Peak Breath Alcohol Concentration Research Articles

Free-access intravenous alcohol self-administration in social drinkers and individuals with alcohol use disorder: Evaluation of relationships with phosphatidylethanol and self-reported alcohol consumption.

The free-access (FA) intravenous alcohol self-administration (IV-ASA) paradigm is an experimental approach that can identify modulators of alcohol consumption in humans. Moreover, the outcome measures of IV-ASA paradigms are associated with self-reported alcohol intake using the timeline follow-back method (TLFB). To evaluate how FA IV-ASA reflects drinking in real life, we examined the relationship between an objective marker of recent alcohol intake, phosphatidylethanol in blood (B-PEth), and TLFB and measures obtained during IV-ASA in individuals with alcohol use disorder (AUD) and social drinkers (SD). We also explored the associations between these measures and gut-brain peptides involved in AUD pathophysiology. Thirty-eight participants completed a laboratory session in which they self-administered alcohol intravenously. The safety limit was 200 mg%, and main outcomes were mean and peak breath alcohol concentrations (BrAC). Blood samples were drawn prior to IV-ASA and subjective alcohol effects were rated during the experiment. The study sample comprised 24 SD and 14 participants with DSM-5 mild AUD. Although BrACs were not associated with B-PEth or TLFB in the full sample or AUD subgroup, there was an association with TLFB in SD. In both subgroups, BrACs were associated with alcohol craving but with differential timing. Total ghrelin levels were higher in AUD participants than in SD. No associations between B-PEth levels and achieved BrACs were observed in the mild AUD group, the SD group, or the full sample. The ability for FA IV-ASA to reflect recent drinking was confirmed only for TLFB in SD, whereas there were no associations within the smaller subsample of participants with mild AUD or in the full sample. Further studies that include a larger AUD sample are warranted. The association of BrACs with craving for alcohol suggests that the IV-ASA method may be useful for assessing interventions that target craving. This could be explored by using the FA IV-ASA model to evaluate the effects on craving of approved pharmacotherapies for AUD.

The effects of post-learning alcohol ingestion on human motor memory consolidation.

The neurochemical mechanisms underlying motor memory consolidation remain largely unknown. Based on converging work showing that ethyl alcohol retrogradely enhances declarative memory consolidation, this work tested the hypothesis that post‐learning alcohol ingestion would enhance motor memory consolidation. In a within‐subject and fully counterbalanced design, participants (n = 24; 12M; 12F) adapted to a gradually introduced visual deviation and ingested, immediately after adaptation, a placebo (PBO), a medium (MED) or high (HIGH) dose of alcohol. The alcohol doses were bodyweight‐ and gender‐controlled to yield peak breath alcohol concentrations of 0.00% in the PBO, ~0.05% in the MED and ~0.095% in the HIGH condition. Retention was evaluated 24 h later through reach aftereffects when participants were sober. The results revealed that retention levels were neither significantly nor meaningfully different in both the MED and HIGH conditions as compared to PBO (all absolute Cohen's dz values < ~0.2; small to negligible effects), indicating that post‐learning alcohol ingestion did not alter motor memory consolidation. Given alcohol's known pharmacological GABAergic agonist and NMDA antagonist properties, one possibility is that these neurochemical mechanisms do not decisively contribute to motor memory consolidation. As converging work demonstrated alcohol's retrograde enhancement of declarative memory, the present results suggest that distinct neurochemical mechanisms underlie declarative and motor memory consolidation. Elucidating the neurochemical mechanisms underlying the consolidation of different memory systems may yield insights into the effects of over‐the‐counter drugs on everyday learning and memory but also inform the development of pharmacological interventions seeking to alter human memory consolidation.

Haven't lost the positive feeling: a dose-response, oral alcohol challenge study in drinkers with alcohol use disorder.

