Alcohol

Effects of Initiating Moderate Alcohol Intake on Cardiometabolic Risk in Adults With Type 2 Diabetes

Yftach Gepner, Rachel Golan, Ilana Harman‐Boehm +24 more · Annals of Internal Medicine · 2015 · 192 citations

Among alcohol-abstaining adults with well-controlled type 2 diabetes following a Mediterranean diet, initiating 150 mL (about 5 oz) of red wine with dinner daily for two years safely and modestly improved certain heart health markers and sleep quality, suggesting it might be a beneficial dietary addition for some.

Brain Morphometry and Cognitive Performance in Detoxified Alcohol-Dependents with Preserved Psychosocial Functioning

Sandra Chanraud, Catherine Martelli, Françoise Delain +5 more · Neuropsychopharmacology · 2006 · 419 citations

Effects of Moderate Alcohol Consumption on Cognitive Function in Women

Meir J. Stampfer, Jae H. Kang, Jennifer Chen +2 more · New England Journal of Medicine · 2005 · 396 citations

BACKGROUND: The adverse effects of excess alcohol intake on cognitive function are well established, but the effect of moderate consumption is uncertain. METHODS: Between 1995 and 2001, we evaluated cognitive function in 12,480 participants in the Nurses' Health Study who were 70 to 81 years old, with follow-up assessments in 11,102 two years later. The level of alcohol consumption was ascertained regularly beginning in 1980. We calculated multivariate-adjusted mean cognitive scores and multivariate-adjusted risks of cognitive impairment (defined as the lowest 10 percent of the scores) and a substantial decline in cognitive function over time (defined as a change that was in the worst 10 percent of the distribution of the decline). We also stratified analyses according to the apolipoprotein E genotype in a subgroup of women. RESULTS: After multivariate adjustment, moderate drinkers (those who consumed less than 15.0 g of alcohol per day [about one drink]) had better mean cognitive scores than nondrinkers. Among moderate drinkers, as compared with nondrinkers, the relative risk of impairment was 0.77 on our test of general cognition (95 percent confidence interval, 0.67 to 0.88) and 0.81 on the basis of a global cognitive score combining the results of all tests (95 percent confidence interval, 0.70 to 0.93). The results for cognitive decline were similar; for example, on our test of general cognition, the relative risk of a substantial decline in performance over a two-year period was 0.85 (95 percent confidence interval, 0.74 to 0.98) among moderate drinkers, as compared with nondrinkers. There were no significant associations between higher levels of drinking (15.0 to 30.0 g per day) and the risk of cognitive impairment or decline. There were no significant differences in risks according to the beverage (e.g., wine or beer) and no interaction with the apolipoprotein E genotype. CONCLUSIONS: Our data suggest that in women, up to one drink per day does not impair cognitive function and may actually decrease the risk of cognitive decline.

Moderate sleep deprivation produces impairments in cognitive and motor performance equivalent to legally prescribed levels of alcohol intoxication

Ann Williamson, Anne-Marie Feyer · Occupational and Environmental Medicine · 2000 · 706 citations

OBJECTIVES: To compare the relative effects on performance of sleep deprivation and alcohol. METHODS: Performance effects were studied in the same subjects over a period of 28 hours of sleep deprivation and after measured doses of alcohol up to about 0.1% blood alcohol concentration (BAC). There were 39 subjects, 30 employees from the transport industry and nine from the army. RESULTS: After 17-19 hours without sleep, corresponding to 2230 and 0100, performance on some tests was equivalent or worse than that at a BAC of 0.05%. Response speeds were up to 50% slower for some tests and accuracy measures were significantly poorer than at this level of alcohol. After longer periods without sleep, performance reached levels equivalent to the maximum alcohol dose given to subjects (BAC of 0. 1%). CONCLUSIONS: These findings reinforce the evidence that the fatigue of sleep deprivation is an important factor likely to compromise performance of speed and accuracy of the kind needed for safety on the road and in other industrial settings.

Executive Functioning in Children With Heavy Prenatal Alcohol Exposure

Sarah N. Mattson, Amy Goodman, Chip Caine +2 more · Alcoholism Clinical and Experimental Research · 1999 · 373 citations

BACKGROUND: Children with heavy prenatal alcohol exposure have well documented deficits in overall cognitive ability. Recently, attention has turned to the executive function (EF) domain in this population. Until recently, comprehensive measures of EF have not been available within one test battery. This study used a battery of tests to assess four domains of EF in alcohol-exposed children. METHODS: The Delis-Kaplan Executive Function Scale was used to evaluate EF in 18 children with heavy prenatal alcohol exposure, with and without a diagnosis of fetal alcohol syndrome (FAS), and 10 nonexposed controls. Children ranged in age from 8 to 15 years. Measures from four domains of executive functioning were analyzed: planning ability, cognitive flexibility, selective inhibition, and concept formation and reasoning. Tasks consisted of primary EF measures as well as measures of secondary component skills. RESULTS: Alcohol-exposed children were deficient on EF measures compared with nonexposed controls. Furthermore, in most cases, children with and without the FAS diagnosis did not differ from one another. These deficits were not entirely explainable by concomitant deficits on component skills. Specific impairments were identified within the domains of planning and response inhibition, with additional deficits in abstract thinking and flexibility. CONCLUSIONS: Deficits in executive functioning were observed in alcohol-exposed children with or without the diagnosis of FAS and in the absence of mental retardation. Performance on these EF tasks provides insight into the cognitive processes driving overall performance and has implications for adaptive and daily functions. These results are consistent with anecdotal and empirical reports of deficits in behavioral control and with neuroanatomical evidence of volumetric reductions in structures within the frontal-subcortical system in children with heavy prenatal alcohol exposure.

