Biphasic Alcohol Effects Scale Research Articles

Acute alcohol rewarding effects as a risk factor for hangover frequency

Background/Purpose: Acute subjective alcohol effects appear to play an important role in predicting alcohol hangover. However, no studies have used a laboratory-based alcohol challenge to examine the concurrent or longitudinal effects of subjective alcohol responses on hangover frequency. As such, we investigated the direct and indirect effects of alcohol stimulation, sedation, liking and wanting, as measured in a controlled setting, on hangover frequency over five years. Method: Participants were 294 young adult light-to-heavy social drinkers (aged 21–35 years, 42% female) enrolled in the Chicago Social Drinking Project. The study utilized a placebo-controlled, double blind, laboratory alcohol challenge and a battery of measures including the Biphasic Alcohol Effects Scale, Drug Effects Questionnaire, Hangover Symptom Scale, and alcohol use Quantity-Frequency Interview, with the latter two re-administered after five years. Results: Through the use of a path analysis, the present study found significant direct effects from alcohol liking to hangover frequency at initial testing. In addition, there were multiple significant indirect effects from greater alcohol liking and wanting to greater alcohol use quantity-frequency and, in turn, greater hangover frequency at initial testing and 5-year follow-up. Last, there were significant indirect effects from greater alcohol sedation to less alcohol use quantity-frequency and, in turn, less hangover frequency at initial testing and 5-year follow-up. Conclusion: This study highlights the role of the hedonic reward and motivational salience of alcohol as potential mechanisms of alcohol-related consequences (i.e., hangover) among light-to-heavy social drinking young adults.

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.

Subjective Effects of Alcohol Predict Alcohol Choice in Social Drinkers.

Alcohol is among the most commonly used psychoactive drugs, yet it can produce markedly different subjective effects in different people. Certain effects, including both heightened stimulatory effects and lesser sedative effects, are thought to predict repeated or excessive use. However, we do not fully understand the nature of these individual differences or their relationships to alcohol consumption. This controlled laboratory study examined subjective and physiologic responses to a moderate dose of alcohol in social drinkers in relation to the subjects' decision to consume alcohol. Healthy adult volunteers (N=95) participated in a 5-session double-blind alcohol choice study. On the first 4 sessions, they received alcohol (0.8g/kg) and placebo in alternating order, and on the fifth session, they chose and consumed whichever of the 2 they preferred. During each session, participants completed the Profile of Mood States (POMS) and Biphasic Alcohol Effects Scale (BAES) questionnaires and had their vitals recorded every 30minutes. We compared subjective and physiologic response to alcohol during the sampling sessions in participants who chose alcohol or placebo on session 5. Of the 95 participants, 55 chose alcohol (choosers) and 40 chose placebo (nonchoosers). In the full sample, alcohol produced its expected effects (e.g., increased friendliness, elation, and vigor (POMS), and stimulation and sedation (BAES)). The chooser and nonchooser groups did not differ in demographic characteristics, blood alcohol levels, or cardiovascular measures. However, the choosers experienced greater alcohol-induced increases in positive mood (POMS) and liked the drug more, whereas the nonchoosers experienced greater anger, anxiety (POMS), and sedation (BAES) after alcohol. Both greater positive mood effects and lesser sedative effects after alcohol predicted preference under controlled conditions, suggesting that both factors can predict future consumption of alcohol.

Poor inhibitory control is associated with greater stimulation and less sedation following alcohol.

