In the company of others: social factors alter acute alcohol effects

Rationale

Alcohol is usually consumed in social contexts. However, the drug has been studied mainly under socially isolated conditions, and our understanding of how social setting affects response to alcohol is limited.

Objectives

The current study compared the subjective, physiological, and behavioral effects of a moderate dose of alcohol in moderate social drinkers who were tested in either a social or an isolated context and in the presence of others who had or had not consumed alcohol.

Methods

Healthy men and women were randomly assigned to either a social group tested in pairs (SOC; N?=?24), or an isolated group tested individually (ISO; N?=?20). They participated in four sessions, in which they received oral alcohol (0.8 g/kg) or placebo on two sessions each, in quasi-randomized order under double-blind conditions. In the SOC condition, the drug conditions of the co-participants were varied systematically: on two sessions, both participants received the same substance (placebo or alcohol) and on the other two sessions one received alcohol while the other received placebo. Cardiovascular measures, breath alcohol levels, and mood were assessed at regular intervals, and measures of social interaction were obtained in the SOC group.

Results

Alcohol produced greater effects on certain subjective measures in the SOC condition compared with the ISO condition, including feelings of intoxication and stimulation, but not on other measures such as feeling sedated or high, or on cardiovascular measures. Within the SOC condition, participants rated themselves as more intoxicated when their partner received alcohol, and paired subjects interacted more when at least one participant received alcohol.

Conclusions

The presence of others enhances some of the subjective and behavioral effects of alcohol, especially the presence of another intoxicated individual. This enhancement of alcohol effects may explain, in part, why it is used in a social context.     

Decreases in recollective experience following acute alcohol: a dose–response study

Rationale

Acute alcohol intoxication induces a selective impairment of recognition memory associated with conscious recollection whilst recognition based on familiarity is left intact.

Objectives

We aimed to further elucidate the acute effects of alcohol on recognition memory by assessing three different doses of alcohol and examining the way in which this affected the recollection and familiarity components of recognition memory in comparison to a placebo group.

Methods

A double-blind independent design was used, and participants received either alcohol (0.4, 0.6 or 0.8 g/kg) or a placebo drink. Participants encoded word pairs with depth of processing manipulated under generate and read conditions. Recognition memory was assessed and recollective awareness was examined through use of the remember–know procedure.

Results

Alcohol produced a dose-dependent reduction in recognition memory associated with recollection, evidenced by decreases in the number of correctly recognised items with ‘remember’ responses compared to placebo. Recognition based on a familiarity, evidenced by ‘know’ responses, showed no differences between groups or pattern of reduction compared to the placebo group. However, a negative correlation was found between recognition based on familiarity and levels of intoxication.

Conclusions

Alcohol-induced impairments in recognition memory occur in a dose-dependent manner, specifically driven by reductions in recognition associated with conscious awareness.     

Reduced Acute Recovery from Alcohol Impairment in Adults with ADHD

Rationale

Prior research has found that adults with attention-deficit/hyperactivity disorder (ADHD) show increased sensitivity to the impairing effects of alcohol (Weafer et al., Exp Clin Psychopharmacol 17: 113–121, 2009). However, these studies have focused exclusively on the ascending limb of the blood alcohol concentration (BAC) curve, and it is unclear whether these adults continue to show increased sensitivity during the later phase of the dose as BAC is declining.

Objective

This study tested the hypothesis that those with ADHD would display increased response to alcohol during the ascending limb of the BAC curve and less recovery from the impairing effects during the descending limb.

Methods

Adult social drinkers with ADHD and control adults completed measures of motor coordination, reaction time (RT), and subjective intoxication twice following 0.64 g/kg alcohol and placebo. The measures were administered during the ascending limb of the BAC curve and again during the descending limb.

Results

During the ascending limb, alcohol reduced motor coordination, slowed RT, and increased self-reports of subjective intoxication. Those with ADHD displayed greater impairment of motor coordination compared with controls. During the descending limb, controls reported diminished subjective intoxication and showed recovery from the impairing effects of alcohol on both their motor coordination and their RT. Those with ADHD showed reduced subjective intoxication and faster RT during this time, but they did not recover motor control.

Conclusions

The protracted time course of motor impairment in adults with ADHD despite reductions in subjective intoxication may contribute to poor decision making and diminished behavioral control in this group.     