Prevalence of cognitive impairment in patients with substance use disorder

Carolien J. W. H. Bruijnen, Boukje A.G. Dijkstra, Serge J. W. Walvoort +4 more · Drug and Alcohol Review · 2019 · 174 citations

INTRODUCTION AND AIMS: Cognitive impairments in substance use disorder predict treatment outcome and are assumed to differ between substances. They often go undetected, thus the current study focuses on the prevalence of and differences in cognitive functioning across substances by means of a cognitive screen at the early stage of addiction treatment. DESIGN AND METHODS: The Montreal Cognitive Assessment was administered to outpatients seeking treatment for substance use disorder. Patient characteristics (age, years of regular use, polysubstance use, severity of dependence/abuse, depression, anxiety and stress) were also taken into account. RESULTS: A total of 656 patients were included (n = 391 used alcohol, n = 123 used cannabis, n = 100 used stimulants and n = 26 used opioids). The prevalence of cognitive impairments was 31%. Patients using alcohol had a lower total- and memory domain score than those using cannabis. Patients using opioids scored lower on visuospatial abilities than those using cannabis or stimulants. Younger patients scored higher than older patients. No effect was found for the other investigated characteristics. DISCUSSION AND CONCLUSIONS: Given the high prevalence of cognitive impairments, standard screening at an early stage of treatment is important to determine the course of treatment and maximise treatment outcome. Caution is needed in interpreting results about opioids due to an underrepresentation of this patient group, and more research is needed on the effect of age on Montreal Cognitive Assessment performance.

Alcohol Consumption Impairs Detection of Performance Errors in Mediofrontal Cortex

K. Richard Ridderinkhof, Yolande de Vlugt, Aldo Bramlage +4 more · Science · 2002 · 348 citations

The anterior cingulate cortex (ACC) is a critical component of the human mediofrontal neural circuit that monitors ongoing processing in the cognitive system for signs of erroneous outcomes. Here, we show that the consumption of alcohol in moderate doses induces a significant deterioration of the ability to detect the activation of erroneous responses as reflected in the amplitude of brain electrical activity associated with the ACC. This impairment was accompanied by failures to instigate performance adjustments after these errors. These findings offer insights into how the effects of alcohol on mediofrontal brain function may result in compromised performance.

Pattern of Motor and Cognitive Deficits in Detoxified Alcoholic Men

Edith V. Sullivan, Margaret J. Rosenbloom, Adolf Pfefferbaum · Alcoholism Clinical and Experimental Research · 2000 · 441 citations

BACKGROUND: Chronic excessive consumption of alcohol produces marked deficits in cognitive and motor abilities, although not all functions are affected to the same extent. Furthermore, although the occurrence of neuropsychological deficits in recently detoxified alcoholics is firmly established, the relative severity of these deficits, the specific neural systems that underlie the deficits, and their relationship to age and alcohol consumption variables either are less established or have proven elusive altogether. METHODS: We administered an extensive battery of neuropsychological tests, chosen for their known sensitivity to brain lesions in specific locations, to 71 recently (1 month) detoxified alcoholic men and 74 healthy controls who spanned the adult age range. Test scores were standardized to the controls for age and grouped a priori into composites that reflected performance in six functional domains: executive functions, short-term memory, upper limb motor ability, declarative memory, visuospatial abilities, and gait and balance. Analogous verbal and nonverbal materials and left- and right-hand upper limb motor tasks were used to test whether alcohol-related deficits were greater for left or right hemisphere. RESULTS: Compared with controls, the alcoholics were impaired on executive functions, visuospatial abilities, and gait and balance even after we accounted for group differences in estimated premorbid IQ and education. Within the alcoholic group, the most salient deficits were in gait and balance and visuospatial abilities. No consistent lateralized deficit was observed across the four domains tested. Unlike the cognitive composites, the upper limb motor ability and gait and balance composites both showed increasing vulnerability to age, with an independent contribution to the gait and balance dysfunction from the amount of alcohol consumed over a lifetime. CONCLUSIONS: The pattern of functional deficits implicates at least two principal neural systems: the cerebellar-frontal system and the corticocortical system between the prefrontal and parietal cortices. In addition, age and amount of alcohol consumption were better predictors of motor than cognitive impairments.

Model-Based and Model-Free Decisions in Alcohol Dependence

Miriam Sebold, Lorenz Deserno, Stephan Nebe +11 more · Neuropsychobiology · 2014 · 196 citations

BACKGROUND: Human and animal work suggests a shift from goal-directed to habitual decision-making in addiction. However, the evidence for this in human alcohol dependence is as yet inconclusive. METHODS: Twenty-six healthy controls and 26 recently detoxified alcohol-dependent patients underwent behavioral testing with a 2-step task designed to disentangle goal-directed and habitual response patterns. RESULTS: Alcohol-dependent patients showed less evidence of goal-directed choices than healthy controls, particularly after losses. There was no difference in the strength of the habitual component. The group differences did not survive controlling for performance on the Digit Symbol Substitution Task. CONCLUSION: Chronic alcohol use appears to selectively impair goal-directed function, rather than promoting habitual responding. It appears to do so particularly after nonrewards, and this may be mediated by the effects of alcohol on more general cognitive functions subserved by the prefrontal cortex.

Mapping callosal morphology and cognitive correlates

ER Sowell, Sarah N. Mattson, Paul M. Thompson +3 more · Neurology · 2001 · 252 citations

BACKGROUND: Abnormalities of the corpus callosum (CC) have been documented in fetal alcohol syndrome (FAS), ranging from subtle decrements in its size to partial and even complete agenesis. Prenatal exposure to alcohol is also known to result in neurocognitive deficits. OBJECTIVE: To 1) investigate abnormalities in size, shape, and location of the CC within the brain in individuals with FAS and in those exposed to high amounts of alcohol prenatally but without FAS (PEA group); and 2) determine if there is a relationship between callosal dysmorphology and cognitive test performance. METHODS: MRI and novel surface-based image analytic methods were used. Twenty alcohol-exposed subjects (8 to 22 years) along with 21 normal controls (8 to 25 years) were studied with high-resolution MRI and measures of verbal learning and visuospatial abilities. RESULTS: In addition to callosal area reductions, most severe in the splenium, the CC is significantly displaced in patients exposed to alcohol prenatally. In the alcohol-exposed group, this structure lies more anterior and inferior in posterior regions with relatively normal localization of anterior regions. These findings are significant in the FAS group, and a similar but less severe pattern is observed in the PEA patients. The authors show that the amount of CC displacement is correlated with impairment in verbal learning ability and that CC displacement is a better predictor of verbal learning than regional CC area. The brain-behavior relationship is only significant within the alcohol-exposed group, and the effect is not solely mediated by overall impaired verbal intellectual functioning. CONCLUSIONS: These results further emphasize the vulnerability of midline brain structures to prenatal alcohol exposure.