Poor inhibitory control is a well-established risk factor for alcohol use disorder (AUD). Similarly, greater sensitivity to the stimulant effects and less sensitivity to the sedative effects of alcohol are also strongly linked to risk for AUD. Traditionally, these two risk factors have been considered to be orthogonal, and thus they have been studied independently. However, recent evidence from animal and human studies suggests that they may be related. The current study examined the relationship between inhibitory control and subjective responses to alcohol in a sample of healthy young adults. Moderate social drinkers (N = 69) first completed the stop signal task to assess inhibitory control. They then participated in four sessions in which they received an oral dose of ethanol (0.8g/kg) or placebo in alternating order, providing self-report measures of stimulation and sedation on the Biphasic Alcohol Effects Scale (BAES) at regular intervals. Linear mixed effects models showed that poor inhibitory control was associated with greater stimulation and less sedation following alcohol compared with placebo. These findings provide the first direct evidence that individuals with poor inhibitory control experience greater sensitivity to the rewarding, stimulant effects of alcohol, and less sensitivity to the negative, sedative effects. These findings suggest that inhibition and subjective response to alcohol are not independent risk factors, and that together they constitute a heightened profile of risk for AUD.

3294 HIGH INTENSITY BINGE DRINKING AND STIMULATING EFFECTS IN HUMAN LABORATORY STUDIES OF ALCOHOL SELF-ADMINISTRATION

OBJECTIVES/SPECIFIC AIMS: Alcohol use disorder (AUD) has previously been studied using Timeline Followback (TLFB) interview measures and administration of alcohol within laboratory sessions. However, most of those studies supplied alcohol orally and analyzed drinking across a range of drinking intensity and frequency measures. High intensity binge drinking, i.e., drinking alcohol at multiple levels of the binge threshold (5+ drinks for males, 4+ drinks for females) has been identified as a significant risk factor for developing AUD. In the present study, we examined the relationship between high intensity binge drinking with the behavioral and subjective response to intravenous alcohol in a lab study. METHODS/STUDY POPULATION: Two hundred participants completed a 90-Day TLFB interview, wherein the maximum number of drinks in a day established the participant’s binge level status as a Non-Binger (N = 37), Binge Level 1 (N = 96), Binge Level 2 (N = 44), or Binge Level 3 (N = 22). Binge Level 1 corresponds with at least one binge (4-7 drinks for women, 5-9 drinks for men); Binge Level 2 requires at least twice the binge level (8-11 drinks for women, 10-14 drinks for men); and Level 3 necessitates a participant to drink at least three times the binge level (12+ drinks for women, 15+ drinks for men) on one day. Non-Bingers had no binge level drinking in the 90-day interview. Participants also underwent a 150-minute intravenous-alcohol self-infusion, where participants would press a button to receive an infusion of an ethanol solution. During this, participants also completed subjective questionnaires including the Alcohol Urge Questionnaire (AUQ), Biphasic Alcohol Effects Scale (BAES), and Drug Effects Questionnaire (DEQ). Kruskal-Wallis and chi-square tests were used to examine the effect of group on alcohol infusion and subjective response measures. RESULTS/ANTICIPATED RESULTS: A chi-square test for association showed significant statistical differences by groups in reaching binge level status (0.08% breath alcohol content) during the alcohol infusion session in the lab, X2 (3) = 23.321, p < 0.001. However, mean difference was not significantly different between Binge Level 2 and Binge Level 3 (0 < 1 < 2 = 3). Binge level groups showed significant differences in the number of button presses during the lab session (H(3) = 36.955, p < 0.001), peak breath alcohol concentration in the lab session (H(3) = 19.870, p < 0.001), and total binges in the TLFB (H(3) = 90.296, p < 0.001). Increased self-administration measures were proportional to the binge intensity level across groups, with no differences between Binge Level 2 and Binge Level 3 (0 < 1 < 2 = 3). For subjective measures, a Kruskal-Wallis H median test showed statistically significant differences between groups in the AUQ score following the priming infusion, H(3) = 11.489, p = 0.009, with bingers at all levels reporting higher scores compared to non-bingers (0 < 1 = 2 = 3). There was also a statistically significant difference between groups in the BAES Stimulation score following the priming infusion, H(3) = 9.023, p = 0.029, with differences seen between non-bingers and level 2 and level 3 bingers (0 = 1 < 2 = 3). DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrated that high intensity binge drinkers were more likely to reach binge level and overall greater alcohol consumption during a human lab alcohol administration study. Binge intensity level was also associated with higher stimulation and urge for alcohol following priming exposures, which may in turn drive the consumption of greater amounts of alcohol, which we know to be associated with greater risk for AUD.