Effects of acute alcohol intoxication on saccadic conflict and error processing

Rationale

Flexible behavior optimization relies on cognitive control which includes the ability to suppress automatic responses interfering with relevant goals. Extensive evidence suggests that the anterior cingulate cortex (ACC) is the central node in a predominantly frontal cortical network subserving executive tasks. Neuroimaging studies indicate that the ACC is sensitive to acute intoxication during conflict, but such evidence is limited to tasks using manual responses with arbitrary response contingencies.

Objectives

The present study was designed to examine whether alcohol's effects on top–down cognitive control would generalize to the oculomotor system during inhibition of hardwired saccadic responses.

Methods

Healthy social drinkers (N?=?22) underwent functional magnetic resonance imaging (fMRI) scanning and eye movement tracking during alcohol (0.6 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions in a counterbalanced design. They performed visually guided prosaccades (PS) towards a target and volitional antisaccades (AS) away from it. To mitigate possible vasoactive effects of alcohol on the BOLD (blood oxygenation level-dependent) signal, resting perfusion was quantified with arterial spin labeling (ASL) and used as a covariate in the BOLD analysis.

Results

Saccadic conflict was subserved by a distributed frontoparietal network. However, alcohol intoxication selectively attenuated activity only in the ACC to volitional AS and erroneous responses.

Conclusions

This study provides converging evidence for the selective ACC vulnerability to alcohol intoxication during conflict across different response modalities and executive tasks, confirming its supramodal, high-level role in cognitive control. Alcohol intoxication may impair top–down regulative functions by attenuating the ACC activity, resulting in behavioral disinhibition and decreased self-control.     

Alcohol attenuates amygdala–frontal connectivity during processing social signals in heavy social drinkers

Rationale

Convergent evidence shows that alcohol exerts its effects on social behavior via modulation of amygdala reactivity to affective stimuli. Given that affective processing involves dynamic interactions between the amygdala and the prefrontal cortex (PFC), alcohol’s effects are likely to extend beyond regional changes in brain activity to changes that manifest on a broader functional circuit level.

Objective

The current study examines alcohol’s effects on functional connectivity (i.e., "coupling") between the amygdala and the PFC during the processing of socio-emotional stimuli using functional magnetic resonance imaging (fMRI).

Methods

In a randomized, double blind, placebo-controlled, within-subjects cross-over design, 12 heavy, social drinkers performed an fMRI task designed to probe amygdala response to socio-emotional stimuli (angry, fearful, and happy faces) following acute ingestion of alcohol or placebo. Functional connectivity between the amygdala and PFC was examined and compared between alcohol and placebo sessions using a conventional generalized psychophysiological interaction (gPPI) analysis.

Results

Relative to placebo, alcohol reduced functional coupling between the amygdala and the right orbitofrontal cortex (OFC) during processing of both angry and fearful faces. Alcohol also reduced functional coupling between the amygdala and left OFC during processing of happy faces.

Conclusions

These preliminary findings suggest that alcohol’s effects on social behavior may be mediated by alternations in functional connectivity between the amygdala and OFC during processing of emotional faces.     

Effects of caffeine on alcohol-related changes in behavioural control and perceived intoxication in light caffeine consumers

Rationale

Caffeinated alcoholic beverages have been associated with increased risk of alcohol-related harms. However, few studies have examined these combined effects on behavioural control, which is believed to underlie many of the negative effects of alcohol consumption. In addition, studies have often omitted subjective measures, and none have directly assessed the role of caffeine consumer history.

Objectives

To examine the combined effects of alcohol and caffeine on measures of behavioural control and perceived intoxication in abstinent, light caffeine consumers.

Methods

Participants (n?=?28; 50% male) attended four sessions at which they consumed one of the following beverages in a randomised order: placebo, alcohol alone (0.6?g/kg), caffeine alone (2.0?mg/kg), and alcohol/caffeine. They completed measures of mood, intoxication, anxiety and alcohol craving before and after a task battery comprising measures of behavioural control and reaction time performance.

Results

Caffeine attenuated alcohol-related performance deficits on stop-signal accuracy, had no effect on go–no-go performance deficits, and worsened accuracy on the Stroop task. Caffeine did not influence absolute changes in perceived intoxication but there was suggestion that caffeine may have changed the nature of intoxication with increases in stimulation.

