextual influences on subjective alcohol response.

Prior research demonstrates contextual influences on drug responses in both animals and humans, although studies in humans typically focus on only one aspect of context (e.g., social) and examine a limited range of subjective experiences. The current study sought to address these limitations by examining the impact of both social and physical context on the full range of subjective alcohol effects. The sample included 448 young adult social drinkers (57% male, 66.5% White) randomly assigned to consume alcohol (target blood alcohol concentration of .08 g%) or placebo in 1 of 4 contexts (solitary lab, group lab, solitary bar, group bar). Results indicated that high arousal positive (HAP) effects of alcohol (e.g., talkative, lively) were stronger in nonbar relative to bar contexts and that low arousal positive (LAP) effects (e.g., relaxed, calm) were only present in the group lab context. There were also main effects of social context such that high arousal effects (both positive and negative) were stronger in group contexts, regardless of beverage condition. These findings highlight the importance of considering context when examining alcohol effects. Studies designed to isolate pharmacological HAP effects may benefit from a nonbar setting, and studies of LAP effects might be most effective in a simulated living room or home environment, although future studies are needed to directly address this possibility. Further, studies with an explicit focus on expectancies or that need strong control for expectancies might benefit from a group context, particularly when studying high arousal effects. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Social facilitation of alcohol subjective effects in adolescents: Associations with subsequent alcohol use.

Laboratory research in adults indicates that alcohol-related subjective effects are enhanced under some social conditions. However, it is unknown whether this "social facilitation" of alcohol effects occurs in adolescents and is associated with alcohol use in the natural ecology. We examined associations of social facilitation of alcohol-related subjective effects with subsequent alcohol use among a relatively high-risk group of adolescents who reported drinking alcohol both with friends and alone. Los Angeles high school students from a prospective study (N = 142; 51% female; 10th graders) completed a baseline survey that assessed alcohol-related "positive" and "negative" subjective effects in two contexts: social (alcohol with friends) and solitary (alcohol alone); social facilitation was calculated as the difference between social and solitary. Students then completed five semi-annual surveys spanning 30months (2014-2017) assessing 30-day alcohol use (days used, number of drinks, binge drinking). Greater social facilitation of positive effects was significantly associated with greater number of alcohol use days (RR [95% CI] = 1.48 [1.19, 1.82]; p < .001), greater number of drinks (RR [95% CI] = 1.38 [1.14, 1.66]; p = .001), and greater odds of binge drinking (OR [95% CI] = 1.75 [1.20, 2.57]; p = .004). Similar associations were found with social positive effects. There were no significant associations between solitary positive effects-or any negative effects-and alcohol use outcomes. Social facilitation can be measured outside of the laboratory. Relatively high-risk drinking adolescents who are more susceptible to the social facilitation of subjective alcohol effects are more likely to use more alcohol and binge drink.

"Buzzwords": Crowd-sourcing and quantifying U.S. young adult terminology for subjective effects of alcohol and marijuana use.

Prevalence of heavy alcohol use remain high, and daily marijuana use is at an all-time high in young adults. As perceptions of drug effects may guide risky decision making, understanding subjective feelings for alcohol and marijuana use is critical. Existing laboratory-based and diary metrics (0-100 rating of "how drunk/high do you feel?") may be problematic in differentiating levels of subjective effects. Measures incorporating contemporary language may better capture subjective feelings in experimental and ambulatory assessment designs. We developed 2 sliding scales based on crowd-sourced and rank-ordered feelings of subjective alcohol and marijuana effects. Two U.S. young adult (18-25 years) samples were drawn from Amazon's Mechanical Turk (MTurk). In the first study, 323 (53.6% women, 68.4% White, M age = 23.0 years) alcohol and marijuana users provided words to describe subjective effects from alcohol use and from marijuana use. In a second study, 289 (46.4% female, 66.4% White, M age = 23.0 years) users rank-ordered the most common terms to correspond with subjective levels. The sliding scale for alcohol effects resulted in 4 anchors ranging from 0 to 100: slightly buzzed, tipsy/"happy," drunk, and wasted. The sliding scale for marijuana effects also had 4 anchors: relaxed, calm/chill, high, and stoned/baked. By incorporating broader and more contemporary subjective effects language, our metrics may better capture variability in young adults' perceived subjective effects from alcohol and marijuana use. Future work could build upon these findings by pairing sliding scales with measures of actual intoxication to understand within- and between-person covariation in subjective effects, actual impairment, and consequences. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

An Exploratory Factor Analysis of the Stimulant, Sedative, and Affective Responses to Alcohol.

