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CORK Bibliography: Craving and Alcohol

34 citations. January 2010 to present

Prepared: March 2011

Adinoff B; Talmadge C; Williams MJ; Schreffler E; Jackley PK; Krebaum SR. Time to Relapse Questionnaire (TRQ): A Measure of Sudden Relapse in Substance Dependence. American Journal of Drug and Alcohol Abuse 36(3): 140-149, 2010. (26 refs.)

Background: Relapse may occur suddenly, following a short period of craving, or after extended consideration. The time to relapse may reveal underlying mechanisms of relapse and have important implications for treatment. Objective: The Time to Relapse Questionnaire (TRQ), a self-administered questionnaire, was designed to assess the time from the initial thought of drug use to actual use. Methods: Psychometric properties of the TRQ were evaluated in two distinct populations (n = 183 and 194) with DSM-IV primary substance use disorders. Results: Factor analysis and item refinement led to a 9-item TRQ with a three-factor solution accounting for 63% of the total variance. Three discrete types of relapse style were identified: Sudden Relapse, Short Delay Relapse, and Long Delay Relapse. The TRQ demonstrated good construct validity and adequate internal consistency for the total (alpha = .61) and individual factor (alpha = .64-.75) scores. Measures to assess convergent validity of the TRQ suggest that Sudden Relapse may not reflect more generalized deficits of inhibitory control. Conclusions and Significance: The TRQ may provide a useful self-report measure to discriminate between addicted patients who relapse without forewarning compared to those with a period of delay. Clinical interventions may be targeted towards different relapse styles.

Bergquist KL; Fox HC; Sinha R. Self-reports of interoceptive responses during stress and drug cue-related experiences in cocaine- and alcohol-dependent individuals. Experimental and Clinical Psychopharmacology 18(3): 229-237, 2010. (56 refs.)

Cocaine dependence is associated with neuroadaptations in stress and reward pathways that could alter stress and drug-related experiences and associated interoceptive sensations and result in enhanced craving states. Subjective interoceptive emotional and physiological responses experienced in stressful and drug cue situations were examined in abstinent cocaine-dependent individuals. Fifty-six treatment engaged cocaine-dependent patients with comorbid alcohol abuse or dependence were interviewed to identify personal stressful, drug cue, and neutral situations using a scene construction questionnaire (SCQ) that includes an emotional and physiological response checklist. Using this checklist, subjects identified emotional and bodily sensations that they recently experienced in the stress- and drug-related scenarios. Kappa coefficients indicated fair to moderate but significant degree of concordance in heart (p < .01), perspiration (p < .05), stomach (p < .05), and blood flow (p < .01) sensations for both stress and drug cue scenarios, while the McNemar change test indicated differential endorsement of interoceptive responses in stress and drug cue situations for breathing (p < .05). stomach (p < .05), tension (p < .05), and chest (p < .05) sensations, and for sad (p < .01), anger (p < .01), and excitement (p < .01) responses. Increased heartbeat and tension, tears, and anger urges were most commonly endorsed in the stress scenarios (between 50% and 79%), whereas butterflies in stomach, increased heartbeat and tension, jittery, restless, and warm excitement (53%-73%) were the most frequently endorsed sensations in the drug cue-related experiences. These self-reported sensations comprise both general arousal and specific interoceptive responses pertaining to stress or drug cue-related experiences in cocaine dependence, with potential value in guiding treatments targeting craving reduction.

Boykoff N; Schneekloth TD; Hall-Flavin D; Loukianova L; Karpyak VM; Stevens SR et al. Gender differences in the relationship between depressive symptoms and cravings in alcoholism. American Journal on Addictions 19(4): 352-356, 2010. (24 refs.)

This study examines the clinical correlates of alcohol craving in men and women self-referred for addiction treatment. Admission clinical data from patients participating in the Mayo Clinic 1-month Intensive Addictions Program were evaluated. Women had higher BDI and PACS scores compared with men in both the entire cohort and Dual Diagnoses group. Alcohol-dependent females had the most marked correlation between BDI and PACS ( = .78). Further prospective study is encouraged to evaluate whether depressive symptoms and concomitant alcohol cravings in women are a marker for relief cravings and, as such, a target symptom for treatment intervention.

Chakravorty S; Kuna ST; Zaharakis N; O'Brien CP; Kampman KM; Oslin D. Covariates of craving in actively drinking alcoholics. American Journal on Addictions 19(5): 450-457, 2010. (63 refs.)