Models of addiction are based on neurobiological, behavioral, and pharmacological studies in animals, but translational support from human studies is limited. Studies are lacking in examining acute responses to alcohol in drinkers with alcohol use disorder (AUD), particularly in terms of relevant intoxicating doses and measurement of stimulating and rewarding effects throughout the breath alcohol concentration (BrAC) time curve. Participants were N = 60 AUD drinkers enrolled in the Chicago Social Drinking Project and examined in three random-order and blinded sessions for subjective and physiological responses to a beverage containing 0.0 g/kg, 0.8 g/kg, and 1.2 g/kg alcohol. BrAC in the alcohol sessions at 60 min was 0.09 g/dL and 0.13 g/dL, respectively. Both doses of alcohol produced significant biphasic effects on subjective measures of stimulation, euphoria, reward (liking and wanting), sedation, and neuroendocrine and cardiovascular factors. Increased pleasurable effects of alcohol were pronounced during the rising limb-to-peak BrAC and sedating effects emerged during the declining limb. Alcohol dose-dependently increased feel drug ratings and rewarding effects at peak BrAC or early declining limb, and physiological responses at the rising limb. Thus, rather than the notion of an overall tolerance, results show an alcohol response phenotype characterized by sensitivity to alcohol's stimulating, rewarding and physiological effects. The results of this study may aid in the conceptualization of alcohol addiction as a disorder characterized by the persistence of enhanced hedonic alcohol responses rather than chronic tolerance and reward deficiency.

The Motivation for Alcohol Reward: Predictors of Progressive-Ratio Intravenous Alcohol Self-Administration in Humans.

The Progressive Ratio (PR) self-administration paradigm is a common pre-clinical method used to examine the motivation for a drug attributed to a craving, reward, or the relief of negative affect. The Computer-assisted Alcohol Infusion System (CAIS) enables intravenous alcohol self-administration behavior in humans. This system provides the investigator with control over the trajectory of each incremental breath alcohol concentration (BrAC) reward and the maximum BrAC allowed in a session. This paradigm allows participants to earn these alcohol rewards using a sequence of button presses specified by the investigator. The system employs a physiologically-based pharmacokinetic model-based algorithm to achieve the same incremental BrAC exposure in every participant. Participants (n = 11) took part in two identical sessions to examine test-retest reliability, and an additional group (n = 73) completed a single session. Sessions began with a 25 min priming phase: participants were instructed to press a button an increasing number of times per reward, accumulating four standardized incremental BrAC trajectories. The second phase comprised an ad-lib, PR paradigm lasting 125 min. Each reward required an increasing number of button presses. Measures of self-administration included: average and peak BrAC, total rewards earned, total grams of ethanol consumed per unit of total body water, the total number of button presses, and the average rate of button pressing. Self-administration measures were highly correlated both between and within sessions, demonstrating test-retest reliability and internal consistency. Recent drinking history was strongly associated with self-administration measures; heavier drinkers chose greater alcohol self-administration. These results indicate the reliability and sensitivity of this progressive-ratio intravenous alcohol self-administration method for assessing the motivational properties of alcohol, with the potential for improved testing of the efficacy of new medications thought to reduce consumption of alcohol. This method can be used to understand the genetic and environmental determinants of alcohol self-administration in humans.

The Motivation for Alcohol Reward: Predictors of Progressive-Ratio Intravenous Alcohol Self-Administration in Humans

The Progressive Ratio (PR) self-administration paradigm is a common pre-clinical method used to examine the motivation for a drug attributed to a craving, reward, or the relief of negative affect. The Computer-assisted Alcohol Infusion System (CAIS) enables intravenous alcohol self-administration behavior in humans. This system provides the investigator with control over the trajectory of each incremental breath alcohol concentration (BrAC) reward and the maximum BrAC allowed in a session. This paradigm allows participants to earn these alcohol rewards using a sequence of button presses specified by the investigator. The system employs a physiologically-based pharmacokinetic model-based algorithm to achieve the same incremental BrAC exposure in every participant. Participants (n = 11) took part in two identical sessions to examine test-retest reliability, and an additional group (n = 73) completed a single session. Sessions began with a 25 min priming phase: participants were instructed to press a button an increasing number of times per reward, accumulating four standardized incremental BrAC trajectories. The second phase comprised an ad-lib, PR paradigm lasting 125 min. Each reward required an increasing number of button presses. Measures of self-administration included: average and peak BrAC, total rewards earned, total grams of ethanol consumed per unit of total body water, the total number of button presses, and the average rate of button pressing. Self-administration measures were highly correlated both between and within sessions, demonstrating test-retest reliability and internal consistency. Recent drinking history was strongly associated with self-administration measures; heavier drinkers chose greater alcohol self-administration. These results indicate the reliability and sensitivity of this progressive-ratio intravenous alcohol self-administration method for assessing the motivational properties of alcohol, with the potential for improved testing of the efficacy of new medications thought to reduce consumption of alcohol. This method can be used to understand the genetic and environmental determinants of alcohol self-administration in humans.