Subjective response (SR) to acute alcohol reflects individual variance to the sensitivity of alcohol's pharmacological effects. It has been argued that measures of stimulation and sedation may not fully capture the full-range SR, with 2 novel domains proposed: high arousal negative and low arousal positive. While substantial progress has been made in the field of SR and alcohol use risk, it remains unknown how these novel domains correspond to traditional SR measures. Therefore, the current study examined the latent structure of traditional and novel SR measures at rising breath alcohol concentrations (BrACs) during alcohol administration. Heavy drinkers (n=67; 36M/31F) participated in an intravenous alcohol administration. Questionnaires assessing stimulation, sedation, mood, valence and arousal, and craving were assessed at baseline and at BrACs of 20, 40, and 60mg%. A series of exploratory factor analyses were conducted to examine the latent factor structure of SR at each time point. Correlations examined the association between the generated factors and measures of problematic alcohol use. The analysis generated a 3-factor solution, consistent across all time points. The factors measured the following effects of SR: (i) stimulation and positive mood, (ii) sedation and aversive effects, and (iii) tension reduction. The tension reduction factor was most commonly associated with problematic alcohol use in this sample. This study extends upon the literature evaluating the biobehavioral effects of alcohol by examining a novel combination of SR to alcohol measures. This study demonstrates that the proposed low arousal positive domain, which loaded onto the tension reduction factor, provides novel information not captured by previous SR measures. Going forward, studies of alcohol's subjective effects should use this dimensional approach to reduce multiple comparisons across a wide range of scales and to build a literature grounded on the underlying structure of SR as a translational phenotype for AUD.

Influence of n-acetylcysteine maintenance on the pharmacodynamic effects of oral ethanol

RationaleGlutamate systems play an important role in the abuse related effects of alcohol. n-Acetylcysteine, a drug that promotes glutamate homeostasis, attenuates a range of alcohol effects in preclinical models. ObjectivesThis human laboratory study determined the influence of n-acetylcysteine maintenance on alcohol self-administration using a model predictive of treatment effectiveness, along with the subjective, performance and physiological effects of alcohol. We hypothesized that n-acetylcysteine would attenuate alcohol self-administration, as well as positive subjective effects of alcohol. MethodsNine subjects with alcohol use disorder completed this within-subjects study. Subjects were maintained on placebo, 1.2 and 2.4 g n-acetylcysteine in random order on an outpatient basis. After five days of maintenance on the target dose, subjects completed overnight inpatient experimental sessions in which the pharmacodynamic effects of alcohol were determined. ResultsAlcohol produced prototypic effects (e.g., increased breath alcohol concentration, increased ratings of Feel Drink). n-Acetylcysteine did not alter the effects of alcohol. ConclusionsThese results indicate that although n-acetylcysteine can safely be combined with alcohol, it does not attenuate the abuse related effects of alcohol and is unlikely to be an effective standalone alcohol use disorder treatment. However, considering study limitations, future work is needed to further understand whether and how n-acetylcysteine might be used as a treatment for alcohol use disorder (e.g., in combination with a behavioral treatment or another pharmacological agent).

Alcohol expectancies change in early to middle adolescence as a function of the exposure to parental alcohol use