The goal of this cross-sectional study was to assess the relationship of alcohol craving with biopsychosocial and addiction factors that are clinically pertinent to alcoholism treatment. Alcohol craving was assessed in 315 treatment-seeking, alcohol dependent subjects using the Penn Alcohol Craving Scale questionnaire. Standard validated questionnaires were used to evaluate a variety of biological, addiction, psychological, psychiatric, and social factors. Individual covariates of craving included age, race, problematic consequences of drinking, heavy drinking, motivation for change, mood disturbance, sleep problems, and social supports. In a multivariate analysis (R2 = .34), alcohol craving was positively associated with mood disturbance, heavy drinking, readiness for change, and negatively associated with age. The results from this study suggest that alcohol craving is a complex phenomenon influenced by multiple factors.

Cherpitel CJ; Borges G; Ye Y; Bond J; Cremonte M; Moskalewicz J et al. Performance of a craving criterion in DSM alcohol use disorders. Journal of Studies on Alcohol and Drugs 71(5): 674-684, 2010. (29 refs.)

Objective: Adding a craving criterion presently in the International Classification of Diseases, 10th Revision, diagnosis of alcohol dependence has been under consideration as one possible improvement to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and was recently proposed for inclusion by the DSM Substance-Related Disorders Work Group in the Fifth Revision of diagnostic criteria for alcohol use disorders. To inform cross-cultural applicability of this modification, performance of a craving criterion was examined in emergency departments in four countries manifesting distinctly different culturally based drinking patterns (Mexico, Poland, Argentina, United States). Method: Exploratory factor analysis and item response theory were used to examine psychometric properties and individual item characteristics of the 11 DSM-IV abuse and dependence criteria with and without craving for each country separately. Differential item functioning analysis was performed to examine differences in the difficulty of endorsement (severity) and discrimination of craving across countries. Results: Exploratory factor analysis found craving fit well within a one-dimensional solution, and factor loadings were high across all countries. Results from item-response theory analyses indicated that both discrimination and difficulty estimates for the craving item were located in the middle of the corresponding discrimination and difficulty ranges for the other 11 items for each country but did not substantially increase the efficiency (or information) of the overall diagnostic scheme. Across the four countries, no differential item functioning was found for difficulty, but significant differential item functioning was found for discrimination (similar to other DSM-IV criteria). Conclusions: Findings suggest that, although craving performed similarly across emergency departments in the four countries, it does not add much in identification of individuals with alcohol use disorders.

Coffey SF; Schumacher JA; Stasiewicz PR; Henslee AM; Baillie LE; Landy N. Craving and physiological reactivity to trauma and alcohol cues in posttraumatic stress disorder and alcohol dependence. Experimental and Clinical Psychopharmacology 18(4): 340-349, 2010. (61 refs.)

The high comorbidity of posttraumatic stress disorder (PTSD) and alcohol dependence (AD) has been firmly established. Although laboratory studies have examined self-reported craving in response to trauma and alcohol cues, no studies have reported on alcohol-related physiological responding in response to trauma cues in PTSD-AD individuals. Using a cue reactivity paradigm, this study examined the impact of personalized trauma-image cues and in vivo alcohol cues on alcohol-related responding (e.g., salivation, craving) in individuals with PTSD and AD (n = 40). Participants displayed reactivity to both trauma and alcohol cues when compared to neutral cues, including increased self-reported craving and distress, as well as greater salivation. These findings suggest that through repeated pairings of trauma memories and alcohol consumption, salivation may become classically conditioned to trauma cues. Moreover, the fact that the trauma-alcohol cue combination elicited greater alcohol craving, salivary responding, distress, and arousal than either the trauma-neutral or neutral-alcohol cue combinations suggests that effects of the trauma and alcohol cues were additive in nature. Evidence that AD individuals with PTSD report increased alcohol craving and display greater salivation in response to trauma memories, supplements prior research indicating that PTSD-related negative emotion and trauma-related alcohol craving may play an important role in the maintenance of AD.

Connor JP; Feeney GFX; Jack A; Young RM. The Obsessive Compulsive Drinking Scale is a valid measure of alcohol craving in young adults. Alcoholism: Clinical and Experimental Research 34(12): 2155-2161, 2010. (45 refs.)