Conclusions

Caffeine appears to have mixed effects on alcohol intoxication that are task-dependent. We found increased stimulation in the alcohol/caffeine condition, supporting the contention that caffeinated alcoholic beverages enable an individual to drink for longer. Future research should model real world drinking behaviour by examining how these effects change across multiple drink administrations.     

Implicit and explicit alcohol-related motivations among college binge drinkers

Rationale

Positive alcohol outcome expectancies and behavioral economic indices of alcohol consumption are related to binge drinking among college students and may reflect explicit and implicit motivations that are differentially associated with this behavior.

Objectives

The present study hypothesized that implicit (alcohol purchase task) and explicit (positive expectancy for alcohol’s effects) motivations for drinking would not be correlated. It was also hypothesized that greater implicit and explicit motivations would predict alcohol-related risk.

Methods

Participants were 297 college student binge drinkers (54% female; 88% European-American; Alcohol Use Disorders Identification Test: M?=?9.53, SD?=?5.04). Three indices from the alcohol purchase task (APT) were modeled as a latent implicit alcohol-related motivations variable. Explicit alcohol-related motivations were measured using a global positive expectancy subscale from the Comprehensive Effects of Alcohol Questionnaire. Alcohol Use Disorders Identification Test total, Rutgers Alcohol Problem Index total, and age of drinking onset were modeled as a latent alcohol-related risk variable. Structural equation modeling was used to examine associations amongst implicit motivations, explicit motivations, and alcohol-related risk.

Results

Implicit and explicit motivations were not correlated. Partially consistent with the second hypothesis, greater implicit motivations were associated with greater alcohol-related risk. Relations between explicit motivations and alcohol-related risk were marginally significant.

Conclusions

Implicit and explicit drinking motivations are differentially associated with problem drinking behaviors. Future research should examine the underlying neurobiological mechanisms associated with these factors.     

Lack of tolerance to the disinhibiting effects of alcohol in heavy drinkers

Rationale

Alcohol tolerance is observed as a diminished response to a given dose as a function of repeated administrations of the drug. Research has consistently shown that heavier drinkers display reduced reactions to alcohol (i.e., tolerance) compared with lighter drinkers. However, the majority of this work has focused primarily on measures of motor performance, whereas the development of tolerance to alcohol's impairing effects on cognitive processes, such as inhibitory mechanisms of behavioral control, remains relatively unexplored.

Objective

The purpose of the present study was to examine the relationship between drinking habits and the degree to which alcohol affects drinkers' inhibitory control and motor coordination.

Methods

Fifty-two non-dependent drinkers reported their recent drinking patterns. Their inhibitory control and motor coordination were measured in response to placebo and 0.65?g/kg alcohol.

Results

Alcohol significantly impaired inhibitory control and motor coordination compared with placebo. Moreover, greater quantity and frequency of recent consumption predicted less alcohol impairment of motor coordination. However, there was no relationship between recent drinking habits and the degree of impairment of inhibitory control.

Conclusions

These findings suggest that tolerance to the disinhibiting effects of alcohol might not readily develop as a result of recent, heavy drinking.     

Alcohol craving in adolescents: bridging the laboratory and natural environment

Rationale

Initial lab studies suggest that adolescent drinkers crave alcohol when presented with alcohol cues. Whether this effect generalizes to the natural environment, however, remains unknown, and studies have not examined whether craving predicts drinking among youths.

Objectives

This study builds on existing research by pairing controlled lab-based cue reactivity assessments (CRAs) with data collected in the natural environment using ecological momentary assessment (EMA) methods. We examined whether alcohol cues evoke craving among adolescent drinkers in the lab and natural environment, and tested the clinical relevance of craving during adolescence by examining the prospective association between craving and alcohol use.

Methods

Non-treatment-seeking adolescent drinkers (N?=?42; ages 15 to 20 years) completed a lab-based CRA followed by a 1-week EMA monitoring period. During the EMA period, youth were prompted randomly throughout the day to record momentary data on craving and contextual factors (e.g., alcohol cues, peers present).

Results

Alcohol cues elicited craving in the lab, and this effect generalized to the natural environment, especially among adolescents with more alcohol problems. In addition, craving predicted subsequent drinking levels in the natural environment.

