Attentional bias to alcohol stimuli predicts elevated cue-induced craving in young adult social drinkers

Considerable evidence has identified biased cognitive processing of alcohol-related stimuli as an important factor in the maintenance of alcohol-seeking and relapse among individuals suffering from alcohol use-disorders (AUDs). In addition, a large body of research has demonstrated that exposure to alcohol cues can elicit powerful alcohol cravings. Little is known, however, about the possible relationship between attentional bias and cue-induced cravings, and even less is known about these processes in social drinkers without a personal history of AUDs. The goal of this study was to examine the possibility that attentional biases toward alcohol-related stimuli would predict elevated cue-induced alcohol craving in this population. Young adult social drinkers (N = 30, Mean age = 22.8 ± 1.9, 61% female) recruited from an urban university population completed a visual dot probe task in which they were presented with alcohol and neutral stimulus pictures that were immediately followed by a visual probe replacing one of the pictures. Attentional bias was measured by calculating reaction times to probes that replaced alcohol stimuli vs. neutral stimuli. Participants then completed a classic alcohol cue-exposure task and reported cravings immediately before and after alcohol and neutral cue-exposures. Not surprisingly, exposure to alcohol cues elicited significant cravings. Consistent with the study hypothesis, larger attentional biases toward alcohol stimuli predicted higher levels of alcohol craving. Findings demonstrate that heightened attention to alcohol stimuli can significantly impact motivation to consume in healthy young adults, and suggest a possible pathway linking cognitive processes early in the drinking trajectory to the later development of AUDs.     

Bupropion reduces methamphetamine-induced subjective effects and cue-induced craving.

Bupropion is an antidepressant with stimulant properties, which inhibits the reuptake of dopamine (DA) and norepinepherine, and is purported to enhance DA neurotransmission. Bupropion is considered an appealing candidate medication for the treatment of methamphetamine dependence. The current laboratory study was set forth to assess the impact of bupropion treatment on the subjective effects produced by methamphetamine in the laboratory. We also assessed the effects of bupropion treatment on craving elicited by exposure to videotaped methamphetamine cues. A total of 26 participants were enrolled and 20 completed the entire study (n=10 placebo and n=10 bupropion, parallel groups design). Bupropion treatment was associated with reduced ratings of 'any drug effect' (p<0.02), and 'high' (p<0.02) following methamphetamine administration. There was also a significant bupropion-by-cue exposure interaction on General Craving Scale total score (p<0.002), and on the Behavioral Intention subscale (p<0.001). Overall, the data reveal that bupropion reduced acute methamphetamine-induced subjective effects and reduced cue-induced craving. Importantly, these data provide a rationale for the evaluation of bupropion in the treatment of methamphetamine dependence.     

A prospective study of stress and alcohol craving in heavy drinkers

Recent work has examined the relationship between stress and relapse to alcohol use in clinical populations. Few prospective studies, however, have examined stress as a precipitant of alcohol problems. The present study is a longitudinal examination of the role of stress reactivity and alcohol craving in the etiology of alcohol problems in a sample of 41 (mean age = 20.8), heavy-drinking, young adults. Participants completed a guided imagery exposure to stressful life events, followed by exposure to a neutral imagery control. Following the exposure, participants completed an alcohol cue exposure paradigm. Measures of negative mood (Profile of Mood States (POMS) depression/dejection scale), tension (POMS tension/anxiety scale) and alcohol craving (measured by the Alcohol Urge Questionnaire (AUQ)) were used as indicators of reactivity to stress and to alcohol cues. Polymorphisms of the corticotropin-releasing hormone binding protein (CRH-BP) gene and of the μ-opioid receptor (OPRM1) gene were examined as moderators of this relationship. Results revealed that stress-induced negative mood predicted negative consequences of drinking (scores on the Drinker's Inventory of Consequences (DrInC-2R)), whereas stress and cue-induced alcohol craving did not predict alcohol use or problems. Additionally, the CRH-BP genotype was found to moderate the relationship between stress-induced negative affect and the negative consequences of drinking. The current study supports and extends laboratory research describing phenotypes of stress-induced alcohol craving.     

