The Impact of Alcohol and Energy Drink Consumption on Intoxication and Risk‐Taking Behavior

Background

It has been argued that consuming alcohol mixed with energy drinks (AmED) causes a subjective underestimation of intoxication and an increased level of risk‐taking behavior. To date, however, there is mixed support for AmED‐induced reductions in perceived intoxication, and no objective assessment of risk‐taking following AmED consumption. Consequently, the present study aimed to determine the effect of alcohol and energy drink (ED) consumption on subjective measures of intoxication and objective measures of risk‐taking.

Methods

Using a placebo‐controlled, single‐blind, cross‐over design, participants (n = 28) attended 4 sessions in which they were administered, in counterbalanced order: 0.5 g/kg alcohol, 3.57 ml/kg ED, AmED, and a placebo beverage. Participants completed the Biphasic Alcohol Effects Scale and a Subjective Effects Scale at baseline and 30 and 125 minutes postbeverage administration; risk‐taking was measured using the Balloon Analogue Risk Task (BART).

Results

Participants reported greater subjective intoxication, impairment, and sedation after active relative to placebo alcohol consumption, with no interactive AmED effects. However, a significant moderate magnitude increase in stimulation ratings was observed in the AmED relative to alcohol, ED, and placebo conditions. There was no independent effect of alcohol, or interactive effect with ED, on the BART. A significant, yet small magnitude, increase in risk‐taking was evident in active relative to placebo ED conditions.

Conclusions

The interactive effect of AmED appears restricted to perceived stimulation, with alcohol‐induced increases in subjective intoxication occurring regardless of presence or absence of ED. Engagement in risk‐taking behavior was only increased by ED consumption; however, this effect was only of small magnitude; at these doses, alcohol consumption, with or without EDs, did not affect risk‐taking. Further research assessing the dose‐dependent effects of AmED on objectively measured risk‐taking behavior could clarify whether the ED effect increases with higher doses and whether an interactive effect is observed with higher alcohol doses.     

Combined Alcohol and Energy Drink Use: Hedonistic Motives,Adenosine, and Alcohol Dependence

Consumption of alcohol mixed with energy drinks (AmED) has been associated with both short‐ and long‐term risks beyond those observed with alcohol alone. AmED use has been associated with heavy episodic (binge) drinking, risky behaviors, and risk of alcohol dependence. Laboratory research has demonstrated that AmED beverages lead to greater motivation to drink versus the same amount of alcohol consumed alone. However, the reason consumers find AmED beverages particularly appealing has been unclear. A recent report by Droste and colleagues (Alcohol Clin Exp Res 2014; 38:2087–2095) is the first study to investigate motivations related to AmED consumption and to determine which motives predict AmED consumption patterns, experience of drinking‐related harms, and risk of alcohol dependence. The findings of this study significantly enhance our understanding of why AmED consumption is related to the risk of alcohol dependence and change our understanding of why consumers choose AmED beverages. The authors report that hedonistic motives strongly predicted AmED use and the harms associated with use. While intoxication‐reduction motives predicted self‐reported accidents and injuries, these motives did not predict AmED consumption patterns and risk of dependence. The risk of alcohol dependence may arise from repeated experiences when drinking alcohol is more pleasurable when energy drinks are consumed with the alcohol. This commentary will focus on why energy drinks might increase the rewarding properties of alcohol in social drinkers. In addition, discussion is provided explaining why more research on the neurotransmitter, adenosine, may actually inform us about the mechanisms contributing to the development of alcohol dependence.     