Conclusions

This study demonstrates the utility of pairing lab paradigms with EMA methods to better characterize adolescents' reactivity to alcohol cues. Results implicate craving as a clinically meaningful motivator for drinking among adolescents and highlight a potentially important target of pharmacological or behavioral intervention.     

Effects of alcohol (BAC 0.5‰) and ecstasy (MDMA 100?mg) on simulated driving performance and traffic safety

Rational

An increasing number of fatal road-accidents have been reported in which ecstasy was found in the blood of drivers. Although, ecstasy is frequently found to have been used in combination with alcohol, studies on the acute effects of ecstasy co-administered with alcohol on driving performance are relatively rare.

Objective

The present study was designed to establish the extent of driver impairment as a consequence of ecstasy or combined ecstasy and alcohol use as compared to driving under the influence of 0.3??, 0.5?? and 0.8?? alcohol. Furthermore, subjective performance was also assessed.

Results

Alcohol and ecstasy mainly influenced automated driving performance such as lateral and speed control. However, small to no effects of the substances were found on more complex driving behaviour. Overall, variance within the different driving measures was high especially when participants were treated with 3.4-methylenedioxy-methamphetamine (MDMA) and alcohol. Furthermore, equivalence testing showed that combined use may lead to impaired driving for some, but not all, drivers. Participants rated their own performance to be slightly worse than normal in both studies. Since driving was actually seriously deteriorated, this was a falsely positive assessment of their condition.

Conclusions

The dissociation between subjective perceptions and objective performance decrements are important notions for traffic safety since this may affect a driver??s judgement of whether or not it is safe to drive. For example, an intoxicated individual might decide to drive because the feelings of alertness caused by MDMA cloud the impairing effects of other drugs such as alcohol, thereby creating a potentially serious risk for traffic safety.     

The effects of energy drink in combination with alcohol on performance and subjective awareness

Rationale

This study investigated the coadministration of an energy drink with alcohol to study the effects on subjective intoxication and objective performance.

Objectives

This study aims to evaluate the objective and subjective effects of alcohol versus placebo at two alcohol doses, alone and in combination with an energy drink, in a balanced order, placebo-controlled, double-blind design.

Methods

Two groups of ten healthy volunteers, mean (SD) age of 24 (6.5), participated in the study. One group consumed energy drink containing 80?mg of caffeine and the other consumed a placebo drink, with both receiving two alcohol doses (0.046 and 0.087% breathalyser alcohol concentration). Tests included breath alcohol assessment, objective measures of performance (reaction time, word memory and Stroop task) and subjective visual analogue mood scales.

Results

Participants showed significantly impaired reaction time and memory after alcohol compared to the no alcohol condition and had poorer memory after the higher alcohol dose. Stroop performance was improved with the energy drink plus alcohol combination compared to the placebo drink plus alcohol combination. Participants felt significant subjective dose-related impairment after alcohol compared to no alcohol. Neither breath alcohol concentration nor the subjective measures showed a significant difference between the energy drink and the placebo energy drink when combined with alcohol.

Conclusions

Subjective effects reflected awareness of alcohol intoxication and sensitivity to increasing alcohol dose. There were no overall significant group differences for subjective measures between energy drink and placebo groups in the presence of alcohol and no evidence that the energy drink masked the subjective effects of alcohol at either dose.     

Alcohol dependent patients have weak negative rather than strong positive implicit alcohol associations

Rationale

Alcohol dependence is characterised by motivational conflict (or ambivalence) in controlled cognitive processes, but it is unclear if ambivalence also exists within automatic cognitive processes, and if ambivalence operates between controlled and automatic processes.

Objective

To investigate ambivalence operating within and between controlled and automatic processes in alcohol dependence.

Method

Alcohol-dependent patients who had recently completed inpatient alcohol detoxification (N?=?47) and social drinking controls (N?=?40) completed unipolar implicit association tests and self-report measures of alcohol approach and avoidance motivation and alcohol outcome expectancies.

Results

As predicted, both positive and negative alcohol outcome expectancies were stronger in alcohol-dependent patients compared to controls, indicative of ambivalence. Groups did not differ on implicit alcohol-positive associations, but alcohol-dependent participants had significantly weaker alcohol-negative associations than controls. Regression analyses revealed that implicit negative associations accounted for unique variance in group membership after controlling for alcohol outcome expectancies.