Can't stop the craving: the effect of impulsivity on cue-elicited craving for alcohol in heavy and light social drinkers

Rationale  

A robust finding in the alcohol literature is that heavy and alcohol-dependent drinkers show stronger reactions to alcohol-related cues than light drinkers. However, there are individual differences in the degree of cue-elicited craving. Personality factors appear to be involved in cue reactivity and impulsivity is a possible candidate.     

Effects of a low dose of alcohol on cognitive biases and craving in heavy drinkers

Rationale Heavy alcohol drinking increases the incentive salience of alcohol-related cues. This leads to increased appetitive motivation to drink alcohol as measured by subjective craving and cognitive biases such as attentional bias and approach bias. Although these measures relate to the same construct, correlations between these variables are often very low. Alcohol consumption might not only increase different aspects of appetitive motivation, but also correlations between those aspects. Objectives To investigate the effect of a low alcohol dose on changes in various measures of appetitive motivation. Materials and methods Twenty-three heavy social drinkers were tested in 2 sessions, once after receiving an alcohol prime dose and once after receiving a placebo drink. After drink administration, attentional bias was measured with a visual-probe task using concurrent eye movement monitoring. Furthermore, we measured the approach bias with a stimulus response compatibility task and subjective craving with the Desires for Alcohol Questionnaire. Results After the alcohol prime dose, participants had higher levels of craving and more pronounced attentional bias (faster reaction times to probes that replaced alcohol rather than control pictures, increased maintenance of gaze on alcohol pictures, and a higher percentage of first eye movements directed toward alcohol pictures). Approach bias was not influenced by the alcohol prime dose. The correlation between attentional bias and approach bias was significantly higher after the alcohol than after the placebo drink. Conclusions A low alcohol dose increased most measures of appetitive motivation for alcohol and increased the interrelation between cognitive measures of this construct.     

The role of impulsivity and perceived availability on cue-elicited craving for alcohol in social drinkers

Rationale

Previous research has demonstrated a role for impulsivity and perceived availability of the substance in cue-elicited craving. However, their effects on cue-elicited craving for alcohol are still ambiguous. Most important is that there has been no empirical evidence for the potential interaction of these factors on alcohol craving.

Objectives

The aim of the present study was to examine the effects of response inhibition and perceived availability on cue-elicited craving for alcohol in social drinkers.

Methods

Participants were light to moderate social drinkers (N?=?75) who were exposed to neutral- and alcohol-related stimuli during a single laboratory session. Response inhibition was assessed with the Stop Signal Task. Participants were randomly assigned to one of two perceived availability groups (n?=?37, expecting alcohol; n?=?38, not expecting alcohol).

Results

Overall craving for alcohol was higher in participants who expected alcohol than in those who did not. This finding was statistically significant only in the alcohol condition. Most important is that there was a significant interaction between response inhibition, perceived availability and time on cue-elicited craving. Regardless of the cue type, impulsive people who expected alcohol experience a significant increase in cue-elicited craving relative to impulsive people who did not expect alcohol. This effect was not observed in the non-impulsive groups.

Conclusions

The results clearly show that perceived availability alone and in combination with response inhibition can modulate alcohol cue reactivity. Theoretical explanations and clinical implications of these findings are discussed.     

Smoking-related videos for use in cue-induced craving paradigms

Environmental cues (e.g., the sight of a cigarette) have long been recognized as important triggers for craving in smokers. Available imaging technologies (e.g., fMRI) allow investigation of the neural mechanisms for cue-induced craving, but there stands a need for a cue-delivery system compatible with an MRI environment. We developed a standardized set of 24 high-resolution videos, 12 containing cigarette smoking scenes (e.g., lighting up), and 12 containing neutral scenes (e.g., reading a book), each 30 s long, with comparable lighting, visual complexity, and background filmed by a professional cinematographer. Study participants were 20 smokers (mean age=37.7 years, 50% female). Each was exposed to the 24 videos in a random order under laboratory conditions. Dependent measures included heart rate, blood pressure, skin conductance, skin temperature, and self-reported craving (0-100) following each video. Overall findings indicated that smokers had greater reactivity to the smoking videos than to neutral videos (p<.01). Follow-up univariate analyses revealed significant cue effects on self-reported craving, galvanic skin response, and skin temperature. Interestingly, exploratory examination of gender revealed that men had higher blood pressure and skin temperature responses than women, and that women had higher responses when viewing videos of women smoking than when viewing men smoking. Results support this set of videos as an effective tool for investigation of cue-elicited craving, and raise the possibility of unique gender effects in cue reactivity.     

