Subjective High Assessment Scale Research Articles

Relationship between level of response to alcohol and acute tolerance.

A low level of response (low LR) to alcohol correlates with the later development of alcohol-related problems. Although some of the underpinnings of LR are understood, little is known about the potential relationship between LR and acute tolerance. The current analyses tested the hypothesis that a low LR will be explained in part by more intense acute tolerance to alcohol during a drinking session. Data were generated through a reanalysis of data from 120 individuals who were 18- to 25-year-old, sex-matched pairs of low and high LR drinkers who at baseline did not meet criteria for an alcohol use disorder. Each subject participated in an oral alcohol challenge in which they consumed about 0.7ml ethanol per kg and acute tolerance was measured as the differences in alcohol's effects at similar breath alcohol levels (BrACs) during the rising and falling breath alcohol concentration (BrAC) curve. Measures included aspects of the Subjective High Assessment Scale (SHAS) and body sway. Contrary to our hypothesis, but similar to results with other alcohol measures, acute tolerance was significantly attenuated in low LR compared with high LR individuals on most SHAS scores. Neither LR group demonstrated acute tolerance to alcohol for sleepiness or body sway. Men and women did not differ on any of these measures. These data do not support a role of acute tolerance in the low LR to alcohol as measured by subjective feelings of intoxication or body sway in these subjects, findings that were similar across males and females. In addition, consistent with the literature, the analyses demonstrated differences across measures such that acute tolerance was observed for most measures of subjective effects but not for body sway. Among the subjective effects, acute tolerance was observed for alcohol's intoxicating effect but not for feeling sleepy.

Effects of Alcohol and Acetate on Cerebral Blood Flow: A Pilot Study.

Acute alcohol produces effects on cerebral metabolism and blood flow. Alcohol is converted to acetate, which serves as a source of energy for the brain and is an agonist at G protein-coupled receptors distributed in different cell types in the body including neurons. Acetate has been hypothesized to play a role in the cerebral blood flow (CBF) response after alcohol ingestion. We tested whether administration of acetate would alter CBF in a pattern similar to or different from that of alcohol ingestion in healthy individuals. Twenty-four healthy participants were assigned by convenience to receive either 0.6g/kg alcohol orally (n=12) or acetate intravenously (n=12). For each participant, CBF maps were acquired using an arterial spin labeling sequence on a 3T magnetic resonance scanner after placebo and after drug administration. Whole-brain CBF maps were compared between placebo and drug using a paired t-test, and set at a threshold of p<0.05 corrected for multiple comparisons (k≥142 voxels, ≥3.78cm3 ), voxel-level p<0.005. Intoxication was measured after placebo and drug administration with a Subjective High Assessment Scale (SHAS-7). Compared to placebo, alcohol and acetate were associated with increased CBF in the medial thalamus. Alcohol, but not acetate, was associated with increased CBF in the right orbitofrontal, medial prefrontal and cingulate cortex, and hippocampus. Plasma acetate levels increased following administration of alcohol and acetate and did not differ between the 2 arms. Alcohol, but not acetate, was associated with an increase in SHAS-7 scores (p<0.001). Increased thalamic CBF associated with either alcohol or acetate administration suggests that the thalamic CBF response after alcohol could be mediated by acetate. Compared to other brain regions, thalamus may differ in its ability to metabolize acetate or expression of receptors responsive to acetate. Increased prefrontal and limbic CBF associated with alcohol may be linked to alcohol's behavioral effects.

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

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

Independent and Interactive Effects of OPRM1 and DAT1 Polymorphisms on Alcohol Consumption and Subjective Responses in Social Drinkers.