A meta-regression of methodological features that predict the effects of medications on the subjective response to alcohol.

Alcohol administration paradigms have been used for early efficacy testing of novel compounds for alcohol use disorder (AUD). There has been an ongoing debate about sample characteristics and methodological features that affect the likelihood of detecting an early efficacy signal for AUD medications. We conducted a meta-regression to test whether the drinking level of the study sample and the peak breath alcohol concentration (BrAC) in the alcohol administration study predict the efficacy of AUD pharmacotherapies on the subjective responses to alcohol. We computed the effects of 21 medications on alcohol-induced stimulation, sedation, negative mood, and craving during alcohol administration in49studies. Meta-regression analyses indicated a significant and positive effect of pre-study drinks per month on alcohol-induced stimulation (β=0.142, p<0.0001), such that as drinking increases, the benefit of medication over placebo decreases. There was an effect of drinks per month on negative mood (β=-0.164, p=0.0248), such that at higher levels of drinks per month, the effects of medications on negative mood are stronger. For sedation, there was an effect of peak BrAC (β=0.119, p=0.0002), such that at low levels of peak BrAC, the effects of medication on sedation were null. For craving, there was a peak BrAC×drinks per month interaction such that at low levels of BrAC, a heavier drinking sample is required to detect the effects of medication on craving. Sensitivity analyses comparing naltrexone studies and non-naltrexone studies suggested that naltrexone was less sensitive to drinks per month across subjective response domains. These analyses show that design features are critical in studies that test the effects of medications on the subjective responses to alcohol. By specifying the significance and directionality of these effects, as well as the specific points in BrAC or drinks per month at which medication effects are detectable, the study offers recommendations for design features of alcohol administration studies that aim to inform AUD medication development.

36344 Effect of CHRNA5 genetic variation and smoking on alcohol related phenotypes in healthy adult drinkers

ABSTRACT IMPACT: Understanding the influence of genetic variation and smoking on alcohol consumption helps in improving the treatment strategies for alcohol addiction OBJECTIVES/GOALS: Variation in the nicotinic receptor gene CHRNA5 (rs16969968) is associated with nicotine use and dependence, however its role in alcohol consumption is unclear. This study examined the effects of rs16969968 and smoking on alcohol related phenotypes in people without alcohol use disorder (AUD). METHODS/STUDY POPULATION: The study included 1,037 healthy adult drinkers without AUD (201 smokers, 836 non-smokers). A subset (n=161) participated in an Intravenous Alcohol Self-Administration (IV-ASA) laboratory session. Alcohol-related measures included Timeline Followback (TLFB), which measures drinking quantity and frequency in the past 90 days, and the Alcohol Use Disorders Identification Test (AUDIT), which measures alcohol use and consequences. IV-ASA measures included average and peak breath alcohol concentration (BrAC). The effect of rs16969968 was tested using a dominant model based on the presence of the A allele, and the influence of the rs16969968 polymorphism and smoking on alcohol phenotypes was assessed using t-tests and two-way ANOVA. RESULTS/ANTICIPATED RESULTS: There was a main effect of rs16969968 genotype with A-allele carriers (AA/AG) showing higher AUDIT-Dependence scores compared to the GG group. A main effect of smoking was observed on all the TLFB and AUDIT measures, with smokers showing greater alcohol consumption and problems compared to non-smokers. In the rs16969968 AA/AG group, smokers reported significantly more drinking days (p&lt;0.0001), and greater number of drinks (p&lt;0.0001), as well as higher AUDIT scores than non-smokers. IV-ASA measures did not show any difference between genotype groups or between smokers and non-smokers. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study identifies both independent and interactive effects of CHRNA5 gene variation and smoking on alcohol drinking measures and provides strong evidence for the effect of smoking on alcohol drinking and its consequences.

Wrist-worn alcohol biosensors: Applications and usability in behavioral research.