Gender differences in moderate drinking effects.

M Mumenthaler, Joy L. Taylor, Ruth O’Hara +1 more · PubMed · 1999 · 339 citations

Women appear to become more impaired than men after drinking equivalent amounts of alcohol, achieving higher blood alcohol concentrations even when doses are adjusted for body weight. This finding may be attributable in part to gender differences in total body water content. Men and women appear to eliminate approximately the same total amount of alcohol per unit body weight per hour. However, women seem to eliminate significantly more alcohol per unit of lean body mass per hour than men. Some studies report that women are more susceptible than men to alcohol-related impairment of cognitive performance, especially in tasks involving delayed memory or divided attention functions. Psychomotor performance impairment, however, does not appear to be affected by gender. This article provides an overview of alcohol metabolism (pharmacokinetics) and reviews recent studies on gender differences in alcohol absorption, distribution, elimination, and impairment. Speculation that gender differences in alcohol pharmacokinetics or alcohol-induced performance impairment may be caused by the menstrual cycle and variations in female sex hormones are discussed. It is concluded that the menstrual cycle is unlikely to influence alcohol pharmacokinetics.

Neuropsychological Deficits Are Correlated with Frontal Hypometabolism in Positron Emission Tomography Studies of Older Alcoholic Patients

Kenneth M. Adams, Sid Gilman, Robert A. Koeppe +5 more · Alcoholism Clinical and Experimental Research · 1993 · 214 citations

In an extension of previous work, we studied the behavioral correlates of medial frontal lobe glucose hypometabolism in chronically alcohol-dependent patients. Thirty-one male patients who were detoxified, medically stable, and free of other central nervous system risk factors for neuropsychological impairment were examined with (1) anatomic imaging (CT or MR), (2) functional imaging with [18F] fluorodeoxyglucose (18F-FDG) and positron emission tomography (PET), and (3) a battery of neuropsychological tests, including two measures of abstraction known to be generally sensitive to frontal lobe disease or dysfunction [the Wisconsin Card Sorting Test (WCST) and the Halstead Category Test (HCT)]. 18F-FDG PET data from 18 age- and sex-matched normal control subjects were used for comparison. All patients met criteria for severe alcohol dependence and for at least a mild degree of alcoholic-induced cognitive impairment. Although the mean IQ level of the alcoholic patients was in the average range, the concepts attained and the error scores on the WCST and HCT were significantly impaired in comparison with established norms. Local cerebral metabolic rate for glucose (LCMRglc) was significantly decreased in a sagittal strip of the medial frontal cortex in the alcoholic patients as compared with the normal controls. Comparison of data from PET scans and anatomic images indicated that the reduced LCMRglc could not be attributed to reduced amounts of tissue alone. A statistically significant relationship was found between LCMRglc in the medial frontal region of the cerebral cortex and performance on the WCST, but not the HCT. These findings suggest that chronic alcohol intake results in impaired function of cerebral tissue in the medial frontal region.(ABSTRACT TRUNCATED AT 250 WORDS)

Executive control deficits in substance-dependent individuals: A comparison of alcohol, cocaine, and methamphetamine and of men and women

Ellen van der Plas, Eveline A. Crone, Wery P. M. van den Wildenberg +2 more · Journal of Clinical and Experimental Neuropsychology · 2008 · 199 citations

Substance dependence is associated with executive function deficits, but the nature of these executive defects and the effect that different drugs and sex have on these defects have not been fully clarified. Therefore, we compared the performance of alcohol- (n = 33; 18 women), cocaine- (n = 27; 14 women), and methamphetamine-dependent individuals (n = 38; 25 women) with sex-matched healthy comparisons (n = 36; 17 women) on complex decision making as measured with the Iowa Gambling Task, working memory, cognitive flexibility, and response inhibition. Cocaine- and methamphetamine-dependent individuals were impaired on complex decision making, working memory, and cognitive flexibility, but not on response inhibition. The deficits in working memory and cognitive flexibility were milder than the decision-making deficits and did not change as a function of memory load or task switching. Interestingly, decision making was significantly more impaired in women addicted to cocaine or methamphetamine than in men addicted to these drugs. Together, these findings suggest that drug of choice and sex have different effects on executive functioning, which, if replicated, may help tailor intervention.

Impairment of Cognitive Abilities and Decision Making after Chronic Use of Alcohol: The Impact of Multiple Detoxifications

Sabine Loeber, Theodora Duka, Helga Welzel +4 more · Alcohol and Alcoholism · 2009 · 184 citations

AIMS: In the present study, the effect of previous detoxifications on prefrontal function and decision making was examined in alcohol-dependent patients. Further, we examined whether the length of abstinence affects cognitive function. METHODS: Forty-eight alcohol-dependent patients were recruited from an inpatient detoxification treatment facility and cognitive function was compared to a control group of 36 healthy controls. The patient population was then divided into a group of patients with less than two previous detoxifications (LO-detox group, n = 27) and a group of patients with two or more previous detoxifications (HI-detox group, n = 21) and cognitive function was compared. In addition, cognitive function of recently (i.e. less than 16 days; median split) and longer abstinent patients was compared. We assessed prefrontal function, memory function and intelligence. RESULTS: Alcoholics, when compared to healthy controls, performed worse with regard to the performance index Attention/Executive function. Cognitive impairment in these tasks was pronounced in recently abstinent patients. We found no significant differences between HI-detox and LO-detox patients with regard to the Attention/Executive function. However, in the IOWA gambling Task, the HI-detox group seemed to be less able to learn to choose cards from the more advantageous decks over time. CONCLUSIONS: Our results provide additional evidence for cognitive impairment of alcohol-dependent patients with regard to tasks sensitive to frontal lobe function and underline the importance of abstinence for these impairments to recover. We found only little evidence for the impairing effects of repeated withdrawal on prefrontal function and we suggest that executive function is affected earlier in dependence.