Conclusions

Our findings demonstrate that alcohol dependent patients possess weak automatic alcohol-negative associations but not strong automatic alcohol-positive associations, and they suggest the presence of conflict between controlled and automatic processes with regard to negative alcohol cognitions.     

Relationship between alcohol dependence,escape drinking,and early neural attention to alcohol-related cues

Rationale

Previous work has indicated that implicit attentional biases to alcohol-related cues are indicative of susceptibility to alcohol dependence and escape drinking, or drinking to avoid dysphoric mood or emotions.

Objective

The goal of the current study was to examine whether alcohol dependence and escape drinking were associated with early neural attentional biases to alcohol cues.

Methods

Electroencephalography data were recorded from 54 college students who reported that they regularly drank alcohol, while they viewed alcohol and control pictures that contained human content (active) or no human content (inactive).

Results

Those who were alcohol dependent showed more neural attentional bias to the active alcohol-related stimuli than to the matched control stimuli early in processing, as indicated by N1 amplitude. Escape drinkers showed greater neural attention to the active alcohol cues than non-escape drinkers, as measured by larger N2 amplitudes.

Conclusions

While alcohol dependence is associated with enhanced automatic attentional biases early in processing, escape drinking is associated with more controlled attentional biases to active alcohol cues during a relatively later stage in processing. These findings reveal important information about the time-course of attentional processing in problem drinkers and have important implications for addiction models and treatment.     

Measurement of alcohol hangover severity: development of the Alcohol Hangover Severity Scale (AHSS)

Objective

This study aims to develop a new alcohol hangover symptom severity scale and compare its effectiveness with the Hangover Symptoms Scale (HSS), the Acute Hangover Scale (AHS), and a one-item hangover score.

Methods

Data from 1,410 Dutch students (Penning et al., Alcohol Alcohol 47:248-252, 2012) on the severity of 47 hangover symptoms were re-analyzed to develop the Alcohol Hangover Severity Scale (AHSS). The psychometric properties of the AHSS were compared with those of the HSS and the AHS. A survey among 1,000 students compared the AHSS and HSS with a one-item hangover severity score. The AHSS was further tested in a naturalistic hangover experiment.

Results

The 12 items of the AHSS were fatigue, clumsiness, dizziness, apathy, sweating, shivering, nausea, heart pounding, confusion, stomach pain, concentration problems, and thirst. The Penning et al. (Alcohol Alcohol 47:248–252, 2012) data revealed that the predictive validity of the AHSS (92.4 %) for the overall hangover score was significantly higher than that of the HSS (81.5 %) and the AHS (71.0 %). The survey data (N?=?966) showed that scores on the AHSS (39.7 %) and the HSS (47.6 %) only moderately predicted the one-item hangover score. A total of 119 subjects completed the naturalistic study. On average, they consumed 9.7 alcoholic consumptions, yielding a mean estimated blood alcohol concentration (BAC) of 0.16 %. During hangover, the AHSS score correlated significantly with the number of alcoholic consumptions (r?=?0.38, p?<?0.0001) and estimated BAC (r?=?0.40, p?<?0.0001).

Conclusions

The AHS, HSS, and AHSS all seem appropriate for application in hangover research. The use of a one-item hangover scale is not recommended.     

Family history of alcoholism interacts with alcohol to affect brain regions involved in behavioral inhibition

Rationale

Impulsive behavior is associated with both alcohol use disorders and a family history of alcoholism (FHA). One operational definition of impulsive behavior is the stop-signal task (SST) which measures the time needed to stop a ballistic hand movement.

Objective

Employ functional magnetic resonance imaging (fMRI) to study right frontal responses to stop signals in heavy drinking subjects with and without FHA, and as a function of alcohol exposure.

Methods

Twenty-two family history-positive (FHP; age?=?22.7 years, SD?=?1.9) and 18 family history-negative (FHN; age?=?23.7, SD?=?1.8) subjects performed the SST in fMRI in two randomized visits: once during intravenous infusion of alcohol, clamped at a steady-state breath alcohol (BrAC) concentration of 60 mg/dL, and once during infusion of placebo saline. An independent reference group (n?=?13, age?=?23.7, SD?=?1.8) was used to identify a priori right prefrontal regions activated by successful inhibition (Inh) trials, relative to “Go” trials that carried no need for inhibition [Inh?>?Go].