IntroductionThe subjective effects of alcohol, i.e., alcohol expectancies (AE), are important predictors of alcohol use. This three-year longitudinal study examined: 1) the development of enhancement, social, coping, and conformity AE from age 10–16; 2) the association between parental alcohol use exposure and positive AE among adolescents and between exposure and changes in AE over the six month period and 3) the moderating effect of gender on the association between exposure and change in AE. MethodsA longitudinal study followed adolescents between 10-13-years old at baseline (N = 755; 45.6 % boys) in six months intervals for three years, resulting in seven measurements. ResultsAdolescents most strongly endorsed enhancement AE. Social and coping AE dimensions positively increased over time. The estimated Multilevel Model of Change revealed that exposure to either fathers ‘or mothers' alcohol use predicted an increase in social AE six months later (B = .129, SE = .032). Exposure to fathers’ drinking predicted an increase in enhancement AE for boys (B = .075, SE = .031) but not for girls (B=-0.045, SE = .030). No associations between parental exposure and other AE dimensions were found. ConclusionThe results add to previous studies in showing that the association between parental drinking behavior and offspring AE develops within short periods. Prevention should, therefore, include explicit guidelines for parents with respect to how their drinking behavior affect their offspring.

Self-fulfilling prophecies: Documentation of real-world daily alcohol expectancy effects on the experience of specific positive and negative alcohol-related consequences.

Alcohol expectancies are consistently associated with alcohol use in cross-sectional and longitudinal studies. However, little research has examined whether alcohol expectancies on specific drinking occasions are associated with reported consequences on those days, particularly when controlling for the amount of alcohol consumed, thus differentiating the extent to which reported consequences may have resulted from alcohol or an "expectancy effect." This study examined consequence-specific daily expectancy effects. College students (N = 342; mean age 19.7 [standard deviation (SD) = 1.25], 52.9% female) participated in a longitudinal measurement burst study. During four 2-week intervals, participants used mobile phones to respond to 3 surveys per day via automated telephone interviews. The results showed that on days when college students had higher-than-average expectancies for specific subjective positive consequences (e.g., feeling more relaxed, being in a better mood), they were more likely to report experiencing those same consequences as a result of their alcohol use that day, even after controlling for how much they actually drank on that day. The same held true for subjective interpersonal negative consequences (e.g., becoming aggressive, rude, or obnoxious; embarrassing oneself), but not for less subjective physical/cognitive negative consequences (e.g., having a hangover, vomiting, getting hurt/injured, forgetting). The results suggest that one's expectations about the particular effects of alcohol tend to be self-fulfilling for subjective effects of alcohol even when they are not directly tied to the physiological effects of alcohol. The findings underscore the important role of alcohol expectancies, particularly the expectation of subjective positive social and tension-reduction/relaxation effects, in understanding problematic alcohol use. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

The Relationship Between Regional Cerebral Blood Flow Estimates and Alcohol Problems at 5-Year Follow-Up: The Role of Level of Response.

Acute alcohol consumption is associated with temporarily increased regional cerebral blood flow (CBF). The extent of this increase appears to be moderated by individual differences in the level of response (LR) to alcohol's subjective effects. The low LR phenotype is a known risk factor for the development of alcohol problems. This study investigates how the low LR phenotype relates to the relationship between alcohol-related changes in CBF and alcohol problems 5years later. Young adults (ages 18 to 25) were selected based on their LR to alcohol and underwent a neuroimaging protocol including arterial spin labeling and functional scans. These participants were recontacted ~5years later and assessed on alcohol outcomes. A final sample of 107 subjects (54 low and 53 high LR subjects) was included in the analyses. Whole-brain analysis revealed 5 clusters of significant alcohol-induced, versus placebo-induced, CBF changes that were consistent with a previous report. Peak alcohol-placebo CBF response was extracted from these regions and, along with the LR group, submitted to a hierarchical linear regression predicting alcohol problems. Analyses controlled for age, sex, and baseline alcohol problems. In the regression analysis, greater alcohol-placebo CBF difference in the right middle/superior/inferior frontal gyri and bilateral anterior cingulate gyri clusters predicted greater future alcohol problems for the low LR group, whereas this relationship was not found to be significant in the high LR group. This study demonstrates a clinically important relationship between CBF and future alcohol problems, particularly in individuals with a low LR phenotype. These initial results help to elucidate the neurobiological pathways involved in the development of alcohol use disorders for individuals with low LR.

