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CORK Bibliography: Craving and Alcohol

71 citations. January 2006 to present

Prepared: March 2010

Ait-Daoud N; Roache JD; Dawes MA; Liu L; Wang XQ et al. Can serotonin transporter genotype predict craving in alcoholism? Alcoholism: Clinical and Experimental Research 33(8): 1329-1335, 2009. (47 refs.)

Background: We hypothesize that functional control of the serotonergic system is regulated in part by differential expression of the serotonin (5-HT) transporter (5-HTT). Alcohol-dependent individuals with the LL/LS genotype (L-carriers), compared with those with the SS genotype, have a lower 5-HT neurotransmission, which we hypothesize would be associated with higher craving for alcohol among L-carriers. We hypothesize further that acute peripheral depletion of tryptophan (5-HT's precursor), while further reducing 5-HT function, might decrease auto-inhibition of 5-HT neuronal firing, thereby increasing 5-HT neurotransmission transiently and lowering alcohol craving. Methods: We tested these hypotheses by examining whether in 34 Hispanic alcohol-dependent individuals subjective and physiological cue craving for alcohol differed by genotype, age of onset of problem drinking, and tryptophan availability. Results: On subjective "urge to drink'' and "crave for a drink,'' we found a significant (p < 0.05) main effect of genotype and cue, as well as an interaction among genotype, age of onset of problem drinking, and tryptophan depletion. For the physiological measure of pulse, there was a main effect of genotype. L-carriers had higher craving than their SS counterparts, an effect that decreased under tryptophan depletion. While craving in L-carriers increased with an earlier age of onset of problem drinking, the opposite effect was seen in those with the SS genotype. Conclusion: These results not only provide support for the hypothesis that alcoholics who are L-carriers have greater alcohol craving and possibly greater propensity for drinking but also propose that there is an important 5-HTT gene-by-environment interaction that alters cue craving response for alcohol.

Allen AM; Allen SS; Widenmier J; al'Absi M. Patterns of cortisol and craving by menstrual phase in women attempting to quit smoking. Addictive Behaviors 34(8): 632-635, 2009. (35 refs.)

Research indicates stress, craving and menstrual phase may play a role in relapse to smoking. It remains unknown how these factors may interact during cessation. This study describes the relationship between craving and cortisol concentrations by menstrual phase during ad libitum smoking and investigates the impact of this relationship on time to relapse. Five assessments of cortisol concentrations and craving levels were collected the day before smoking cessation in female smokers (n = 38) during either the follicular (n = 21; F) or luteal (n 17; Q phase. Craving at wake-up was significantly greater in the F phase than the L phase (2.5 +/- 1.9 vs. 1.1 +/- 1.4; p = 0.018; respectively). Decreased levels of morning cortisol concentrations and a greater decline from morning to the nadir levels in cortisol were associated with increased craving at bedtime in the L (r = -0.68, p = 0.002; r = -0.67, p = 0.003; respectively), but not in the F phase. Craving at wake-up was a significant predictor of time to relapse (p = 0.008). Our results indicate that menstrual phase may play a role in the relationship among craving, cortisol concentrations, and risk for relapse.

Anderson AL; Reid MS; Li SH; Holmes T; Shemanski L; Slee A et al. Modafinil for the treatment of cocaine dependence. Drug and Alcohol Dependence 104(1-2): 133-139, 2009. (27 refs.)

Aim: Modafinil was tested for efficacy in facilitating abstinence in cocaine-dependent patients, compared to placebo. Methods: This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Six outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, having a diagnosis of cocaine dependence; 72 participants were randomized to placebo, 69 to modafinil 200 mg, and 69 to modafinil 400 mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments and urine drug screens, and had one hour of individual psychotherapy weekly. The primary outcome measure was the weekly percentage of cocaine non-use days. Results: The GEE regression analysis showed that for the total sample, there was no significant difference between either modafinil group and placebo in the change in average weekly percent of cocaine non-use days over the 12-week treatment period (p > 0.79). However, two secondary outcomes showed significant effects by modafinil 200 mg: the maximum number of consecutive non-use days for cocaine (p = 0.02), and a reduction in craving (p = 0.04). Also, a post hoc analysis showed a significant effect of modafinil that increased the weekly percentage of non-use days in the subgroup of those cocaine patients who did not have a history of alcohol dependence (p < 0.02). Conclusions: These data suggest that modafinil, in combination with individual behavioral therapy, was effective for increasing cocaine non-use days in participants without co-morbid alcohol dependence, and in reducing cocaine craving.

Brown ES; Carmody TJ; Schmitz JM; Caetano R; Adinoff B; Swann AC et al. A randomized, double-blind, placebo-controlled pilot study of naltrexone in outpatients with bipolar disorder and alcohol dependence. Alcoholism: Clinical and Experimental Research 33(11): 1863-1869, 2009. (39 refs.)

Background: Alcohol dependence is extremely common in patients with bipolar disorder and is associated with unfavorable outcomes including treatment nonadherence, violence, increased hospitalization, and decreased quality of life. While naltrexone is a standard treatment for alcohol dependence, no controlled trials have examined its use in patients with co-morbid bipolar disorder and alcohol dependence. In this pilot study, the efficacy of naltrexone in reducing alcohol use and on mood symptoms was assessed in bipolar disorder and alcohol dependence. Methods: Fifty adult outpatients with bipolar I or II disorders and current alcohol dependence with active alcohol use were randomized to 12 weeks of naltrexone (50 mg/d) add-on therapy or placebo. Both groups received manual-driven cognitive behavioral therapy designed for patients with bipolar disorder and substance-use disorders. Drinking days and heavy drinking days, alcohol craving, liver enzymes, and manic and depressed mood symptoms were assessed. Results: The 2 groups were similar in baseline and demographic characteristics. Naltrexone showed trends (p < 0.10) toward a greater decrease in drinking days (binary outcome), alcohol craving, and some liver enzyme levels than placebo. Side effects were similar in the 2 groups. Response to naltrexone was significantly related to medication adherence. Conclusions: Results suggest the potential value and acceptable tolerability of naltrexone for alcohol dependence in bipolar disorder patients. A larger trial is needed to establish efficacy.

Ceccanti M; Vitali M. Alcoholics with a history of heroin consumption: Clinical features and chronology of substance abuse. Heroin Addiction and Related Clinical Problems 11(3): 35-38, 2009. (6 refs.)