Background: Alcohol craving is associated with greater alcohol-related problems and less favorable treatment prognosis. The Obsessive Compulsive Drinking Scale (OCDS) is the most widely used alcohol craving instrument. The OCDS has been validated in adults with alcohol use disorders (AUDs), which typically emerge in early adulthood. This study examines the validity of the OCDS in a nonclinical sample of young adults. Methods: Three hundred and nine college students (mean age of 21.8 years, SD = 4.6 years) completed the OCDS, Alcohol Use Disorders Identification Test (AUDIT), and measures of alcohol consumption. Subjects were randomly allocated to 2 samples. Construct validity was examined via exploratory factor analysis (n = 155) and confirmatory factor analysis (n = 154). Concurrent validity was assessed using the AUDIT and measures of alcohol consumption. A second, alcohol-dependent sample (mean age 42 years, SD 12 years) from a previously published study (n = 370) was used to assess discriminant validity. Results: A unique young adult OCDS factor structure was validated, consisting of Interference/Control, Frequency of Obsessions, Alcohol Consumption and Resisting Obsessions/Compulsions. The young adult 4-factor structure was significantly associated with the AUDIT and alcohol consumption. The 4 factor OCDS successfully classified nonclinical subjects in 96.9% of cases and the older alcohol-dependent patients in 83.7% of cases. Although the OCDS was able to classify college nonproblem drinkers (AUDIT <13, n = 224) with 83.2% accuracy, it was no better than chance (49.4%) in classifying potential college problem drinkers (AUDIT score >= 13, n = 85). Conclusions: Using the 4-factor structure, the OCDS is a valid measure of alcohol craving in young adult populations. In this nonclinical set of students, the OCDS classified nonproblem drinkers well but not problem drinkers. Studies need to further examine the utility of the OCDS in young people with alcohol misuse.

Dunbar MS; Scharf D; Kirchner T; Shiffman S. Do smokers crave cigarettes in some smoking situations more than others? Situational correlates of craving when smoking. Nicotine & Tobacco Research 12(3): 226-234, 2010. (52 refs.)

Smokers tend to smoke when experiencing craving, but even within smoking occasions, craving may vary. We examine variations in craving when people were smoking in various real-world situations. Using Ecological Momentary Assessment, 394 smokers recorded smoking, craving, and smoking context in real time on electronic diaries over 2 weeks of ad libitum smoking. Assessments occurred immediately prior to smoking. Mixed modeling was used to analyze associations between craving and situational variables. Craving varied across smoking situations, but the differences were small (< 1 on a 0-10 scale). Specifically, craving was higher in smoking situations where smoking was restricted, likely because high craving leads smokers to violate restrictions. Controlling for restrictions, craving was higher when cigarettes were smoked while eating or drinking, were with other people (vs. alone), were in a group of people (vs. other people simply in view), during work (vs. leisure), and during activity (vs. inactivity). In addition, craving was higher for cigarettes smoked early in the day. No differences in craving were observed in relation to drinking alcohol or caffeine (vs. doing anything else), being at work (vs. home), being at a bar or restaurant (vs. all other locations), interacting with others (vs. not interacting), or other people smoking (vs. no others smoking). Even though most craving reports prior to smoking were high, and situations were thus expected to have little influence on craving, results suggest that some cigarettes are craved more than others across different smoking situations, but differences are small.

Evren C; Cetin R; Durkaya M; Dalbudak E. Clinical factors associated with relapse in male alcohol dependents during six-month follow-up. Bulletin of Clinical Psychopharmacology 20(1): 14-22, 2010. (60 refs.)

Objective: Aim of this study was to evaluate the clinical factors associated with relapse to alcohol use during six-month after inpatient treatment in male alcohol dependents. Method: Participants were 156 consecutively admitted male alcohol dependents. Among these patients 107 were available to examine 6 months after inpatient treatment. Patients were administered the Symptom Checklist-Revised-90 (SCL-90-R), and Michigan Alcoholism Screening Test (MAST) at baseline and the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), AMATEM Motivation for Treatment Scale (AMTS), and the PENN Alcohol Craving Scale (PACS) six-month later at follow-up. Results: Among 107 alcohol dependent inpatients 53.3% (n=57) were considered as relapsed to alcohol use. Current age, age at regular alcohol use, duration of education, and marital and employment status did not differ between groups. Mean scores of MAST, awareness of problems of AMTS and GSI also did not differ significantly between groups, whereas depression, anxiety and craving scores were higher and "treatment motivation and readinees to change" subscale of AMTS was lower in relapsed group. Relapsed group had less outpatient clinic control, attendance to outpatient treatment program, change in social milieu to protect themselves and use of medicine for craving but experienced more life stressors during six-month follow-up. Severity of craving (particularly 5th item), not changing social milieu and life stressors experienced during six-month follow-up predicted relapse in alcohol dependents after inpatient treatment. Conclusions: Craving seems to be the main factor associated with relapse. Also factors that increase craving (i.e., not changing risky environment, experiencing life stressor during remission and higher negative affect) may put sober alcohol dependents at risk of relapse. Adjunct anti-craving medications, regular attendance to the outpatient treatment may motivate patients for life changes and teach them how to cope with life-stressors.