The current study examined independent and interactive effects of polymorphisms of the mu opioid receptor gene (OPRM1, A118G) and variable number tandem repeats of the dopamine transporter gene (DAT1, SLC6A3) on alcohol consumption and subjective responses to alcohol in 127 young, healthy, social drinkers. Participants completed an in-person assessment, which included self-reported alcohol drinking patterns and blood sampling for DNA, and in a second visit, a cumulative alcohol dosing procedure with subjective ratings across multiple time points and breath alcohol contents (0.03 to 0.1%). DNA was analyzed for OPRM1 AA versus AG/GG (*G) genotypes, DAT1 10-repeat allele (A10) versus 9 or lesser alleles (A9), and ancestral informative markers. There were significant epistatic interactions between OPRM1 and DAT1 genotypes. Subjective High Assessment Scale scores after alcohol consumption were highest in *G and A9 carriers, and lowest in *G and A10 carriers. Negative subjective effects were also highest in *G and A9 carriers. Effects were similar in a sensitivity analysis limited to Caucasian subjects. There were independent and epistatic interactions on drinking. The OPRM1 *G allele was independently associated with fewer heavy drinking days. The A9 allele was associated with a greater number of drinking days, which was attenuated in carriers of the *G allele. These findings highlight the biological importance of interactions between these 2 genes and interactions between brain opioid and dopamine systems.

Low voltage alpha EEG phenotype is associated with reduced amplitudes of alpha event-related oscillations, increased cortical phase synchrony, and a low level of response to alcohol

Low voltage EEG (LVEEG) is a heritable phenotype that differs depending on ancestral heritage, yet its impact on brain networks and cognition remain relatively unexplored. In this study we assessed energy and task related phase locking of event-related oscillation (EROs), behavioral responses, measures of IQ and personality, and expected responses to alcohol in a large sample of individuals with LVEEG compared to those with higher voltage variants. Participants (n=762) were recruited from a Native American community and completed a diagnostic interview, the Quick Test, the Subjective High Assessment Scale Expectation Version (SHAS-E) and the Maudsley Personality Inventory. Clinical and spectral analyzed EEGs were collected for determination of the presence of a LVEEG variant. EROs were generated using a facial expression recognition task. Participants with LVEEG (n=451) were significantly more likely to be older, married and have higher degrees of Native American heritage but did not differ in gender, income or education. Individuals with LVEEG were also found to have decreased energy in their alpha EROs, increased phase locking between stimulus trials, and increased phase-locking between cortical brain areas. No significant differences in the cognitive tests, personality variables or alcohol dependence or anxiety diagnoses were found, however, individuals with LVEEG did report a larger number of drinks ever consumed in a 24-h period and a less intense expected response to alcohol. These data suggest that alpha power in the resting EEG is highly associated with energy and cortical connectivity measures generated by event-related stimuli, as well as potentially increased risk for alcohol use.

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

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

Subjective response to alcohol and ADH polymorphisms in a select sample of young adult male East Indians and Africans in Trinidad and Tobago.

Level of response to alcohol has been associated with risk of alcohol dependence in a number of ethnic groups. In the present study, subjective and objective responses to alcohol were evaluated in Indo-Trinidadians (Indo-T) and Afro-Trinidadians (Afro-T). Associations of alcohol dehydrogenase polymorphisms with response to alcohol, using the Subjective High Assessment Scale (SHAS), and breath alcohol concentrations (BrAC) were tested. Regular male drinkers without alcohol dependence (n = 112) ages 18-25 years participated in alcohol challenge sessions consisting of placebo and two doses of alcohol (target BrAC: 0 g/dl for placebo, .04 g/dl low dose, and .08 g/dl high dose) and genotyped for variants in ADH1B*3 and ADH1C*2. Indo-T had significantly higher BrAC, pulse rates, and cortisol levels when compared with Afro-T but did not have significantly higher SHAS values. Higher responses on the SHAS items muddle/confused and nauseated were significantly associated with the presence of at least one ADH1B*3 allele following the high dose of alcohol in Afro-T. Indo-T with at least one ADH1C*2 allele displayed significantly different Drug × Time interactions for the SHAS item effects of alcohol at the low dose and for the SHAS items clumsy, muddle/confused, effects of alcohol, floating, drunk, and total at the high dose from Indo-T with two ADH1C*1 alleles. This is the first study that has investigated individual sensitivity to alcohol in a Caribbean population and in people of East Indian descent. Indo-T with at least one ADH1C*2 allele may be at higher risk for heavy drinking by feeling less of the effects of alcohol, including nausea. In Afro-T, having at least one ADH1B*3 allele appears to exert a protective effect by enhancing the unpleasant effects of alcohol, such as nausea and confusion.