Assessment of Skin Blood Flow Following Acute Intravenous Alcohol, and Association with Subjective Perceptions, in Social Drinkers.

The objective of this study was to determine the effect of acute intravenous (IV) alcohol infusion on skin blood flow (SBF) response, measured at fingertip and earlobe, and subjective responses associated with SBF in social drinkers. Twenty-four social drinkers underwent a computer-assisted alcohol self-infusion study. SBF was measured continuously using laser Doppler flow meter, with the probe placed on the fingertip or earlobe. Perfusion recordings were collected at baseline, and at 0-minute (0 to 5minutes), 10-minute (10 to 15minutes), and 20-minute (20 to 25minutes) time points during the priming phase of IV alcohol self-administration paradigm at low breath alcohol levels of approximately 30mg%. Subjective response was measured using the Drug Effects Questionnaire (DEQ) and Biphasic Alcohol Effects Scale. Overall SBF (collective data from both fingertip and earlobe) and SBF by each site showed significant drop at 0minutes and then subsequent significant elevation with alcohol self-administration. Males showed higher overall SBF at baseline and 0minutes than the females. At fingertip site, lowering in 0-minute SBF compared to baseline, and subsequent significant increase at the 10- and 20-minute SBF recordings were observed. DEQ measures of "like" and "want more" alcohol were significantly associated with 10- and 20-minute SBF recordings collected at fingertip site. The changes in SBF following acute IV alcohol exposure are consistent with the sympathetic response of alcohol on the cardiovascular system. This acute hemodynamic effect characterizes differences in blood flow that are sensitive to relatively low levels of acute alcohol exposure. The association of subjective perceptions with the SBF response provides evidence of the psychophysiological effects of alcohol at low levels of exposure.

Does Self-Reported or Behavioral Impulsivity Predict Subjective Response to Low-Dose Alcohol?

Subjective response to alcohol and impulsivity are both independent predictors of alcohol use and may be related risk factors for alcohol use disorders (AUDs). Recent findings suggest that more impulsive individuals may experience higher risk subjective response patterns at moderate-to-high doses of alcohol. However, whether these relationships are observable early in a drinking occasion remains an open question. This study examined multiple measures of impulsivity in relation to subjective response following low-dose alcohol. Eighty-seven non-treatment-seeking heavy drinkers were enrolled in a placebo-controlled alcohol administration study testing the effects of NMDA receptor antagonist, Memantine. Baseline impulsivity assessments included the Cued Go/No-Go Task, Experiential Discounting Task, and Barratt Impulsiveness Scale, Version 11 (BIS-11). Following consumption of low-dose alcohol aimed to increase blood alcohol concentration (BAC) to 0.03%, subjective stimulation and sedation were measured using the Biphasic Alcohol Effects Scale. Models were tested to relate impulsivity measures to subjective response with a post hoc exploratory model exploring boredom as an alternate predictor. Increases in stimulation and sedation were observed following low-dose alcohol, but were not predicted significantly by impulsivity measures. Although greater impulsivity on the BIS-11 was a trend-level predictor of increased sedation, post hoc analyses suggested these results were an artifact of boredom. Although impulsivity did not predict subjective response to low-dose alcohol, the results suggest that small amounts of alcohol can produce a range of subjective effects, even among heavy drinkers. Future studies would benefit by examining subjective response across a range of BACs among both light and heavy drinkers.

Using Baclofen to Explore GABA-B Receptor Function in Alcohol Dependence: Insights From Pharmacokinetic and Pharmacodynamic Measures.