Fecteau S; Fregni F; Boggio PS; Camprodon JA; Pascual-Leone A. Neuromodulation of decision-making in the addictive brain. Substance Use & Misuse 45(11): 1766-1786, 2010. (133 refs.)

Noninvasive brain stimulation of the dorsolateral prefrontal cortex with repetitive transcranial magnetic stimulation and transcranial direct current stimulation can modify decision-making behaviors in healthy subjects. The same type of noninvasive brain stimulation can suppress drug craving in substance user patients, who often display impaired decision-making behaviors. We discuss the implications of these studies for the cognitive neurosciences and their translational applications to the treatment of addictions. We propose a neurocognitive model that can account for our findings and suggests a promising therapeutic role of brain stimulation in the treatment of substance abuse and addictive behavior disorders.

Gauggel S; Heusinger A; Forkmann T; Boecker M; Lindenmeyer J; Cox WM et al. Effects of alcohol cue exposure on response inhibition in detoxified alcohol-dependent patients. Alcoholism: Clinical and Experimental Research 34(9): 1584-1589, 2010. (37 refs.)

Background: There is evidence that exerting self-control during alcohol craving can diminish performance on subsequent tasks that require self-control. Based on the resource depletion model (Muraven and Baumeister, 2000), we examined the influence of alcohol cue exposure on detoxified alcohol-dependent patients' ability to inhibit ongoing responses. Methods: Twenty alcohol-dependent patients were randomly assigned to an alcohol-cue exposure and a control-cue exposure condition and thereafter had to perform an inhibition task (i.e., stop-signal task). Results: Participants who sniffed alcohol before performing the inhibition task reported a stronger urge to drink alcohol than the control group that sniffed water. Participants who sniffed alcohol were also impaired in their inhibitory performance but not in their noninhibitory performance on the stop-signal task. Conclusions: The urge to drink presumably reduced participants' self-control, and this interfered with their ability to inhibit responding.

Han DH; Kim YS; Lee YS; Min KJ; Renshaw PF. Changes in cue-induced, prefrontal cortex activity with video-game play. Cyberpsychology, Behavior and Social Networking 13(6): 655-661, 2010. (27 refs.)

Brain responses, particularly within the orbitofrontal and cingulate cortices, to Internet video-game cues in college students are similar to those observed in patients with substance dependence in response to the substance-related cues. In this study, we report changes in brain activity between baseline and following 6 weeks of Internet video-game play. We hypothesized that subjects with high levels of self-reported craving for Internet video-game play would be associated with increased activity in the prefrontal cortex, particularly the orbitofrontal and anterior cingulate cortex. Twenty-one healthy university students were recruited. At baseline and after a 6-week period of Internet video-game play, brain activity during presentation of video-game cues was assessed using 3T blood oxygen level dependent functional magnetic resonance imaging. Craving for Internet video-game play was assessed by self-report on a 7-point visual analogue scale following cue presentation. During a standardized 6-week video-game play period, brain activity in the anterior cingulate and orbitofrontal cortex of the excessive Internet game-playing group (EIGP) increased in response to Internet video-game cues. In contrast, activity observed in the general player group (GP) was not changed or decreased. In addition, the change of craving for Internet video games was positively correlated with the change in activity of the anterior cingulate in all subjects. These changes in frontal-lobe activity with extended video-game play may be similar to those observed during the early stages of addiction.

Heffner JL; Mingione C; Blom TJ; Anthenelli RM. Smoking history, nicotine dependence, and changes in craving and mood during short-term smoking abstinence in alcohol dependent vs. control smokers. Addictive Behaviors 36(3): 244-247, 2011. (22 refs.)