Wrist-worn alcohol biosensor technology has developed rapidly in recent years. These devices are light, easy to wear, relatively inexpensive, and resemble commercial fitness trackers. As a result, they may be more suitable for a wide range of clinical and research applications. In this paper, we describe three pilot projects examining the associations between reported drinking behavior and transdermal alcohol concentration (TAC) derived from a new, wrist-worn alcohol biosensor (BACtrack Skyn) in diverse participant groups and settings. Study 1 (N=3) compared Skyn-derived TAC with that from an ankle-worn alcohol sensor (SCRAM CAM) and breath alcohol concentration (BrAC) in a laboratory setting. Study 2 (N=10) compared Skyn TAC with BrAC during a naturalistic drinking episode in the field. Study 3 (N=12) used the Skyn to monitor alcohol use in the field for 2 weeks. Studies 2 and 3 also collected usability and acceptability data from participants. The results of Study 1 showed that the Skyn produced a TAC curve that closely resembled that of the validated SCRAM CAM anklet. In Study 2, Skyn detected drinking for all 10 participants (peak BrAC range: 0.02-0.21) with an average delay of 35.6±10.2min after the start of self-reported drinking. In Study 3, Skyn reliably recorded continuous TAC data showing multiple drinking episodes over the monitoring period. Participants in Studies 2 and 3 both reported Skyn as highly acceptable. Collectively, the results of these pilot studies show that the Skyn was able to reliably detect drinking events in the laboratory and natural environments. We offer suggestions for further refinements of alcohol biosensors and accompanying analytic software that may facilitate adoption of these devices as cost-effective, user-friendly, and reliable tools to passively and accurately assess alcohol use in the field.

Circadian regulation of breath alcohol concentration.

The role of the circadian clock in regulating blood/breath alcohol levels after consuming alcohol is uncertain. Our goal was to evaluate the degree to which the circadian system regulates breath alcohol concentration (BrAC) pharmacokinetic parameters. Twenty healthy adults aged 21-30 years took part in a 4-day laboratory study. A 40-h constant routine procedure was used to assess circadian rhythms. Every 4 h, participants were given a fixed oral dose of alcohol with breathalyzer measurements taken every 5 min to construct BrAC curves. Sinusoidal models were used to test for circadian variation of the peak BrAC, the time to reach peak BrAC, the absorption rate, the elimination rate, and the time for BrAC to return to zero after alcohol was ingested. A significant circadian rhythm was detected for group-averaged peak BrAC values and the time for BrAC to return to zero, but not other BrAC variables. Peak BrAC values were lowest in the evening near the peak of the core body temperature rhythm and nadir of the salivary cortisol rhythm. Peak BrAC values increased during the night and reached their highest levels in the morning and afternoon. The time needed for BrAC to return to zero was also longest in the late morning and afternoon. The circadian system modulates some BrAC pharmacokinetic parameters. In normally entrained individuals, taking the same oral dose of alcohol at different times of day can result in different BrAC responses. These findings have potential implications for alcohol-related accidents and alcohol toxicity.

Effects of Alcohol, Condom Request Style, and State Anger on Men’s Condom Use Resistance

The purpose of this study was to examine the distal predictors (alcohol expectancies, adversarial heterosexual beliefs) and proximal predictors (alcohol intoxication, partner's condom use request style, state anger) of young men's condom use resistance (CUR). Young, male, non-problem drinking, inconsistent condom users (N = 297) completed an alcohol administration experiment. After completing background measures, participants were randomly assigned to receive a control or alcoholic beverage (target peak breath alcohol concentration = .08%). They then read a randomly assigned hypothetical sexual scenario in which their female partner requested to use a condom either indirectly, directly, or insistently. Participants' desire to have condomless sex, state anger, and both coercive and noncoercive CUR intentions were assessed. Path analyses demonstrated that alcohol intoxication directly predicted noncoercive CUR intentions. In addition, a moderated mediation pathway was found such that, relative to sober participants, intoxicated men's sexual aggression-related alcohol expectancies were positively associated with their state anger in response to the partner's condom use request. This increased anger was related to stronger noncoercive CUR intentions. Adversarial heterosexual beliefs both directly and indirectly predicted coercive and noncoercive CUR intentions. Path analysis demonstrated that alcohol intoxication increased intentions to resist condom use through noncoercive tactics. In addition, men's misogynistic attitudes and alcohol intoxication were associated with greater feelings of anger, which predicted stronger coercive and noncoercive CUR intentions.

The Association between Ethanol Elimination Rate and Hangover Severity.