Background: The role of GABA-B neurotransmission in addiction has recently received increased attention, with clinical trials indicating that baclofen, a GABA-B receptor agonist, may reduce alcohol consumption, craving and promote abstinence. However, the optimal dose to treat alcohol dependence is unclear with patients requesting and tolerating much higher doses of baclofen, compared with other clinical uses. We assessed the pharmacokinetics and pharmacodynamics (PK/PD) of baclofen to provide insight into GABA-B sensitivity in this patient group, relative to controls.Methods: Male healthy volunteers (controls, n = 12) and abstinent alcohol dependent individuals (AD, n = 8) received single oral doses of baclofen or placebo in a 3-way crossover design. Controls received placebo/10 mg/60 mg baclofen in a randomized, double-blind design, AD received placebo/60 mg/90 mg baclofen in a single-blind design. PK/PD measures were recorded at baseline and multiple time-points up to 6 h post-dosing, including plasma baclofen, plasma growth hormone (GH), Subjective High Assessment Scale (SHAS) and biphasic alcohol effects scale (BAES). Repeated measures ANOVA analysis explored “change from baseline” dose, time, group, and interaction effects, t-tests compared peak effects.Results: Dose-dependent effects of baclofen on PK and PD measures were observed in both control and AD groups. Whilst there were no significant group differences in any baclofen PK parameters (t1/2, tmax, Cmax, AUC), marked differences in PD effects were clearly evident. In controls, 60 mg baclofen significantly increased total SHAS and BAES scores, and significantly increased plasma GH levels compared with placebo, with peak effects at 60–120 min, in line with its PK profile. In AD, 60 mg baclofen had limited effects on these parameters; SHAS scores, BAES scores and plasma GH levels were significantly blunted compared with controls (significant group*time interactions P = 0.0014, 0.0015 and P < 0.0001, respectively).Conclusions: Our study shows blunted sensitivity to baclofen in AD relative to controls, with no difference in PK suggesting a lower GABA-B receptor sensitivity. This may explain why higher baclofen doses are requested and tolerated in the treatment of alcohol dependence. Our data has implications for choice of dose in future clinical trials in AD and possibly other substances of dependence.

The Role of Impulsivity and Expectancies in Predicting Marijuana Use: An Application of the Acquired Preparedness Model

ABSTRACTImpulsivity and substance use covary. Smith and Anderson’s acquired preparedness model proposes that impulsivity predicts substance use through a mediational model such that substance use expectancies mediate the relation between impulsivity and drug use. The present study seeks to examine the relation between positive urgency, an important component of impulsivity with specific relations to substance use behavior, marijuana expectancies, and marijuana use patterns. The study focused on a sample of frequent marijuana users (n = 3,616) and assessed positive urgency using the UPPS-P, expectancies using the Biphasic Marijuana Effects Scale, an adapted form of the Biphasic Alcohol Effects Scale to measure the sedative and stimulant properties of marijuana, and also assessed use patterns. Findings suggest that stimulant expectancies predict heavier, more frequent marijuana use than sedative expectancies and that marijuana expectancies vary based on the limb of marijuana intoxication. Examination of the acquired preparedness model revealed that positive urgency’s link to marijuana use was fully mediated by expectancies.

Faster alcohol metabolism is associated with increased stimulation and within session consumption.

Variability in subjective response (SR) to alcohol predicts drinking and the development of Alcohol Use Disorders (AUDs). Although both alcohol pharmacokinetics (i.e., absorption and metabolism) and SR are impacted by aspects of the drinking situation (e.g., rate of consumption), relations between individual differences in pharmacokinetics and SR have received little attention. The current study examined the extent to which alcohol pharmacokinetics impact SR and drinking during a single alcohol administration session. A total of 119 (67% male) social drinkers were administered a dose of alcohol with a target blood alcohol concentration (BAC) of 0.08g%. The Biphasic Alcohol Effects Scale was administered twice at matched ascending and descending limb BACs following alcohol consumption to assess SR. Pharmacokinetic properties (absorption and metabolism) were inferred using multiple BAC readings to calculate the area under the curve during the ascending limb (absorption) and descending limb (metabolism). Following completion of SR measures, an ad libitum taste rating task utilizing nonalcoholic beer was implemented to assess voluntary 'alcohol' consumption. Results indicated that participants who metabolized alcohol more quickly maintained a greater level of subjective stimulation on the descending limb. Faster metabolism was indirectly related to ad lib nonalcoholic beer consumption through greater maintenance of stimulant effects. Absorption did not significantly predict SR or within session drinking. The results increase understanding of SR variability and suggest that heightened stimulation that is sustained across limbs of the BAC curve may increase risk for excessive consumption. Individual differences in alcohol metabolism may be an identifiable biomarker of this high risk pattern of SR. (PsycINFO Database Record