Objective: The goal of this study was to compare lifetime cigarette smoking, severity of nicotine dependence, and subjective effects of short-term tobacco abstinence in abstinent alcohol dependent (AD) and control smokers. Method: AD (n = 119) and control (n = 55) ever-smokers were compared on tobacco use history and nicotine dependence. Negative affect and craving to smoke were examined in a subsample of currently smoking AD (N = 34) and control (N = 19) participants during a 6-h period of tobacco abstinence using the Profile of Mood States (POMS) and the Questionnaire on Smoking Urges-Brief (QSU-B). Results: Although AD smokers did not differ from controls on heaviness of smoking, they were more likely to meet lifetime criteria for nicotine dependence. AD smokers also reported more withdrawal symptoms and were more likely to endorse withdrawal-related depressed mood during past smoking reduction or abstinence periods. During short-term abstinence. AD smokers were more likely to report high craving to smoke for negative affect relief within the first 150 min of tobacco abstinence, but did not differ from controls on overall craving to smoke or withdrawal-related negative affect on the POMS. Conclusions: Results support previous findings that AD smokers have a greater prevalence of nicotine dependence and more severe nicotine withdrawal, with a greater propensity toward withdrawal-related depressed mood. These results, along with our novel finding that greater craving to smoke in abstaining smokers with AD is specific to negative affect-related craving, suggest that negative reinforcement may be a particularly salient factor in the maintenance of tobacco use among individuals with AD.

Hintzen AK; Cramer J; Karagulle D; Heberlein A; Frieling H; Kornhuber J et al. Does alcohol craving decrease with increasing age? Results from a cross-sectional study. Journal of Studies on Alcohol and Drugs 72(1): 158-162, 2011. (29 refs.)

Objective: Long-term studies on patients with impulsive behavior have shown a decrease of symptoms with increasing age. Alcohol craving has many analogies in psychopathology with obsessive-compulsive behavior patterns. The aim of the present study was to find evidence of a possible decrease of craving in elderly alcohol-dependent patients. Method: One hundred ninety-eight alcohol-dependent patients at the beginning of alcohol withdrawal therapy were included in this study. The extent of craving was measured using the Obsessive Compulsive Drinking Scale on the day of hospital admission before starting the detoxification regime and 1 week after admission. Results: Linear regression analysis showed a significant negative association between craving and age after 1 week of treatment (no association at admission). T test for independent samples confirmed lower obsessive-compulsive craving in older patients. Conclusions: The lack of association between craving and age at the beginning of the detoxification can be explained by the influence of other different (e.g., neurobiological) parameters during acute withdrawal. At the end of the physical detoxification after 1 week of treatment, a significant negative association between patient's age and Obsessive Compulsive Drinking Scale score occurred, which points to a decrease of alcohol craving in later years. Alterations in endocrinological functions or in mesolimbic neurotransmission are discussed as possible reasons for this finding.

Hormes JM; Rozin P. Does "craving" carve nature at the joints? Absence of a synonym for craving in many languages. Addictive Behaviors 35(5): 459-463, 2010. (22 refs.)

Introduction: Craving is a term commonly used by North American lay people, and is also used as an important category in psychological and addiction research. However, difficulties in defining craving suggest that it may not be a natural category. Methods: Assuming that lexicalization of a concept is an indicator of its importance and/or universality, the presence of synonyms for craving is examined in a range of natural languages, using both dictionaries and native speaker informants. Related words, such as "love," "like," "urge," "desire," "adore" and "addiction" are also explored in 20 languages, in terms of meaning and the domains of life to which these words are applied. Results: Based on automated translations, 64% of 25 languages have a craving synonym, and based on native speaker, only 17% of 20 languages lexicalize craving; when there is a synonym, it seems to mean a desire for a potential ingestant or a drug, that is, it is a desire restricted to certain domains of activity. Discussion: The concept of "craving" appears to be limited in its importance and relevance in languages and cultures outside of English and North America. This finding has important implications for the understanding of "craving" as a natural category in the study of drug and other addictions. A similar though less extensive lack of synonyms for "addiction" is also reported.

Kambouropoulos N; Rock A. Extraversion and altered state of awareness predict alcohol cue-reactivity. Journal of Individual Differences 31(4): 178-184, 2010. (37 refs.)

Studies have shown that regular drinkers respond to alcohol-related stimuli with increases in urge to drink and changes in affect. Evidence indicates that there is individual variability in responses to alcohol-related cues. The current study aimed to examine (1) the role of extraversion in understanding variability in responses to alcohol cues and (2) whether cue-elicited altered states of awareness are related to urge to drink and affective responses. Forty-one participants were exposed first to a neutral and then to an alcohol cue; urge and affective responses were then measured. Extraversion was a significant positive predictor of urge to drink, while altered state of awareness was a significant positive predictor of urge to drink and positive affect. Interestingly, altered state of awareness significantly improved prediction of both urge to drink and positive affect after controlling for levels of extraversion. These findings suggest that changes in states of awareness following presentation of alcohol cues may facilitate the observed increases in urge to drink and positive affect.