Acute alcohol effects on cognitive function in social drinkers: their relationship to drinking habits

Ruth Weissenborn, Theodora Duka · Psychopharmacology · 2003 · 310 citations

Qualitative similarities in cognitive impairment associated with 24 h of sustained wakefulness and a blood alcohol concentration of 0.05%

Marina G. Falleti, Paul Maruff, Alex Collie +2 more · Journal of Sleep Research · 2003 · 161 citations

Previous studies that have quantified fatigue-related cognitive impairment as blood alcohol concentration (BAC) equivalents have been limited by two issues: the effect of practice on tests of cognition and, more importantly, the statistic used to quantify change in cognitive performance. The current study addressed these issues by adopting an ABACA design, which allowed for the adequate control of practice effects, and by using effect size metrics, which enabled direct comparisons to be made in performance impairments as a result of fatigue (i.e. sustained wakefulness of 24 h) and alcohol (i.e. BAC of 0.05%). Cognitive performance under the fatigue and alcohol conditions required the use of the CogState battery. It was demonstrated that fatigue caused greater impairment than alcohol on the speed of continuous attention and memory and learning, and on the accuracy of complex matching. Alcohol was more detrimental than fatigue only on the accuracy of memory and learning. Performances on the remaining tasks were the same for both the fatigue and alcohol conditions. These differences and similarities in performance impairment are discussed emphasizing the deleterious cognitive effects of relatively short periods of sustained wakefulness.

Alcohol and cognitive control: Implications for regulation of behavior during response conflict.

John J. Curtin, Bradley A. Fairchild · Journal of Abnormal Psychology · 2003 · 285 citations

Alcohol intoxication often leads to dysregulated behavior in contexts characterized by conflict between prepotent response tendencies and incompatible alternative responses. Recent research has identified 2 components of an anterior executive attention system that are essential for adaptive behavior when response conflict exists. Event-related potential (ERP) measures of evaluative and regulative cognitive control were collected to determine if impaired executive attention was responsible for observed behavior deficits when intoxicated. Intoxicated participants displayed task performance deficits on incongruent color-naming trials relative to sober controls. Alcohol did not affect P3 magnitude/latency, indicating that timing and integrity of stimulus evaluation remained intact. In contrast, alcohol did reduce frontal components of ERP that index evaluative and regulative cognitive control processes.

Neuropsychological Profile of Acute Alcohol Intoxication during Ascending and Descending Blood Alcohol Concentrations

Tom A. Schweizer, M. Vogel‐Sprott, James Danckert +3 more · Neuropsychopharmacology · 2005 · 130 citations

Dose‐Related Impact of Alcohol Consumption on Cognitive Function in Advanced Age: Results of a Multicenter Survey

Giuseppe Zuccalà, Graziano Onder, Claudio Pedone +4 more · Alcoholism Clinical and Experimental Research · 2001 · 115 citations

BACKGROUND: Moderate alcohol consumption has been associated in several studies with decreased risk of cardiovascular and cerebrovascular events; however, available data on the effects of alcohol intake on cognitive functioning are conflicting. We assessed the association between alcohol consumption and cognitive impairment in a series of older subjects enrolled in a multicenter pharmacoepidemiology survey. METHODS: The association between average alcoholic intake and cognitive performance was assessed in 15,807 patients admitted to participating centers during the survey periods. Demographic variables, comorbid conditions, medications, and objective tests that were associated with cognitive impairment (as indicated by a Hodkinson Abbreviated Mental Test score <7) in separate logistical regression models were examined as potential confounders in a summary model. RESULTS: Cognitive impairment was detected in 1693 (19%) of 8755 drinkers and 2008 (29%) of 7052 nondrinkers (Fisher's exact test, p < 0.0001). After adjusting for potential confounders, alcohol consumption was associated with decreased probability of cognitive impairment (odds ratio, 0.75; 95% confidence interval, 0.66-0.85). The relationship between drinking level and cognitive dysfunction was nonlinear, because the probability of cognitive impairment was decreased for moderate alcohol use as compared with abstinence, but it was increased for daily consumption exceeding one wine-equivalent liter among men and 0.5 liter among women. This nonlinear association persisted when cerebrovascular and Alzheimer's disease were considered separately. CONCLUSIONS: Alcohol abuse is associated with increased prevalence of cognitive dysfunction among older subjects; however, a daily alcohol consumption of less than 40 g for women and 80 g or less for men might be associated with a decreased probability of cognitive impairment. This possible protective effect of alcohol consumption should be further assessed by prospective studies.

Neuropsychological performance of individuals dependent on crack–cocaine, or crack–cocaine and alcohol, at 6 weeks and 6 months of abstinence

Victoria Di Sclafani, Marina Tolou‐Shams, Leonard J. Price +1 more · Drug and Alcohol Dependence · 2002 · 155 citations

Neurobehavioral Sequelae of Alcoholism

Oscar A. Parsons, Sara Jo Nixon · Neurologic Clinics · 1993 · 181 citations

Prenatal alcohol exposure and offspring cognition and school performance. A 'Mendelian randomization' natural experiment.

Zuccolo L, Lewis SJ, Smith GD +10 more · Int J Epidemiol · 2013 · 89 citations

Executive Functioning Early in Abstinence From Alcohol

Sandra Zinn, Roy Stein, H. Scott Swartzwelder · Alcoholism Clinical and Experimental Research · 2004 · 129 citations

BACKGROUND: Executive dysfunction is among the cognitive impairments that may persist after abstinence in alcohol-dependent persons. The type(s) and extent of executive dysfunction early in abstinence have not been well characterized, but they may have important implications for the evolution of behavioral treatment strategies. METHODS: To determine which aspects of executive functioning were impaired in early abstinence, we administered memory and executive function tests to veterans who successively presented for treatment at an outpatient substance abuse clinic. We then compared the neuropsychological performance of these recovering alcoholics (n = 27) with that of age-matched primary care outpatients (n = 18). We also examined group differences in self-evaluation of cognitive decline and evaluated associations between drinking history and cognitive impairment in the index group. RESULTS: We found that the normal and alcohol-dependent groups differed on abstract reasoning, memory discrimination, and effectiveness on timed tasks. Patients in the alcohol-dependent sample were also more likely to perceive themselves as cognitively impaired. It is interesting to note that the duration of alcohol use did not relate to neuropsychological test performance, but recent quantity consumed and days of sobriety were associated with nonverbal abstract reasoning ability. CONCLUSIONS: Executive functions are impaired early in abstinence and should, therefore, be taken into account when early behavioral treatments are being developed.