Results

FHA interacted with alcohol exposure in right prefrontal cortex, where alcohol reduced [Inh?>?Go] activation in FHN subjects but not in FHP subjects. Within this right frontal cortical region, stop-signal reaction time also correlated negatively with [Inh?>?Go] activation, suggesting that the [Inh?>?Go] activity was related to inhibitory behavior.

Conclusions

The results are consistent with the low level of response theory (Schuckit, J Stud Alcohol 55:149–158, 1980; Quinn and Fromme, Alcohol Clin Exp Res 35:1759–1770, 2011), with FHP being less sensitive to alcohol’s effects.     

Disruption of sensory gating by moderate alcohol doses

Rationale

Evidence from a growing body of literature suggests that alcohol, even at moderate-dose levels, disrupts the ability to ignore distractors. However, little work has been done to elucidate the neural processes underlying this deficit.

Objective

The present study was conducted to determine if low-to-moderate alcohol doses affect sensory gating, an electrophysiological phenomenon believed to reflect the pre-attentive filtering of irrelevant sensory information.

Methods

Sixty social drinkers were administered one of three doses intended to produce breath alcohol concentrations of 0.0 % (placebo), 0.04 % (i.e., low dose), and 0.065 % (i.e., moderate dose). A paired-click paradigm consisting of 100 pairs of identical tones (S1 and S2) was used to assess sensory gating. Amplitudes of P50, N100, and P200 auditory evoked potentials (AEPs) were used to calculate gating difference (S1–S2) and ratio (S2/S1) scores.

Results

The moderate alcohol dose significantly decreased P50 and N100 gating relative to placebo. Comparisons between the difference and ratio scores helped characterize the gating mechanisms affected at these stages of information processing. Alcohol did not alter P200 sensory gating.

Conclusions

These data suggest that alcohol disrupts pre-attentional sensory-filtering processes at breath alcohol concentrations (BrACs) below the current 0.08 % legal limit. Future studies should perform a combined assessment of sensory gating and selective attention to better understand the relationship between these two alcohol-induced deficits.     

Effect of prenatal stress on alcohol preference and sensitivity to chronic alcohol exposure in male rats

Rationale

In rats, prenatal restraint stress (PRS) induces persistent behavioral and neurobiological alterations leading to a greater consumption of psychostimulants during adulthood. However, little is known about alcohol vulnerability in this animal model.

Objectives

We examined in adolescent and adult male Sprague Dawley rats the long-lasting impact of PRS exposure on alcohol consumption.

Methods

PRS rats were subjected to a prenatal stress (three daily 45-min sessions of restraint stress to the mothers during the last 10?days of pregnancy). Alcohol preference was assessed in a two-bottle choice paradigm (alcohol 2.5%, 5%, or 10% versus water), in both na?ve adolescent rats and adult rats previously exposed to a chronic alcohol treatment. Behavioral indices associated with incentive motivation for alcohol were investigated. Finally, plasma levels of transaminases (marker of hepatic damages) and ??FosB levels in the nucleus accumbens (a potential molecular switch for addiction) were evaluated following the chronic alcohol exposure.

Results

Alcohol preference was not affected by PRS. Contrary to our expectations, stressed and unstressed rats did not display signs of compulsive alcohol consumption. The consequences of the alcohol exposure on locomotor reactivity and on transaminase levels were more prominent in PRS group. Similarly, PRS potentiated alcohol-induced ??FosB levels in the nucleus accumbens.

Conclusion

Our data suggest that negative events occurring in utero do not modulate alcohol preference in male rats but potentiate chronic alcohol-induced molecular neuroadaptation in the brain reward circuitry. Further studies are needed to determine whether the exacerbated ??FosB upregulation in PRS rats could be extended to other reinforcing stimuli.     

Dutasteride reduces alcohol’s sedative effects in men in a human laboratory setting and reduces drinking in the natural environment

Rationale

Preclinical studies support the hypothesis that endogenous neuroactive steroids mediate some effects of alcohol.

Objectives

The aim of this study was to examine the effect of dutasteride inhibition of 5α-reduced neuroactive steroid production on subjective responses to alcohol in adult men.

