Individual Differences in the Biphasic Effects of Ethanol

Ethanol exerts both stimulant-like and sedative-like subjective and behavioral effects in humans depending on the dose, the time after ingestion and, we will argue, also on the individual taking the drug. This study assessed stimulant-like and sedative-like subjective and behavioral effects of ethanol during the ascending and descending limbs of the blood alcohol curve across a range of doses in nonproblem social drinkers. Forty-nine healthy men and women, 21 to 35 years old, consumed a beverage containing placebo or ethanol (0.2, 0.4, or 0.8 g/kg) on four separate laboratory sessions, in randomized order and under double-blind conditions. Subjective and behavioral responses were assessed before and at regular intervals for 3 hr after ingestion of the beverage. The lowest dose of ethanol (0.2 g/kg) only produced negligible subjective effects compared to placebo. The moderate dose (0.4 g/kg) increased sedative-like effects 90 min after ethanol ingestion but did not increase ratings of stimulant effects at any time. The highest dose (0.8 g/kg) increased ratings of both stimulant- and sedative-like effects during the ascending limb and produced only sedative-like effects during the descending limb. Closer examination of the data revealed that individual differences in response to the highest dose of ethanol accounted for this unexpected pattern of results: about half of the subjects reported stimulant-like effects on the ascending limb and sedative-like effects on the descending limb after 0.8 g/kg ethanol, whereas the other half did not report stimulant-like effects at any time after administration of ethanol. These results challenge the simple assumption that ethanol has biphasic subjective effects across both dose and time, and extend previous findings demonstrating individual differences in response to ethanol.     

Confirming the Factor Structure of the Anticipated Biphasic Alcohol Effects Scale

This study of the Anticipated Biphasic Alcohol Effects Scale (A-BAES) examined the factor structure of expected stimulant and sedative effects on the ascending and descending limbs of the blood alcohol curve. Subjects reported the effects they anticipated they would experience immediately after drinking four drinks (ascending) and 1 1/2 hr later (descending). The proposed 4-factor model of stimutant and sedative effects on the ascending and descending limbs fit the data significantly better than single-factor, null, limb-only, and effect-only models, suggesting that the A-BAES has a confirmable structure. In addition, anticipated effects varied with limb of the blood alcohol curve, gender, and drinking habits. Anticipated stimulant effects were higher on the ascending than descending limbs; anticipated sedative effects were higher on the descending than ascending limbs. Women and men differed in their anticipated effects of alcohol, even when differences in drinking habits were controlled. Anticipated sedative effects correlated significantly with alcohol consumption, offering further support for the relation between expectancies and 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.     

The biphasic effects of alcohol: comparisons of subjective and objective measures of stimulation, sedation, and physical activity

BACKGROUND: Alcohol produces biphasic effects of both stimulation and sedation. Sensitivity to these effects may increase the risk for the development of alcoholism. Alcohol-induced changes in stimulation and sedation are commonly assessed with self-report questionnaires in human research and with physical activity monitoring in animal research. However, little is known about the effects of alcohol on physical activity or the relationship between physical activity and subjective self-report measures of stimulation and sedation following alcohol consumption in humans. METHODS: Thirty healthy men and women (n = 15 each) from 21 to 38 years old completed daily measurements of physical activity and self-reports of stimulation and sedation following alcohol or placebo consumption. Across each of the four experimental days, all participants consumed a placebo, 0.4, 0.6, or 0.8 g/kg dose of 95% alcohol in a counterbalanced order. Breath alcohol concentrations, physical activity levels, and self-reported stimulation and sedation were measured at baseline and on the ascending and descending limbs of the breath alcohol concentration (BrAC) curve. RESULTS: All alcohol doses increased physical activity, but these increases were time- and dose-dependent. Increases in physical activity lasted across both ascending and descending limbs of the BrAC curve. Following the 0.6 g/kg dose, both physical activity and self-reported stimulation increased during the ascending BrAC. Separate analyses of self-reported sedation scores indicated that alcohol consumption also increased sedation for the 0.6 and 0.8 g/kg doses. Physical activity was not significantly correlated with either self-reported stimulation or sedation at any time point. CONCLUSIONS: These findings suggest that assessments of subjectively measured stimulation and sedation and objectively measured physical activity each assess unique aspects of the effects of alcohol. Used simultaneously, these measures may be useful for examining underlying mechanisms of the effects of alcohol on behavior.     

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.     

