The effects of alcohol and alcohol expectancies on subjective reports and physiological reactivity: a meta-analysis

The balanced placebo design (BPD) has been used to understand the etiology and maintenance of alcohol consumption. The utility of this design lies in its ability to examine both actual alcohol consumption and the expectation of alcohol consumption. A meta-analysis of the BPD literature was conducted in the context of cue-reactivity, which may be characterized as an experimental phenomenon observed in studies utilizing alcohol. Sixty-four studies were obtained in literature searches and coded for type of experimental setting and cues present during the actual beverage consumption. Lab setting was a moderator for both pharmacological (alcohol) and expectancy effects with the largest effects (in the same direction) noted in natural environment labs (i.e., an easy chair and casual environment). Contrary to predictions, the bar lab produced the smallest effects. Cues present during alcohol consumption served as a moderator of pharmacological effect, with the largest effect observed when alcohol was placed on the rim of the glass. Implications of these findings for cue-reactivity studies and the treatment of alcohol abuse are discussed.     

The effect of alcohol on emotional response to a social stressor.

Social drinkers were administered either an alcoholic, placebo or no-alcohol control beverage. Subjects were next informed that they were to give a self-disclosing speech about their body and physical appearance. Subjects' heart rate and videotapes of their facial expression were recorded during this instruction. Facial reactions to the stressor were analyzed using a system based on the Maximally Discriminative Facial Coding System (Izard, 1979). Subjects who were intoxicated showed significantly less negative emotion, as measured by the facial expression analysis, than those subjects consuming either the control or placebo beverage. We attribute this effect of alcohol to its actions on subjects' appraisal of anxiety-inducing information.     

Gender specific effects of a mild stressor on alcohol cue reactivity in heavy social drinkers

RATIONALE: Stress plays an important role in the development and maintenance of alcohol-abuse. Some of the effects of stress on alcohol-related behaviours, however, appear to be gender-dependent. AIM: The present study set out to examine the effects of stress on feelings of desire for alcohol, skin conductance response and alcohol consumption in the presence of alcohol-related cues in relation to gender. Participants were heavy non-dependent alcohol drinkers. METHODS: Thirty-two (16 males) participants drinking more than 21 units of alcohol per week were randomly allocated to undergo the experimental stress (based on the 'Trier Social Stress' Test) or the non-stress procedure before the alcohol cue exposure procedure, during which participants handled and smelled their preferred drink. Mood and saliva cortisol level changes were used as indices of the stress effects, while alcohol craving, skin conductance and alcohol consumption were the cue reactivity measures. RESULTS: Self ratings of anxiety and tension increased and cortisol levels remained high in the stress compared to the non-stress condition; no gender differences were found. Stress induced gender-specific effects with regard to skin conductance response and alcohol consumption measurements. Stressed females did not show an increase from baseline in the skin conductance response during the alcohol cue-exposure session, which was observed in the non-stressed females; they also consumed less alcohol than males under stress. CONCLUSION: Female participants respond less to alcohol-related cues when in a negative mood state. Such a finding suggests that females when in a negative mood may be less sensitive to positive incentive processes mediating cue reactivity compared to males.     

Acute tolerance to alcohol: changes in subjective effects among social drinkers

The development of acute of acute tolerance to the subjective effects of alcohol was examined in 32 social drinkers. Measures were made of self-reported level of intoxication and responses to questions from the alcohol scale of the Addiction Research Centre Inventory. The time to peak self-reported intoxication level was found to be 20 min earlier than the time to peak blood alcohol concentration. Changes from the ascending to the descending limb of the blood alcohol curve were found with five of the ARCI questions. In all cases the proportion of alcohol-typical responses was lower on the descending portion of the curve. even though blood alcohol levels were equivalent. Further analyses examined the effects of prior drinking history on the development of acute tolerance. Peak self-reported intoxication levels were significantly lower and occurred earlier for heavier drinkers. Furthermore, for four of the five ARCI questions heavier drinkers were less likely to give analcohol-typical response than lighter drinkers on the ascending portion of the curve.     