Methods

Using a within-subject factorial design, 70 men completed four randomly ordered monthly sessions in which pretreatment with 4 mg dutasteride or placebo was paired with a moderate dose of alcohol (0.8 g/kg) or placebo beverage. The pharmacologic effect of dutasteride was measured by an assay of serum androstanediol glucuronide. Self-reports of alcohol effects were obtained at 40-min intervals following alcohol administration using the Biphasic Alcohol Effects Scale (BAES) and the Alcohol Sensation Scale (SS). We used linear mixed models to examine the effects of dutasteride and alcohol on BAES and SS responses and the interaction of dutasteride with the GABRA2 alcohol dependence-associated polymorphism rs279858. We also examined whether exposure to dutasteride influenced drinking in the weeks following each laboratory session.

Results

A single 4-mg dose of dutasteride produced a 70 % reduction in androstanediol glucuronide. Dutasteride pretreatment reduced alcohol effects on the BAES sedation and SS anesthesia scales. There was no interaction of dutasteride with rs279858. Heavy drinkers had fewer heavy drinking days during the 2 weeks following the dutasteride sessions and fewer total drinks in the first week after dutasteride.

Conclusions

These results provide evidence that neuroactive steroids mediate some of the sedative effects of alcohol in adult men and that dutasteride may reduce drinking, presumably through its effects on neuroactive steroid concentrations.     

Tolerance and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis users

Introduction

Previous research has shown that heavy cannabis users develop tolerance to the impairing effects of ??9-tetrahydrocannabinol (THC) on neurocognitive functions. Animal studies suggest that chronic cannabis consumption may also produce cross-tolerance for the impairing effects of alcohol, but supportive data in humans is scarce.

Purpose

The present study was designed to assess tolerance and cross-tolerance to the neurocognitive effects of THC and alcohol in heavy cannabis users.

Methods

Twenty-one heavy cannabis users participated in a double-blind, placebo-controlled, three-way study. Subjects underwent three alcohol-dosing conditions that were designed to achieve a steady blood alcohol concentration of about 0, 0.5, and 0.7?mg/ml during a 5-h time window. In addition, subjects smoked a THC cigarette (400???g/kg) at 3?h post-onset of alcohol dosing during every alcohol condition. Performance tests were conducted repeatedly between 0 and 7?h after onset of drinking and included measures of perceptual motor control (critical tracking task), dual task processing (divided-attention task), motor inhibition (stop-signal task), and cognition (Tower of London).

Results

Alcohol significantly impaired critical tracking, divided attention, and stop-signal performance. THC generally did not affect task performance. However, combined effects of THC and alcohol on divided attention were bigger than those by alcohol alone.

Conclusion

In conclusion, the present study generally confirms that heavy cannabis users develop tolerance to the impairing effects of THC on neurocognitive task performance. Yet, heavy cannabis users did not develop cross-tolerance to the impairing effects of alcohol, and the presence of the latter even selectively potentiated THC effects on measures of divided attention.     

A critical analysis of alcohol hangover research methodology for surveys or studies of effects on cognition

Rationale

Alcohol hangover may be defined as an adverse effect of heavy alcohol consumption present after sufficient time has elapsed for the alcohol to have been eliminated from the blood. Understanding how hangover may impair performance is important for public safety; yet, there is relatively little hangover research. This paper outlines good practice for future studies.

Objectives

This paper presents a critical analysis of hangover methodology for surveys or studies of effects on cognition with human subjects and provides suggestions for optimum research practice for laboratory-based and naturalistic alcohol hangover studies.

Results

Four hangover symptom scales have been developed and subjected to psychometric testing. For retrospective assessment, we recommend the Hangover Symptoms Scale (HSS) or the Alcohol Hangover Severity Scale (AHSS). For concurrent assessment of hangover symptoms, we recommend either the Acute Hangover Scale (AHS), the five-item version of the HSS, or the AHSS. In research aiming to assess the cognitive effects of alcohol hangover, we suggest focusing on the cognitive domains of attention, memory and executive function, and we specify a number of tests within these cognitive domains that are likely to be sensitive to any decrements due to hangover. Finally, we argue that naturalistic studies should assess biological markers to improve the accuracy of estimates of alcohol consumption. Specifically, we recommend the assessment of ethyl glucuronide (EtG) for this purpose.

Conclusions

Recommendations are made with respect to assessing hangover symptoms, cognitive effects of hangover and biological markers of alcohol consumption.