Associations between a history of binge drinking during adolescence and self-reported responses to alcohol in young adult Native and Mexican Americans.

Binge drinking during adolescence is common and may predict increased drinking in young adulthood and enhanced risk of alcohol dependence. Variation in level of response to the hedonic and adverse effects of alcohol is in part an inherited factor that may also influence its use, abuse, and dependence. This study investigated, in young adults, whether an association could be demonstrated between variation in self-reported responses to alcohol and a history of binge drinking during adolescence. Young adult (18 to 30 years, n = 790) Native Americans and Mexican Americans were recruited from the community and completed a structured diagnostic interview. Response to alcohol was indexed using the expectation version of the Subjective High Assessment Scale (SHAS-E). An adolescent history of regular binge drinking was defined as drinking 5 or more drinks for boys and 4 or more drinks for girls per drinking occasion at least once a month during their highest drinking period prior to the age of 18. An adolescent history of regular binge drinking was found to be associated with a lower level of self-reported responses to the negative aspects of alcohol intoxication (feeling terrible) as well as to the overall level of intoxication, but not to the positive impressions of intoxication (feeling great) on the SHAS-E. A history of regular adolescent binge drinking was also correlated with less feelings of the "terrible" and "total" effects of alcohol, as indexed by the SHAS-E, in a linear regression model that included several diagnostic and demographic variables such as a history of conduct disorder and current levels of drinking. These data suggest that a history of adolescent binge drinking is associated with a reduction in the self-reported level of intoxication in young adulthood, a factor that could theoretically lead to increased risk of alcohol dependence.

The Investigation into CYP2E1 in Relation to the Level of Response to Alcohol Through a Combination of Linkage and Association Analysis

A low level of response to alcohol during an individual's early experience with alcohol is associated with an increase risk of alcoholism. A family-based genome-wide linkage analysis using sibling pairs that underwent an alcohol challenge where the level of response to alcohol was measured with the Subjective High Assessment Scale (SHAS) implicated the 10q terminal (10qter) region. CYP2E1, a gene known for its involvement with ethanol metabolism, maps to this region. Variance component multipoint linkage analysis was performed on a combined map of single-nucleotide polymorphism (SNP) and microsatellite data. To account for the heterogeneity evident in the dataset, a calculation assuming locus heterogeneity was made using the Heterogeneity Log of Odds (HLOD) score. Association between SNP marker allele counts and copy number and SHAS scores were evaluated using a logistic regression model. Linkage analysis detected significant linkage to CYP2E1, which was diminished because of apparent locus heterogeneity traced to a single family with extreme phenotypes. In retrospect, circumstances recorded during testing for this family suggest that their phenotype data are likely to be unreliable. Significant allelic associations were detected for several CYP2E1 polymorphisms and the SHAS score. DNA sequencing from families that contributed the greatest evidence for linkage did not detect any changes directly affecting the primary amino acid sequence. With the removal of a single family, combined evidence from microsatellites and SNPs offers significant linkage between the level of response to alcohol and the region on the end of chromosome 10. Combined linkage and association indicate that sequence changes in or near CYP2E1 affect the level of response to alcohol providing a predictor of risk of alcoholism. The absence of coding sequence changes indicates that regulatory sequences are responsible. Implicating CYP2E1 in the level of response to alcohol allows inferences to be made about how the brain perceives alcohol.

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

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. 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 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. 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.

Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians

BackgroundVariation in response to the hedonic and adverse effects of a substance is in part an inherited factor that may influence its use, abuse and dependence. The mu opioid receptor is the primary site of action for opiates and individuals with polymorphisms in this receptor appear to have variation in the CNS effects of opiates. Several studies have suggested that this receptor may also mediate some of the effects of non-opioid drugs, such as alcohol. The purpose of this study was to investigate associations between 13 single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) with self-reported responses to alcohol, an endophenotype associated with the development of alcohol dependence, in American Indians living on eight contiguous reservations.MethodsEach participant gave a blood sample and completed a structured diagnostic interview. Additionally, response to alcohol was indexed using the expectation version of the subjective high assessment scale (SHAS-E). SNPs were genotyped in 251 participants and data analyses were conducted using SOLAR.ResultsThe estimated heritability (h2) for the SHAS-E phenotypes ranged from 0.01 to 0.28. Endorsing the expectation of a more intense response on one or more of the following items from the SHAS-E: buzzed, clumsy, dizzy, drunk, effects, high, nausea, sleepy, talkative, terrible, and/or uncomfortable after imbibing 2–3 drinks was significantly associated with having at least one minor allele for at least one of 7 SNPs (p < 0.01) in the OPRM1 receptor gene.ConclusionThese studies provide data to suggest that the minor allele, for most of the polymorphisms in the OPRM1 receptor gene investigated, was found to be associated with a more intense, and/or more adverse, response to alcohol, traits that are significantly correlated with lowered quantity of alcohol consumption and less susceptibility to dependence in this Indian population. These data further suggest that making conclusions on the role of the mu opiod receptor gene in the development of alcohol dependence may be limited if only one polymorphism in the gene is evaluated in isolation.

Autosomal Linkage Analysis for the Level of Response to Alcohol

The level of response (LR) to alcohol is a genetically-influenced phenotype related to the alcoholism risk. Usually measured by evaluating psychological and physiological changes that follow the administration of alcohol, the heritability of LR is estimated to be between 0.4 and 0.6, and efforts are being made to find genes related to this phenotype. This paper presents data from a family-based genome with linkage analysis focusing on alcohol challenge determinants of LR. The subjects were 18-to-29-year-old sibling pairs with at least one parent who was alcohol-dependent and who had experience with alcohol but were not yet alcohol-dependent themselves. Both members of the sibling pairs were given oral alcohol challenges (0.75-0.90 ml/kg of ethanol for females and males, respectively), with LR established using the Subjective High Assessment Scale (SHAS) and changes in body sway (BS) repeatedly over a 3.5-hr. period. Blood samples from siblings and at least one parent were genotyped using 811 microsatellite markers, with results evaluated using several related variance component approaches as implemented in SOLAR for continuous traits. In addition, association was tested using single nucleotide polymorphisms (SNPs) within the KCNMA1, HTR7 and SLC18A2 genes that may relate to a finding on chromosome 10. Data were generated from 238 sib-pairs representing 365 individuals (41.6% were males) from 165 families. The most consistent results across methods and samples were observed for SHAS on chromosome 10 between 120 and 140 cM (with a maximum LOD score of 2.6 at 122 cM), and a second region of possible interest at 173 cM (LOD = 1.2). Statistical analysis with the KCNMA1, HTR7 and SLC18A2 genes, which lie in the support region of interest revealed no evidence for association after correction for multiple comparisons. These evaluations from the largest known alcohol challenge-based genetic study to date highlight the potential importance of genes on chromosome 10 as possible contributors to the low LR to alcohol as a risk factor for alcoholism.