GRIK1 and GABRA2 Variants Have Distinct Effects on the Dose-Related Subjective Response to Intravenous Alcohol in Healthy Social Drinkers.

The heritable risk for alcohol use disorder (AUD) is expressed partly through alterations in subjective alcohol response. In this study, we investigated the effects of 2 AUD-risk-associated single nucleotide polymorphisms, GABRA2 rs279858 and GRIK1 rs2832407, on the subjective response to alcohol administered intravenously to healthy social drinkers in a laboratory setting. In total, 93 self-identified European American social drinkers underwent 3 blinded laboratory sessions in which they received intravenous infusions of ethanol at 3 target blood alcohol levels (0.00mg%, 40mg%, and 100mg%) using a "clamp" procedure. The self-reported Biphasic Alcohol Effects Scale (BAES) stimulation and sedation subscales were the primary outcome measures. We examined the effects of these 2 genetic variants on subjective response to alcohol. For the BAES stimulation subscale scores, adjusting for age, baseline scores, and time effects, individuals with 2 copies of the GABRA2 rs279858 C "risk" allele for AUD exhibited the greatest stimulant responses to high-dose alcohol compared to the other risk allele counts (dose-by-allele count interaction effect, p=0.001, post hoc contrast for C-allele, p=0.012). For the BAES sedation subscale scores, adjusting for the same covariates, we detected a dose-by-allele count interaction effect (p=0.0044) such that subjects with 2 copies of the GRIK1 C "risk" allele reported the greatest sedative response to the higher alcohol dose. This study suggests that gene variants contributing to the risk for AUD may alter features of the alcohol dose-response relationship in specific ways. GABRA2 rs279858*C enhances stimulant responses to higher levels of alcohol, while the GRIK1 rs2832407*C-allele increases sedative responses. In summary, GRIK1 and GABRA2 variants have distinct effects on the dose-related subjective response to intravenous alcohol in humans.

Alcohol Stimulation and Sedation: a Critical Review of the Biphasic Alcohol Effects Scale

Purpose of Review The Biphasic Alcohol Effects Scale (BAES) is widely used to assess stimulant and sedative alcohol effects. This paper reviews (a) recent measurement developments, (b) behavioral and physiological correlates, and (c) the role of the BAES in refining theories of SR and pharmacological interventions.

A cis-eQTL in OPRM1 is Associated with Subjective Response to Alcohol and Alcohol Use.

A functional polymorphism within the μ-opioid receptor (OPRM1) gene, rs1799971 (A118G), previously has been associated with measures of alcohol use and sensitivity to its effects, but findings have been inconclusive. A recent study suggested that a second nearby variant within OPRM1, rs3778150, is robustly associated with heroin dependence and fully explained a smaller observed association with rs1799971. Given evidence that the rs3778150-C allele is associated with decreased OPRM1 expression levels in the human brain, the current study sought to test the hypothesis that rs3778150 represents a causal variant within OPRM1 that increases risk for a variety of alcohol use phenotypes. Participants with genotype and phenotype data from a larger experimental study (N=152) were assessed on measures of subjective response to alcohol and alcohol use. Measures included (i) the Self-Rating of the Effects of Alcohol and the Alcohol Sensitivity Questionnaire, (ii) the Biphasic Alcohol Effects Scale (BAES) and ratings of subjective intoxication, and (iii) average number of drinks per week in the past month. Compared to rs3778150-T homozygous individuals, carriers of the rs3778150-C allele exhibited significantly lower retrospective self-report levels of alcohol sensitivity. Carriers of the rs3778150-C allele also exhibited lower levels of BAES alcohol-related stimulation during an alcohol challenge and reported higher levels of drinking in the last 30days. With the exception of lower levels of BAES alcohol-related sedation, the rs1799971 variant did not show consistent significant association with any of the alcohol phenotypes in the presence of rs3778150. Results suggest that rs3778150 may be causally related to alcohol use phenotypes, and could potentially account for previously observed associations of rs1799971 with substance use phenotypes. Future studies may investigate potential causal relations among genetic variants in OPRM1, subjective response to alcohol, and drinking phenotypes to further delineate the effects of rs3778150.

