Comparison of Subjective Responses to Oral and Intravenous Alcohol Administration under Similar Systemic Exposures

Objective To test whether an individual's subjective responses to alcohol are similar when the breath alcohol concentration (BrAC) trajectory resulting from oral administration is matched by intravenous administration. Background Individuals perceive the effects of alcohol differently, and the variation is commonly used in research assessing the risk for developing an alcohol use disorder. Such research is supported by both oral and intravenous alcohol administration techniques, and any differences attributable to the route employed should be understood. Methods We conducted a 2‐session, within‐subject study in 44 young adult, healthy, non‐dependent drinkers (22 females and 22 males). In the first session, subjects ingested a dose of alcohol which was individually calculated, on the basis of total body water, to yield a peak BrAC near 80 mg/dl, and the resulting BrAC trajectory was recorded. A few days later, subjects received an intravenous alcohol infusion rate profile, pre‐computed to replicate each individual's oral alcohol BrAC trajectory. In both sessions, we assessed 4 subjective responses to alcohol: SEDATION, SIMULATION, INTOXICATION, and HIGH; at baseline and frequently for 4 hours. We compared the individuals’ baseline‐corrected responses at peak BrAC and at half‐peak BrAC on both the ascending and descending limbs. We also computed and compared Pearson‐product moment correlations of responses by route of administration, the Mellanby measure of acute adaptation to alcohol, and the area under the entire response curve for each subjective response. Results No significant differences in any measure could be attributed to the route of alcohol administration. Eleven of 12 response comparisons were significantly correlated across the routes of alcohol administration, with 9 surviving correction for multiple measures, as did the Mellanby effect and area under the response curve correlations. Conclusion The route of alcohol administration has a minimal effect on subjective responses to alcohol when an individual's BrAC exposure profiles are similar

Pairing Neutral Cues with Alcohol Intoxication: New Findings in Executive and Attention Networks

Rationale: Alcohol-associated stimuli capture attention, yet drinkers differ in the precise stimuli that become paired with intoxication. Objectives: 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. Methods: Sixty healthy drinkers performed task-irrelevant alcohol conditioning that presented geometric shapes as conditioned stimuli. Shapes were paired with a rapidly rising alcohol limb (CS+) using intravenous alcohol infusion targeting a final peak breath alcohol concentration of 0.045 g/dL or saline (CS−) infusion at matched rates. On day two, 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. Results: 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. Conclusions: 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

Correspondence on gender disparities in the initial psychological impact of the U.S. COVID-19 pandemic

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemicThe COVID-19 pandemic has led to a variety of mental health symptoms, including increased stress, depression, and anxiety, which may be worse in women. Gender-related factors, such as higher rates of mood disorders in women and differential utilization of coping strategies, may further exacerbate the pandemic's burden on women. Additionally, young and elderly groups may be more vulnerable to psychological distress due to COVID-19. Our aim was to examine gender differences in the psychological impact of the first month of the U.S. COVID-19 pandemic. We hypothesized that women would report worse psychosocial outcomes, prior mental health diagnosis and age would exacerbate gender differences, and there would be gender differences in the utilization of coping strategies. This study uses cross-sectional, self-report data, which relies on subjective experience and may limit generalizability. This study provides preliminary evidence that men and women may be experiencing the psychosocial impacts of the pandemic differently, which should be tracked overtime. Failing to address gender-specific implications of the pandemic may deepen disparities for women, highlighting the need to implement targeted interventions.This research was supported by funding from the office of the Vice President of Research at Indiana University Purdue University – Indianapolis

Laboratory alcohol self-administration experiments do not increase subsequent real-life drinking in young adult social drinkers

BACKGROUND: While the utility of experimental free-access alcohol self-administration paradigms is well established, little data exist addressing the question of whether study participation influences subsequent natural alcohol consumption. We here present drinking reports of young adults before and after participation in intravenous alcohol self-administration studies. METHODS: Timeline Follow-back drinking reports for the 6 weeks immediately preceding the first, and the 6 weeks after the last experimental alcohol challenge were examined from subjects completing 1 of 2 similar alcohol self-administration paradigms. In study 1, 18 social drinkers (9 females, mean age 24.1 years) participated in 3 alcohol self-infusion sessions up to a maximum blood alcohol concentration (BAC) of 160 mg%. Study 2 involved 60 participants (30 females, mean age 18.3 years) of the Dresden Longitudinal Study on Alcohol Use in Young Adults (D-LAYA), who participated in 2 sessions of alcohol self-infusion up to a maximum BAC of 120 mg%, and a nonexposed age-matched control group of 42 (28 females, mean age 18.4 years) subjects. RESULTS: In study 1, participants reported (3.7%) fewer heavy drinking days as well as a decrease of 2.5 drinks per drinking day after study participation compared to prestudy levels (p < 0.05, respectively). In study 2, alcohol-exposed participants reported 7.1% and non-alcohol-exposed controls 6.5% fewer drinking days at poststudy measurement (p < 0.001), while percent heavy drinking days and drinks per drinking day did not differ. CONCLUSIONS: These data suggest that participation in intravenous alcohol self-administration experiments does not increase subsequent real-life drinking of young adults