Assessments in blood and saliva suggests that the amount of ethanol present in the first hours after alcohol consumption and into the following morning is associated with hangover severity. The current analysis determines how ethanol elimination rate is related to hangover severity reported throughout the day. n = 8 subjects participated in two studies. The first was a naturalistic study comprising an evening of alcohol consumption. Hangover severity was assessed hourly from 10 a.m. to 4 p.m., using a 1-item hangover severity scale ranging from 0 (absent) to 10 (extreme). The second study comprised a highly controlled alcohol challenge to reach a breath alcohol concentration (BrAC) of 0.05%. Breathalyzer tests were conducted every 5 min until BrAC reached zero. The ethanol elimination rate, expressed in BrAC%/hour, was computed by dividing the peak BrAC (%) by the time to BrAC of zero (h). At 11:00, 13:00, and 14:00, there were significant negative partial correlations, controlling for estimated BrAC, between ethanol elimination rate and hangover severity. The findings suggest that drinkers with a faster ethanol elimination rate experience less severe hangovers. The observations should be confirmed in a larger sample of subjects who participate in a single study that assesses both hangover severity and ethanol elimination rate.

The Effects of SJP-001 on Alcohol Hangover Severity: A Pilot Study.

Background. Despite a clear market need and many hangover products available, currently there is no hangover treatment that is supported by substantial scientific evidence demonstrating its efficacy and safety. A pilot study was conducted to investigate the effects of a potential new hangover treatment, SJP-001, and its constituents (220 mg naproxen and 60 mg fexofenadine) on hangover severity. Methods. N = 13 healthy social drinkers (36.3 ± 8.9 years old) participated in a double-blind, factorial design, cross-over study. On each test day, they consumed their own choice of alcohol up to a self-reported level sufficient to elicit a next-day hangover. Treatments were administered prior to onset of drinking. Next morning, hangover severity was assessed with the Acute Hangover Scale (AHS). Subjects were included in the efficacy analysis only if they reported a hangover after placebo. Results. N = 5 subjects (60% male, 35.2 ± 9.0 years old) were included in the analysis. They consumed a mean (SD) of 4.6 ± 1.1 units of alcohol and had an average peak breath alcohol concentration (BrAC) of 0.065% across conditions. Compared to placebo, SJP-001 significantly improved the AHS overall hangover severity score (0.8 ± 0.3 versus 1.5 ± 0.9, p = 0.042). Compared to placebo, SJP-001 also reduced scores on the individual item ‘hangover’, although the observed improvement (−1.6) did not reach statistical significance (p = 0.102). The differences from placebo after naproxen alone and fexofenadine alone were not statistically significant. SJP-001 also improved scores for the individual hangover symptoms tired, thirsty, headache, dizziness, nausea, and loss of appetite, but these effects did not reach statistical significance. Discussion. Compared to placebo, SJP-001 significantly reduced overall hangover severity. The effects of SJP-001 should be further examined in a double-blind, placebo-controlled trial with a larger sample size and controlled administration of sufficient amounts of alcohol to provoke a more substantial alcohol hangover.

3255 Association between dopaminergic genetic variants, COMTrs4680 and DRD2rs1076560, and alcohol consumption and reward behaviors in non-dependent drinkers

OBJECTIVES/SPECIFIC AIMS: The objective of this exploratory study is to evaluate the relationship between the individual genetic variants in COMTrs4680 and DRDrs1076560 and relevant alcohol use behaviors (i.e. alcohol consumption and reward processing behaviors) in non-dependent drinkers within experimentally controlled IV-ASA CAIS sessions. The overall goal of this study is to begin gathering data on the influence of individual genetic variants on alcohol consumption and other drinking-related behaviors. This will aid in the creation of a polygenic model of risk for AUD which will provide more insight into how the mesolimbic pathway is affected by alcohol use. METHODS/STUDY POPULATION: Study population: The sample included male and female non-dependent drinkers (N=149). Genotypes for functional polymorphisms in COMT (rs4680) and DRD2 (rs1076560) genes were determined for all subjects from blood samples obtained during screening. Alcohol consumption was assessed using the 90-day Timeline Followback Interviews (TLFB). Study population demographics: Self-reported gender (53.5% identified as male); Self-reported race (61.2% identified as white); Age ranged from 21-46 years old, with 22 years being the mode. Experiment: Free access (open-bar) intravenous alcohol self-administration (IV-ASA) using the computer-assisted alcohol infusion system (CAIS) paradigm; Subjects had the choice of pressing a button ad libitum for IV alcohol infusions during the session, neurobehavioral questionnaires were collected throughout the 2.5-hr alcohol infusion session. Primary outcome measures included: Total Rewards, Peak breath alcohol concentration (BrAC) achieved, and Total Ethanol consumed. Statistical Analyses: Conducted using SPSS IBM Statistics Versions 1.0.0-2482; non-dependent drinkers were organized into two groups based on their genotypes, minor allele carriers and major allele homozygotes. Outcome measures were compared between genotype groups using analysis of variance or non-parametric Mann-Whitney U-test as appropriate. RESULTS/ANTICIPATED RESULTS: -We expect the genetic makeup of the sample to be reflective of larger genome samples that are publically available (e.g. e!Ensembl) - Initial analysis for COMTrs4680 did not reveal significant effects on IV-ASA measures. Specifically, the majo DISCUSSION/SIGNIFICANCE OF IMPACT: Alcohol Use Disorder (AUD) affects millions of men and women globally. The heterogeneity within AUD individuals has made it difficult to identify biological and/or psychological factors that could be targeted for the development of treatments. By using the human laboratory model of free access IV-ASA, this study evaluated the relationship between dopaminergic genetic variants, COMTrs4680 and DRDrs1076560, and alcohol consumption in non-dependent drinkers within a controlled experimental environment. This study will begin to evaluate genetic and behavioral data that can be used to create a polygenic model of risk for AUD, which will provide more insight as to how the mesolimbic reward pathway is affected by alcohol use and contributes to 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 &lt; 0.001. However, mean difference was not significantly different between Binge Level 2 and Binge Level 3 (0 &lt; 1 &lt; 2 = 3). Binge level groups showed significant differences in the number of button presses during the lab session (H(3) = 36.955, p &lt; 0.001), peak breath alcohol concentration in the lab session (H(3) = 19.870, p &lt; 0.001), and total binges in the TLFB (H(3) = 90.296, p &lt; 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 &lt; 1 &lt; 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 &lt; 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 &lt; 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.