Effects of caffeine on alcohol reinforcement: beverage choice, self-administration, and subjective ratings.

Combining alcohol and caffeine is associated with increased alcohol consumption, but no prospective experimental studies have examined whether added caffeine increases alcohol consumption. This study examined how caffeine alters alcohol self-administration and subjective reinforcing effects in healthy adults. Thirty-one participants completed six double-blind alcohol self-administration sessions: three sessions with alcohol only (e.g., beverage A) and three sessions with alcohol and caffeine (e.g., beverage B). Participants chose which beverage to consume on a subsequent session (e.g., beverage A or B). The effects of caffeine on overall beverage choice, number of self-administered drinks, subjective ratings (e.g., Biphasic Alcohol Effects Scale), and psychomotor performance were examined. A majority of participants (65%) chose to drink the alcohol beverage containing caffeine on their final self-administration session. Caffeine did not increase the number of self-administered drinks. Caffeine significantly increased stimulant effects, decreased sedative effects, and attenuated decreases in psychomotor performance attributable to alcohol. Relative to nonchoosers, caffeine choosers reported overall lower stimulant ratings and reported greater drinking behavior prior to the study. Although caffeine did not increase the number of self-administered drinks, most participants chose the alcohol beverage containing caffeine. Given the differences in subjective ratings and pre-existing differences in self-reported alcohol consumption for caffeine choosers and nonchoosers, these data suggest that decreased stimulant effects of alcohol and heavier self-reported drinking may predict subsequent choice of combined caffeine and alcohol beverages. These predictors may identify individuals who would benefit from efforts to reduce risk behaviors associated with combining alcohol and caffeine.

Alcohol-Induced Stimulation Mediates the Effect of a GABRA2 SNP on Alcohol Self-Administrated among Alcohol-Dependent Individuals.

A single-nucleotide polymorphism (SNP) in GABRA2 (rs279858) may moderate subjective response (SR) to alcohol. Results of studies in non-dependent drinkers examining this GABRA2 SNP on SR have been equivocal. This study examined this SNP's direct and indirect effects on alcohol self-administration in dependent drinkers. The sample consisted of 63 Caucasian, non-treatment-seeking individuals with alcohol dependence. Subjective stimulation was assessed using the Biphasic Alcohol Effects Scale following consumption of an alcoholic priming drink (targetbreath alcohol content=0.02 g%). Participants were subsequently offered the opportunity to self-administer up to eight additional drinks. Controlling for baseline stimulation, T-allele homozygotes, relative to individuals with at least one copy of the C-allele, reported greater initial stimulation, t(58)=2.011, p=0.049. Greater stimulation predicted greater subsequent alcohol self-administration, t(57)=2.522, p=0.015. Although rs279858 genotype did not directly impact self-administration (t(57)=-0.674, p=0.503), it did have an indirect effect (95% confidence interval [0.068, 1.576]), such that T-allele homozygotes reported greater stimulation, which in turn predicted greater self-administration. These results suggest that the influence of this SNP on SR differs depending on dose or stage of dependence. This study is the first to demonstrate an indirect effect of rs279858 genotype on drinking through SR. Although C-allele carriers have been shown to have an increased risk for alcohol dependence, in our dependent sample, greater stimulation was found among T-allele homozygotes, suggesting that the influence of SR on developing and maintaining dependence differs based on rs279858 genotype.This study demonstrates an indirect effect of rs279858 genotype on drinking through SR. Although C-allele carriers have an increased risk for alcohol dependence, in our dependent sample, greater stimulation was found among T-allele homozygotes, suggesting that the influence of SR on developing dependence differs based on rs279858 genotype.