Optimal Dose of Baclofen for the Treatment of Alcohol Use Disorder: A Systematic Review and Dose-Response Meta-analysis.

Kotake K, So R, Hashimoto N +4 more · CNS Drugs · 2025 · 4 citations

Alcohol, cognitive impairment and expectancies.

Mark T. Fillmore, Janis Carscadden, M. Vogel‐Sprott · Journal of Studies on Alcohol · 1998 · 99 citations

OBJECTIVE: This experiment tested the hypothesis that differences in subjects' expectations about the impairing effect of alcohol on cognitive performance predict their responses to alcohol and to a placebo. METHOD: Twenty-seven male social drinkers were randomly assigned to one of three treatment groups: alcohol (0.62 g/kg), placebo, or no treatment control. All groups practiced a Rapid Information Processing Task that measured cognitive performance by the speed of information processed. After practice, they rated the degree of impairment they expected alcohol to have on their performance, and then performed the task under their different treatments. RESULTS: Alcohol slowed (i.e., impaired) information processing compared with placebo and no treatment. In addition, those who expected more impairment performed more poorly under alcohol, and under the placebo when alcohol was expected. When no beverage was received, no expectancy-performance relationship was obtained. CONCLUSIONS: The findings call attention to expectancies as an important factor that may contribute to individual differences in cognitive functioning under alcohol and placebo.

Association between alcohol consumption and mild cognitive impairment: A protocol of dose-response meta-analysis.

Hui X, Li J, Lao Y +8 more · Medicine (Baltimore) · 2019 · 5 citations

From Herbal Roots to Synthetic Medicines: A Historical Perspective

Ting‐Kai Li · Alcoholism Clinical and Experimental Research · 2009 · 95 citations