Applying a novel population-based model approach to estimating breath alcohol concentration (BrAC) from transdermal alcohol concentration (TAC) biosensor data.

Alcohol biosensor devices have been developed to unobtrusively measure transdermal alcohol concentration (TAC), the amount of ethanol diffusing through the skin, in nearly continuous fashion in naturalistic settings. Because TAC data are affected by physiological and environmental factors that vary across individuals and drinking episodes, there is not an elementary formula to convert TAC into easily interpretable metrics such as blood and breath alcohol concentrations (BAC/BrAC). In our prior work, we addressed this conversion problem in a deterministic way by developing physics/physiological-based models to convert TAC to estimated BrAC (eBrAC), in which the model parameter values were individually determined for each person wearing a specific transdermal sensor using simultaneously collected TAC (via a biosensor) and BrAC (via a breath analyzer) during a calibration episode. We found these individualized parameter values produced relatively good eBrAC curves for subsequent drinking episodes, but our results also indicated the models were not fully capturing the dynamics of the system and variations across drinking episodes. Here, we report on a novel mathematical framework to improve our ability to model eBrAC from TAC data that uses aggregate population data instead of individualized calibration data to determine model parameter values via a random diffusion equation. We first provide the theoretical mathematical basis for our approach, and then test the efficacy of this method using datasets of contemporaneous BrAC/TAC measurements obtained by a) a single subject during multiple drinking episodes and b) multiple subjects during single drinking episodes. For each dataset, we used a set of drinking episodes to construct the population model, and then ran the model with another set of randomly selected test episodes. We compared raw TAC data to model-simulated TAC curve, breath analyzer BrAC data to model eBrAC curve with 75% credible bands, episode summary scores of peak BrAC, times of peak BrAC, and area under the drinking curve also with 75% credible intervals, and report the percent of the raw BrAC captured within the eBrAC curve credible bands. We also display results when stratifying the data based on the relationship between the raw BrAC and TAC data. Results indicate the population-based model is promising, with better fit within a single participant when stratifying episodes. This study provides initial proof-of-concept for constructing, fitting, and using a population-based model to obtain estimates and error bands for BrAC from TAC. The advancements in this study, including new applications of math, the development of a population-based model with error bars, and the production of corresponding MATLAB codes, represent a major step forward in our ability to produce quantitatively- and temporally-accurate estimates of BrAC from TAC biosensor data.

Explicit Attitudes, Working Memory Capacity, and Driving After Drinking.