Alcohol Affects the P3 Component of an Adaptive Stop Signal Task ERP

BACKGROUND The P3 component of the event-related potential (ERP) has been particularly useful in alcohol research for identifying endophenotypes of alcohol use disorder (AUD) risk in sober subjects. However, practice and/or fatigue reduces P3 amplitude, limiting the ability to ascertain acute and adaptive effects of alcohol exposure. Here, we report acute alcohol effects on P3 amplitude and latency using an adaptive stop signal task (aSST). METHODS One hundred and forty eight nondependent moderate to heavy social drinkers, age 21 to 27, participated in 2 single-blind, alcohol or placebo, counterbalanced sessions approximately one week apart. During each session, subjects performed an adaptive stop signal task (aSST) at (1) baseline, (2) upon reaching the target 60 mg/dL breath alcohol concentration or at the equivalent time during the placebo session, and (3) approximately 135 minutes later while the breath alcohol concentration was clamped. Here, we report on differences between baseline and first subsequent measurements across the experimental sessions. During each aSST run, the stop signal delay (SSD, the time between stop and go signals) adjusted trial-by-trial based on the subject’s performance. RESULTS The aSST reliably generated a STOP P3 component that did not change significantly with repeated task performance. The pre-infusion SSD distribution was bimodal, with mean values several hundred msec apart (FAST: 153 msec and SLOW: 390 msec). This suggested different response strategies: FAST SSD favoring “going” over “stopping,” and SLOW SSD favoring “stopping” over “going”. Exposure to alcohol at 60 mg/dL differentially affected the amplitude and latency of the STOP P3 according to SSD group. Alcohol significantly reduced P3 amplitude in the SLOW SSD compared to FAST SSD group, but significantly increased P3 latency in the FAST SSD compared to SLOW SSD group. CONCLUSIONS The aSST is a robust and sensitive task for detecting alcohol induced changes in inhibition behavior as measured by the P3 component in a within subject design. Alcohol was associated with P3 component changes which varied by SSD group, suggesting a differential effect as a function of task strategy. Overall, the data support the potential utility of the aSST in the detection of alcohol response related AUD risk

Early Impact of the U.S. COVID-19 Pandemic on Drinking Motives and Alcohol Use

Background: The goal of this study was to empirically examine the degree to which alcohol use and drinking motives changed during the first month of the pandemic and to examine individual differences associated with such changes. Methods: A U.S. nationwide survey of 500 adults was conducted; data from 201 individuals (Mage=38.98, SD=12.04, 52.2% female, 76.1% White) who endorsed current alcohol use were included in this study. Results: Paired-samples t-tests indicated that there was a significant decrease in drinking quantity [t(199)=3.74, p<.001], but no change in drinking frequency [t(198)=0.19, p=.849] overall during the first month of the U.S. pandemic. There were significant decreases in enhancement [t(201)=4.55, p<.001], social [t(201)=9.39, p<.001] and conformity [t(201)=3.58, p<.001] motives, but a significant increase in coping motives [t(201)=-3.71, p<.001]. Regression analyses showed that increases in enhancement [β=0.46, p<.001] and coping [β=0.27, p=.004] motives were significantly related to increases in drinking frequency, and increases in coping motives [β=0.32, p=.002] were related to increases in drinking quantity. Riskier drinking prior to the pandemic was significantly related to greater increase in drinking quantity in the first month of the U.S. pandemic [β=0.31, p<.001]. Conclusion: Results of this study provide initial support that changes in drinking motives were important predictors for changes in alcohol use during the first month of the U.S. pandemic. Contrary to anecdotal reports, drinking decreased overall during the first month of the U.S. pandemic; however, those with existing risky patterns of drinking prior to the start of the U.S. pandemic were at greatest risk for drinking escalation during this time

Adolescent women induce lower blood alcohol levels than men in a laboratory alcohol self-administration experiment

Background Adolescence is a critical period for the development of alcohol use disorders; drinking habits are rather unstable and genetic influences, such as male sex and a positive Family History of alcoholism (FH), are often masked by environmental factors such as peer pressure. Methods We investigated how sex and FH modulate alcohol use in a sample of 18-19-year-olds from the Dresden Longitudinal Study on Alcohol use in Young Adults (D-LAYA). Adolescents reported their real-life drinking in a TimeLine Follow-Back (TLFB) interview. They subsequently completed a training and an experimental session of free-access intravenous Alcohol Self-Administration (i.v. ASA) using the computer-assisted alcohol infusion system in order to control for environmental cues as well as for biological differences in alcohol pharmacokinetics. During i.v. ASA, we assessed subjective alcohol effects at eight time points. Results Women reported significantly less real-life drinking than men and achieved significantly lower mean arterial Blood Alcohol Concentrations (aBACs) in the laboratory. At the same time, women reported greater sedation relative to men and rated negative effects as high as did men. A positive FH was associated with lower real-life drinking in men but not in women. In the laboratory, FH was not linked to i.v. ASA. Greater real-life drinking was significantly positively associated with higher mean aBACs in the laboratory, and all i.v. ASA indices were highly correlated across the two sessions. Conclusions We conclude that adolescent women chose lower aBACs because they experienced adverse alcohol effects, namely sedation and negative effects, at lower aBACs than men. A positive FH was not apparent as risk factor for drinking in our young sample. The i.v. ASA method demonstrated good external validity as well as test-retest reliability, the latter indicating that a separate training session is not required when employing the i.v. ASA paradigm