The level of response to alcohol in daughters of alcoholics and controls

Background: The low level of response (LR) to alcohol is a genetically influenced characteristic related to the development of alcohol use disorders (AUDs). This phenotype is found in men with a family history (FH) of alcoholism, predicts future AUDs, and has heritabilities as high as 60%. However, despite evidence of genetic influences for AUDs in both sexes, the majority of studies evaluating differences in LR across high- and low-risk groups have been conducted on males, and it is unclear how generalizable these results are to women. Methods: Twenty-five women who are family history positive (FHP) for alcohol dependence were matched with 25 women with no FH of alcoholism (FHN) on factors that may impact LR. Using an alcohol challenge paradigm, data on the reaction to a moderate dose of alcohol were gathered over a period of 3.5 h. Assessments included breath alcohol concentrations (BrACs), the Subjective High Assessment Scale (SHAS), as well as body sway or static ataxia. Results: Family history positives reported lower subjective intoxication than FHNs. In addition, when body sway scores were corrected for skewness, FHPs had significantly lower scores on alcohol-related changes in lateral sway. These differences remained after considering the effects of drinking history and BrAC values. Conclusions: This study evaluated the LR to alcohol in the largest sample of alcohol challenges in matched FHP and FHN women to date. Overall, the findings are consistent with most data from earlier investigations of smaller sized samples of FHP women. The results suggest that, similar to sons of alcoholics, a low LR to alcohol might also be characteristic of daughters of alcoholics.

EEG alpha and level of response to alcohol in Hispanic- and non-Hispanic-American young adults with a family history of alcoholism.

A person's level of response to alcohol is associated with family history of alcoholism, ethnic heritage and electroencephalogram (EEG) phenotype. The present study's aims were to investigate EEG alpha and response to alcohol in Hispanic-American and non-Hispanic-American young adults. EEG power in the slow and fast alpha frequency ranges (7.5-9 Hz, 9-12 Hz) was obtained at baseline and at 74 minutes following the administration of alcohol to Hispanic-American (n = 79) and white non-Hispanic-American (n = 208) young adult men and women (18-25 years old), all of whom had a family history but no personal history of alcohol dependence. Measures of breath alcohol concentrations and subjective responses to alcohol (Subjective High Assessment Scale [SHAS]) also were ascertained. Alcohol was found to produce significant effects on EEG power in the slow (F = 79.5, p < .0001) alpha frequency range. Although no overall effects of alcohol were found in the fast alpha frequency range, Hispanic participants had decreases in EEG fast alpha activity following alcohol administration, whereas non-Hispanics had alcohol-induced increases in power in this frequency range (F = 4.0, p < .04). EEG power, in the fast alpha frequency range (9-12 Hz) at baseline, also was found to be negatively associated with level of response to alcohol, as indexed by SHAS scores (F = 5.2, 2/283 df, p < .023). Previous studies in Native Americans, Asians and Euro-Americans have suggested genetic stratification in EEG response to alcohol as well as significant associations with family history of alcoholism. The present results extend previous studies to Hispanics and further confirm that increased EEG alpha power at baseline is predictive of a less intense response to alcohol, as indexed by the SHAS.

The search for genes related to a low-level response to alcohol determined by alcohol challenges.

A low level of response (LR) to alcohol seems to relate to a substantial proportion of the risk for alcoholism and to have significant heritability. This report describes the results of a genome-wide segregation analysis for the first 139 pairs of full siblings by using an alcohol challenge protocol as a direct measure of LR. Subjects from 18 to 29 years old were selected if the original screen indicated they had an alcohol-dependent parent, reported a personal history of drinking but had no evidence of alcohol dependence, and had a full sibling with similar characteristics. Body sway and Subjective High Assessment Scale scores were measured at baseline and at regular intervals after the administration of a measured dose of alcohol. Participants and available parents were genotyped for 811 microsatellite markers, and resulting data were analyzed with a variance component method. Nine chromosome regions with logarithm of the odds ratio (LOD) between 2.2 and 3.2 were identified; several had previously been implicated regarding phenotypes relevant to alcoholism and the LR to alcohol. Several regions identified in the previous linkage study by using a retrospective self-report questionnaire were potentially confirmed by this study. The strongest evidence was on chromosomes 10, 11, and 22. Several chromosomal areas seem to relate to the low LR to alcohol as a risk factor for alcohol dependence.

