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Individual differences in subjective alcohol responses and alcohol-related disinhibition.

ABSTRACT: There are important individual differences in acute subjective responses to alcohol, which have often been assessed using self-report measures. There is also evidence of meaningful between-persons variation in alcohol's disinhibiting effects on behavior, such that some individuals become more impaired on tasks of inhibition than do others after an intoxicating dose. The degree to which subjective alcohol responses correspond with these disinhibition effects is not yet clear. In this study, we tested associations among indices of subjective alcohol responses and their correspondence with sensitivity to alcohol-related disinhibition. We recruited recent-binge-drinking emerging adults (N = 82) for a group-administered, placebo-controlled, within-subject, counterbalanced alcohol challenge in a simulated bar laboratory. Confirmatory factor analyses revealed that a 2-factor model with several cross-loadings explained associations among the subjective measures well, replicating a differentiation between stimulant-like and sedative-like subjective responses. Controlling sex and placebo performance, participants who reported greater subjective stimulant-like effects-but not sedative-like effects-experienced more alcohol-related disinhibition, as measured by cued go/no-go task inhibitory failures. This association was small-to-moderate in magnitude. The results of this study highlight the distinction between stimulant-like and sedative-like subjective alcohol effects. They suggest, additionally, that there may be modest commonalities between alcohol's acute impacts on subjective stimulation and objective disinhibition.

SUBMITTER: Quinn PD

PROVIDER: S-EPMC4795977 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Individual differences in subjective alcohol responses and alcohol-related disinhibition.

Quinn Patrick D PD Fromme Kim K

Experimental and clinical psychopharmacology 20160211 2

There are important individual differences in acute subjective responses to alcohol, which have often been assessed using self-report measures. There is also evidence of meaningful between-persons variation in alcohol's disinhibiting effects on behavior, such that some individuals become more impaired on tasks of inhibition than do others after an intoxicating dose. The degree to which subjective alcohol responses correspond with these disinhibition effects is not yet clear. In this study, we te ...[more]

PMID: 26867000

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Project description:Polydrug use is common, and might occur because certain individuals experience positive effects from several different drugs during early stages of use. This study examined individual differences in subjective responses to single oral doses of d-amphetamine, alcohol, and delta-9-tetrahydrocannabinol (THC) in healthy social drinkers. Each of these drugs produces feelings of well-being in at least some individuals, and we hypothesized that subjective responses to these drugs would be positively correlated. We also examined participants' drug responses in relation to personality traits associated with drug use. In this initial, exploratory study, 24 healthy, light drug users (12 male, 12 female), aged 21-31 years, participated in a fully within-subject, randomized, counterbalanced design with six 5.5-hour sessions in which they received d-amphetamine (20mg), alcohol (0.8 g/kg), or THC (7.5 mg), each paired with a placebo session. Participants rated the drugs' effects on both global measures (e.g. feeling a drug effect at all) and drug-specific measures. In general, participants' responses to the three drugs were unrelated. Unexpectedly, "wanting more" alcohol was inversely correlated with "wanting more" THC. Additionally, in women, but not in men, "disliking" alcohol was negatively correlated with "disliking" THC. Positive alcohol and amphetamine responses were related, but only in individuals who experienced a stimulant effect of alcohol. Finally, high trait constraint (or lack of impulsivity) was associated with lower reports of liking alcohol. No personality traits predicted responses across multiple drug types. Generally, these findings do not support the idea that certain individuals experience greater positive effects across multiple drug classes, but instead provide some evidence for a "drug of choice" model, in which individuals respond positively to certain classes of drugs that share similar subjective effects, and dislike other types of drugs.

Project description:BACKGROUND:Human twin studies have shown that certain responses to alcohol, including subjective perceptions, are genetically influenced. Previous studies have provided evidence that a low level of response to alcohol predicts future alcohol use disorders in humans. Recent genetic studies suggest an association between alcohol dependence and genetic variation in the ?-aminobutyric acid A (GABA(A)) receptor ?2 subunit gene (GABRA2). Based on a haplotypic association of alcohol dependence with GABRA2, we investigated whether GABRA2 alleles are associated with the subjective responses to clamped alcohol concentration. METHODS:One hundred and ten healthy social drinkers (53 men) underwent the alcohol clamp. Fifteen minutes after the start of an intravenous infusion of alcohol, the breath alcohol concentration was clamped at a target of 50 ± 5 mg/dl for 165 minutes. Subjective physiologic responses to alcohol and stimulant and sedative effects of alcohol were measured repeatedly during the alcohol clamp. Because aldehyde dehydrogenase 2 (ALDH2) has been shown to have a great impact on the subjective responses to alcohol, we divided subjects by ALDH2 genotype for further analyses. To examine the role of genetic variation in GABRA2, 7 single nucleotide polymorphisms (SNPs) that were informative in association studies were included as factors in the analysis. RESULTS:Among these 7 SNPs, 3 SNPs (rs279869, rs279858, and rs279837) located in the middle of the GABRA2 gene showed significant associations with subjective effects of alcohol. Subjects with 1 or 2 copies of the more common allele showed greater subjective responses to alcohol than did individuals homozygous for the alcohol dependence-associated allele regardless of ALDH2 genotype. CONCLUSIONS:These findings confirm and extend the observation that the GABRA2 alleles affect the subjective responses to alcohol, and suggest that the genetic variations in GABRA2 might play a role in the risk of alcohol use disorders by moderating the subjective effects of alcohol.

Project description:Aims:Converging evidence has implicated perturbed inflammatory signaling in alcohol use disorders (AUDs), and both animal and human studies suggest that alcohol-induced inflammatory signaling is mediated by Toll-Like Receptor 4 (TLR4). We previously demonstrated that TLR4 is hypermethylated in subjects with AUD compared to control individuals. Examining the relationship between TLR4 methylation and subjective alcohol responses could shed light on the role of TLR4 in promoting AUDs, thereby highlighting its potential as a treatment target. Short summary:Significant interactions were demonstrated between Toll-like Receptor 4 (TLR4) methylation and human alcohol consumption patterns, such that greater methylation was associated with decreased positive and negative self-reported arousal during an alcohol infusion among light-to-moderate drinkers, but increased self-reported positive arousal and physiological arousal (i.e. systolic blood pressure) among heavy drinkers. Methods:Latent growth models were used to examine the relationship between TLR4 methylation and subjective responses and physiological measures of arousal during an alcohol infusion across 222 drinkers. Results:We observed significant interactions of TLR4 methylation and alcohol use (drinks per week) on intercepts for self-report and physiological arousal measures. Specifically, light-to-moderate drinkers had positive associations between methylation and stimulation and tension (r's = 0.21-0.24), and heavy drinkers had negative associations (r's = -0.15 to -0.21). There were also significant interaction effects on changes in tension (? = 0.31, P < 0.01), systolic blood pressure (? = 0.74, P < 0.01) and marginal effects on stimulation (? = 0.15, P = 0.07) during the infusion, such that methylation was associated with decreased arousal among light-to-moderate drinkers (r's = -0.12 to -0.25) but stable or increased arousal among heavy drinkers (r's = 0.05-0.19). Conclusions:Findings suggest that the relationship between TLR4 methylation and subjective and physiological arousal during acute alcohol intoxication depends upon on self-reported alcohol use. These data demonstrate the influence of TLR4 on subjective responses to alcohol, thereby supporting the need for further research on its potential as a pharmacological treatment target.

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Individual differences in subjective alcohol responses and alcohol-related disinhibition.

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Individual differences in subjective alcohol responses and alcohol-related disinhibition.

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