Suggestibility is associated with alcohol self-administration, subjective alcohol effects, and self-reported drinking behavior

Suggestibility, defined as an individual's inclination to accept and internalize messages, has not been studied in relation to alcohol use. Peer conformity, a component of suggestibility, may be related to alcohol use, as peer groups show similarities in patterns of alcohol use. Few studies have assessed how suggestibility and peer conformity relate to alcohol self-administration or to reinforcing effects of alcohol. This study assessed whether suggestibility and peer conformity were associated with drinking behavior, alcohol self-administration, subjective response to alcohol, and drinking motives and expectancies. Study 1 participants were alcohol drinkers (n=20), who completed a laboratory study of free-access intravenous alcohol self-administration. Study 2 participants were adolescents and young adults, age 14-25 (n=150), with lifetime alcohol use. Participants completed surveys of suggestibility and drinking patterns (Study 1 and 2), subjective alcohol effects (Study 1 only), and alcohol motives and expectancies (Study 2 only). In Study 1, participants with higher levels of suggestiblity self-administered more alcohol, and reported greater subjective alcohol effects. Peer conformity, though correlated with suggestibility, was not related to these measures. In Study 2, participants with higher suggestiblity reported more alcohol consumption, higher drinking motives and alcohol expectancies. Peer conformity was not related to alcohol consumption, but was related to coping and enhancement drinking motives, and all expectancies measures. Results indicate that suggestibility, beyond peer conformity, may be a critical factor to study when examining alcohol consumption behavior, and may provide insight into the development of alcohol use disorder.

3207 Relation between Dopamine Transporter (DAT1) polymorphism and subjective effects of alcohol among non-dependent drinkers

OBJECTIVES/SPECIFIC AIMS: Dopamine transporter (DAT1) gene variation is associated with reward-related phenotypes including alcohol response. There is also evidence for a potential moderating role for mu-opioid receptor (OPRM1) gene variation on the relationship between DAT1 variation and alcohol response measures. We aimed at studying the interaction between the DAT1 VNTR and OPRM1 A118G polymorphisms on alcohol consumption and subjective responses among non-dependent drinkers. METHODS/STUDY POPULATION: We employed a progressive ratio (PR) paradigm of intravenous alcohol self-administration (IV-ASA) using the Computer-Assisted Infusion System (CAIS) to assess the motivation for alcohol seeking and consumption in a sample of nondependent drinkers. We used the Drug Effects Questionnaire (DEQ) and Biphasic Alcohol Effects Questionnaire (BAES) to assess subjective response. IV-ASA measures included average breath alcohol concentration (BrAC) and total ethanol infused. Peripheral blood samples were collected for genotyping. Ethics approval was obtained from the NIH Addictions Institutional Review Board. RESULTS/ANTICIPATED RESULTS: Fifty participants completed the PR IV-ASA session after informed consent. There were significant interactions between the DAT1 and OPRM1 genotypes in subjective effects of alcohol. Simple main effects analysis showed that DAT1 10a allele carriers that were also OPRM1 G allele carriers had significantly higher scores for several measures: “feel the drug effects” (F (1,46)=6.573, P = 0.014), “feel intoxicated”(F(1,46)=8.613, P = 0.005) and “feeling high” (F(1,46)=10.889, P = 0.002) in DEQ and higher sedation (F(1,46)=4.575, P = 0.038) in BAES. The genotypes statistically significantly predicted average breath alcohol (F (1,61) =3.295, p=0.044) and total ethanol infused(F(1,61)=3.632, p=0.032. DAT1 VNTR and OPRM1 A118G polymorphisms taken together accounted for 6.9 and 7.8% of variations in average breath alcohol and total ethanol infused respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Polymorphic variations in DAT1 and OPRM1 interact with each other in determining subjective effects of alcohol in intravenous alcohol infusion assessing motivation for alcohol seeking and consumption in nondependent drinkers. These epistatic interactions in subjective effects of alcohol are salient in the context of predicting and understanding neurobiological effects of alcohol and thereby the therapeutic responses in treating alcohol use disorders.

Cannabidiol as a Novel Candidate Alcohol Use Disorder Pharmacotherapy: A Systematic Review.