In our clinical experience, when alcohol is used as a surrogate for heroin, social adjustment improves, although the metabolic destiny does not change, and the medical outcome is worsened to some extent by alcoholism itself. Alcohol abusers with a history of heroin use engage in alcohol use in a more intensive way. Alcohol consumption is higher right from the start, and reaches higher maximum levels, whereas heroin use dwindles, in some cases to extinction. The results of our studies support the hypothesis that alcohol replaces opiate craving in former heroin consumers who break away from heroin, and often become alcohol abusers or at least increase their use of alcohol.

Connolly KM; Coffey SF; Baschnagel JS; Drobes DJ; Saladin ME. Evaluation of the Alcohol Craving Questionnaire-Now factor structures: Application of a cue reactivity paradigm. Drug and Alcohol Dependence 103(1-2): 84-91, 2009. (46 refs.)

The current study compared the psychometric properties and clinical/research utility of four distinct factor/subscale models of alcohol craving (three factor-derived models, and one rationally derived model) as measured by the Alcohol Craving Questionnaire-Now in social (n = 52) and alcohol dependent (n = 71) drinkers. All participants completed a self-report measure of alcohol abuse in addition to engaging in a structured interview and cue reactivity protocol. Participants provided self-reported craving, as well as desire to approach or avoid drinking, during a Cue exposure task using separate analog scales. Factor/subscale models were compared in terms of internal consistency, convergent and divergent validity, and ability to predict cue-elicited approach and craving in addition to diagnostic status. All models demonstrated high levels of internal consistency, convergent and divergent validity, and the ability to predict both cue-elicited craving and alcohol dependence status. Specific strengths and weaknesses of each model are examined and the theoretical, clinical, and research utility of the current findings are discussed.

Cordero M; Solis L; Cordero R; Torruco M; Cruz-Fuentes C. Factor structure and concurrent validity of the Obsessive Compulsive Drinking Scale in a group of alcohol-dependent subjects of Mexico City. Alcoholism: Clinical and Experimental Research 33(7): 1145-1150, 2009. (26 refs.)

Background: Obsessive thoughts and compulsive drinking behaviors have been proposed as key factors associated with the loss of control over alcohol consumption experienced by alcohol-dependent patients. The self-report 14-item Obsessive Compulsive Drinking Scale (OCDS; Anton et al., 1995) was designed in order to rate these features. Methods: A Spanish-translated version of the OCDS was applied to a group of 159 alcohol-dependent subjects while in abstinence, and data were analyzed in order to evaluate the factor structure and concurrent validity of the scale. Results: Several solutions were explored after applying the principal factor analysis to the data. The most plausible result was obtained after excluding the items on quantity and frequency of drinking. This model explaining 56.9% of the variance included 2 factors: obsessive thoughts related to drinking and interference/behaviors related to drinking. Additionally, OCDS scores were significantly correlated with measures for the Alcohol Dependence Scale, number of DSM-IV criteria met for alcohol dependence as well as the number of days in a week engaged in heavy drinking, indicating concurrent validity. Conclusions: Our results support the use of OCDS as a valid self-rated instrument that can be broadly applied in research and treatment settings. However, its current version includes questions that may not represent the core concept of craving. The abridged 12-item version of the scale (excluding the items on drinking habits) maintains good psychometrics features and seems to be adequate when different cognitive and behavioral dimensions are explored.

Dayan PBoning J. Addiction memory as a specific, individually learned memory imprint. Pharmacopsychiatry 42(Supplement 1): S66-S68, 2009. (20 refs.)

The construct of "addiction memory" (AM) and its importance for relapse occurrence has been the subject of discussion for the past 30 years. Neurobiological findings from "social neuroscience" and biopsychological learning theory, in conjunction with construct-valid behavioral pharmacological animal models, can now also provide general confirmation of addiction memory as a pathomorphological correlate of addiction disorders. Under multifactorial influences, experience-driven neuronal learning and memory processes of emotional and cognitive processing patterns in the specific individual "set" and "setting" play an especially pivotal role in this connection. From a neuropsychological perspective, the episodic (biographical) memory, located at the highest hierarchical level, is of central importance for the formation of the AM in certain structural and functional areas of the brain and neuronal networks. Within this context, neuronal learning and conditioning processes take place more or less unconsciously and automatically in the preceding long-term-memory systems (in particular priming and perceptual memory). They then regulate the individually programmed addiction behavior implicitly and thus subsequently stand for facilitated recollection of corresponding, previously stored cues or context situations. This explains why it is so difficult to treat an addiction memory, which is embedded above all in the episodic memory, from the molecular carrier level via the neuronal pattern level through to the psychological meaning level, and has thus meanwhile become a component of personality.

Diehl A; Nakovics H; Mutschler J; Hermann D; Kiefer F. Rivastigmine reduces tobacco craving in alcohol-dependent smokers. Pharmacopsychiatry 42(3): 89-94, 2009. (36 refs.)

Introduction: Although alcohol-dependent smokers represent an important group for applying smoking interventions, a sufficient pharmacotherapy has not been established in this high-risk group so far. Methods: In order to examine the effect of the acetylcholinesterase inhibitor rivastigmine on tobacco dependence, we performed a 12-week, randomized, placebo-controlled trial. 26 alcohol-dependent smokers were randomized to rivastigmine 6 mg/day (n = 14) or placebo (n = 12). Assessments on addictive behavior included carbon monoxide (CO), severity of tobacco dependence (FTND), daily smoked cigarettes (diaries), and craving for tobacco (QSU) and alcohol (AUQ). Results: ANOVA revealed a significant treatment-by-time interaction for tobacco consumption and tobacco craving (each p<0.0001). The rivastigmine group showed a decrease in daily smoked cigarettes (-30%), in exhaled carbon monoxide (-32%) and in tobacco craving (-18%) whereas controls did not show significant changes. ANCOVA revealed rivastigmine effects to be more prominent in smokers suffering from more severe tobacco dependence. None of the patients developed an alcohol relapse or an increase in alcohol craving. Discussion: Our preliminary data indicate an effect of rivastigmine on tobacco craving and sonsumption. This pilot study encourages further investigation of acetylcliolinesterase-inhibitors as a promising treatment approach regarding tobacco dependence.

Doyle SR; Donovan DM. A validation study of the Alcohol Dependence Scale. Journal of Studies on Alcohol and Drugs 70(5): 689-699, 2009. (76 refs.)