Imaging stress- and cue-induced drug and alcohol craving: association with relapse and clinical implications

Stress- and drug-related cues are major factors contributing to high rates of relapse in addictive disorders. Brain imaging studies have begun to identify neural correlates of stress and drug cue-induced craving states. Findings indicate considerable overlap in neural circuits involved in processing stress and drug cues with activity in the corticostriatal limbic circuitry underlying both affective and reward processing. More recent efforts have begun to identify the relationships between neural activity during stress and drug cue exposure and drug relapse outcomes. Findings suggest medial prefrontal, anterior and posterior cingulate, striatal and posterior insula regions to be associated with relapse outcomes. Altered function in these brain regions is associated with stress-induced and drug cue-induced craving states and an increased susceptibility to relapse. Such alterations can serve as markers to identify relapse propensity and a more severe course of addiction. Efficacy of pharmacological and behavioral treatments that specifically target stress and cue-induced craving and arousal responses may also be assessed via alterations in these brain correlates. [Sinha R, Li C-SR. Imaging stress- and cue-induced drug and alcohol craving: association with relapse and clinical implications. Drug Alcohol Rev 2007;26:25 - 31]     

Relative reinforcing efficacy of alcohol among college student drinkers

The construct of relative reinforcing efficacy (RRE) is central to many laboratory and theoretical models of drug abuse, but it has not been widely measured in applied clinical research contexts. The authors used a simulated alcohol purchase task to measure RRE in a sample of 267 college student drinkers. Participants reported their alcohol consumption across a range of prices, and their responses were well-described by a regression equation that has been used to construct demand curves in drug self-administration studies. Several measures of relative reinforcing efficacy were generated, including breakpoint, intensity of demand, elasticity, P-sub(max) (price at which response output is maximized), and O-sub(max) (maximum alcohol expenditures). Demand for alcohol was inelastic across the initial range of prices but became elastic as price increased. Students who reported recent heavy drinking reported significantly greater intensity of demand, O-sub(max), and breakpoint. These results provide initial support for the validity of the RRE indices generated with the alcohol purchase task. These results also provide empirical support for programs that attempt to reduce alcohol abuse by eliminating low-cost access to alcohol.     

Effects of d-amphetamine and smoking abstinence on cue-induced cigarette craving

In this study, the authors investigated the effects of the indirect dopamine agonist d-amphetamine (AMPH) on cue-induced cigarette craving in smokers. Abstinent or nonabstinent cigarette smokers (N=21) rated their cravings for cigarettes and for food (control) after pretreatment with AMPH (15 mg) or placebo and before and after viewing blocks of smoking-related, food-related, and neutral pictures. Before the cues were presented, AMPH increased cigarette craving and decreased food craving. Smoking and food cues increased craving for cigarettes and for food, respectively. AMPH also further increased cigarette craving (and decreased food craving) after cue presentation, but it did so regardless of cue type (food or smoking). Smoking abstinence markedly increased craving regardless of cue presentation or drug condition. These results suggest that both AMPH and smoking abstinence can increase cigarette craving, but they do not appear to specifically affect responses to conditioned smoking-related cues.     

Gender, alcohol consumption, and differing alcohol expectancy dimensions in college drinkers

Examinations of gender differences in alcohol expectancies among college drinkers typically have used self-report measures to assess single expectancy dimensions and often have been confounded by drinking level. This study examined gender differences in alcohol expectancies using 2 assessment methods. College students (N = 88) completed self-report questionnaires, including expectancy likelihood and subjective evaluation endorsements of expectancies, and a computerized expectancy accessibility task. Expectancy accessibility and endorsement were modestly correlated, with higher alcohol consumption and female gender linked to greater accessibility and endorsement of social enhancement expectancies. Gender moderated the relation between consumption and sociability expectancy accessibility; among men, heavier drinking was associated with more rapid activation of expectancies. Findings suggest complexity in associations among these variables and underscore the need to capture the multidimensionality of the expectancy construct and its relationship to alcohol use.     