MacKillop J; O'Hagen S; Lisman SA; Murphy JG; Ray LA; Tidey JW et al. Behavioral economic analysis of cue-elicited craving for alcohol. Addiction 105(9): 1599-1607, 2010. (63 refs.)

Aims: Craving as a motivational determinant of drug use remains controversial because of ambiguous empirical findings. A behavioral economic approach may clarify the nature of craving, theorizing that subjective craving functionally reflects an acute increase in a drug's value. The current study tested this hypothesis via a multidimensional assessment of alcohol demand over the course of an alcohol cue reactivity procedure. Design: One-way within-subjects design. Setting: Human laboratory environment. Participants: Heavy drinkers (n = 92) underwent exposures to neutral (water) cues followed by personalized alcohol cues. Assessments: Participants were assessed for craving, alcohol demand, affect, and salivation following each exposure. Findings: Alcohol versus neutral cues significantly increased craving and multiple behavioral economic measures of the relative value of alcohol, including alcohol consumption under conditions of zero cost (intensity), maximum expenditure on alcohol (O-max), persistence in drinking to higher prices (breakpoint) and proportionate price insensitivity (normalized P-max). Craving was significantly correlated with demand measures at levels ranging from 0.21-0.43. Conclusions: These findings support the potential utility of a behavioral economic approach to understanding the role of environmental stimuli in alcohol-related decision making. Specifically, they suggest that the behavioral economic indices of demand may provide complementary motivational information that is related to though not entirely redundant with measures of subjective craving.

Mahler SV; de Wit H. Cue-reactors: Individual differences in cue-induced craving after food or smoking abstinence. PLoS ONE 5(11): e15475, 2010. (20 refs.)

Background: Pavlovian conditioning plays a critical role in both drug addiction and binge eating. Recent animal research suggests that certain individuals are highly sensitive to conditioned cues, whether they signal food or drugs. Are certain humans also more reactive to both food and drug cues? Methods: We examined cue-induced craving for both cigarettes and food, in the same individuals (n = 15 adult smokers). Subjects viewed smoking-related or food-related images after abstaining from either smoking or eating. Results: Certain individuals reported strong cue-induced craving after both smoking and food cues. That is, subjects who reported strong cue-induced craving for cigarettes also rated stronger cue-induced food craving. Conclusions: In humans, like in nonhumans, there may be a "cue-reactive'' phenotype, consisting of individuals who are highly sensitive to conditioned stimuli. This finding extends recent reports from nonhuman studies. Further understanding this subgroup of smokers may allow clinicians to individually tailor therapies for smoking

Maremmani I; Pacini M; Lamanna F; Pani PP; Perugi G; Deltito J et al. Mood stabilizers in the treatment of substance use disorders. (review). CNS Spectrums 15(2): 95-109, 2010. (160 refs.)

Individuals suffering from drug addiction may also manifest features of bipolar spectrum disorders. Hyperthymic and cyclothymic temperaments may render individuals vulnerable to later development of substance abuse. Bipolar disorders themselves may be altered or precipitated by substance use, most notably by stimulants (amphetamines), alcohol, and cannabinoids. The clinical usefulness of mood stabilizers, particularly antiepileptics, has been established as safe and effective in substance abusers with and without comorbid mood disorders. Most studies on this issue have been of short duration and focused on the resolution of a currently manifest period of illness. Few studies have been conducted on the usefulness of these drugs on the long-term longitudinal course of these diseases, such as frequently encountered recurrent relapses into states of agitation, impulsivity, and/or dissatisfaction. As opposed to the clinical experience with traditional antidepressants and neuroleptics, antiepileptics do not induce counter-polar states (depressed patients abruptly turning manic or hypomanic; nor patients currently hypomanic or manic turning abruptly depressed). Many clinicians consider antiepileptic mood stabilizers to be the preferred category of medications for the treatment of such patients. Valproate appears to be a potentially fruitful medication to study in these dual diagnosis patients due to preliminary evidence demonstrating its anticraving efficacy.

Martinotti G; Di Nicola M; Tedeschi D; Andreoli S; Reina D; Pomponi M et al. Pregabalin versus naltrexone in alcohol dependence: A randomised, double-blind, comparison trial. Journal of Psychopharmacology 24(9): 1367-1374, 2010. (52 refs.)