Objective: The primary purpose of this study was to provide a comprehensive assessment of the underlying factor structure of the Alcohol Dependence Scale (ADS). Secondary goals included assessing concurrent validity of the total ADS and subscales derived from the factor analyses with variables related to alcohol dependence and further evaluating the validity of two proposed dichotomously scored, reduced-item ADS measures. Method: Researchs to the ADS were obtained from participants who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for alcohol dependence in two large randomized clinical trials: COMBINE (Combining Medications and Behavioral Interventions Study; n = 1,335; 69% male) and Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity; n = 1,666; 75% male). Both exploratory and confirmatory factor analyses were conducted, and validity coefficients were obtained. Results: Across samples, analyses supported a correlated, three-factor solution representing loss of behavioral control and heavy drinking, obsessive-compulsive drinking style, and psychoperceptual and psychophysical withdrawal. The ADS was significantly related to other measures of severity of dependence, craving for and preoccupation with drinking, temptation to drink and confidence in the ability to not drink in high-risk relapse situations, heavy and sustained drinking patterns, concerns about negative alcohol-related consequences, and awareness of problematic drinking. Conclusions: These findings support a three-factor solution for the ADS and its ability to assess the construct of alcohol dependence in a reliable and valid manner. The 12-item reduced ADS measure (reflecting mostly dependence-related items), as opposed to the 9-item reduced ADS measure (generally excessive drinking items), provided validity coefficients comparable to the total, 25-item ADS.

Eastwood B; Bradley B; Mogg K; Tyler E; Field M. Investigating the effects of a craving induction procedure on cognitive bias in cannabis users. Addiction Research & Theory 18(1): 97-109, 2010. (34 refs.)

In tobacco smokers and heavy drinkers, the manipulation of subjective craving influences the biased cognitive processing of substance-related cues. In the present study, we used a within-subjects design to examine the effects of a cannabis craving-induction procedure (imagery scripts and cannabis-related videos) on craving and cognitive biases for cannabis cues, in a sample of regular cannabis users (N = 33). Results indicated that the craving induction procedure produced the predicted increases in subjective craving (as assessed with the Marijuana Craving Questionnaire), although the effect size was small and effects were not maintained for the duration of the laboratory session. Although cognitive biases (attentional, approach, and perceived pleasantness) were observed for cannabis-related cues relative to control stimuli, these were not significantly influenced by the craving manipulation. Theoretical implications and methodological issues are discussed.

Erblich J; Montgomery GH; Bovbjerg DH. Script-guided imagery of social drinking induces both alcohol and cigarette craving in a sample of nicotine-dependent smokers. Addictive Behaviors 34(2): 164-170, 2009. (36 refs.)

Laboratory exposure to alcoholic beverage cues has been demonstrated to elicit urges to drink. Less well examined is the possibility that imaginal cues also elicit such urges, providing a model of conditioned effects not dependent on the presence of physical stimuli associated with alcohol. Studies of possible cross-reactivity between smoking and drinking cues are also scarce. To that end, nicotine-dependent nonalcoholic smokers (n = 54) were exposed to social drinking-relevant, and for comparison, neutral and smoking-relevant standardized script-guided imagery. Cravings were measured before and after each imaginal exposure. As hypothesized, the drinking script induced alcohol and cigarette cravings, providing support for both direct and cross-cue reactivity effects. Further validating the social-drinking script, craving reactions were significantly stronger among participants who reported frequent drinking in social situations. Finally, smoking imagery induced both cigarette and alcohol cravings, providing further Support for the cross-cue-induced craving phenomenon. Results suggest that the present alcohol script may be a useful tool for eliciting craving responses under laboratory conditions, and provide an additional means for better understanding addiction.

Evans SM; Bisaga A. Acute interaction of baclofen in combination with alcohol in heavy social drinkers. Alcoholism: Clinical and Experimental Research 33(1): 19-30, 2009. (71 refs.)

There is growing evidence that gamma-amino butyric acid-B receptor agonists may be effective in the treatment of alcohol abuse or dependence. The primary goal of this study was to determine the safety of baclofen in combination with alcohol consumption in heavy drinkers. In addition, the effects of baclofen alone, and in combination with alcohol, on subjective effects, cognitive performance effects, as well as alcohol craving, were assessed. Eighteen non-treatment-seeking heavy social drinkers (mean of 28 drinks per week), who did not meet the criteria for alcohol dependence participated. All individuals were tested using a double-blind double-dummy design with six 2-day inpatient phases. Baclofen (0, 40, and 80 mg) was administered 2.5 hours before alcohol (1.5 g/l body water or approximately 0.75 g/kg) or placebo beverages, given in 4 divided doses every 20 minutes. Baclofen, either alone or in combination with alcohol, produced only modest increases in heart rate and blood pressure and no adverse effects were reported. Baclofen did not increase positive subjective effects (e.g., Stimulant effects, Drug Liking) but did increase sedation and impair performance. Even though both baclofen and alcohol impaired performance, for the most part performance was not impaired to a greater extent when baclofen was combined with alcohol. Among this population of nondependent drinkers, baclofen did not alter alcohol craving or alcohol-induced positive subjective effects. Baclofen alone has minimal abuse liability in heavy social drinkers, and baclofen is relatively well tolerated and safe when given in combination with intoxicating doses of alcohol.

Field M; Munafo MR; Franken IHA. A meta-analytic investigation of the relationship between attentional bias and subjective craving in substance abuse. (review). Psychological Bulletin 135(4): 589-607, 2009. (136 refs.)

Theoretical models of addiction suggest that attentional bias for substance-related cues should be associated with self-reported craving. The authors evaluated the strength of the association by performing a meta-analysis on 68 independent data sets from which correlation coefficients between subjective craving and attentional bias indices were derived. Additional stratified analyses were conducted to identify any variables that might moderate the association between craving and attentional bias. The primary meta-analysis indicated a significant, albeit weak (r = .19), association between attentional bias and craving. Stratified analyses revealed that the association was larger for illicit drug and caffeine craving than for alcohol and tobacco craving, larger for direct measures of attention (eye movement measures and event-related potential measures) than for indirect behavioral measures of attentional bias, and larger when craving strength was high than when it was low (all ps < .05). The size of the correlation did not differ among patients in treatment and individuals who were not seeking treatment. These results suggest that attentional bias and craving are related phenomena, although the relationship is generally modest and appears to be moderated by various factors. Theoretical implications are discussed.