Stress Vulnerability And Alcohol Use And Consequences: From Human Laboratory Studies To Clinical Outcomes

It is well known that vulnerability to stress is a risk factor for alcohol use disorder (AUD). Chronic alcohol use can result in neuroadaptations in cortico-striatal pathways and hypothalamic pituitary adrenal (HPA) axis function that are manifested in altered behavioral and cognitive control functions contributing to alcohol craving, compulsive motivation, consumption and consequences. This symposium brings together studies utilizing novel approaches to help improve our understanding of stress – past, acute and chronic - on alcohol seeking and consumption and related outcomes using a combination of human laboratory models, neuroimaging and clinical measures. Examining factors that determine vulnerability as well as resilience to stress are of particular interest in the study of AUD because, in addition to increasing our understanding of the risk factors for AUD, such knowledge can be used to develop more effective treatments. Dr. Stangl presented a novel human experimental model that demonstrates, for the first time, stress-induced increases in alcohol self-administration in binge drinkers using a guided imagery paradigm combined with intravenous alcohol self-administration (IV-ASA). Dr. Blaine presented data demonstrating that glucocorticoid response to stress drives compulsive alcohol motivation and intake in binge/heavy drinkers. Dr. Plawecki presented data examining sex differences in the effect of two distinct stress paradigms – mood induction and abstinence – on IV-ASA in moderate drinkers. Dr. Schwandt presented clinical data providing a new perspective on the relationship between childhood trauma and AUD by suggesting possible underlying mechanisms that confer resilience, rather than vulnerability, to severe early life stress exposure

Sensation Seeking, Impulsivity, and Aggression Moderate Sex Effects on Adolescent Laboratory Binging

Sex, comprising biological and gender-related distinctions, is a known risk factor for alcohol use disorders. Moreover, sensation seeking, impulsivity, and aggression have been found to predict binge drinking and to reflect behavioral disinhibition. We tested effects of these disinhibited traits on binging during intravenous alcohol self-administration (ivASA), a method that eliminates sex differences in the pharmacokinetics of alcohol. Eighty-five German social drinkers (49 men) completed 3 questionnaires assessing sensation seeking, impulsivity, and aggression, as well as an ivASA session at ages 18–19. Sixty-five of them were retested at ages 21–22. Participants reported real-life drinking problems and the number of binge days in the 45 days preceding lab testing. Analyses employed continuous data and median splits to examine associations between disinhibited traits and the portion of women and men in the sample who achieved a breath alcohol concentration of 80 mg% during ivASA (“binge fraction”). At ages 18–19, and only if scoring low on sensation seeking, impulsivity, or aggression, women had significantly lower binge fractions during ivASA than men. Further, low compared to high impulsivity or aggression predicted lower binge fractions in women but not in men. Neither first- nor second-wave disinhibited traits significantly predicted binge fractions at ages 21–22. We perceive that personality traits reflecting behavioral disinhibition might be a strong indicator of drinking problems, specifically among young women. Targeted brief interventions might therefore be used in educational or clinical settings to inform such women about their increased risk and the potential health and behavioral problems associated with binge drinking

Offspring of parents with an alcohol use disorder prefer higher levels of brain alcohol exposure in laboratory experiments involving computer-assisted self-infusion of ethanol (CASE)

Rationale: Acute alcohol effects may differ in social drinkers with a positive family history of alcohol use disorders (FHP) compared to FH negative (FHN) controls. Objectives: To investigate whether FHP subjects prefer higher levels of brain alcohol exposure than do FHN controls. Materials and methods: Twenty-two young healthy nondependent social drinkers participated in two identical sessions of computer-assisted self-infusion of ethanol (CASE); the first for practicing the procedures, the second to test hypotheses. All 12 FHP (four women) and ten FHN (three women) participants received a priming exposure, increasing arterial blood alcohol concentration (aBAC) to 30 mg% at 10 min and decreasing it to 15 mg% at 25 min. A 2-h self-administration period followed, during which only the subjects could increase their aBAC by pressing a button connected to a computer controlling the infusion pump. Infusion rate profiles were calculated instantaneously to increase aBAC by precisely 7.5 mg% within 2.5 min after each button press, followed by a steady descent. Subjects were instructed to produce the same alcohol effects as they would do at a weekend party. Results: The mean and maximum aBAC during the self-administration period and the number of alcohol requests (NOAR) were significantly higher in the FHP vs. FHN participants. Conclusions: This is the first laboratory experiment demonstrating higher alcohol self-administration in FHP compared to FHN subjects. A practice session increases the sensitivity of CASE experiments for detection of subtle differences in human alcohol self-administration