The Alcohol Sensitivity Questionnaire: Evidence for Construct Validity.

Variability in sensitivity to the acute effects of alcohol is an important risk factor for the development of alcohol use disorder (AUD). The most commonly used retrospective self-report measure of sensitivity, the Self-Rating of the Effects of Alcohol (SRE) form, queries a limited number of alcohol effects and relies on respondents' ability to recall experiences that might have occurred in the distant past. Here, we investigated the construct validity of an alternative measure that queries a larger number of alcohol effects, the Alcohol Sensitivity Questionnaire (ASQ), and compared it to the SRE in predicting momentary subjective responses to an acute dose of alcohol. Healthy young adults (N = 423) completed the SRE and the ASQ and then were randomly assigned to consume either alcohol or a placebo beverage (between-subjects manipulation). Stimulation and sedation (Biphasic Alcohol Effects Scale) and subjective intoxication were measured multiple times after drinking. Hierarchical linear models showed that the ASQ reliably predicted each of these outcomes following alcohol but not placebo consumption, provided unique prediction beyond that associated with differences in recent alcohol involvement, and was preferred over the SRE (in terms of model fit) in direct model comparisons of stimulation and sedation. The ASQ compared favorably with the better-known SRE in predicting increased stimulation and reduced sedation following an acute alcohol challenge. The ASQ appears to be a valid self-report measure of alcohol sensitivity and therefore holds promise for identifying individuals at-risk for AUD and related problems.

High cortisol responders to stress show increased sedation to alcohol compared to low cortisol responders: An alcohol dose–response study

AimsThe present study was designed to examine the relationship between high and low cortisol response to an acute stressful situation and the subjective effects after different doses of alcohol, in healthy social drinkers. MethodSixty-four subjects (32 men and 32 women) participated in one laboratory session. They performed a modified version of the Trier Social Stress Test (TSST) immediately before consumption of either placebo or alcohol (0.2, 0.4 or 0.8g/kg). Subjects in each dose group were then divided into high (HCR; n=32) or low (LCR; n=32) cortisol responders. Primary dependent measures were self-report questionnaires of mood. ResultsThe HCR reported increased ratings on Sedation on the Biphasic Alcohol Effects Scale (BAES) with increased dose in comparison with the LCR. This increase in sedation also correlated to the increase in cortisol levels. ConclusionWe conclude that a high cortisol response to stress modulates the subjective response to alcohol, dose-dependently. HCR subjects experience increased sedative effects of alcohol after consumption of higher doses of alcohol following stress compared to LCR subjects.

Different Subjective and Objective Responses to Alcohol Among Heavy and Light Drinkers of Han and Uyghur Nationalities in China.

Given the observed differences in alcohol consumption characteristics between the Han and Uyghur nationalities in clinical reports and in daily life, the subjective and objective responses to alcohol in heavy drinkers (HDs) and light drinkers (LDs) in the Han and Uyghur nationalities in China were compared. A within-subject, double-blind, placebo-controlled human laboratory paradigm was performed. Each subject completed three experimental sessions in random order. Biphasic Alcohol Effects Scale and Positive and Negative Affect Schedule scales were administered, and heart rate (HR), blood pressure, and salivary cortisol levels were measured at predrink baseline and 30, 60, 120, and 180 minutes after the initial alcohol beverage consumption. Compared with LDs, HDs exhibited higher stimulation, positive affect, and lower sedation in both ethnicities. Han drinkers (both HDs and LDs) exhibited higher sedation and lower positive affect and stimulation than Uyghur drinkers after consumption of alcohol. Moreover, HDs exhibited more HR increase during the ascending limb of breath alcohol content (p < .05) and less cortisol level during the declining limb of breath alcohol content (p < .05). Both HDs and LDs exhibited decreased systolic and diastolic pressures for both high- and low-dose beverages (ps < .01). Compared with LDs, HDs exhibited more HR increase and lower salivary cortisol level after alcohol consumption. Han drinkers (both HDs and LDs) exhibited higher sedation and lower positive affect and stimulation after consumption of alcohol as compared with Uyghur drinkers. This modality of subjective and physiological responses to alcohol in the Han and Uyghur ethnicities is similar.