There is substantial interest in the therapeutic potential of cannabidiol (CBD), a nonpsychoactive cannabinoid found in plants of the genus Cannabis. The goal of the current systematic review was to characterize the existing literature on this topic and to evaluate the credibility of CBD as a candidate pharmacotherapy for alcohol use disorder (AUD). Using a comprehensive search strategy, 303 unique potential articles were identified and 12 ultimately met criteria for inclusion (8 using rodent models, 3 using healthy adult volunteers, and 1 using cell culture). In both rodent and cell culture models, CBD was found to exert a neuroprotective effect against adverse alcohol consequences on the hippocampus. In rodent models, CBD was found to attenuate alcohol-induced hepatotoxicity, specifically, alcohol-induced steatosis. Finally, findings from preclinical rodent models also indicate that CBD attenuates cue-elicited and stress-elicited alcohol seeking, alcohol self-administration, withdrawal-induced convulsions, and impulsive discounting of delayed rewards. In human studies, CBD was well tolerated and did not interact with the subjective effects of alcohol. Collectively, given its favorable effects on alcohol-related harms and addiction phenotypes in preclinical models, CBD appears to have promise as a candidate AUD pharmacotherapy. This is further bolstered by the absence of abuse liability and its general tolerability. A clear limitation to the literature is the paucity of human investigations. Human preclinical and clinical studies are needed to determine whether these positive effects in model systems substantively translate into clinically relevant outcomes.

Acute alcohol effects on impulsive choice in adolescents.

Neurodevelopmental and alcohol-induced changes in decision-making have been proposed to critically influence impulsive behaviour in adolescents. This study tested the influence of acute alcohol administration on impulsive choice in adolescents. Fifty-four males aged 18-19 years were tested in a single-blind placebo-controlled cross-over design. During alcohol administration (infusion resulting in an arterial blood alcohol concentration of 80 mg%) and placebo condition (saline infusion), participants performed a task battery providing estimates of delay discounting, probability discounting for gains, for losses and loss aversion, and also rated subjectively experienced alcohol effects. Additionally, baseline alcohol consumption (Alcohol Use Disorders Identification Test, blood phosphatidylethanol levels), motives (Drinking Motive Questionnaire, Alcohol Expectancy Questionnaire and Obsessive Compulsive Drinking Scale), family history and self-report measures of impulsivity (Barratt Impulsiveness Scale, Substance Use Risk Profile Scale) were provided. No overall effects of treatment on choice behaviour were found. However, individual differences were observed. In the alcohol condition, more impulsive choice tendencies for delay discounting were associated with higher subjectively experienced alcohol effects. Further, higher risk aversion for probabilistic gains and higher loss aversion during alcohol condition were related to higher levels of real-life alcohol consumption and a family history of alcohol problems, respectively. Finally, the time to make a decision was substantially shortened for choices involving negative prospects. Contrary to common beliefs, acute alcohol intoxication did not generally incite impulsive decision-making. It rather appears that alcohol-induced behavioural changes in adolescents vary considerably depending on prior experiences and subjective effects of alcohol.

α5GABAA subunit-containing receptors and sweetened alcohol cue-induced reinstatement and active sweetened alcohol self-administration in male rats.

GABAA receptors containing the α5 subunit (i.e., α5GABAA receptors) appear to be critically involved in the reinforcing and subjective effects of alcohol. Their role in alcohol relapse remains unknown. Pharmacological approaches were used to probe the role of α5GABAA receptors in alcohol seeking induced by re-exposure to a sweetened alcohol-paired cue, as well as in alcohol + sucrose vs. sucrose self-administration. For reinstatement studies, rats were trained to self-administer alcohol under a fixed-ratio schedule in which responding was maintained by alcohol + sucrose deliveries and an alcohol-paired stimulus. Sweetened alcohol seeking was extinguished by eliminating solution deliveries and the sweetened alcohol-paired stimulus. During reinstatement tests, animals received pretreatments of an α5GABAA inverse agonist (L-655,708) or an agonist (QH-ii-066) prior to sessions in which presentation of the sweetened alcohol-paired stimulus was restored, but no solution was delivered. For self-administration studies, rats were trained to self-administer alcohol + sucrose or sucrose under a fixed-ratio schedule. Once stable, animals received pretreatments of QH-ii-066, L-655,708, the inverse agonist RY-023, or naltrexone. L-655,708 attenuated reinstatement of sweetened alcohol seeking by alcohol + sucrose-paired cues; whereas sweetened alcohol-seeking behavior was augmented by QH-ii-066, albeit at different doses in different rats. Both L-655,708 and RY-023 selectively reduced alcohol + sucrose vs. sucrose self-administration. In contrast, naltrexone reduced both alcohol + sucrose and sucrose self-administration; whereas QH-ii-066 enhanced sucrose self-administration only. α5GABAA receptors play a key role in the modulation of sweetened alcohol cue-induced reinstatement, as well as in alcohol + sucrose but not sucrose self-administration. Inverse agonist activity at α5GABAA receptors may offer a novel strategy for both the reduction of problematic drinking and the prevention of relapse.