Reliability and validity of alcohol-induced heart rate increase as a measure of sensitivity to the stimulant properties of alcohol.

Alcohol-induced heart rate (HR) stimulation during the rising limb of the blood alcohol curve reliably discriminates between individuals at differential risk for alcoholism, and appears to be a potential psychophysiological index of psychomotor stimulation from alcohol. Three studies are presented which explore the reliability and convergent and discriminant validity of this alcohol response index. Young men with and without a multigenerational family history of alcoholism were administered a 1.0 ml/kg dose of 95% USP alcohol. Resting baseline cardiac and subjective measures were assessed before and after alcohol consumption. Study 1 demonstrated that alcohol-induced HR stimulation was significantly and positively related to alcohol-induced changes in mood. Study 2 demonstrated that alcohol-induced HR stimulation was reliable across two alcohol administration sessions (r=0.33-0.66, P<0.01). Study 3 explored the relationship between the proposed index and measures of sensitivity to alcohol previously linked to genetic predisposition to alcoholism. Multiple regression analysis indicated that alcohol-induced HR increase and reduced subjective intoxication (measured using the Subjective High Assessment Scale) were both positively associated with alcohol-induced changes in mood states that have previously been shown to be sensitive to the effects of stimulant drugs and the reinforcing effects of alcohol. Sensitivity to alcohol-induced heart-rate stimulation during the ascending limb of the blood alcohol curve may be a useful and informative marker for understanding susceptibility to alcoholism.

Response to alcohol in daughters of alcoholics: a pilot study and a comparison with sons of alcoholics.

Drinking, but not alcohol-dependent, 18-29-year-old daughters of alcoholics (n = 38) from the Collaborative Study on the Genetics of Alcoholism were compared to 75 family-history-positive (FHP) men from the same families, and 68 family-history-negative (FHN) male controls. Subjects received 0.75 ml/kg of ethanol (for women), 0.9 ml/kg of ethanol (for men), and placebo, each of which was consumed over 8 min on different occasions. The breath-alcohol concentrations (BrAC) and reactions to alcohol [using the Subjective High Assessment Scale (SHAS) and body sway measures] were evaluated over 210 min. The results indicate that, despite slightly higher BrAC values for the FHP men, on the SHAS the FHP women and the FHP men demonstrated significantly lower scores than the FHN male controls, although the values for FHP men and women did not differ. On body sway, the FHP men showed evidence of less alcohol-related increases than FHN men, and there was a trend in the same direction for FHP women, but only early in the session (e.g. at 60 min). Pilot data for 11 FHN women revealed higher scores for both SHAS and body sway at 60 min, compared to FHP women, but, perhaps reflecting the small number of subjects, the family history differences were not significant. Overall, the results in FHP women resemble those for FHP men, and suggest that a low level of response to alcohol might also be a characteristic of daughters of alcoholics.

Clamping Breath Alcohol Concentration Reduces Experimental Variance: Application to the Study of Acute Tolerance to Alcohol and Alcohol Elimination Rate

An oral loading dose was combined with intravenous infusion of 6% alcohol at rates adjusted on-line to close the gap between measurements of breath alcohol concentration (BrAC) and a target of 50 mg%. The goal was to minimize the deviation from a prescribed course of BrAC over time. In a pilot study of 10 young men, subjects underwent three experimental sessions: twice at 50 mg% and once in a 0 mg% control condition. The pilot study assessed the performance of the BrAC clamp, its potential utility in studies of acute tolerance to alcohol, and the retest reliability of directly measuring the alcohol elimination rate (AER) calculated from the steady-state infusion rate. Reduced variance was demonstrated in 4 of 5 experimental parameters, compared with results of an earlier approach using a split-dose oral administration procedure. Subjects' perceptions about alcohol effects were measured in one BrAC clamping session, using Schuckit's Subjective High Assessment Scale: 3 of 15 Schuckit's items demonstrated statistically significant indices of acute tolerance to alcohol. Within-subject AERs calculated in the steady-state had a coefficient of variation of 6.5%. Details of the BrAC clamping procedure are provided. The pilot study demonstrated the ability to prescribe experimental parameters of the brain's exposure to alcohol while preserving experimental flexibility in studies of acute tolerance to alcohol and AER.