Goldstein RZ; Craig AD; Bechara A; Garavan H; Childress AR; Paulus MP et al. The neurocircuitry of impaired insight in drug addiction. (review). Trends In Cognitive Sciences 13(9): 372-380, 2009. (80 refs.)

More than 80% of addicted individuals fail to seek treatment, which might reflect impairments in recognition of severity of disorder. Considered by some as intentional deception, such 'denial' might instead reflect dysfunction of brain networks subserving insight and self-awareness. Here we review the scant literature on insight in addiction and integrate this perspective with the role of: (l) the insula in interoception, self-awareness and drug craving; (ii) the anterior cingulate in behavioral monitoring and response selection (relevant to disadvantageous choices in addiction); (iii) the dorsal striatum in automatic habit formation; and (iv) drug-related stimuli that predict emotional behavior in addicted individuals, even without conscious awareness. We discuss implications for clinical treatment including the design of interventions to improve insight into illness severity in addiction.

Hillemacher T; Frieling H; Hartl T; Wilhelm J; Kornhuber J; Bleich S. Promoter specific methylation of the dopamine transporter gene is altered in alcohol dependence and associated with craving. Journal of Psychiatric Research 43(4): 388-392, 2009. (31 refs.)

Dopaminergic neurotransmission plays a crucial role in the genesis and maintenance of alcohol dependence. Epigenetic regulation via promoter specific DNA methylation of the dopamine transporter gene (DAT) may influence altered dopaminergic neurotransmission in alcoholism. Aim of the present study was to investigate DNA promoter methylation of DAT in early alcohol withdrawal and in relation to alcohol craving. We analyzed blood samples of 76 patients admitted for detoxification treatment and compared them to 35 healthy controls. Methylation specific quantitative real-time PCR was used to measure the promoter specific DNA methylation of the dopamine transporter. We assessed the extent of alcohol craving using the obsessive compulsive drinking scale (OCDS). Compared to healthy controls we found a significant hypermethylation of the DAT-promoter (Mann-Whitney U-test: p = 0.001). Ln-transformed methylation of the DAT-promoter was negatively associated with the OCDS (linear regression: Beta = -0.275, p = 0.016), particularly with the obsessive subscale (Beta = -0.300, p = 0.008). Findings of the present study show that the epigenetic regulation of the DAT-promoter is altered in patients undergoing alcohol withdrawal. Furthermore, hypermethylation of the DAT-promoter may play all important role in dopaminergic neurotransmission and is associated with decreased alcohol craving.

Hillemacher T; Weinland C; Heberlein A; Groschl M; Schanze A; Frieling H et al. Increased levels of adiponectin and resistin in alcohol dependence-possible link to craving. Drug and Alcohol Dependence 99(1-3): 333-337, 2009. (26 refs.)

Recent studies suggested a role of appetite regulating peptides like leptin and ghrelin in alcohol dependence and particularly in the neurobiology of alcohol craving. Aim of the present study was to investigate alterations of the adipocytokines adiponectin and resistin in alcohol-dependent patients. We analyzed a sample of 88 patients at admission for alcohol detoxification and after I week of withdrawal treatment in comparison to 89 healthy controls. Adiponectin and resistin serum levels were measured using commercial ELISA kits. The extent of alcohol craving was obtained using the obsessive Compulsive Drinking Scale (OCDS). Adiponectin and resistin serum levels were significantly elevated in patients with alcohol dependence at both dates (admission and after I week of treatment) compared to healthy controls. Adiponectin decreased significantly during the course of withdrawal (T = 3.44, p = 0.001) while resistin serum levels showed a slight increase (T = -1.83, p = 0.071). In a multivariate approach the extent of alcohol craving was significantly associated with adiponectin but not with resistin serum levels in male patients (Beta = -0.255, p = 0.025). Results for female patients were not significant. Our findings provide first evidence for an alteration of file adipocytokines adiponectin and resistin during alcohol withdrawal. Furthermore, adiponectin may be involved in the neurobiology of alcohol craving, possibly via its effects on the hypothalamic circuits.

Houben K; Wiers RW. Response inhibition moderates the relationship between implicit associations and drinking behavior. Alcoholism: Clinical and Experimental Research 33(4): 626-633, 2009. (48 refs.)

Contemporary dual-process models of alcohol abuse propose that alcohol abuse develops because of dysfunctions in the impulsive system, which generates automatic impulses to drink alcohol, and disruptions in the reflective system, which becomes unable to inhibit the influence of these automatic impulses. Based on these insights, this study investigated whether individual differences in the ability of the reflective system to exert response inhibition moderate the relationship between automatic cognitive processes and drinking behavior. Specifically, it was examined whether the interaction between implicit alcohol-related associations and response inhibition predicted drinking behavior. Seventy-one university students completed the study online via the Internet. Implicit alcohol associations with positive affect and with arousal were assessed with variants of the Implicit Association Test. Response inhibition was measured using the original Stroop task. Participants also reported their weekly alcohol use and alcohol-related problems. As predicted, implicit associations were unrelated to drinking behavior when response inhibition was high. In contrast, when response inhibition was low, stronger implicit associations between alcohol and positive affect predicted increased alcohol use and alcohol-related problems. These findings indicate that the relationship between automatic cognitive processes, originating in the impulsive system, and drinking behavior depends on individual differences in response inhibition exerted by the reflective system. As prolonged alcohol abuse is known to impair response inhibition, alcohol abusers may benefit from interventions that increase response inhibition, thereby restoring inhibitory control over automatic impulses.

Jimenez M; Grana JL; Montes V; Rubio G. Alcohol Craving Scale Based on Three Factors. European Addiction Research 15(3): 135-142, 2009. (47 refs.)

Background: Alcohol craving is a central aspect of alcoholism about which various explanatory theories and assessment questionnaires, based on such craving, have been developed. However, there are no instruments for the assessment of craving in line with the integrative hypotheses recently formulated that propose three types of craving: positive reinforcement, negative reinforcement, and loss of control. Objectives: The construction and validation of a craving scale based on three factors. We expect to obtain a correlation between each factor and associated variables from prior studies. We also expect significant differences in craving between alcoholic individuals and controls. Sample: The scale was administered to 209 alcohol-dependent subjects and 137 controls. Instruments: Alcohol Craving Scale Based on Three Factors (ACS-3F); Sensitivity to Punishment and Sensitivity to Reward Questionnaire, Barratt Impulsiveness Scale, Severity of Alcohol Dependence Scale. Results: We confirmed the existence of the three factors initially proposed in the structure of the instrument, with high reliability. The relationship between the scale and the measures employed for its validation was confirmed. Adequate capacity of the scale to discriminate between the sample of alcoholics and the controls was observed. Conclusions: The ACS-3F has adequate psychometric properties and may be useful in future research and in clinical practice.