Attitudes toward driving after drinking are strongly predictive of drinking and driving behavior. This study tested working memory capacity (WMC) as a moderator of the association between attitudes and drinking and driving behavior. Consistent with dual process models of cognition, we hypothesized that the association between perceived danger and drinking and driving would be stronger for individuals with higher WMC. Participants (N=161) enrolled in larger alcohol administration study were randomly assigned to an alcohol (n=57), placebol (n=52), or control (n=52, not included) beverage condition. Past-year frequency of driving after drinking and WMC were assessed at baseline. Attitudes were assessed by asking participants to rate the perceived danger of driving at their current level of intoxication twice on the ascending limb (AL1, AL2), at peak breath alcohol concentration (BrAC), and twice on the descending limb (DL1, DL2). Analyses across the BrAC curve indicated that the hypothesized interaction was observed for the alcohol but not placebo condition. Analyses for each assessment point indicated that the interaction was significant for the ascending limb and peak BrAC. In the alcohol condition, for those higher in WMC, lower perceived dangerousness was strongly associated with increased driving after drinking (AL1: incident rate ratios [IRR]=5.87, Wald's χ2 =12.39, p=0.006, 95% CI [2.19, 15.75]; AL2: IRR=8.17, Wald's χ2 =11.39, p=0.001, 95% CI [2.41, 27.66]; Peak: IRR=5.11, Wald's χ2 =9.84, p=0.002, 95% CI [1.84, 14.16]). Associations were not significant at low WMC. Results suggest that individuals higher in WMC are more likely to act consistently with their explicit attitudes toward drinking and driving. Findings may have implications for existing drinking and driving interventions and suggest the potential for novel interventions targeting implicit associations or WMC.

Pairing neutral cues with alcohol intoxication: new findings in executive and attention networks.

Alcohol-associated stimuli capture attention, yet drinkers differ in the precise stimuli that become paired with intoxication. Extending our prior work to examine the influence of alcoholism risk factors, we paired abstract visual stimuli with intravenous alcohol delivered covertly and examined brain responses to these Pavlovian-conditioned stimuli in fMRI when subjects were not intoxicated. Sixty healthy drinkers performed task-irrelevant alcohol conditioning that presented geometric shapes as conditioned stimuli. Shapes were paired with a rapidly rising alcohol limb (conditioned stimulus; CS+) using intravenous alcohol infusion targeting a final peak breath alcohol concentration of 0.045g/dL or saline (CS-) infusion at matched rates. On day 2, subjects performed monetary delay discounting outside the scanner to assess delay tolerance and then underwent event-related fMRI while performing the same task with CS+, CS-, and an irrelevant symbol. CS+ elicited stronger activation than CS- in frontoparietal executive/attention and orbitofrontal reward-associated networks. Risk factors including family history, recent drinking, sex, and age of drinking onset did not relate to the [CS+ > CS-] activation. Delay-tolerant choice and [CS+ > CS-] activation in right inferior parietal cortex were positively related. Networks governing executive attention and reward showed enhanced responses to stimuli experimentally paired with intoxication, with the right parietal cortex implicated in both alcohol cue pairing and intertemporal choice. While different from our previous study results in 14 men, we believe this paradigm in a large sample of male and female drinkers offers novel insights into Pavlovian processes less affected by idiosyncratic drug associations.