The effects of alcohol cues and an alcohol priming dose on a multi-factorial measure of subjective cue reactivity in social drinkers

Rationale: Exploring subjective alcohol cue reactivity in non-clinical samples should assist understanding in clinical samples where additional problems muddy the water. However, exploration is stalled through using insensitive, single-item representations. Objective: The effect of alcohol cues and a priming dose of alcohol on a new multi-factorial representation of cue reactivity is sought (DAQ, Desire for Alcohol Questionnaire). Methods: Prime and Cue exposure are variables in a standard 2×2 between subjects design set within a stooge taste-evaluation experiment. The DAQ was administered after a Prime and Cue exposure phase. Results: Main effects for Cue exposure but not Prime were found for the DAQ total and the subscales Mild desires (positively reinforcing items) and Strong desires/intentions but not Negative reinforcement (negatively reinforcing items) and Controllability; however, there was no interaction. Conclusion: The DAQ is a sensitive measure of subjective cue reactivity in social drinkers and its potential in the evaluation of pharmacological interventions is proposed. Received: 14 May 1999 / Final version: 4 June 1999     

Delta and kappa opioid receptor polymorphisms influence the effects of naltrexone on subjective responses to alcohol

Naltrexone, one of four FDA-approved pharmacotherapies for alcohol dependence, has shown moderate efficacy in clinical trials. Pharmacogenetic effects have been reported such that allelic variation at the gene encoding the mu-opioid receptor (OPRM1, rs1799971) predicts naltrexone-induced blunting of the positively reinforcing effects of alcohol. However, naltrexone also binds, albeit to a lesser degree, to kappa and delta opioid receptors in the brain. This alternate binding presents the possibility that single nucleotide polymorphisms (SNPs) in the kappa and delta opioid receptor (OPRK1 and OPRD1) genes may contribute to naltrexone pharmacogenetics. Therefore, the goal of this exploratory study was to re-examine data from a double-blind placebo controlled laboratory trial of naltrexone for pharmacogenetic effects at kappa and delta opioid receptor tag SNPs. Participants were 40 heavy drinkers (12 female) who underwent an intravenous alcohol challenge paradigm after receiving naltrexone (50 mg) or placebo in randomized and crossover fashion. Dependent variables were self-reported alcohol-induced stimulation, sedation, and craving. Multilevel models revealed a significant Naltrexone × OPRK1 Genotype (rs997917) interaction predicting alcohol-induced sedation, such that TT homozygotes reported lower naltrexone-induced alcohol sedation as compared to carriers of the C allele. Moreover, there was a significant Naltrexone × OPRD1 Genotype (rs4654327) interaction predicting alcohol-induced stimulation and craving, such that carriers of the A allele at this locus reported greater naltrexone-induced blunting of alcohol stimulation and alcohol craving compared to GG homozygotes. These findings suggest that additional pharmacogenetic effects in the opioid receptor system may account for individual differences in response to naltrexone in the human laboratory.     

Alcohol and anxiety: Postdrink-performance feedback alters affective and self-evaluative responses to a subsequent social stressor

Several models of alcohol use and abuse implicate self-evaluation as a variable that mediates alcohol's anxiolytic effects. Self-evaluation when drinking, in turn, is affected by people's causal attributions for their behavior and alcohol expectancies. Accordingly, postdrink performance feedback was manipulated by having 20 subjects engage in a set of tasks before and after a moderate dose of alcohol. Half of the subjects received feedback that alcohol impaired their task performance whereas the other half received feedback that alcohol did not impair their performance. All subjects then participated in a stressful social interaction. As expected, subjects in the high behavioral impairment condition made more external performance attributions during the social stressor and reported less negative self-evaluation and subjective anxiety than subjects in the low behavioral impairment condition. Alcohol expectancies appeared to account partially for the data. The results indicate that information concerning alcohol-induced behavioral impairment moderates alcohol's effects on self-evaluation and subjective anxiety.     

Autonomic and subjective responses to alcohol stimuli with appropriate control stimuli

Previous studies on "craving" for alcohol after exposure to olfactory stimuli for alcohol may be criticized on the grounds that the control stimuli were not really appropriate. We included exposure to a preferred nonalcoholic beverage and to a sweet food item as additional control stimuli in order to better compare the salivary, autonomic, and self-reported craving responses of alcoholics with normal social drinkers. The results indicated that the salivation measure was differentially sensitive to the alcohol stimulus, even when compared to appropriate control stimuli. It is possible that self-reported craving is a biased measure in alcoholic inpatients in treatment.     

The effects of alcohol alone or in combination with other drugs on information processing,task performance and subjective responses

This paper reviews the effects of alcohol on human psychomotor performance and cognitive function. It concentrates particularly on effects on reaction time and on skills related to car driving. The effects of alcohol on performance are very variable at low doses (under 1 g per kg body weight). The variability is due to the different measures and methods employed by the researchers and to the large interindividual and interoccasional differences in the effects of alcohol. That is, alcohol affects different people in different ways and it affects the same person differently on separate occasions. Greater performance deficits are observed as the dose increases and as the tasks become more complex. Although results vary, both nicotine and caffeine appear to antagonize the detrimental effects of alcohol on performance. Many other drugs interact with alcohol, the most important of which are sedative agents that can combine synergistically with alcohol to produce profound psychomotor and cognitive impairment. © 1998 John Wiley & Sons, Ltd.     