Alcohol-predictive cues enhance tolerance to and precipitate "craving" for alcohol in social drinkers

This study attempts to show that tolerance to alcohol is in large part a "learned" response, precipitated by contextual cues predictive of the unconditional drug effect. It also aims to show that the contextual cues integral to such "environment-dependent" tolerance function to increase motivational desire to drink alcohol. Male students (N = 40), drinking on average 10-20 units of alcohol per week, were randomly assigned to one of four groups. Two groups ingested 1.2ml/kg alcohol: one (AL-EXPT) with exteroceptive contextual cues typically associated with alcohol use, and the other (AL-UNEXPT) in a context not normally associated with alcohol. A third group (placebo) believed that they were drinking alcohol but, in fact, consumed a nonalcoholic beverage in the alcohol-expected context. The fourth group drank juice in the alcohol-unexpected context. As predicted, tolerance to the deleterious effects of alcohol on cognition and motor-performance, and subjective desire to consume alcohol, were influenced by the alcohol-predictive contextual cues. A physiological index (pulse rate) also tended to confirm that these cues elicited a conditioned compensatory response to alcohol. The implications of these findings for tolerance to and motivation to drink alcohol in a nonpathological population are discussed.     

An acute dose of nicotine enhances cue-induced cocaine craving

The present study examined whether the active component in tobacco, nicotine, can modulate cocaine craving in patients with a history of smoking crack cocaine when exposed to crack cocaine related environmental cues. Twenty patients, all cigarette smokers, were randomly assigned to nicotine (two 22 mg transdermal patches) or placebo in a single-dose, placebo-controlled, crossover, double-blind study. Craving and anxiety were measured before and after cocaine cues with visual analog scales for desire to use cocaine and mood. Skin conductance and skin temperature were recorded before and during cocaine cues. Following exposure to cocaine cues, all patients reported an increase in cocaine craving and anxiety relative to the pre-cue measures. Cue exposure also produced an increase in skin conductance and decrease in skin temperature. The cue-induced increase in cocaine craving was strongly enhanced by nicotine, while the increase in anxiety was slightly augmented. Cue-induced skin conductance and temperature responses were unaffected by nicotine. These findings show that cue-induced cocaine craving is enhanced by nicotine. This occurred in the absence of any tobacco smoking-related cues, suggesting that nicotine may have direct psychopharmacological effects on conditioned cocaine craving.     

Differential brain activity in alcoholics and social drinkers to alcohol cues: relationship to craving.

Using fMRI, our group previously found that after a sip of alcohol and exposure to alcohol beverage pictures, alcoholics compared to social drinkers had increased differential brain activity in the prefrontal cortex and anterior thalamus. This study extends this earlier work with several improvements including imaging the entire brain (rather than the anterior half previously) and recording craving, while the subjects viewed images within the scanner. In a Philips 1.5 T MRI scanner, 10 nontreatment-seeking alcoholics and 10 age-matched healthy social drinkers were given a sip of alcohol before viewing a 12 min randomized presentation of pictures of alcoholic beverages, nonalcoholic beverages, and two different visual control tasks. During picture presentation, changes in regional brain activity were measured in 15 transverse T2(*)-weighted blood oxygen level dependent slices. Subjects rated their urge to drink after each picture sequence. After a sip of alcohol, while viewing alcohol cues compared to viewing other beverage cues, the alcoholics, but not social drinkers, reported higher craving ratings and had increased activity in the prefrontal cortex and anterior limbic regions. Brain activity in the left nucleus accumbens, anterior cingulate, and left orbitofrontal cortex significantly correlated with subjective craving ratings in alcohol subjects but not in control subjects. This study suggests, as did our earlier study, that alcoholics and not social drinkers, when exposed to alcohol cues, have increased brain activity in areas that reportedly subserve craving for other addictive substances.     