The relationship between Self-Rating of the Effects of alcohol and alcohol challenge results in ninety-eight young men.

The level of intensity of response to a drug is likely to influence the future pattern of intake of the substance. This article evaluates a simple Self-Rating of the Effects (SRE) of alcohol form, and reports the relationship between a person's estimate of the amounts of alcohol usually required for four possible effects during three different time frames and his subjective feelings reported during an alcohol challenge. SRE forms and results of a challenge with 0.9 ml/kg (0.72 g/kg) of ethanol were available for 18 to 29 year old drinking, but not alcohol dependent, men (N = 98). A subset of 40 subjects completed a second SRE form approximately 1 year later. The correlation between the two SRE administration was .82 (p < .0001), and the results on the SRE were internally consistent, with a higher number of drinks associated with more intense alcohol effects. Focusing on the subjective feelings reported at the 60-minute timepoint during the alcohol challenge, 11 of the 12 alcohol effect categories on the SRE correlated in the predicted direction, including eight that were statistically significant. Evaluating all seven timepoints during the drinking experiment, the average number of drinks on the SRE correlated significantly with the Subjective High Assessment Scale (SHAS) total score at all but the final timepoint. Sons of alcoholics and controls demonstrated similar levels of correlation between SRE and alcohol challenge results. Finally, the SRE correctly identified 79% of the individuals whose levels of response to alcohol fell into the lowest third of intensity during the alcohol challenge, and it correctly classified 60% to 67% of the alcohol challenge subjects who did not fall into that low response category. The SRE is a simple and reliable measure of a person's estimate of the number of drinks required to achieve a response. The form might be helpful in educating people about the intensity of their response to alcohol and might be useful as a point of discussion in curricula focusing on genetic aspects of alcoholism. When alcohol challenges are not possible in a research protocol, the SRE might help identify a less heterogeneous subgroup of individuals at high risk for alcoholism who have a common mechanism increasing their vulnerability.

Alcohol and Secobarbital Effects as a Function of Familial Alcoholism: Extended Intoxication and Increased Withdrawal Effects

Response differences following administration of alcohol between adult males with a positive (FHP) versus negative (FHN) family history of alcoholism have been demonstrated in previous research and are thought to be related to risk for developing alcoholism. If this is so, the pharmacological breadth of addiction risk conferred by a positive family alcoholism history might be studied by determining whether FHP subjects show different responses than FHN to drug classes other than alcohol. We have previously reported on the acute effects of ethanol as compared with secobarbital in FHP and FHN subjects and found that FHP subjects showed greater sensitivity across a variety of subjective measures than FHN subjects for both drug classes. The data reported here are based on an extended data collection period of 3 to 18 hr postingestion, following completion of the acute laboratory portion of the study. Specifically, in the present study, dose-effect timecourse functions for a variety of physiological (heart rate, blood pressure, and breath alcohol level), subjective (analog mood, drug effect, and withdrawal, Subjective High Assessment Scale (SHAS], and psychomotor measures (Digit Symbol Substitution Test and numeric recall) were examined in FHP and FHN college-aged males for secobarbital (0, 100, 200 mg daily) and ethanol (1 g/kg daily). FHP and FHN subjects were matched on light-to-moderate drinking patterns, anthropometric dimensions, age, years of schooling, and drug use. FHP subjects reported more extended intoxication and greater withdrawal effects following both ethanol and the high dose of secobarbital than did FHN subjects.(ABSTRACT TRUNCATED AT 250 WORDS)