Behavioral Effects and Pharmacokinetics of Low-Dose Intravenous Alcohol in Humans

Alcohol has physiological effects on the human central nervous system at blood alcohol concentrations (BACs) as low as 9 mg/dl. It is unknown, however, if humans can perceive the effects of such low doses of alcohol. Furthermore, low BACs can be difficult to measure. The purpose of this experiment was to: (1) assess the ability of humans to perceive subjective effects of low BACs; (2) measure behavioral effects of low BACs on a psychomotor performance task; and (3) test the sensitivity and accuracy of the transdermal alcohol sensor (TAS) for measuring low BACs from skin. Five men and seven women were administered single-blind intravenous infusions of ethyl alcohol in 5% dextrose/water to achieve peak BACs of 0,10,20, and 40 mg/dl. Subjective intoxication scales and a computer administered continuous performance task (CPT) were used to assess alcohol effects. BACs were estimated from skin, blood, and breath. The only alcohol-induced sensation significantly increased during the alcohol infusions was anesthesia measured by the Alcohol Sensation Scale on the descending limb of the BAC curve. The subjective positive-reinforcing stimulant and mood effects of alcohol were not reported until subjects were administered the 40 mg/dl alcohol infusion. Other measures of subjective intoxication and sedation, and the CPT were unaffected by the alcohol infusions. The TAS provided a noninvasive method for estimating BACs that was comparable with estimates obtained from blood and breath, although delayed in time.     

Genetic Analyses of the Biphasic Nature of the Alcohol Dose-Response Curve

Ethanol (ETOH)-induced locomotor activation and depression were studied in 23 genotypes of mice. This included a diallel cross of four inbred strains tested with a range of ETOH doses from 0 to 2.75 g/kg. The diversity in shapes of the biphasic ETOH dose-response curves was both qualitative and quantitative, and additive gene action characterized the genetic control of the dose-response curve. Small dominance effects were typically directional in the direction of more activation, or resistance to sedation. No evidence was found for maternal effects, sex linkage, or epistasis. Sex differences were seen in the increased susceptibility of male mice to locomotor sedation at higher ETOH doses. In the diallel cross, there was no correlation between the degree of activation produced by low ETOH doses and sedation produced by higher doses. This indicates that while considerable genetic influences exist for both activational and sedative domains of ETOH effects, these genetic influences are relatively independent.     

A Rating Scale for Assessment of Alcohol Withdrawal Psychopathology (AWIP)

For patients in alcohol withdrawal, there are several scales designed to assess physiological disturbances, but there seems to be a lack of scales for assessment of psychopathology. To develop and evaluate a rating scale for psychopathology, items from the Comprehensive Psychopathological Rating Scale (CPRS) were selected, and patients meeting the DSMR-III-R criteria for alcohol dependence (303.90) were rated on these items. The patients were divided into two groups according to the length of time passed since their last period of alcohol consumption. The groups are referred to as the group (n = 53) in early withdrawal, rated daily during 1 week and the group (n = 13) in late withdrawal, rated once a week for 7 weeks. To justify inclusion in the new scale, items had to either indicate psychopathology in at least half of the patients in one of the groups in withdrawal, or be sensitive to changes over time at a 0.1% level of significance. Seventeen items fulfilled one of these criteria. The scale was tested for inter-rater reliability in a new sample of patients (n = 30) in early withdrawal. Inter-rater reliability, as well as internal consistency, was found satisfactory. This new scale, capable of identifying psychopathology and changes over time, may be used alone or together with physiological scales to identify subgroups of patients undergoing withdrawal.     

Electrophysiological Assessment (The Multiple Sleep Latency Test) of the Biphasic Effects of Ethanol in Humans

The Multiple Sleep Latency Test (MSLT) was used to assess the effects of ethanol at the peak and descending phases of the breath ethanol curve. Ethanol (0.75 g/kg) was administered (at 0900 hr) to 8 healthy, normal-sleeping men, aged 21 to 45 years old after 8 hr of sleep the previous night. MSLTs were conducted and breath ethanol concentrations (BrECs) were measured at 15, 45, 75, 105, 225, and 345 min after drinking was completed. Subjective measures were administered immediately before each sleep latency test. BrECs over the first 75 min (tests 1 to 3) peaked and differed from all subsequent tests (tests 4 to 6) over which BrECs declined. Sleep latency and subjective measures were averaged over tests 1 to 3 and 4 to 6. There was a significant increase in mean sleep latency relative to placebo for tests 1 to 3 and a significant reduction for tests 4 to 6. The subjective measure of stimulation sedation, the Biphasic Alcohol Effects Scale, showed lessened sedation after ethanol versus placebo on tests 1 to 3, compared with tests 4 to 6. This study confirmed the presence of a biphasic ethanol effect using an electrophysiological method (MSLT), showing increased physiological alertness on the peak phase of the BrEC curve and increased sedation on the descending phase. Relative to the effects observed on the MSLT with other low-dose stimulant drugs, the stimulatory effect of ethanol was mild.     

Anticipated Stimulant and Sedative Effects of Alcohol Vary with Dosage and Limb of the Blood Alcohol Curve

Anticipations of alcohol's effects reportedly covary with the amount consumed. Alcohol's stimulant and sedative properties also may contribute to alcohol consumption. Anticipations of stimulant and sedative effects have not been investigated extensively. The present study examined the stimulant and sedative effects subjects anticipated experiencing if they were on the ascending or descending limb of the blood alcohol curve after consuming two or four standard drinks. One hundred sixty-six undergraduates reported anticipating greater stimulant effects than sedative effects on the ascending limb of the blood alcohol curve, and greater sedative effects than stimulant effects on the descending limb. Subjects also reported anticipating larger effects with larger doses. Men tended to anticipate smaller effects than women. These results support the notion that specific anticipated effects vary with dosage and the limb of blood alcohol curve, suggesting that the study of anticipated effects of alcohol should employ these variables.     