Dose-related effects of alcohol among male alcoholics, problem drinkers and nonproblem drinkers

Cognitive variables, such as expectancies regarding the usefulness of alcohol, have been receiving increased attention in recent years because these expected effects can influence decisions to drink and mediate responses to alcohol. In the present study, alcohol expectancies were assessed using the Alcohol Beliefs Scale, a measure that yields dose-related data on expected effects of alcohol. The subjects were male alcoholics, problem drinkers and nonproblem drinkers. The central finding was that drinker group membership and rated dose level interacted in predicting subjects' estimates of the usefulness of alcohol for them. On the "useful for feeling better" factor, the greatest benefit was expected from a moderate dose, particularly among alcoholics. On the "useful for relieving emotional distress" factor, usefulness ratings increased with dose, with alcoholics expecting the greatest rate of increase. A similar pattern was found for the "useful for feeling in charge" factor, except that the ratings for problem drinkers and alcoholics paralleled each other. These findings have implications for our efforts to understand drinkers' motivations to initiate and continue drinking.     

眶额叶皮质在条件性线索诱发渴求神经生物学机制的研究进展

世界范围内的毒品蔓延与泛滥已成为国际公害，严重影响了人类健康与社会稳定。在我国滥用人数最多、复吸率最高、危害最严重的毒品为海洛因。目前普遍认为对药物的强烈渴求（craving）是导致复吸的重要原因之一。国外学者研究发现与药物有关的环境线索与药物滥用多次同时出现后可演变为与成瘾药物同等的条件反射刺激，甚至比药物本身具有更大的吸引力，足以诱发出成瘾者对药物强烈的渴求心理和情绪反应，并进一步导致强迫性的觅药和用药行为。     

Cannabis and cue-induced craving in cocaine-dependent individuals: A pilot study

BackgroundCannabis consumption is common among cocaine users; however, little is known about its effect on cocaine craving. The objective of this study was to assess whether cannabis co-use is associated with lower cue-induced cocaine craving in non-treatment-seeking cocaine-dependent individuals.MethodsData from twenty-eight cocaine-dependent men were analyzed in this pilot study. Cocaine-dependent subjects (n = 12) were compared with cocaine-dependent subjects who also abused or were dependent on cannabis (n = 16). After at least 72 h of cocaine abstinence, verified using the Timeline Followback and a drug screening test, subjects participated in a functional magnetic resonance imaging session during which neutral and drug cue video sequences were presented. Each sequence comprised four video blocks alternating with resting blocks. We report here subjective craving measures that were collected using the Visual Analog Scale, administered before and after each video block as per standard craving measurement paradigms.ResultsCocaine craving was successfully induced, with no significant difference in cue-induced craving between the two groups. However, post-hoc analyses revealed a significant increase in pre-video cocaine craving scores over time among individuals with cannabis use disorders.ConclusionWe could not highlight significant differences in cocaine craving induction between groups, but we observed a possible deficit in craving decay in the cocaine and cannabis group. In light of this finding, methodology of craving assessment in non-treatment-seeking users, particularly when different substances are combined, should possibly include outcomes linked to craving decay. Studies examining the association between cocaine craving decay and other outcome measures, such as relapse, are also warranted.     

Tetrodotoxin reduces cue-induced drug craving and anxiety in abstinent heroin addicts

Background

Tetrodotoxin (TTX) is a neurotoxin found in puffer fish and other marine animals. New clinical studies suggest that low-dose TTX can safely relieve severe, treatment-resistant cancer pain. The therapeutic potential of TTX in addiction is supported by studies in laboratory animals. The purpose of this double-blind, placebo-controlled study was to assess the effect of a single intramuscular dose of TTX on cue-induced craving and anxiety in abstinent heroin addicts.

Methods

Forty-five abstinent heroin addicts were randomly assigned to three treatment groups: placebo, 5 µg TTX, or 10 µg TTX. Participants were exposed to a neutral video or a heroin-related video. Craving, anxiety, blood pressure, and heart rate were measured pre- and post-exposure.

Results

Heroin-related cues increased both craving and anxiety and had no effect on blood pressure and heart rate. A single dose of TTX dose-dependently attenuated the increases in craving and anxiety while having no effect on blood pressure or heart rate.

Conclusion

The results suggest that low-dose TTX is acutely effective in reducing cue-induced increases in heroin craving and associated anxiety.     

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.