Tolerance to repeated nicotine administration on performance, subjective, and physiological responses in nonsmokers

RATIONALE: When administered acutely to nonsmokers, nicotine's effects on performance are inconsistent, perhaps because of suboptimal dosing or initial dysphoria that could interfere with performance. OBJECTIVE: The purpose of this study was to determine if a range of nicotine doses administered for 8 days to nonsmokers would enhance psychomotor and cognitive abilities and to document the development of nicotine tolerance or sensitization. METHODS: Twelve male volunteers, who reported ever smoking five cigarettes or less, participated in 8 consecutive experimental days in which they were administered four doses of nicotine polacrilex gum each day in this order: 0, 2, 4, and 8 mg. Performance, subjective, and physiological measures were assessed before and after each dose. RESULTS: Plasma nicotine concentration ranged from 6.9 to 11.5 ng/ml following the 8 mg dose. Nicotine increased rate of responding and decreased response time on working memory (digit recall); however, accuracy was impaired. Nicotine also decreased accuracy on visual scanning and attention (two-letter search), and the 8 mg dose impaired gross motor coordination (circular lights). Tolerance did not develop to the performance impairing effects of nicotine. Nicotine produced dose-related increases in ratings of dysphoria and negative mood, including tension, anxiety, nervousness, turning of stomach, and sedation. Tolerance developed to some, but not all, of these aversive effects. Tolerance also was not observed to the increased cardiovascular measures. CONCLUSION: Although tolerance developed to some of the aversive effects of nicotine, performance enhancement was not observed. These data do not support the hypothesis that nicotine-induced performance enhancement contributes to the reinforcing effects of tobacco use during the early stages of dependence development.     

A low dose alcohol drug discrimination in social drinkers: relationship with subjective effects

RATIONALE: Although well characterised in animals, relatively little is known about alcohol discriminative stimulus effects in humans. OBJECTIVE: The study was carried out to investigate the correspondence of subjective effects and the discriminative response during the acquisition of a low dose alcohol discrimination in humans. METHODS: Healthy volunteers completed an Alcohol Use Questionnaire and were then trained to discriminate a dose of 0.2 g/kg alcohol from placebo using a money reinforced technique. Subjects sampled drinks during training, but also completed rating scales measuring Taste, Like/Dislike and Subjective Effects for each drink. RESULTS: Thirty-two subjects learned the discrimination (discriminators; Ds). In these subjects, differences between placebo scores and alcohol scores for Lightheadedness, Relaxed, Arousal and Fatigue were greater following acquisition of the discrimination, compared with differences at the start of training. Differences in other measures remained consistent. Twenty-six of the volunteers failed to learn the discrimination (non-discriminators; NDs). These subjects reported drinking approximately twice as much alcohol during the preceding 6 months, as the Ds (4.35+/-0.53 g/kg per week versus 2.08+/-0.19 g/kg per week, respectively, P<0.001). There were no alcohol specific differences in ratings for Lightheadedness, Relaxed, Arousal or Fatigue between the Ds and the NDs. However, Dislike scores did differentiate between the Ds and the NDs in that the NDs had reduced ratings for the alcohol drink only compared with the Ds (P<0.02). CONCLUSIONS: These results support the suggestion from animal studies, that the alcohol stimulus is a compound, and characterise the subjective effects which contribute to a low dose cue in humans. In addition, the data suggest that previous drinking experience may selectively alter aversive responses to alcohol and that this, in addition to differences in general arousal levels, may have affected subjects' ability to learn the discrimination.     

Naltrexone alters subjective and psychomotor responses to alcohol in heavy drinking subjects.

Preclinical studies support endogenous opioid system involvement in alcohol reinforcement and consumption; however, recent clinical trials and human laboratory studies have provided mixed findings of the effects of naltrexone (a non-selective opioid antagonist) on alcohol responses. This study used a within-subject design (n = 23) to investigate naltrexone effects (0, 50 and 100 mg qd) on subjective and psychomotor responses to alcohol (none, moderate, high) in heavy drinkers. Before alcohol administration, subjects reported decreased desire to drink alcohol when maintained on 50 mg compared with placebo naltrexone. Following alcohol administration, active naltrexone significantly increased subjective ratings of sedative, and unpleasant/sick effects and decreased ratings of liking, best effects and desire to drink. Naltrexone generally did not alter subjective or objective indicators of drunkenness. Finally, high doses of naltrexone and alcohol interacted to produce the greatest decreases in liking and best effects. Findings support the role of endogenous opioids as determinants of alcohol's effects and suggest that naltrexone may be particularly clinically useful in those treatment patients who continue to drink heavily.     