King A; McNamara P; Conrad M; Cao DC. Alcohol-induced increases in smoking behavior for nicotinized and denicotinized cigarettes in men and women. Psychopharmacology 207(1): 107-117, 2009. (64 refs.)

Alcohol has been shown to increase smoking urges and smoking behavior. However, alcohol's effects on specific components of smoking behavior for nicotine versus non-nicotine factors and potential sex differences in this response have not been investigated. Forty-two young male and female non-dependent, heavy social drinking smokers participated in two double-blind laboratory sessions. They were randomized to either an alcohol (0.8 g/kg; n = 29) or placebo (n = 13) beverage pre-administration group. After beverage consumption, they were assessed for smoking urges and then given the opportunity to smoke cigarettes which were either all nicotinized (0.6 mg/cigarette) or denicotinized (a parts per thousand currency sign0.05 mg/cigarette) over a 3-h period; smoking behavior was quantified by a smoking topography device. Subjects took standardized puffs of the session's cigarette both before and after beverage administration to provide a reference when making future smoking choices. Alcohol, compared with placebo beverage, increased both men's and women's smoking urge, as well as subjective ratings of smoking reference puffs for either nicotinized or denicotinized cigarettes. In terms of smoking choice behavior, regardless of cigarette type, alcohol (> placebo) increased men's smoking behavior, including puff count, volume, and duration. In contrast, for women, smoking topography measures did not differ between alcohol and placebo conditions. In summary regardless of nicotine content, in men, alcohol increased smoking urge and behavior, whereas in women, alcohol increased smoking urge but did not increase smoking behavior. These results indicate that the mechanisms underlying co-use of alcohol and tobacco in women may be more complex than in men.

King A; McNamara P; Angstadt M; Phan KL. Neural substrates of alcohol-induced smoking urge in heavy drinking nondaily smokers. Neuropsychopharmacology 35(3): 692-701, 2010. (66 refs.)

A strong link exists between cigarette smoking and alcohol use, which may be explained by the experimental observation that alcohol ingestion promotes cigarette craving and precipitates smoking. At the neuroanatomic level, it is unclear where and how alcohol exerts these effects, although the process likely involves the ventral striatum given its function in motivational salience and appetitive reinforcement. In a double-blinded, placebo-controlled, crossover study, heavy drinking nondaily social smokers (ie, light smokers or 'chippers') were examined using functional magnetic resonance imaging after they ingested an acute dose of alcohol or placebo. We probed reactivity in the ventral striatum and other brain regions during exposure to visual smoking vs nonsmoking control cues. We found that alcohol enhanced self-reported ratings of desire to smoke, and in this context, significantly increased ventral striatum responses to smoking compared with control cues. In exploratory analyses, we observed that alcohol dampened orbitofrontal activity across both cue types, whereas dorsolateral prefrontal and anterior cingulate cortex activation to smoking cues was not affected by alcohol. This study bridges a pharmacological challenge approach to the study of brain reactivity to smoking cues, extends prior cigarette cue imaging studies to nondependent smokers, and elucidates a potential neurobiological mechanism to explain the co-consumption of alcohol and cigarettes in nondependent users.

Kramer JR; Chan G; Hesselbrock VM; Kuperman S; Bucholz KK; Edenberg HJ et al. A principal components analysis of the abbreviated Desires for Alcohol Questionnaire (DAQ). Journal of Studies on Alcohol and Drugs 71(1): 150-155, 2010. (33 refs.)

Objective: The aim of this study was to examine the abbreviated Desires for Alcohol Questionnaire (DAQ) with respect to component structure and concurrent validity. Method: The DAQ was administered to 2,960 adults participating in the Collaborative Studies on the Genetics of Alcohol. Rotated principal components analysis was conducted on 1,500 subjects with an alcohol-use disorder (AUD) and on 1,460 non-AUD subjects. Total DAQ scores were compared for these two subsamples. In addition, correlations were computed between DAQ scores and the following: (1) a sum of alcohol symptoms, and (2) endorsement of a single interview craving question. Results: Similar solutions emerged in the AUD and non-AUD subsamples, with dimensions characterized by (1) strong desires/intentions to drink, (2) negative reinforcement, and (3) positive reinforcement + ability to control drinking. Each component was significantly correlated with the alcohol symptom scale in both subsamples (r(s) = .25-.64 and .31-.40, respectively, p < .0001) and with the interview craving item in the AUD subsample (r(s) = .22-.55, p < .0001). Total DAQ score was significantly higher for AUD subjects (40.5) than for non-AUD subjects (23.1, p < .0001) and exhibited significant correlations with the alcohol symptom scale in the AUD and non-AUD subsamples (r(s) = .61 and .39, respectively, p < .0001) and with the interview craving item in the AUD subsample (r(s) = .51, p < .0001). Conclusions: The DAQ is an appropriate measure of alcohol craving, as demonstrated by similar component structures across two samples as well as its concur-rent validity.

Larsen H; Engels RCME; Granic I; Overbeek G. An experimental study on imitation of alcohol consumption in same-sex dyads. Alcohol and Alcoholism 44(3): 250-255, 2009. (34 refs.)

Aim: In order to study the role of imitation in relation to drinking, alcohol consumption among two peers was examined with experiments in a naturalistic drinking setting. Method: In a bar lab, 135 young adults (52% women) were exposed to either a non-drinking, a light-drinking or a heavy-drinking same-sex model (i.e. a confederate) in a 30-min time-out session. Instead of using a taste task (Quigley and Collins, 1999. The modeling of alcohol consumption: a meta-analytic review. J Stud Alcohol 60:90-8) in which participants were obliged to consume alcohol, in the current udy, a design was used in which participants were allowed to drink alcohol but could also choose non-alcoholic beverages. Results: Craving for alcohol was included as a covariate in ANCOVAs. Results showed that the participants consumed substantially more alcohol when exposed to heavy-drinking models compared to light- and non-drinking models. Craving levels were positively related to alcohol consumption during the experiment. Conclusion: Both men and women imitated same-sex peers' drinking behavior in an ad lib naturalistic bar setting.