Alcohol is one of our most ancient intoxicants. A recent anthropological study revealed that a fermented mixed beverage of rice, honey and fruit had existed during the Neolithic era. Written history documented the manufacturing of barley beer and other cereal beverages in Egypt and China as far back as 6000 and 4000 years, respectively (El-Guebaly and el-Guebaly, 1981; McGovern et al., 2004). History also attributed the downfall of empires and dynasties to excessive alcohol use by ruling courts more than 3000 years ago. Grecian scholars 2500 years ago issued warnings about the harm of acute and chronic inebriation arising from drinking too much wine too fast and too often. Plato even provided drinking guidelines: no use under age 18, use in moderation between 18 and 30, and no restriction for those older than 40. Descriptions of modalities for the treatment of acute and chronic inebriation began appearing when alcoholic beverages became more available to the populace. In China, herbal medicines were recommended to combat the progression of what was a common saying: “first a man takes a glass, then the glass takes a glass, finally the glass takes the man” (Sournia, 1990). Many of these herbal medicines contained extracts from the Pueraria plant, commonly known as Kudzu. In Western medicine, disulfiram (Antabuse®), the first medication to treat chronic inebriation, now called alcoholism, alcohol dependence, or alcohol addiction, was approved by the US Food and Drug Administration (FDA) in 1949. Discovered through astute serendipitous observation, Hald and Jacobsen (1948) found that disulfiram (tetraethylthiuram disulphide) used in the rubber industry evoked an aversive reaction in workers who subsequently ingested alcohol. Although the underlying mechanism was unknown at the time, the authors showed that disulfiram plus ingested alcohol produced elevation of blood acetaldehyde concentration and that infusion of acetaldehyde evoked the same alcohol-disulfiram reaction. Subsequent work showed that disulfiram inhibited both cytosolic and mitochondrial aldehyde dehydrogenase (ALDH) in vitro (Kitson, 1977), but it was Deitrich and Erwin (1971) who demonstrated in vivo that disulfiram administration to rats decreased ALDH activity in the liver irreversibly and that recovery was dependent upon new enzyme synthesis. Subsequent to early clinical studies reporting good results, the efficacy of disulfiram in treating all patients diagnosed with chronic relapsing alcoholism was questioned because of its failure to curb craving, its low compliance rate among patients, and its side-effects (e.g., liver toxicity). Disulfiram irreversibly inhibits ALDH2 through reaction with essential sulfhydryl groups of the enzyme; it also inactivates many other enzymes similarly, possibly contributing to undesirable side effects. Nonetheless, as recently reviewed, it may still have a role under supervised administration and in treating subsets of patients who are impulsive or who are older and better motivated (Fuller and Gordis, 2004). ALDH is an attractive medications target; it has been firmly established in East Asian populations, Chinese, Japanese, and Koreans in particular, that functional polymorphisms of alcohol dehydrogenase (ADH) and of mitochondrial aldehyde dehydrogenase (ALDH2) lead to genetically based variation both in alcohol metabolism (pharmacokinetics) and in responses to alcohol (pharmacodynamics) mediated, at least in part, through acetaldehyde. Those individuals who have alleles of ADH that code for a higher activity ADH enzyme (ADH2*2) and for low/absent ALDH2 activity (ALDH 2*2) are protected against heavy drinking and alcoholism because they have the alcohol-flush reaction, a genetic equivalent to the alcohol-disulfiram reaction. Hence alcoholism qualifies as a pharmacogenetic disorder with genetic variation as a major biological reason for individual differences in drinking behavior (Li, 2000). Interestingly, individuals who are heterozygous at the ALDH2 locus (ALDH2*1-ALDH2*2) have reduced risk of developing alcoholism, but some do become alcoholic. A recent study showed that alcoholic and nonalcoholic ALDH2 heterozygotes do not differ in alcohol and acetaldehyde pharmacokinetics, i.e., acetaldehyde is equally elevated in both groups, but the alcoholic subjects exhibit lower alcohol flush reaction responses, i.e., less pharmacodynamic sensitivity to acetaldehyde (Chen et al., 2009). In the last 25 years, investigators began investigating the purported antidipsotropic effects of isolated components of Kudzu. A report appeared in 1989 that the isoflavone fractions from the Pueraria plant when given to mice orally together with ethanol attenuated blood ethanol and acetaldehyde levels and ethanol’s effect on spontaneous motor activity (Niiho et al., 1989). These findings were replicated in rats (Xie et al., 1994). Then several reports appeared that a number of isoflavones isolated from Kudzu root suppressed ethanol intake in Syrian golden hamsters (Keung and Vallee, 1993) and in rats (Lin et al., 1996; Overstreet et al., 1996). The major active compounds that suppressed free-choice drinking were daidzin, daidzein, and puerarin (Lin et al., 1996). In humans, a study of the efficacy of Kudzu extract containing these three major isoflavones has been performed in heavy drinking subjects. The Kudzu extract produced significant reductions in total intake in a drinking session, accompanied by increases in the number of small sips and the time to consume a unit of beverage (Lukas et al., 2005). Although all the animal models studies and the human efficacy trial have shown that the major isoflavone components in Kudzu reduced free-choice alcohol drinking, their mechanism of action was unclear. Initially thought to be mediated by inhibition of ALDH2 and elevation of acetaldehyde as is seen with disulfiram, bioavailability and different effects on ethanol pharmacokinetics when administered by oral or intraperitoneal routes blurred interpretation (Keung et al., 1996; Xie et al., 1994). Since then, a clearer picture has emerged. Importantly, isoflavones are not sulfhydryl-reactive compounds. In vitro studies (Keung and Vallee, 1993) had found daidzin to be a potent and a reversible, competitive inhibitor of ALDH2. Surprisingly, they found that daidzin at the doses effective in suppressing ethanol consumption in the hamsters did not affect overall acetaldehyde metabolism in vivo (Keung et al., 1995). However, ALDH2 also catalyzes the oxidation of other aldehydes. Because ALDH2 together with monoamine oxidase (MAO) in mitochondria are responsible for the oxidative deamination of biogenic amines, Heyman and colleagues (1996) suggested that, rather than ethanol-derived acetaldehyde, it may be an endogenous physiological substrate of ALDH2 that is involved in the regulation of drinking in these experiments. In support of this hypothesis, Keung and colleagues showed that daidzin and its antidipsotropic analogs inhibited the metabolism of serotonin (5HT) and dopamine (DA) to 5-hydroxyindoleacetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in isolated mitochondria. Concomitantly, there was an accumulation of 5-hydroxyindole-3-acetaldehyde (5HIAL) and 3, 4 dihydroxyphenyl acetaldehyde (DOPAL). Through its inhibitory action on ALDH2, the potential site of action of daidzin is ALDH2 in the MAO-ALDH2 pathway of biogenic amine metabolism. Thus, elevation of biogenic aldehydes such as 5HIAL and DOPAL, might serve as feedback regulators of neuronal 5-HT, and DA synthesis and content (Keung and Vallee, 1998; Rooke et al., 2000). If this were the case, what aspects of ethanol consummatory behavior, thus far measured only with two-bottle free-choice drinking, are being affected by the isoflavonoids in Kudzu, and is there potential for this class of compounds in the development of medications for the treatment of alcoholism? A major step forward in this journey is the article in the November 2009 issue of Alcoholism Clinical and Experimental Research (ACER), the result of collaborative research from multiple laboratories in the United States and Australia, and orchestrated by Ivan Diamond from CV Therapeutics (now Gilead) in Palo Alto, CA (Arolfo et al., 2009). Based on the X-ray crystal structure of daidzin in complex with human ALDH2 (Lowe et al., 2008), more potent and selective ALDH2 inhibitors were synthesized. One of them, CVT-10216, was studied in three different heavy drinking rat strains under several different drinking paradigms: two-bottle free-choice drinking, deprivation-induced drinking, operant response to self-administration, and cue-induced reinstatement. Alcohol gavage (2 g/kg) did increase acetaldehyde concentration in blood 2- to 7-fold indicating that ALDH2 was, indeed, inhibited by CVT-10216 in vivo under conditions of the experiment. However, it should be noted that even the highest drinking rat strains do not usually self-administer this amount of alcohol in a bolus, even in the deprivation-induced paradigm. Although not proven directly, elevation of acetaldehyde is not likely to be the mediating agent in vivo. In support of this conclusion, both operant alcohol-seeking and cue-induced reinstatement of operant alcohol-seeking behaviors were diminished with CVT 10216 administration, even in the absence of alcohol and hence of alcohol-derived acetaldehyde. Is there evidence that neuronal biogenic amine content and response to stimulation are affected? Data are presented showing that CVT 10216 does not alter the basal DA levels in the nucleus accumbens in vivo, but does prevent ethanol-stimulated release, supporting the hypothesis that one mechanism of action of CVT-10216 is, at least in part, its interference with the DA reward pathway. The question is then does the effect of CVT-10216 on biogenic amine metabolism mediated by inhibition of ALDH2 generalize to the self-administration of other drugs such as cocaine? Further, does this class of compounds also affect comorbid entities such as mood and anxiety disorders wherein there is 5HT dysfunction? Tantalizing clues can be culled from reports that: (i) puerarin reduces the anxiety induced by alcohol withdrawal and by the administration of 5 HT agonists (Overstreet et al., 2003); (ii) disulfiram diminishes cocaine-associated subjective effects (“high” and “rush”) in non-treatment-seeking cocaine-dependent volunteers (Baker et al., 2007); and (iii) a beneficial effect of disulfiram in co-occurring cocaine and alcohol dependent subjects has been observed in a number of studies, the latest being the report by Pettinati and colleagues (2008). The neurocircuitry and neurotransmitter/neuromodulator systems that mediate the development of addiction to alcohol and drugs are complex and many. Two outstanding reviews have appeared this year, one emphasizing more the neurocircuitry (Koob and Volkow, 2009) and the other the molecular physiology of alcohol-sensitive sites on receptors and ion channels (Spanagel, 2009). The latter discusses potential targets for medications development and a very comprehensive list is provided. In medications development for alcoholism, behavioral outcomes for a successful candidate should include: attenuation of the positive and negative reinforcement of ethanol self-administration, reduction of the negative affect associated with withdrawal, diminution of craving, and the prevention of relapse. Ideally, this can be accomplished with a single agent or a combination of a minimum number of agents. An ALDH2 inhibitor without the negative side effects of disulfiram attributable to inhibition of other sulfhydryl enzymes might fit this role! Is this a pipedream or attainable reality? Time and more research in animal models as was reported in the article by Arolfo and colleagues (2009) and in human subjects will tell. The assistance of Brenda G. Hewitt in the preparation of this manuscript is gratefully acknowledged.