Pregabalin (PRE) acts as a presynaptic inhibitor of the release of excessive levels of excitatory neurotransmitters by selectively binding to the alpha(2)-delta subunit of voltage-gated calcium channels. In this randomised, double-blind comparison trial with naltrexone (NAL), we aimed to investigate the efficacy of PRE on alcohol drinking indices. Craving reduction and improvement of psychiatric symptoms were the secondary endpoints. Seventy-one alcohol-dependent subjects were detoxified and subsequently randomised into two groups, receiving 50 mg of NAL or 150-450 mg of PRE. Craving (VAS; OCDS), withdrawal (CIWA-Ar) and psychiatric symptoms (SCL-90-R) rating scales were applied. Alcohol drinking indices and craving scores were not significantly different between groups. Compared with NAL, PRE resulted in greater improvement of specific symptoms in the areas of anxiety, hostility and psychoticism, and survival function (duration of abstinence from alcohol). PRE also resulted in better outcome in patients reporting a comorbid psychiatric disorder. Results from this study globally place PRE within the same range of efficacy as that of NAL. The mechanism involved in the efficacy of PRE in relapse prevention could be less related to alcohol craving and more associated with the treatment of the comorbid psychiatric symptomatology.

Martinotti G; Reina D; Di Nicola M; Andreoli S; Tedeschi D; Ortolani I et al. Acetyl-l-carnitine for alcohol craving and relapse prevention in anhedonic alcoholics: A randomized, double-blind, placebo-controlled pilot trial. Alcohol and Alcoholism 45(5): 449-455, 2010. (62 refs.)

Aim: The study aimed to evaluate the efficacy of acetyl-l-carnitine (ALC), at different doses, in relapse prevention and craving in anhedonic detoxified alcohol-dependent subjects. Method: Randomized, double-blind, placebo-controlled, pilot study in 64 alcohol-dependent anhedonic patients: 23 received ALC at a dose of 3 g/day, 21 received ALC at a dosage of 1 g/day and 20 were given placebo. Intensity of alcohol craving was evaluated by Visual Analogue Scale. Subjects were evaluated at the beginning of treatment and after 10, 30, 60 and 90 days. Results: Survival analysis showed that patients treated with ALC remained completely abstinent for longer than those treated with placebo (Z = -2.27; P < 0.05). From the 10th day onwards, a greater reduction of craving was observed in the ALC 1 g group than with placebo (P = 0.035). The two groups did not differ in the percentage of subjects remaining abstinent for the entire study period or the number of subjects who relapsed (defined as five or more standard drinks (four for women) on a single occasion or drinking on five or more days in 1 week). Conclusions: The results of this study suggest that ALC can reduce craving and the time to first drink. ALC use was safe. Further studies are needed to clarify to confirm, over longer periods, these short-term outcome benefits.

Myers KM; Carlezon WA. Extinction of drug- and withdrawal-paired cues in animal models: Relevance to the treatment of addiction. (review). Neuroscience and Biobehavioral Reviews 35(2 (special issue)): 285-302, 2010. (307 refs.)

Conditioned drug craving and withdrawal elicited by cues paired with drug use or acute withdrawal are among the many factors contributing to compulsive drug taking. Understanding how to stop these cues from having these effects is a major goal of addiction research. Extinction is a form of learning in which associations between cues and the events they predict are weakened by exposure to the cues in the absence of those events. Evidence from animal models suggests that conditioned responses to drug cues can be extinguished, although the degree to which this occurs in humans is controversial. Investigations into the neurobiological substrates of extinction of conditioned drug craving and withdrawal may facilitate the successful use of drug cue extinction within clinical contexts. While this work is still in the early stages, there are indications that extinction of drug- and withdrawal-paired cues shares neural mechanisms with extinction of conditioned fear. Using the fear extinction literature as a template, it is possible to organize the observations on drug cue extinction into a cohesive framework.

Ray LA. Stress-induced and cue-induced craving for alcohol in heavy drinkers: Preliminary evidence of genetic moderation by the OPRM1 and CRH-BP genes. Alcoholism: Clinical and Experimental Research 35(1): 166-174, 2011. (58 refs.)