Effects of energy drink ingestion on alcohol intoxication

BACKGROUND: Well-known reports suggest that the use of energy drinks might reduce the intensity of the depressant effects of alcohol. However, there is little scientific evidence to support this hypothesis. OBJECTIVE AND METHODS: The present study aimed at evaluating the effects of the simultaneous ingestion of an alcohol (vodka(37.5%v/v)) and an energy drink (Red Bull-3.57 mL/kg), compared with those presented after the ingestion of an alcohol or an energy drink alone. Twenty-six young healthy volunteers were randomly assigned to 2 groups that received 0.6 or 1.0 g/kg alcohol, respectively. They all completed 3 experimental sessions in random order, 7 days apart: alcohol alone, energy drink alone, or alcohol plus energy drink. We evaluated the volunteers' breath alcohol concentration, subjective sensations of intoxication, objective effects on their motor coordination, and visual reaction time. RESULTS: When compared with the ingestion of alcohol alone, the ingestion of alcohol plus energy drink significantly reduced subjects' perception of headache, weakness, dry mouth, and impairment of motor coordination. However, the ingestion of the energy drink did not significantly reduce the deficits caused by alcohol on objective motor coordination and visual reaction time. The ingestion of the energy drink did not alter the breath alcohol concentration in either group. CONCLUSIONS: Even though the subjective perceptions of some symptoms of alcohol intoxication were less intense after the combined ingestion of the alcohol plus energy drink, these effects were not detected in objective measures of motor coordination and visual reaction time, as well as on the breath alcohol concentration.     

Alcohol impairment of behavior in men and women

AIMS: Studies have shown that alcohol impairs the ability to inhibit behavioral responses in humans and some evidence suggests that men might display greater impairment than women. The present study compared men and women in the degree to which a moderate dose of alcohol impaired their inhibitory control at comparable blood alcohol concentrations. DESIGN: Twelve male and 12 female adult social drinkers received a moderate dose of alcohol (0.65 g/kg) and a placebo in a counterbalanced order and performed a cued go/no-go task that measured the ability to inhibit and execute behavioral responses. FINDINGS: When the behavioral response was pre-potent (i.e. instigated), men displayed greater impairment of inhibitory control under alcohol than women. Men also reported greater levels of subjective stimulation from alcohol compared with women, who reported more sedation from the drug. CONCLUSIONS: A gender difference in alcohol impairment of inhibitory control could account for observations that disinhibited and aggressive behaviors under alcohol are more pronounced in men than in women.     

Estimation of Blood Alcohol Concentrations in Young Male Drinkers

This research examined individual differences in the ability to self-monitor the effects of alcohol. Thirty-nine male subjects consumed 0.75 ml/kg alcohol and estimated their blood alcohol concentrations (BACs) at peak BAC and on the ascending and descending limbs of the blood alcohol curve. Family history of alcohol dependence did not affect the accuracy of estimation of BACs. Subjects who reported lower levels of subjective intoxication underestimated their BACs more than did subjects who reported higher levels of subjective intoxication. Subjects with less behavioral impairment underestimated their BACs more than subjects with greater behavioral impairment on the ascending limb of the blood alcohol curve. Accuracy was better on the ascending limb compared with peak BAC and the descending limb, and accuracy became worse over time on the descending limb. It appears that cues to the effects of alcohol rapidly become unavailable on the descending limb, which may contribute to decisions concerning further alcohol consumption and driving after drinking.     

Effects of Assessment Frequency on Subjective Intoxication Ratings After Alcohol Consumption

BACKGROUND: It is common for subjective intoxication measures to be administered frequently throughout an experimental session. It is unclear, however, whether repeated assessments affect the experience of intoxication. This study examined the effect of assessing subjective intoxication levels during alcohol consumption on subsequent perceptions of intoxication after drinking. METHODS: Forty-two participants consumed a moderate dose of alcohol (men, 82 g/kg; women, 0.74 g/kg) during a 30-min period. Participants either reported or did not report subjective intoxication levels at 10-min intervals during the drinking period. After the drink, all participants rated their level of subjective intoxication on several occasions. RESULTS: Individuals who reported their intoxication during the drinking period reported higher levels after consumption than did those who did not rate their intoxication during drinking. CONCLUSIONS: These data suggest the potential for reactivity effects when conducting repeated assessments of perceived subjective intoxication.     