Effect of GABA Extract of Black Sticky Rice with Giant Embryo on Alcohol-Related Indices After Acute Alcohol Intake in Social Drinkers.

This study was performed to evaluate the effect and safety of a high-gamma-aminobutyric acid-containing extract (GABA extract) of black sticky rice with giant embryo (BSRGE) on alcohol-related indices after acute alcohol intake in social drinkers. Subjects were randomized to the GABA extract (G) group, GABA extract and alcohol drinking (GA) group, or placebo intake and alcohol drinking (PA) group in a double-blind design. All subjects were administered GABA extract (200mg GABA) or placebo at 9 am on study days 2 and 3, respectively. Subjects in the GA and PA groups were administered an equivalent dose of alcohol that was diluted in a drinking beverage for a total amount of 240ml at 11 am on day 3. Blood alcohol concentration (BAC) and the Biphasic Alcohol Effects Scale were measured just before alcohol drinking, and 6 times after alcohol drinking. The peak and area under the curve (AUC) of the total stimulation scale score after alcohol intake in females were significantly higher in the GA than in the PA group, whereas no significant difference was found between the 2 groups in males. The peak and AUC of the total score on the sedation scale after alcohol intake in males were significantly lower in the GA than in the PA group, whereas both were significantly higher in the GA than in the PA group of females. The AUC for BAC in males was significantly lower in the GA than in the PA group, whereas no significant difference was found in females. No adverse events were reported in any of the groups including the G group. Coadministration of a GABA extract to social drinkers while drinking alcohol is supposed to affect alcohol-related indices in terms of pharmacodynamics and pharmacokinetics and did not induce any adverse events.

Factor Structure of Subjective Responses to Alcohol in Light and Heavy Drinkers.

Subjective responses (SRs) to alcohol have been implicated in alcoholism etiology, yet less is known about the latent factor structure of alcohol responses. The aim of this study was to examine the factor structure of SR using a battery of self-report measures during a controlled alcohol challenge. Nontreatment seeking drinkers (N=242) completed an intravenous alcohol challenge including the following SR measures: Biphasic Alcohol Effects Scale, Subjective High Assessment Scale, Profile of Mood States, Alcohol Urge Questionnaire, and single items assessing alcohol "Liking" and "Wanting." Ascending limb target breath alcohol concentrations were 0.02, 0.04, and 0.06, and descending limb target was 0.04g/dl. Exploratory factor analyses were conducted separately on estimates of mean and dose responses on the ascending limb and on descending limb data. To examine the generalizability of this factor structure, these analyses were repeated in heavy drinkers (≥14 drinks/wk for men, ≥7 for women; n=132) and light drinkers (i.e., nonheavy drinkers; n=110). In the full sample, a 4-factor solution was supported for ascending limb mean and dose responses and descending limb data representing the following SR domains: Stimulation/Hedonia, Craving/Motivation, Sedation/Motor Intoxication, and Negative Affect. This 4-factor solution was replicated in heavy drinkers. In light drinkers, however, SR was better summarized by a 3-factor solution where ascending mean and descending limb responses consisted of Stimulation/Hedonia, Craving/Motivation, and a general negative valence factor, and dose responses consisted of a general positive valence factor, Sedation/Motor Intoxication, and Negative Affect. These findings suggest that SR represents a multifaceted construct with consistent factor structure across both ascending and descending limbs. Further, as drinking levels escalate, more defined Craving/Motivation and negative valence dimensions may emerge. Longitudinal studies examining these constructs are needed to further our understanding of SR as potentially sensitive to alcohol-induced neuroadaptation.