2138 Susceptibility to social influence is associated with alcohol self-administration and subjective alcohol effects

OBJECTIVES/SPECIFIC AIMS: Peer groups are one of the strongest determinants of alcohol use and misuse. Furthermore, social influence plays a significant role in alcohol use across the lifespan. One of the factors that most consistently predicts successful treatment outcomes for alcohol use disorders is one’s ability to change their social network. However, the concept of social influence as defined by suggestibility or susceptibility to social influence has not yet been studied as it relates to drinking behavior and acute subjective response to alcohol. Our objective was to examine the relationship between suggestibility and alcohol consumption and responses, using an intravenous alcohol self-administration (IV-ASA) paradigm in social drinkers. METHODS/STUDY POPULATION: Healthy, social drinkers (n=20) completed a human laboratory session in which they underwent the IV-ASA paradigm. This consisted of an initial 25-minute priming phase, where participants were prompted to push a button to receive individually standardized IV alcohol infusions, followed by a 125-minute phase during which they could push the button for additional infusions. IV-ASA measures included the peak and average breath alcohol concentration (BrAC) and number of button presses. Subjective responses were assessed using the Drug Effects Questionnaire (DEQ) and Alcohol Urge Questionnaire (AUQ) collected serially during the session. Participants completed the Multidimensional Iowa Suggestibility Scale (MISS) to assess suggestibility. The Alcohol Effects Questionnaire (AEFQ) was used to assess alcohol expectancies and the Timeline Followback questionnaire measured recent drinking history. RESULTS/ANTICIPATED RESULTS: After controlling for drinking history, greater suggestibility significantly predicted greater average BrAC, greater peak BrAC, and a greater number of button presses (p=0.03, p=0.02, p=0.04, respectively) during the early open bar phase. Suggestibility significantly predicted subjective alcohol effects following the priming phase which included “Feel,” “Want,” “High,” and “Intoxicated” and was trending for “Like” (p=0.02, p=0.03, p=0.01, p=0.03, p=0.054, respectively) as well as AUQ (p=0.03). After controlling for drinking history, suggestibility significantly predicted “Feel,” “Like,” “High,” and “Intoxicated” peak scores during the open bar phase (p=0.03, p=0.009, p=0.03, p=0.03, respectively). There was no association between suggestibility and “Want More” alcohol. Suggestibility was positively associated with three positive expectancies (global positive; p=0.04, social expressiveness; p=0.005, relaxation; p=0.03), and one negative expectancy (cognitive and physical impairment; p=0.02). DISCUSSION/SIGNIFICANCE OF IMPACT: These results indicate that social drinkers that were more suggestible had higher alcohol consumption, greater acute subjective response to alcohol, and more positive alcohol expectancies. As such, susceptibility to social influence may be an important determinant of alcohol consumption, and may provide insight into harmful drinking behavior such as binge drinking. Future analyses should examine the impact of suggestibility on alcohol-related phenotypes across the spectrum of drinking from social to binge and heavy drinking patterns.

Preliminary evaluation of a human laboratory model of impaired control over alcohol using intravenous alcohol self-administration.

Impaired control over alcohol is central to alcohol use disorder, but most research on impaired control is limited to self-report methods. This study applied intravenous alcohol self-administration to conduct a preliminary investigation of a novel human laboratory model of impaired control. Heavy episodic drinkers (ages 19-22 years) completed a two-hour intravenous alcohol self-administration session that involved an incentive to maintain breath alcohol concentration below 80 mg%. Impaired control was operationalized based on whether participants exceeded (impaired control positive; IC+) or adhered to (impaired control negative; IC-) the breath alcohol concentration limit, as well as the discrepancy between intended and actual peak breath alcohol concentration. Analyses of subjective processes revealed that IC+ participants tended to underestimate their peak breath alcohol concentration relative to IC- participants. Further, IC+ reported greater craving after an initial priming phase, and craving mediated the relationship between self-report impaired control and discrepancies between intended and actual breath alcohol concentration. IC+ participants also showed stronger within-person associations between state changes in stimulation and momentary alcohol self-administration throughout the session. Laboratory impaired control indices demonstrated convergent validity with an established self-report measure of impaired control. These findings provide preliminary validation of a novel human laboratory model of impaired control in a sample of young heavy episodic drinkers, and offer insight into the role of subjective responses (craving, stimulation) in impaired control.

Acute Effects of Moderate Alcohol Consumption on Postural Stability in Older Adults.

This study involved healthy community-living older adults in an investigation of the association between moderate alcohol consumption (AC) and acute changes in postural stability and whether the association differed according to pre-AC balance skills. Thirty-nine moderate drinkers aged ≥ 65 years (62% women; mean age: 73.9 ± 6.1 years) consumed a moderate dose of alcohol (0.4 g/kg; administered as two drinks). Breath alcohol concentration and postural stability were measured at five time points (pre-AC and 40, 80, 120, and 160 minutes post-AC) using unipedal stance time (UPST) and center of pressure (CoP) displacement. Pre-AC UPST was used to categorize participants into good-balance (≥30 seconds) and poor-balance (<30 seconds) groups. Peak breath alcohol concentration was 30 mg/dL at 40 minutes post-AC. For all participants, postural stability declined significantly at 80 minutes post-AC (UPST, p = .005; anterior-posterior CoP displacement, p = .029). While the poor-balance group did not show a significant decrease in UPST duration over the course of the study, the good-balance group experienced significant decline at 80 minutes compared with baseline ( p < .001) and remained above the 30-second UPST cutoff. Both groups experienced similar worsening in anterior-posterior CoP displacement at 80 minutes post-AC. Thus, moderate AC was associated with acute decline in postural stability in older adults. The worsened anterior-posterior CoP displacement post-AC in the poor-balance group was of particular concern because these participants were already at lower balance functioning pre-AC. Larger, more representative studies of varying groups of participants are needed to further explore how this change relates to fall incidents and fall risk.