A prospective study of alcohol involvement and the dual-systems model of adolescent risk-taking during late adolescence and emerging adulthood.

To estimate interactions and unique effects of behavioral approach and behavioral control on alcohol involvement hypothesized by dual-systems models, during adolescence and emerging adulthood. In a longitudinal study, behavioral approach and behavioral control were examined in relation to alcohol involvement, cross-sectionally and prospectively. A total of 846 general population twins born in Colorado, USA were assessed twice (mean=17.3 and 22.8years; female=51.4%; white=91.8%). Behavioral approach was measured by self-report questionnaires of sensation-seeking and subjective effects of alcohol. Behavioral control was measured by self-reported lack of planning and nine executive functioning (EF) tasks. Interviewers administered semi-structured clinical interviews to assess alcohol use and disorder (AUD). None of 36 interaction effects was statistically significant (β=-0.16-0.14, P>0.06), suggesting that dual systems are additively related to alcohol involvement. In multiple regression models, behavioral approach and behavioral control explained independent variance in alcohol use quantity (β=0.09-0.33, P<0.04) and frequency (β=-0.11-0.29, P<0.03) at both waves. During adolescence, only subjective effects (β=0.27-0.28, P<0.001) explained independent variance in AUD. Moreover, measures of the same construct explained independent variance in alcohol involvement: for behavioral control, lack of planning and EF were associated with alcohol frequency in adolescence (β=-0.11-0.25, P<0.02) and AUD in emerging adulthood (β=-0.09-0.16, P<0.03). For the behavioral approach, subjective effects were associated with all measures at both waves (β=0.20-0.33, P<0.01) and sensation-seeking was associated with all measures in emerging adulthood (β=0.09-0.11, P<0.04). In prospective models, adolescent alcohol involvement was associated with later lack of planning (β=0.12-0.18, P<0.03) and lack of planning in adolescence was associated with later alcohol involvement (β=0.12-0.14, P<0.02). Both the behavioral approach and behavioral control components of dual-systems models explain alcohol involvement during adolescence and adulthood, and different measures of the same system assess separate risk processes. The relations between alcohol involvement and the dual systems appear to be bidirectional.

The Impact of Alcohol and Social Context on the Startle Eyeblink Reflex.

Researchers have long sought to understand how individuals respond to alcohol in social settings with the aim of elucidating pathways of risk for alcohol use disorder (AUD). But studies that incorporate a social context are still outnumbered by those that examine alcohol's subjective effects among participants drinking alcohol in isolation. Further, perhaps due to the challenges of capturing automatic affective processes in these settings, prior studies of alcohol response in social context have relied mainly on self-report measures, and so relatively little is known about alcohol's psychophysiological effects in social settings. Using a novel paradigm that integrated alcohol-administration procedures, startle methodology, and social context, this study examined the impact of alcohol and social context on startle eyeblink reflex among 40 social drinkers. Results indicated that there was a significant effect of group presence, indicating that startle magnitude was larger when people were alone than with others. There was a significant group presence-by-alcoholic beverage interaction, with the effect of alcohol being significantly larger when people were alone versus with others. These effects were found both for the startle habituation data and during the picture-viewing task. Results of this study highlight the importance of considering the presence of other individuals for understanding alcohol response and mechanisms of AUD risk. Findings are discussed in light of both emotional and cognitive correlates of startle reflex magnitude. Future research should examine these effects within larger samples of participants and further explore mechanisms that might underlie these effects.