Leeman RF; Corbin WR; Fromme K. Craving predicts within session drinking behavior following placebo. Personality and Individual Differences 46(7): 693-698, 2009. (30 refs.)

Tiffany's (1990) cognitive processing model postulates that craving will only occur when access to alcohol is blocked. To test a hypothesis based on this model, we analyzed data from a naturalistic laboratory alcohol challenge study involving moderate-to-heavy drinking young adults (N = 174) with a focus on the placebo beverage condition of this study. Our hypothesis was that self-reports of "wanting more alcohol" (i.e., craving) in the lab, following placebo, would predict subsequent ad libitum consumption because placebo administration would constitute partial blocking of access to alcohol. We also tested the possibility that craving might mediate associations between personality traits and ad libitum consumption. Both trait disinhibition and reports of craving following the placebo beverage significantly predicted ad libitum consumption. Further, craving partially mediated the association between trait disinhibition and ad libitum consumption. Potential implications of these findings are discussed.

Leggio L. Understanding and treating alcohol craving and dependence: Recent pharmacological and neuroendocrinological findings. (review). Alcohol and Alcoholism 44(4): 341-352, 2009. (127 refs.)

There is a substantial need for discovering innovative ways to provide more information on the neurobiology of alcohol dependence as well as to discover more effective pharmacotherapies for alcohol dependence. Current research includes exploring new pathways able to modulate alcohol craving. In particular, research shows that several neuroendocrinological pathways may be involved in the neurobiology of alcohol craving and dependence. The first part of this review examines recent clinical findings on the role of feeding-related peptides in alcohol craving and dependence. Second, this review focuses on the need to discover new medications that may prove to be safe and effective in the treatment of alcohol dependence. For example, the GABA(B) receptor has been suggested as a new possible neuropharmacological target in the treatment of alcohol dependence. Accordingly, the second part of this review examines recent clinical findings on the role of the selective GABA(B) receptor agonist baclofen in the treatment of alcohol-dependent subjects. These two distinct topics will be both analyzed and discussed. The final part of this review discusses possible connections between these two topics, as an example of possible interactions between psychoneuroendocrinology and neuropharmacology. These possible interactions could lead to future intriguing research aimed at understanding and treating alcohol craving and dependence.

Leggio L; Ferrulli A; Abenavoli L; Malandrino N; D'Angelo C; Vonghia L et al. Relationship between ghrelin levels, nutritional status and craving in current alcoholics. European Review for Medical and Pharmacological Sciences 13(Supplement 1): 103-103, 2009. (0 refs.)

Leggio L; Ray LA; Kenna GA; Swift RM. Blood glucose level, alcohol heavy drinking, and alcohol craving during treatment for alcohol dependence: Results from the combined pharmacotherapies and behavioral interventions for alcohol dependence (COMBINE) Study. Alcoholism: Clinical and Experimental Research 33(9): 1539-1544, 2009. (40 refs.)

Background: Heavy drinking may increase blood glucose levels. Moreover, in alcohol-dependent subjects, glucose may play a putative role in alcohol preference. Methods: This study investigated the relationship between blood glucose levels and both alcohol heavy drinking and craving in alcohol-dependent subjects participating in the COMBINE Study. The primary objective was to evaluate the relationship between baseline (pretreatment) glucose levels and percentage of heavy drinking day (PHDD) during treatment. The secondary objective was to evaluate the relationship between glucose levels, baseline PHDD, and craving measured by the Obsessive Compulsive Drinking Scale (OCDS). Results: This analysis consisted of 1,324 participants. Baseline glucose levels were significantly and positively associated with PHDD during treatment [F(1, 1225) = 5.21, p = 0.023], after controlling for baseline PHDD [F(1, 1225) = 36.25, p < 0.0001], gender [F (1, 1225) = 3.33, p = 0.07], and body mass index (BMI) [F(1, 1225) = 0.31, p = 0.58]. Higher glucose levels at baseline were associated with a higher percentage of PHDD at pretreatment [F(1, 1304) = 5.96, p = 0.015], after controlling for gender [F(1, 1304) = 0.29, p = 0.59] and BMI [F(1, 1304) = 0.90, p = 0.34]. Glucose was not significantly associated with the OCDS total score [F(1, 1304) = 0.12, p = 0.73], the OCDS Obsessive subscale [F(1, 1304) = 0.35, p = 0.56], or the OCDS Compulsive subscale [F(1, 1304) = 1.19, p = 0.28] scores, after controlling for gender and BMI. Discussion: A link between pretreatment glucose levels and heavy drinking during treatment was found, suggesting a role of glucose in predicting heavy alcohol consumption. Although caution is needed in the interpretation of these results, elevated glucose and heavy drinking may be affected by a common mechanism and manipulations affecting glucose regulation may influence alcohol consumption.

MacKillop J; Miranda R; Monti PM; Ray LA; Murphy JG; Rohsenow DJ et al. Alcohol demand, delayed reward discounting, and craving in relation to drinking and alcohol use disorders. Journal of Abnormal Psychology 119(1): 106-114, 2010. (62 refs.)

A behavioral economic approach to alcohol use disorders (AUDs) emphasizes both individual and environmental determinants of alcohol use. The current study examined individual differences in alcohol demand (i.e., motivation for alcohol under escalating conditions of price) and delayed reward discounting (i.e., preference for immediate small rewards compared to delayed larger rewards) in 61 heavy drinkers (62% with an AUD). In addition, based on theoretical accounts that emphasize the role of craving in reward valuation and preferences for immediate rewards, craving for alcohol was also examined in relation to these behavioral economic variables and the alcohol-related variables. Intensity of alcohol demand and delayed reward discounting were significantly associated with AUD symptoms, but not with quantitative measures of alcohol use, and were also moderately correlated with each other. Likewise, craving was significantly associated with AUD symptoms, but not with alcohol use, and was also significantly correlated with both intensity of demand and delayed reward discounting. These findings further emphasize the relevance of behavioral economic indices of motivation to AUDs and the potential importance of craving for alcohol in this relationship.

Mason SJ; Deane FP; Kelly PJ; Crowe TP. Do spirituality and religiosity help in the management of cravings in substance abuse treatment? Substance Use & Misuse 44(13): 1926-1940, 2009. (39 refs.)