Alcohol and Neural Dynamics: A Meta-analysis of Acute Alcohol Effects on Event-Related Brain Potentials.

Fairbairn CE, Kang D, Federmeier KD · Biol Psychiatry · 2021 · 31 citations

Acute alcohol consumption consistently reduces the amplitude of the P300 event-related brain potential by approximately 1–2 microvolts (a medium-to-large effect, Hedges' g ≈ 0.6–0.8), indicating slowed and less efficient neural processing of unexpected or meaningful stimuli — a measurable brain-level effect that persists even when a person feels only mildly intoxicated.

Effects of acute alcohol administration on working memory: a systematic review and meta-analysis.

Spinola S, De Vita MJ, Gilmour CE +1 more · Psychopharmacology (Berl) · 2022 · 19 citations

Moderate prenatal alcohol exposure impairs cognitive control, but not attention, on a rodent touchscreen continuous performance task

Sarah L. Olguin, Shannon M. Thompson, Jared W. Young +1 more · Genes Brain & Behavior · 2020 · 31 citations

A common feature associated with fetal alcohol spectrum disorders is the inability to concentrate on a specific task while ignoring distractions. Human continuous performance tasks (CPT), measure vigilance and cognitive control simultaneously while these processes are traditionally measured separately in rodents. We recently established a touchscreen 5-choice CPT (5C-CPT) that measures vigilance and cognitive control simultaneously by incorporating both target and nontargets and showed it was sensitive to amphetamine-induced improvement in humans and mice. Here, we examined the effects of moderate prenatal alcohol exposure (PAE) in male and female mice on performance of the 5-choice serial reaction time task (5-CSRTT), which contained only target trials, and the 5C-CPT which incorporated both target and nontarget trials. In addition, we assessed gait and fine motor coordination in behavioral naïve PAE and control animals. We found that on the 5-CSRTT mice were able to respond to target presentations with similar hit rates regardless of sex or treatment. However, on the 5C-CPT PAE mice made significantly more false alarm responses vs controls. Compared with control animals, PAE mice had a significantly lower sensitivity index, a measure of ability to discriminate appropriate responses to stimuli types. During 5C-CPT, female mice, regardless of treatment, also had increased mean latency to respond when correct and omitted more target trials. Gait assessment showed no significant differences in PAE and SAC mice on any measure. These findings suggest that moderate exposure to alcohol during development can have long lasting effects on cognitive control unaffected by gross motor alterations.

Childhood cognitive measures as predictors of alcohol use and problems by mid-adulthood in a non-Western cohort.

Luczak SE, Yarnell LM, Prescott CA +3 more · Psychol Addict Behav · 2015 · 13 citations

Drinking and driving: A systematic review of the impacts of alcohol consumption on manual and automated driving performance.

Dong M, Lee YY, Cha JS +1 more · J Safety Res · 2024 · 22 citations

Acute Alcohol Intoxication: Sex Comparisons on Pharmacokinetic and Mood Measures

Patricia B. Sutker, Kenneth C. Goist, Albert N. Allain +1 more · Alcoholism Clinical and Experimental Research · 1987 · 50 citations

This study explored sex differences in pharmacokinetic and mood state responses to acute alcohol intoxication among socially drinking women demonstrated to be normally cycling across two consecutive menstrual cycles and men with similar drinking habits. Subjects were administered moderate or high alcohol doses in six experimental sessions over a 60-day period. Women were tested during the early follicular, ovulatory, and midluteal phases of the cycle, and men were administered alcohol at comparable time intervals. Results showed that men did not differ in alcohol pharmacokinetics across sessions, but women showed significantly shorter elimination times and faster disappearance rates during the midluteal phase of the menstrual cycle compared to the early follicular and ovulatory phases and to their male counterparts. There were no sex or within-group differences in self-reported negative mood states prior to alcohol administration, but women described increased anxiety and depression while intoxicated during the early follicular compared to ovulatory and midluteal phases. Affective responses to intoxication were a complex function of sex, limb of the blood alcohol concentration-time curve, and dose.

Parental history of alcohol abuse and the effects of alcohol and expectations of intoxication on social stress.

Michael A. Sayette, F. Curtis Breslin, G. Terence Wilson +1 more · Journal of Studies on Alcohol · 1994 · 47 citations

Male and female social drinkers, half of whom had a biological father who abused alcohol, were exposed to a social stressor (anticipation and delivery of a public speech) after consuming either a moderate dose of alcohol or tonic water. Half of each group were led to believe that they had consumed alcohol, the other half tonic water, yielding a 2 x 2 x 2 x 2 factorial design. Intoxication, but not beliefs about having consumed alcohol, significantly reduced subjective anxiety and negative self-evaluation in response to the stressor in both men and women. Parental history of alcohol abuse differentially affected alcohol's influence on mood, but not measures of subjective intoxication, subjective physiological responses to alcohol, beliefs about alcohol's effects on behavior, or reactivity to the stressor.

The effects of acute alcohol intoxication on the cognitive mechanisms underlying false facial recognition.

Colloff MF, Flowe HD · Psychopharmacology (Berl) · 2016 · 31 citations

Chronic alcohol consumption impairs visuo-spatial associative memory in periadolescent rhesus monkeys.

Crean RD, Vandewater SA, Katner SN +2 more · Drug Alcohol Depend · 2011 · 29 citations

Acute effects of kava, alone or in combination with alcohol, on subjective measures of impairment and intoxication and on cognitive performance

Heidi Foo, James Lemon · Drug and Alcohol Review · 1997 · 55 citations

Kava (Piper methysticum) and alcohol were administered either separately or in combination to human subjects. Self-reports of their levels of impairment and intoxication were collected, and performance skills on a number of cognitive and visuomotor tests were determined, before and three times after consumption of the experimental drink. Kava alone had no effect on reported condition. In contrast, alcohol produced marked changes in each of the five subjective measures, all of which were in the direction of lowered ability. The combination of these two substances produced even larger negative changes on these measures. In the cognitive tests, kava produced a decrement in performance on Digit Symbol Coding. Alcohol produced a significant decrease in performance on a divided attention test, which was almost entirely on the peripheral, discontinuous component of the test. The combination of kava and alcohol produced an even greater decrease in performance on this test, and in the same component. The present findings suggest that kava alone has little effect on reported condition and cognitive performance, but appears to potentiate both perceived and measured impairment when combined with alcohol.