Varenicline potentiates alcohol-induced negative subjective responses and offsets impaired eye movements

Background: Varenicline (VAR) is a partial nicotinic receptor agonist that is an effective smoking cessation medication. Preliminary evidence indicates that it may also reduce alcohol consumption, but the underlying mechanism is not clear. For example, VAR may reduce alcohol consumption by attenuating its subjectively rewarding properties or by enhancing its aversive effects. In this study, we examined the effects of an acute dose of VAR upon subjective, physiological, and objective responses to low and moderate doses of alcohol in healthy social drinkers. Methods: Healthy men and women (N = 15) participated in 6 randomized sessions; 3 sessions each with 2 mg VAR and placebo (PL) followed 3 hours later by a beverage containing PL, low‐dose alcohol (0.4 g/kg), or high‐dose alcohol (0.8 g/kg). Subjective mood and drug effects (i.e., stimulation, drug liking), physiological measures (heart rate, blood pressure), and eye tracking tasks were administered at various intervals before and after drug and alcohol administration. Results: VAR acutely increased blood pressure, heart rate, ratings of dysphoria and nausea, and also improved eye tracking performance. After alcohol drinking (vs. PL), VAR increased dysphoria and tended to reduce alcohol liking ratings. It also attenuated alcohol‐induced eye‐tracking impairments. These effects were independent of the drug’s effects on nausea before drinking. Conclusions: Our data support the theory that VAR may reduce drinking by potentiating aversive effects of alcohol. VAR also offsets alcohol‐induced eye movement impairment. The evidence suggests that VAR may decrease alcohol consumption by producing effects, which oppose the rewarding efficacy of alcohol.     

Artificial sweeteners, caffeine, and alcohol intoxication in bar patrons

Background: Previous laboratory research on alcohol absorption has found that substitution of artificially sweetened alcohol mixers for sucrose‐based mixers has a marked effect on the rate of gastric emptying, resulting in elevated blood alcohol concentrations. Studies conducted in natural drinking settings, such as bars, have indicated that caffeine ingestion while drinking is associated with higher levels of intoxication. To our knowledge, research has not examined the effects of alcohol mixers that contain both an artificial sweetener and caffeine, that is, diet cola. Therefore, we assessed the event‐specific association between diet cola consumption and alcohol intoxication in bar patrons. We sought to determine whether putative increases in blood alcohol, produced by accelerated gastric emptying following diet cola consumption, as identified in the laboratory, also appear in a natural setting associated with impaired driving. Methods: We conducted a secondary analysis of data from 2 nighttime field studies that collected anonymous information from 413 randomly selected bar patrons in 2008 and 2010. Data sets were merged and recoded to distinguish between energy drink, regular cola, diet cola, and noncaffeinated alcohol mixers. Results: Caffeinated alcohol mixers were consumed by 33.9% of the patrons. Cola‐caffeinated mixed drinks were much more popular than those mixed with energy drinks. A large majority of regular cola‐caffeinated mixed drink consumers were men (75%), whereas diet cola‐caffeinated mixed drink consumers were more likely to be women (57%). After adjusting for the number of drinks consumed and other potential confounders, number of diet cola mixed drinks had a significant association with patron intoxication (β = 0.233, p < 0.0001). Number of drinks mixed with regular (sucrose‐sweetened) cola and energy drinks did not have significant associations with intoxication (p > 0.05). Conclusions: Caffeine’s effect on intoxication may be most pronounced when mixers are artificially sweetened, that is, lack sucrose which slows the rate of gastric emptying of alcohol. Risks associated with on‐premise drinking may be reduced by greater attention given to types of mixers, particularly diet colas.     