The purpose of this study was to examine the relationship of spirituality, religiosity and self-efficacy with drug and/or alcohol cravings. A cross-sectional survey was completed by 77 male participants at an Australian Salvation Army residential rehabilitation service in 2007. The survey included questions relating to the participants' drug and/or alcohol use and also measures for spirituality, religiosity, cravings, and self-efficacy The sample included participants aged between 19 and 74 years, with more than 57% reporting a diagnosis for a mental disorder and 78% reporting polysubstance misuse with alcohol most frequently endorsed as the primary drug of concern (71%). Seventy-five percent of the clients reported that spirituality and religious faith were useful components of the treatment program. A multivariate multiple regression analysis identified that spirituality and self-efficacy have significant relationships with cravings. Self-efficacy mediated the relationship between spirituality and drug and/or alcohol cravings. The limitations of this study included its cross-sectional design and a sample that was drawn from a faith-based program. Future research would benefit from the longitudinal examination of the relationship between spirituality, self-efficacy, and cravings: the exploration of a broader range of client-specific and interpersonal variables; and the inclusion of a control group from a secular treatment facility.

Mishra BR; Nizamie SH; Das B; Praharaj SK. Efficacy of repetitive transcranial magnetic stimulation in alcohol dependence: A sham-controlled study. Addiction 105(1): 49-55, 2010. (24 refs.)

Objective: To study the anticraving efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral pre-frontal cortex (DLPFC) in patients with alcohol dependence. Methods: We performed a prospective, single-blind, sham-controlled study involving 45 patients with alcohol dependence syndrome (according to ICD-10 DCR), with Clinical Institute of Withdrawal Assessment in Alcohol Withdrawal (CIWA-Ar) scores < 10. Patients were allocated to active and sham rTMS in a 2 : 1 ratio, such that 30 patients received active and 15 patients sham rTMS to the right DLPFC (10 Hz frequency, 4.9 seconds per train, inter-train interval of 30 seconds, 20 trains per session, total 10 sessions). The Alcohol Craving Questionnaire (ACQ-NOW) was administered to measure the severity of alcohol craving at baseline, after the last rTMS session and after 1 month of the last rTMS session. Results: Two-way repeated-measures analysis of variance (ANOVA) showed significant reduction in the post-rTMS ACQ-NOW total score and factor scores in the group allocated active rTMS compared to the sham stimulation. The effect size for treatment with time interaction was moderate (eta 2 = 0.401). Conclusions: Right dorsolateral pre-frontal high-frequency rTMS was found to have significant anticraving effects in alcohol dependence. The results highlight the potential of rTMS which, combined with other anticraving drugs, can act as an effective strategy in reducing craving and subsequent relapse in alcohol dependence.

Nakovics H; Diehl A; Geiselhart H; Mann K. Development and validation of an overall instrument to measure craving across multiple substances: The Mannheimer Craving Scale (MaCS) (German). Psychiartische Praxis 36(2): 72-78, 2009. (32 refs.)

Objective Based on the Obsessive Compulsive Drinking Scale (OCDS) we developed and validated the Mannheimer Craving Scale (MaCS) for quantitative measurements of craving across different substances and suitable for multiple Substance abuse. Methods The MaCS questionnaire measures obsessive-compulsive symptoms in the context Of Substance abuse and dependence similar to the OCDS. The MaCS consists of 12 items and 4 additional items. Validation of the instrument was performed by means of 3 assessments of each subject within a project for the evaluation of a detox treatment on n = 292 alcohol and drug-dependent patients with multiple substance abuse. Results: The MaCS showed a very high measurement reliability (0.87Copyright 2009, Georg Thieme Verlag

Naqvi NH; Bechara A. The hidden island of addiction: the insula. (review). Trends in Neurosciences 32(1): 56-67, 2009. (143 refs.)

Most prior research on the neurobiology of addiction has focused on the role of subcortical systems, such as the amygdala, the ventral striatum and mesolimbic dopamine system, in promoting the motivation to seek drugs, Recent evidence indicates that a largely overlooked structure, the insula, plays a crucial part in conscious urges to take drugs. The insula has been highlighted as a region that integrates interoceptive (i.e. bodily) states into conscious feelings and into decision-making processes that involve uncertain risk and reward. Here, we propose a model in which the processing of the interoceptive effects of drug use by the insula contributes to conscious drug urges and to decision-making processes that precipitate relapse.

Oslin DW; Cary M; Slaymaker V; Colleran C; Blow FC. Daily ratings measures of alcohol craving during an inpatient stay define subtypes of alcohol addiction that predict subsequent risk for resumption of drinking. Drug and Alcohol Dependence 103(3): 131-136, 2009. (37 refs.)

Background: Both depressive symptoms and alcohol craving have been postulated as important redictors of relapse in patients with addictive disorders. The purpose of this Ssudy was to examine the course of affective symptoms and cravings for alcohol use during the initial 25 days of residential treatment for middle aged and older adults addicted to alcohol and the relationship between these symptoms and recovery outcomes. Methods: 95 alcohol-dependent Subjects were enrolled in this observational Study. Participants completed a daily diary of alcohol craving, positive affect, and negative affect during residential treatment. Participants were interviewed I and 6 months after discharge to assess clinical symptoms of relapse and functioning. Results: Latent class analysis identified three groups of individuals for each of the three daily measures. For alcohol craving, 17 subjects reported elevated cravings during the entire treatment stay, 37 subjects reported initially elevated but then a slight improvement in craving, and 41 Subjects reported relatively low craving from the time of admission to the end of residential treatment. Alcohol craving class was associated with negative affect but not Positive affect. Alcohol craving class but not affective class was predictive of time to relapse to any drinking in the 6 months after residential treatment (p < 0.05). Conclusion: Results suggest that non-cue induced alcohol craving may define a subtype of alcohol dependence that is less responsive to treatment and may explain heterogeneity in treatment outcomes. These results also may suggest a role for differential treatment programming to address high states of craving for alcohol.

Pavlick M; Hoffmann E; Rosenberg H. A nationwide survey of American alcohol and drug craving assessment and treatment practices. Addiction Research & Theory 17(6): 591-600, 2009. (44 refs.)