Evaluation of the Yale-Brown Obsessive Compulsive Scale (YBOCS-hd) for Heavy Drinking With Mild to Moderately Dependent Alcohol Abusers

BACKGROUND: Many similarities have been noted between urges and desires to drink heavily and obsessive-compulsive disorders (OCD). Based on such similarities, Modell et al. (1992) developed the Yale-Brown Obsessive Compulsive Scale for heavy drinking (YBOCS-hd), a modified version of YBOCS, to assess obsessions and compulsions related to heavy drinking. Evaluation of the YBOCS-hd has been limited to more severely dependent alcohol abusers. METHODS: The present study used a self-administered version of the YBOCS-hd to evaluate (1) the severity of drinking-related obsessive compulsive symptoms with mild to moderately dependent alcohol abusers (problem drinkers), and (2) whether end-of-treatment changes in YBOCS-hd scores would be related to within-treatment functioning. RESULTS: Results indicated that problem drinkers have lower alcohol-related Obsessive and Compulsive subscale scores than did more severely dependent drinkers, but higher scores than did non-problem drinkers, supporting the construct validity of the YBOCS-hd. In addition, at the end of treatment, the YBOCS-hd scores of alcohol abusers who drank at low-risk levels during treatment were significantly lower than the scores of those who drank at high-risk levels. Lastly, exploratory factor analysis did not provide support for the two purported YBOCS-hd subscales (Obsessive, Compulsive). Instead, the analysis yielded a single general factor and a second factor that contained two questions measuring heavy drinking. CONCLUSIONS: Despite the fact that total YBOCS-hd scores covaried with drinking, neither the total YBOCS-hd pretreatment score nor the two subscale scores predicted functioning at the end of treatment. The present results call into question the utility of the YBOCS-hd, because a single item measuring the heaviness of drinking was as useful as the total YBOCS-hd and its two subscales in relating changes during treatment to end-of-treatment functioning for problem drinkers. However, although the YBOCS-hd does not predict changes in drinking, it may have value as an indirect measure of drinking in situations where direct measurement of alcohol consumption is undesirable (i.e., direct measurement might be reactive). Because the present findings are derived from problem drinkers, further research is needed to confirm the factor structure of the YBOCS-hd with clients who represent a broader range of alcohol problem severity.     

Effects of aripiprazole on subjective and physiological responses to alcohol

Background:  Aripiprazole is an atypical antipsychotic with partial agonist activity at D₂ receptors, which could reduce the reinforcing effects of alcohol. The present study examined whether aripiprazole modifies the behavioral and physiological effects of a moderate dose of alcohol in a group of social drinkers.
Methods:  Eighteen healthy subjects (9 men; mean age = 27.6 years) completed a double-blind, within-subject study with 3 experimental sessions in a randomized sequence, during which they received no medication, aripiprazole 2.5 mg, or aripiprazole 10 mg on the day prior to the laboratory session. During the session, subjects consumed alcohol that was served as three standardized drinks (i.e., a total of 0.8 g/kg for men and 0.7 g/kg for women). Breath alcohol concentration (BrAC), heart rate, blood pressure, static ataxia, and subjective effects were measured regularly throughout the laboratory sessions.
Results:  Alcohol consumption produced physiological and subjective responses that were consistent with the literature on its effects. Pre-treatment with aripiprazole was generally well tolerated, with tiredness being the most commonly reported adverse event. The medication was associated with modest physiological effects. It also significantly and dose-dependently increased the sedative effects of alcohol and, to a lesser degree, decreased the euphoric effects of alcohol.
Conclusions:  These findings require replication in a larger subject sample that includes heavy drinkers and in a study that employs a placebo session. Based on its capacity to increase the sedative effects and decrease the euphoric effects of alcohol, aripiprazole could be of value in the treatment of heavy drinking.     

Comparison of the Alcohol Dependence Scale and Diagnostic Interview Schedule in Homeless Women

The Alcohol Dependence Scale (ADS) is a 25 item self-report instrument designed to evaluate the degree of severity of alcohol dependence. Although previous studies have reported on the validity of the ADS, no studies using the ADS have been done on the homeless population, a special and rapidly growing population. To assess the utility of the ADS in a population of homeless, substance-abusing women, the ADS questionnaire was compared with the DSM-III-R alcohol use disorder diagnosis as measured by the Diagnostic Interview Schedule (DIS). Both the ADS and the DIS were administered to 149 homeless, substance-abusing women by trained, lay interviewers. There was good agreement between the ADS and the past-year DIS diagnosis of alcohol use disorder. The level of agreement between the ADS and DIS, as well as sensitivity and specificity, for various ADS cutoff scores are reported to facilitate selection of cutoff scores by clinicians and future researchers.