Effects of alcohol on simulated driving and perceived driving impairment in binge drinkers

Background:  Binge drinking (heavy episodic alcohol use) is associated with high rates of impaired driving and myriad alcohol-related accidents. However, the underlying reasons for the heightened accident risk in this demographic group are not known. This research examined acute alcohol effects on simulated driving performance and subjective ratings of intoxication and driving ability in binge and nonbinge drinkers.
Methods:  Young social drinking college students (24 binge drinkers and 16 nonbinge drinkers) participated in this study. Participants attended a session during which they received a moderate dose of alcohol (0.65 g/kg) and a session during which they received a placebo. A simulated driving task measured participants' driving performance in response to each dose. Subjective responses to each dose were also assessed, including ratings of sedation, stimulation, and driving ability.
Results:  The acute dose of alcohol impaired multiple aspects of driving performance in both binge and nonbinge drinkers. Under alcohol, all participants had greater difficulty in maintaining their lane position, maintaining the appropriate speed and made multiple driving errors compared to placebo performance. By contrast, compared with nonbinge drinkers, binge drinkers reported feeling less sedated by the alcohol and reported having a greater ability to drive following the acute dose of alcohol.
Conclusions:  Reduced subjective intoxication and perceived driving impairment in binge drinkers may account for the greater accident risk in this demographic group. Binge drinkers may lack the internal sedation cue that helps them accurately assess that they are not able to effectively drive a vehicle after drinking.     

Subjective Response to Alcohol: A Critical Review of the Literature

Background: Subjective response to alcohol (SR), which reflects individual differences in sensitivity to the pharmacological effects of alcohol, may be an important endophenotype in understanding genetic influences on drinking behavior and alcohol use disorders (AUDs). SR predicts alcohol use and problems and has been found to differ by a range of established risk factors for the development of AUDs (e.g., family history of alcoholism). The exact pattern of SR associated with increased risk for alcohol problems, however, remains unclear. The Low Level of Response Model (LLR) suggests that high‐risk individuals experience decreased sensitivity to the full range of alcohol effects, while the Differentiator Model (DM) asserts that high risks status is associated with increased sensitivity to alcohol's positive effects but decreased sensitivity to negative effects. Aims: The current paper (1) reviews two prominent models of subjective response, (2) reviews extant laboratory‐based research on subjective response, (3) highlights remaining gaps in our understanding and assessment of subjective response, and (4) encourages collaborative efforts to address these methodological and conceptual concerns. Methods: This paper reviews studies which employed placebo‐controlled and non‐placebo‐controlled alcohol challenge paradigms to assess a range of alcohol effects including impairment, stimulation, and sedation. Results: The research literature provides at least partial support for both the LLR and DM models. High‐risk individuals have been shown to have a reduced response to alcohol with respect to sedative or impairing effects, particularly on the descending limb of the blood alcohol curve (BAC). There is also evidence that ascending limb stimulant effects are more pronounced or operate differently for high‐risk individuals. Discussion: Despite commendable advances in SR research, important questions remain unanswered. Inconsistent results across studies may be attributable to a combination of an inadequate understanding of the underlying construct and methodological differences across studies (e.g., number and timing of assessments across the BAC, inclusion of a placebo condition). With respect to the underlying construct, existing measures fail to adequately distinguish between cognitive/behavioral impairment and sedation, aspects of which may be perceived positively (e.g., anxiolysis) due to their ability to act as negative reinforcers. Conclusions: Addressing the concerns raised by the current review will be integral to making meaningful scientific progress in the field of subjective response.     

Catching the Alcohol Buzz: An Examination of the Latent Factor Structure of Subjective Intoxication

Background:  The goal of this study was to examine the latent structure among measures of alcohol-induced subjective feelings of intoxication from a behavioral pharmacology perspective.
Methods:  Data on subjective intoxication, measured concomitantly by the Subjective High Assessment Scale, Biphasic Alcohol Effect Scale, and the Short Version of the Profile of Mood States, were collected at 3 levels of breath alcohol concentration during an alcohol administration study in a sample of heavy drinkers ( n  = 135).
Results:  Results of exploratory factor analyses supported a 3-factor model which captured the following dimensions of subjective intoxication: (1) stimulation and other pleasant effects, (2) sedative and unpleasant effects, and (3) alleviation of tension and negative mood. The tension-reduction factor was most consistently associated with more frequent drinking and alcohol problems in this sample.
Conclusions:  These findings support the notion that the neuropharmacological and behavioral effects of alcohol are multifaceted and cannot be simply defined as either positive or negative. Rather, moderate levels of intoxication appear to have concomitant dimensions of positive reinforcement, negative reinforcement, and punishment. This study also suggests that factor scores may be useful in future alcohol administration studies to reduce the number of comparisons and perhaps increase statistical power to detect meaningful effects.     