A four-page paper survey was mailed to 500 randomly-selected substance abuse treatment agencies listed in a national directory to evaluate how often specific methods are employed to assess and treat craving in American substance abuse agencies. Of 426 eligible agencies, 149 (35%), located in 41 states, returned 152 usable replies. Although counselors regularly assessed craving during intake evaluations, they rarely used published self-report questionnaires. Almost one-half of respondents made craving a target of treatment with at least a majority (and sometimes all) of their clients, and only 5% of respondents reported never making craving a target of treatment. A variety of interventions are employed to address craving, including coping skills training, encouraging clients to avoid/leave situations where craving occurs, and providing clients with education about craving. We recommend additional professional education and training to familiarize counselors with standardized craving instruments and exposure interventions that hold promise to ameliorate craving.

Schoenmakers TM; Wiers RW. Craving and attentional bias respond differently to alcohol priming: A field study in the pub. European Addiction Research 16(1): 9-16, 2010. (41 refs.)

Background: Several experimental laboratory studies have shown that subjective craving for alcohol increases as a result of low-to-moderate levels of alcohol consumption. Less is known about alcohol prime effects on relatively automatic appetitive motivational processes such as attentional bias (AB). Also, it is not known whether the effects from laboratory studies can be generalized to real-life drinking environments, and whether effects change after higher alcohol doses than those that have been administered in lab studies. Method: In two pubs, we investigated alcohol prime dose effects in self-reported craving and AB, measured by a modified Flicker Paradigm. We included an opportunistic sample of 72 social drinkers who had been drinking various amounts of alcohol. Results: Self-reported craving was positively predicted by dose of alcohol consumed, from one up to 16 drinks. In contrast, AB was negatively predicted by dose consumed in participants who had been binge drinking. Conclusion: This field study validates earlier experimental research on alcohol prime effects in a real drinking situation. Further, it demonstrates prime effects up to much higher alcohol doses than in previous lab studies.

Sinha R. Modeling stress and drug craving in the laboratory: Implications for addiction treatment development. (review). Addiction Biology 14(1): 84-98, 2009. (132 refs.)

Addition is a chronic relapsing illness affected by multiple social, individual and biological factors that significantly impact course and recovery of the illness. Stress interacts with these factors and increases addiction vulnerability and relapse risk, thereby playing a significant role in the course of the illness. This paper reviews our efforts in developing and validating laboratory models of stress and drug cue-related provocation to assess stress responses and stress-related adaptation in addicted individuals compared with healthy controls. Empirical findings from human laboratory and brain imaging studies are presented to show the specific stress-related dysregulation that accompanies the drug-craving state in addicted individuals. In order to adequately validate our laboratory model, we have also carefully examined relapse susceptibility in the addicted individuals and these data are reviewed. The overarching goal of these efforts is to develop a valid laboratory model to identify the stress-related pathophysiology in addiction with specific regard to persistent craving and compulsive seeking. Finally, the significant implications of these findings for the development of novel treatment interventions that target stress processes and drug craving to improve addiction relapse outcomes are discussed.

Tiffany ST; Wray J. The continuing conundrum of craving. (editorial). Addiction 104(10): 1618-1619, 2009. (4 refs.)

Trafton JA. Commentary on Mishra et al. (2010): Transcranial magnetic stimulation effects on craving: Impressive therapy or therapeutic impressions? (editorial). Addiction 105(1): 56-56, 2010. (6 refs.)

Vollstadt-Klein S; Loeber S; von der Goltz C; Mann K; Kiefer F. Avoidance of alcohol-related stimuli increases during the early stage of abstinence in alcohol-dependent patients. Alcohol and Alcoholism 44(5): 458-463, 2009. (37 refs.)

Aims: The aim of this study was to analyse initial orienting processes as well as maintenance of attention towards alcohol cues in recently detoxified alcoholics and light social drinkers. Furthermore, we investigated the influence of pre-treatment alcohol consumption and abstinence duration onto alcohol-related attentional bias. Methods: We used an alcohol-visual-dot-probe-task with two different stimulus onset asynchronies (SOA) to examine processes of initial orienting and maintenance of attention separately (50 and 500 ms SOA). Results: With short SOA, we found a positive attentional bias towards alcohol cues in alcohol-dependent patients and light social drinkers that was positively associated with pre-treatment alcohol consumption in alcoholics. Using a longer SOA, a negative attentional bias was found in light social drinkers and in patients abstinent for more than 2 weeks indicating alcohol stimuli avoidance. In patients, we found a negative correlation between attentional bias and duration of abstinence. Conclusions: After initial visual orienting towards alcohol-related stimuli, light social drinkers as well as longer abstinent alcohol-dependent patients disengage their attention. In patients, this disengagement increased during the first 3 weeks after detoxification indicating assimilation to the attentional bias pattern of light social drinkers.

Yoder KK; Morris ED; Constantinescu CC; Cheng TE; Normandin MD; O'Connor SJ et al. When what you see isn't what you get: Alcohol cues, alcohol administration, prediction error, and human striatal dopamine. Alcoholism: Clinical and Experimental Research 33(1): 139-149, 2009. (97 refs.)

The mesolimbic dopamine (DA) system is implicated in the development and maintenance of alcohol drinking; however, the exact mechanisms by which DA regulates human alcohol consumption are unclear. This study assessed the distinct effects of alcohol-related cues and alcohol administration on striatal DA release in healthy humans. Subjects underwent 3 PET scans with [C-11]raclopride (RAC). Subjects were informed that they would receive either an IV Ringer's lactate infusion or an alcohol (EtOH) infusion during scanning, with naturalistic visual and olfactory cues indicating which infusion would occur. Scans were acquired in the following sequence: (1) Baseline Scan: Neutral cues predicting a Ringer's lactate infusion, (2) CUES Scan: Alcohol-related cues predicting alcohol infusion in a Ringer's lactate solution, but with alcohol infusion after scanning to isolate the effects of cues, and (3) EtOH Scan: Neutral cues predicting Ringer's, but with alcohol infusion during scanning (to isolate the effects of alcohol without confounding expectation or craving). Relative to baseline, striatal DA concentration decreased during CUES, but increased during EtOH. While the results appear inconsistent with some animal experiments showing dopaminergic responses to alcohol's conditioned cues, they can be understood in the context of the hypothesized role of the striatum in reward prediction error, and of animal studies showing that midbrain dopamine neurons decrease and increase firing rates during negative and positive prediction errors, respectively. We believe that our data are the first in humans to demonstrate such changes in striatal DA during reward prediction error.