Contributions of Zebrafish Studies to the Behavioural Consequences of Early Alcohol Exposure: A Systematic Review.

Schaidhauer FG, Caetano HA, da Silva GP +1 more · Curr Neuropharmacol · 2022 · 0 citations

The effects of alcohol intoxication on cognitive functions critical for driving: A systematic review.

Garrisson H, Scholey A, Ogden E +1 more · Accid Anal Prev · 2021 · 66 citations

Female rats exposed to stress and alcohol show impaired memory and increased depressive-like behaviors

Juan L. Gomez, Victoria N. Luine · Physiology & Behavior · 2013 · 32 citations

Acute neurocognitive and subjective effects of oral methamphetamine with low doses of alcohol: A randomised controlled trial.

Hayley AC, Shiferaw B, Rositano J +1 more · J Psychopharmacol · 2023 · 8 citations

The effects of alcohol on interrogative suggestibility: The role of State‐Anxiety and mood states as mediating factors

Pekka Santtila, Magnus Ekholm, Pekka Niemi · Legal and Criminological Psychology · 1999 · 29 citations

Purpose. The goal of this study was to determine whether alcohol would increase or decrease interrogative suggestibility. Methods. Four groups of participants (N = 51) were administered the story and immediate recall of the Gudjonsson Suggestibility Scale 2. After this they were administered one of three doses of alcohol or a placebo followed by delayed recall and the questioning part of the scale. Changes in mood and anxiety were monitored with the help of Profile of Mood States and Spielberger State‐Anxiety Scale. Results. Alcohol decreased yielding to leading questions both before (Yield 1) and after (Yield 2) interrogative pressure was applied but had no effect on changing answers in response to the pressure (Shift). State‐Anxiety and Clearheaded‐Confused mood were found to mediate the effects of alcohol on Yield 2. No other significant mediational relationships were found. Conclusions. Alcohol appears to decrease suggestibility with the exception of reactions to applied interrogative pressure. This decrease is not totally explainable by the mediating effects of either mood states or anxiety.

Effects of prenatal alcohol exposition on cognitive outcomes in childhood and youth: a longitudinal analysis based on meconium ethyl glucuronide.

Roetner J, Van Doren J, Maschke J +10 more · Eur Arch Psychiatry Clin Neurosci · 2024 · 7 citations

Physical activity as treatment for alcohol use disorders (FitForChange): study protocol for a randomized controlled trial.

Hallgren M, Andersson V, Ekblom Ö +1 more · Trials · 2018 · 31 citations

6-Methoxyflavone and Donepezil Behavioral Plus Neurochemical Correlates in Reversing Chronic Ethanol and Withdrawal Induced Cognitive Impairment.

Arif M, Rauf K, Rehman NU +3 more · Drug Des Devel Ther · 2022 · 8 citations

RELATED COORDINATIVE, REACTIVE AND COGNITIVE PERFORMANCES AS IMPAIRED BY DRUGS AND ALCOHOL: COMPARISON WITH CLINICAL TEST FOR DRIVING FITNESS

M. J. Mattila, Tapio Kuitunen, J. Veilahti · Journal of traffic medicine · 1993 · 13 citations

Cognitive, coordinative and reactive functions, separately and combined to a 'global test', and the clinical test for drunkenness were compared in two placebo-controlled double-blind crossover studies with 12 healthy subjects in each. In Trial I, oral single doses of lorazepam (LZ) 2 mg in two formulations and ethanol (EOH) 1 g/kg were given in balanced order. In Trial II, EOH (0.8 g/kg) was given during the treatment with an H1-antihistamine ebastine (20 mg daily) or placebo. Performance was tested before and after the intake of the drugs. LZ given in capsules or sublingual tablets similarly caused drowsiness, mental slowness and clumsiness, and impaired cognitive (digit substitution), reactive and coordinative (simulated driving) performances at 2, 4 and 6 h after intake. Mean blood alcohol concentrations (BACs) were 1.27, 0.92 and 0.61 g/l at 1.5, 3.5 and 5.5 h after EOH which much resembled LZ in its effects, with some qualitative (drowsiness, body sway) differences. The 'global effect' (tracking error severity + 10 reaction time/digits substituted) provided a single variable for the comparison of LZ and EOH, its justification being confirmed by the subsequent G-test computed for the same variables. In the clinical test, LZ and EOH impaired motor and mental subtests but EOH also impaired vestibular functions. In Trial II, the mean BACs (0.82, 0.53 and 0.25 g/ml at 2, 4 and 6 h) and EOH-induced decrement of performance were less than in Trial I. Ebastine neither impaired performance nor increase EOH effects. As to the clinical test, significant drug effects due to EOH or ebastine + EOH were seen only in vestibular and motor subtests at 2 h but not at 5 h. We conclude that the two LZ formulations are similar in practice; LZ 2 mg is more detrimental than 1 g/kg EOH in laboratory tests but not in the clinical test; and the empirically chosen 'global test' might be useful when comparing the decrements of performance caused by drugs and alcohol.

Effects of maternal drinking patterns and epigallocatechin-3-gallate treatment on behavioural and molecular outcomes in a mouse model of fetal alcohol spectrum disorders.

Vieiros M, Almeida-Toledano L, Serra-Delgado M +8 more · Biomed Pharmacother · 2025 · 4 citations

The effects of histone deacetylase inhibitors on the attentional set-shifting task performance of alcohol-dependent rats.

Zhang X, Sun L, Wang L +8 more · Brain Res Bull · 2019 · 2 citations

Does sleep deprivation impair cognitive and motor performance as much as alcohol intoxication?

Alice A. Kuo · Western Journal of Medicine · 2001 · 7 citations

OBJECTIVESTo compare the relative effects on performance of sleep deprivation and alcohol.

Synaptic and mitochondrial mechanisms behind alcohol-induced imbalance of excitatory/inhibitory synaptic activity and associated cognitive and behavioral abnormalities.

Arzua T, Yan Y, Liu X +3 more · Transl Psychiatry · 2024 · 13 citations