Kudzu extract treatment does not increase the intoxicating effects of acute alcohol in human volunteers

Background: Isoflavone administration in the form of a purified extract from the herbal medication kudzu root has been shown to reduce, but not eliminate, alcohol consumption in alcohol‐abusing and alcohol‐dependent men. The precise mechanism of this action is unknown, but 1 possible explanation for these results is that the isoflavones in kudzu might actually increase the intensity or duration of alcohol’s effects and thus delay the desire for subsequent drinks. This study was designed to test this hypothesis. Methods: Twelve (12) healthy adult men and women (27.5 ± 1.89 years old) who consumed moderate amounts of alcohol (7.8 ± 0.63 drinks/wk) participated in a double‐blinded, placebo‐controlled crossover study in which they were treated with either kudzu extract (total isoflavone dose of 750 mg/d) or matched placebo for 9 days. On days 8 and 9, participants received an acute challenge of ethyl alcohol (either 0.35 or 0.7 g/kg alcohol). During the challenges, the following measures were collected: subjective effects, psychomotor (body sway), cognitive performance (vigilance/reaction time), physiological measures (heart rate and skin temperature), and plasma ethanol concentration. Results: Alcohol resulted in a dose‐related alteration in subjective measures of intoxication, impairment of stance stability, and vigilance/reaction time. Kudzu extract did not alter participants’ subjective responses to the alcohol challenge or to alcohol’s effects on stance stability or vigilance/reaction time. However, individuals treated with kudzu extract experienced a slightly more rapid rise in plasma ethanol levels, but only after the 0.7 g/kg dose. This transient effect during the first 30 minutes of the ascending plasma alcohol curve lasted only 10–15 minutes; there were no differences in peak plasma alcohol levels or alcohol elimination kinetics. Additionally, kudzu pretreatment enhanced the effects of the 0.7 g/kg dose of alcohol on heart rate and skin temperature. Conclusions: These data suggest that individuals who drink alcohol while being treated with kudzu extract experience no adverse consequences, and furthermore the reported reductions in alcohol intake after kudzu extract treatment are not related to an alteration in alcohol’s subjective or psychomotor effects.     

Bidirectional interactions between acute psychosocial stress and acute intravenous alcohol in healthy men

Background: The biological mechanisms by which acute stress increases alcohol consumption are unclear. One potential mechanism is that stress acts by altering the pharmacological and subjective effects of alcohol. Acute stress produces a cascade of physiological and psychological effects, each with a distinctive time course. In this study, we investigated whether different phases of response to an acute stress alter the subjective effects of intravenous alcohol, by administering the drug at 2 different times after the stress. Methods: Healthy men (n = 25) participated in 2 sessions: 1 with the Trier Social Stress Test and the other with a nonstressful control task, each followed by infusions of intravenous alcohol (targeting 40 mg% in 5 minutes) and placebo. One group of participants received alcohol within 1 minute of completing the tasks (Alc0, n = 11), followed by placebo 30 minutes later. In the other group (Alc30, n = 14), the order of alcohol and placebo infusions was reversed. Subjective effects (i.e., anxiety, stimulation, want more) and physiological measures (heart rate, blood pressure, salivary cortisol) were measured before and at repeated intervals after the tasks and infusions. Results: Stress did not change the subjective effects of alcohol in either group. However, when individual differences in alcohol responses were considered, stress differentially altered the stimulant‐like and sedative effects of alcohol. Among individuals who exhibited predominantly stimulant responses to alcohol in the nonstressful condition, stress decreased the stimulant‐like effects of alcohol and “wanting more.” By contrast, among participants who did not report stimulation after alcohol in the control session, stress decreased the sedative effects and increased “want more.” In addition, alcohol administered immediately after the Trier Social Stress Test dampened cortisol responses yet prolonged negative subjective responses to the stress. Conclusions: These findings demonstrate that there are bidirectional relationships between alcohol and stress. Alcohol influences responses to stress, and stress changes reactions to alcohol, depending on an individual’s pattern of response to alcohol. This study highlights the fact that stress–alcohol interactions vary among individual drinkers, suggesting that the effects of stress on motivation to drink alcohol may also differ between individuals.     