Reactivity to alcohol-related cues: physiological and subjective responses in alcoholics and nonproblem drinkers

Physiological reactivity and self-reported desire to drink in nonproblem drinkers (N = 11 women and 15 men) and hospitalized alcoholics (N = 25 women and 34 men) were examined while subjects held and sniffed their preferred alcoholic beverage. Skin conductance level (SCL) and heart rate during alcohol exposure were significantly higher in the alcoholics than in the non-alcoholics. Self-reported desire to drink and SCL during alcohol exposure were correlated for alcoholics but not for nonalcoholics. Among alcoholics, SCL change was positively correlated with the number of heavy-drinking days in the month preceding admission to treatment. Consistent with conditioning models of relapse, alcoholics showed a distinctive response to alcohol cues, characterized by autonomic reactivity and concordance between this reactivity and self-reported desire for alcohol.     

The long-term effects of diazepam and pentylenetetrazol on behavioral sensitivity to a stressor

Rats were trained to bar press for sucrose reinforcement following daily injections of 20 mg/kg pentylenetetrazol (PTZ), 5 mg/kg diazepam (DZ), or saline. At the end of 12 days of this training, all injections were suspended for the remainder of the experiment. Five days later, the rats were given 10 days of Pavlovian fear conditioning (two trials per day) to establish a light as a shock signal. Next, the rats were returned to the bar press situation to test the capacity of the light to suppress responding. Rats previously treated with DZ showed stronger conditioned fear of the light than did rats originally trained following injections of either PTZ or saline. In contrast, bar pressing by PTZ-treated rats was less suppressed by light than was control performance. The results indicate that modification of the behavioral effects of environmental stressors can be a long-term consequence of drug treatments. DZ treatments had the long-term effect of increasing behavioral disruption by a stressor, while treatment with PTZ reduced the stressor's negative behavioral impact. These findings appear compatible with the idea that behavioral sensitivity to stressors is dependent, in part, on learning about the stimulus properties of internal states.     

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.     

The effects of acute haloperidol or risperidone on subjective responses to methamphetamine in healthy volunteers

Despite extensive evidence that selective dopamine antagonists attenuate the reinforcing effects of stimulants in laboratory animals, there is little evidence that dopamine antagonists block the positive subjective effects of stimulants in humans. However, recent evidence suggests that the subjective effects of stimulants in humans may depend in part on serotonin. The goal of this study was to examine the effects of haloperidol, a drug that primarily blocks dopamine receptors, and risperidone, a drug that blocks both dopamine and serotonin receptors, on the physiological and subjective effects of methamphetamine in healthy volunteers. Two groups of subjects participated in a placebo-controlled, within-subject, 2 x 2 repeated measures design. One group was tested with haloperidol (3 mg; N = 18), the other with risperidone (0.75 mg; N = 18). Each subject participated in four sessions receiving all combinations of antagonist or placebo and methamphetamine (20 mg) or placebo. Dependent measures included vital signs and standardized questionnaires of subjective effects. At these doses, both haloperidol and risperidone produced mild sedative-like effects compared to placebo. However, neither drug consistently reduced the stimulant-like effects of methamphetamine. These results add to the growing body of literature suggesting that D(2) dopamine receptor antagonists do not block the euphorigenic subjective effects of stimulant drugs in humans, and also do not support the idea that serotonin contributes significantly to these effects.     

Hypophagic,endocrine and subjective responses to m-chlorophenylpiperazine in healthy men and women

We studied the effect of the 5-HT receptor agonist, m-chlorophenylpiperazine (mCPP) (0.4 mg orally), on food intake, plasma prolactin and subjective state in 24 healthy male and female volunteers, using a double-blind, placebo-controlled design. mCPP lowered food intake, and increased plasma prolactin to the same extent in both sexes. Increased anxiety ratings, however, occurred more in females. Other mCPP-induced subjective changes in nausea, light-headedness and hunger did not distinguish the sexes. There was no significant correlation between the decrease in food intake produced by mCPP and any of the subjective ratings. Overall, the data indicate that mCPP produces significant hypophagia in both men and women. The greater anxiogenic effect of mCPP in female subjects is of interest in view of the increased prevalence of clinical anxiety disorders in women.