Aripiprazole effects on alcohol consumption and subjective reports in a clinical laboratory paradigm--possible influence of self-control

Introduction: There has been increasing interest in the use of medications that affect the dopamine receptor in the treatment of alcoholism. Aripiprazole has the unique pharmacology of being a partial dopamine agonist serving to stabilize brain dopamine systems in both frontal cortical and subcortical areas. As such, it might act to dampen alcohol reinforcement and craving and/or alter control over alcohol use. The current clinical laboratory study was conducted to evaluate the safety and efficacy of aripiprazole as a potential agent to alter drinking and objective effects of alcohol. Methods: Thirty nontreatment seeking alcoholics were enrolled in a subacute human laboratory study and received double‐blind treatment with up to 15 mg of aripiprazole (n = 15) or identical placebo (n = 15) for 8 days. Tolerability and utility of aripiprazole was monitored during natural drinking over the first 6 days of medication treatment and also during a free choice limited access alcohol consumption paradigm following an initial drink of alcohol in a bar‐lab setting on Day 8. Results: Aripiprazole was well tolerated and reduced drinking in nontreatment seeking alcoholics over 6 days of natural drinking—especially in those with lower self control (more impulsive). It also reduced drinks in the bar‐lab after a priming drink and broke the link between priming drink induced stimulation and further drinking. During the bar‐lab drinking session, there were no differences in subjective high, intoxication, or craving between subjects treated with aripiprazole or placebo. Discussion: This study joins several others in demonstrating the utility of subacute dosing laboratory paradigms for evaluating medication effects in alcoholics. Aripiprazole was well tolerated and lowered alcohol use, especially in those with lower impulse control. Further study is needed to determine the safety and utility of aripiprazole in the treatment of alcoholism and if subgroups of alcoholics are more likely to respond.     

Alcohol control policies and alcohol consumption by youth: a multi-national study

Aims The study examined relationships between alcohol control policies and adolescent alcohol use in 26 countries. Design Cross‐sectional analyses of alcohol policy ratings based on the Alcohol Policy Index (API), per capita consumption and national adolescent survey data. Setting Data are from 26 countries. Participants Adolescents (aged 15–17 years) who participated in the 2003 European School Survey Project on Alcohol and Other Drugs (ESPAD) or national secondary school surveys in Spain, Canada, Australia, New Zealand and the United States. Measurements Alcohol control policy ratings based on the API; prevalence of alcohol use, heavy drinking and first drink by age 13 based on national secondary school surveys; per capita alcohol consumption for each country in 2003. Analysis Correlational and linear regression analyses were conducted to examine relationships between alcohol control policy ratings and past 30‐day prevalence of adolescent alcohol use, heavy drinking and having first drink by age 13. Per capita consumption of alcohol was included as a covariate in regression analyses. Findings More comprehensive API ratings and alcohol availability and advertising control ratings were related inversely to the past 30‐day prevalence of alcohol use and prevalence rates for drinking three to five times and six or more times in the past 30 days. Alcohol advertising control was also related inversely to the prevalence of past 30‐day heavy drinking and having first drink by age 13. Most of the relationships between API, alcohol availability and advertising control and drinking prevalence rates were attenuated and no longer statistically significant when controlling for per capita consumption in regression analyses, suggesting that alcohol use in the general population may confound or mediate observed relationships between alcohol control policies and youth alcohol consumption. Several of the inverse relationships remained statistically significant when controlling for per capita consumption. Conclusions More comprehensive and stringent alcohol control policies, particularly policies affecting alcohol availability and marketing, are associated with lower prevalence and frequency of adolescent alcohol consumption and age of first alcohol use.     

Sleep following alcohol intoxication in healthy, young adults: effects of sex and family history of alcoholism

Background: This study evaluated sex and family history of alcoholism as moderators of subjective ratings of sleepiness/sleep quality and polysomnography (PSG) following alcohol intoxication in healthy, young adults. Methods: Ninety‐three healthy adults [mean age 24.4 ± 2.7 years, 59 women, 29 subjects with a positive family history of alcoholism (FH+)] were recruited. After screening PSG, participants consumed alcohol (sex/weight adjusted dosing) to intoxication [peak breath alcohol concentration (BrAC) of 0.11 ± 0.01 g% for men and women] or matching placebo between 20:30 and 22:00 hours. Sleep was monitored using PSG between 23:00 and 07:00 hours. Participants completed the Stanford Sleepiness Scale and Karolinska Sleepiness Scale at bedtime and on awakening and a validated post‐sleep questionnaire. Results: Following alcohol, total sleep time, sleep efficiency, nighttime awakenings, and wake after sleep onset were more disrupted in women than men, with no differences by family history status. Alcohol reduced sleep onset latency, sleep efficiency, and rapid eye movement sleep while increasing wakefulness and slow wave sleep across the entire night compared with placebo. Alcohol also generally increased sleep consolidation in the first half of the night, but decreased it during the second half. Sleepiness ratings were higher following alcohol, particularly in women at bedtime. Morning sleep quality ratings were lower following alcohol than placebo. Conclusions: Alcohol intoxication increases subjective sleepiness and disrupts sleep objectively more in healthy women than in men, with no differences evident by family history of alcoholism status. Evaluating moderators of alcohol effects on sleep may provide insight into the role of sleep in problem drinking.     

Subjective intoxication in response to alcohol challenge: heritability and covariation with personality,breath alcohol level,and drinking history

BACKGROUND: Numerous studies have identified differences in subjective response to alcohol in subjects differentiated by family history of alcoholism. Results suggest that genetic influences on individual variation in subjective response to alcohol may be a mechanism for genetic effects on alcohol problems. However, direct evidence for genetic effects on subjective response to alcohol is very limited. METHODS: In a sample of 99 adult twin pairs, we studied genetic influences on subjective intoxication after alcohol challenge. The twins ingested a standard dose of ethanol (0.70 g/kg for men/0.65 g/kg for women), and two measures of subjective response to alcohol were assessed. RESULTS: Genetic effects on variation in subjective intoxication reported 1 hr after drinking were significant and substantial: heritability was 0.60 for a 22-item scale and 0.48 for a brief 2-item measure. Self-report measures of neuroticism, psychasthenia, hostility, and family problems shared significant genetic covariation with subjective intoxication. Achieved breath alcohol level, rate of change in breath alcohol on the descending limb, and individual drinking history all shared familial variation with subjective intoxication. No significant genetic effects for subjective intoxication were found 2 hr after drinking, but familial influences remained present, and many of the same personality, drinking history, and breath alcohol variables were predictive of intoxication. CONCLUSIONS: Subjective response to alcohol is heritable, and genetic effects on subjective intoxication are partly shared with genetic effects on personality.     

Alcohol effects during acamprosate treatment: a dose-response study in humans

BACKGROUND: Acamprosate (calcium acetyl homotaurinate) reduces alcohol intake in animals and increases abstinence rates in alcohol-dependent persons. Acamprosate's mechanism of action, however, remains poorly understood. In order to examine whether acamprosate/alcohol interactions contribute to acamprosate's efficacy, the present double-blind, placebo-controlled human laboratory study examined effects of acamprosate on the pharmacokinetics and subjective, psychomotor, and physiological effects of alcohol in heavy drinkers. METHODS: In a six-week within-subject design, participants were maintained on acamprosate (0, 2, and 4 g, p.o., double-blind, in counterbalanced order) for 11 days at each dose. Physiological, subjective, and psychomotor measures were collected daily during each dosing cycle. During each acamprosate dose condition, subjects were challenged with 0, 0.5, and 1.0 g/kg ethanol (p.o., counterbalanced order) during three separate laboratory sessions. Subjective, physiological, and psychomotor effects of alcohol, and breath alcohol levels were collected at baseline and at 30-min intervals for a 3-hr post-administration period. RESULTS: Acamprosate alone did not substantially affect subjective, physiological, or psychomotor performance measures. Acamprosate did not alter alcohol pharmacokinetics, or alcohol-induced behavioral impairment or tachycardia, and most subjective alcohol effects were also unaltered by acamprosate as well. Although a trend appeared for acamprosate to increase subjective ratings of intoxication following the lower (0.5 g/kg) alcohol dose, adjustment for individual differences in blood alcohol level eliminated this effect, suggesting the trend was not due to a central effect of acamprosate. CONCLUSIONS: Acamprosate does not alter alcohol pharmacokinetics, acute physiological or psychomotor alcohol effects, or most subjective alcohol effects.     

Fetal and infantile alcohol-mediated associative learning in the rat

BACKGROUND: Infant rats express conditioned responses to an odor experienced prenatally as a chemosensory cue associated with moderate alcohol intoxication. This study examined postnatal intake of a chemosensory cue (cineole) that had been paired with alcohol's unconditioned effects. It also tested the interaction between prenatal association and postnatal conditioning with cineole and alcohol. METHODS: Pregnant female rats intubated with cineole were given ethanol (EtOH).25 or 4.0 hr later. Other groups received only water or water paired with ethanol. During postnatal day 15 (PD15), infant consumption of cineole solution was assessed. After the cineole drinking test, pups were intubated with EtOH or water to assess infant conditioning. On PD16, all pups were tested for mouthing to milk alone or to a milk-cineole solution. RESULTS: Statistical analysis confirmed fetal associative conditioning attributable to the unconditioned effects of prenatal alcohol. Fetuses given explicit pairings of cineole and alcohol ingested less cineole on PD15 than control fetuses given a 4-hr interval between cineole and alcohol. On PD16, consumption of cineole was significantly increased by prenatal exposure to cineole. Teratogenic effects of this dose of prenatal alcohol did not affect postnatal associative or nonassociative behavior. CONCLUSIONS: Prenatal associative learning can be established through temporal contiguity between fetal chemosensory stimulation and alcohol's unconditioned properties. This associative memory survives to infancy and modulates intake patterns and behavioral reactivity to substances that were prenatally paired with alcohol intoxication.     

Effects of naltrexone during the descending limb of the blood alcohol curve

The neuropharmacological effects of alcohol are known to vary by limb of the blood alcohol curve, yet human laboratory studies of alcoholism pharmacotherapies have largely failed to consider limb of intoxication when examining medication effects on subjective responses to alcohol. This study examined the effects of naltrexone compared to placebo on subjective responses to alcohol at the descending limb of the blood alcohol curve following a controlled intravenous (IV) alcohol administration. Non-treatment-seeking hazardous drinkers (n = 38) completed two double-blind counterbalanced IV alcohol challenge sessions, one after taking naltrexone (50 mg) for three days and one after taking a placebo for three days. During each session, participants reported on subjective responses to alcohol during the descending limb of the blood alcohol curve. Analyses revealed significant main effects of naltrexone, reflecting significantly decreased alcohol-induced stimulation, craving, vigor, positive mood, and alcohol "high" and increased tension as compared to placebo. These findings suggest that naltrexone may exert some of its therapeutic effects via alterations to experiential aspects of intoxication during the descending limb of alcohol intoxication. Additionally, these results highlight the potential utility of considering limb of blood alcohol curve when examining the mechanisms of action of pharmacotherapies thought to alter subjective responses to alcohol.