Background: Neurobiological theories of addiction have highlighted disruption in stress pathways as a central feature of addictive disorders, and pharmacological treatments targeting stress mechanisms hold great promise. This study examines genetic determinants of stress-induced and cue-induced craving in heavy drinkers by testing single-nucleotide polymorphisms (SNPs) of the corticotrophin-releasing hormone binding protein (CRH-BP) gene and the mu-opioid receptor (OPRM1) gene. Methods: This study combines guided imagery stress exposure and in vivo alcohol cue exposure in a sample of 64 (23 women) non-treatment-seeking heavy drinkers. Results: Analyses, uncorrected for multiple comparisons, revealed that a tag SNP of the CRH-BP gene (rs10055255) moderated stress-induced craving in this sample. The same SNP predicted greater affective responses to the stress manipulation, including greater levels of subjective tension and negative mood. The Asp40 allele of the OPRM1 was associated with greater cue-induced alcohol craving following the neutral imagery condition. Conclusions: These initial results extend recent preclinical and clinical findings implicating the CRH-BP in stress-related alcoholism and confirm the role of the Asp40 allele of the OPRM1 gene in reward-driven alcohol phenotypes. Human laboratory models of stress and cue-induced craving may be useful in pharmacotherapy development targeting dysregulation of stress systems. Larger studies are needed to validate these preliminary findings, which should also be extended to clinical samples.

Rose AK; Hobbs M; Klipp L; Bell S; Edwards K; O'Hara P et al. Monitoring drinking behaviour and motivation to drink over successive doses of alcohol. Behavioural Pharmacology 21(8): 710-718, 2010. (46 refs.)

The objective of this study was to compare alcohol urge, drinking behaviour and mood across two beverage conditions (alcohol/soft drink), over multiple drinks. Forty-five (22 men) participants completed two conditions (alcohol/soft-drink). Baseline alcohol urge and mood was measured before an initial drink consumed (0.2 g/kg alcohol or lemonade). Four drinking phases, which provided alcohol and lemonade, followed. Alcohol urge, mood and liking/enjoyment of beverages were measured. Participants' typical drinking habits were recorded, allowing comparisons across drinking factors. Alcohol urge was greater in the alcohol condition (P < 0.03), which positively correlated with liking and drinking enjoyment of the alcohol beverage (P < 0.04). Binge drinking and weekly alcohol consumption positively related to alcohol urge during the first half of the alcohol condition (P < 0.02). Feeling stimulated was positively related to alcohol urge (P < 0.01). Sip latency was quickest for alcohol in the alcohol condition (P < 0.001) and did not increase over time as in the soft-drink condition (P < 0.001). This study presents a paradigm in which alcohol motivation can be assessed within more typical drinking occasion parameters. Urge related to alcohol's positive reinforcing effects. As more alcohol was consumed, a disassociation of liking and wanting alcohol occurred, indicating that different processes may underlie behaviour during different periods of a drinking occasion.

Sarid-Segal O; Knapp CM; Burch W; Richardson MA; Bahtia S; DeQuattro K et al. The anticonvulsant Zonisamide reduces ethanol self-administration by risky drinkers. American Journal of Drug and Alcohol Abuse 35(5): 316-319, 2009. (24 refs.)

Objective: The purpose of this study is to examine the effects of zonisamide on ethanol self-administration and subjective effects in risky drinkers using a human laboratory paradigm. Method: We conducted a double-blind, placebo-controlled study of the effects of zonisamide 100 mg on ethanol self-administration and urge to drink in risky drinkers (N = 10) (1). Result: During the second hour of a 2-hour self-administration session ethanol consumption was 50% lower in the zonisamide group as compared to the placebo group. Urge to drink was also significantly lower under the zonisamide condition. Conclusion: These results indicate that a single dose of zonisamide reduces urge to drink and the quantity of ethanol self-administered by risky drinkers during their second hour of access to alcohol. Scientific Significance: Zonisamide may help individuals drinking at risky levels reduce their intake of alcohol.

Schoenmakers TM; de Bruin M; Lux IFM; Goertz AG; Van Kerkhof DHAT; Wiers RW. Clinical effectiveness of attentional bias modification training in abstinent alcoholic patients. Drug and Alcohol Dependence 109(1-3): 30-36, 2010. (52 refs.)

A new training to decrease attentional bias (attentional bias modification training, ABM) was tested in a randomized controlled experimental study with alcohol-dependent patients as an addition to cognitive behavioral therapy. In alcohol dependence, attentional bias has been associated with severity of alcoholism, craving, treatment outcome, and relapse. Forty-three patients with DSM-IV diagnosis of alcohol dependence were randomly assigned to an ABM intervention or control training. The procedure consisted of five sessions in which patients were trained to disengage attention from alcohol-related stimuli (ABM condition) or in which they were trained on an irrelevant reaction-time test (control condition). We measured the effects of ABM on the visual-probe task, with stimuli that were presented in the ABM and with new stimuli. Craving was measured with the Desires for Alcohol Questionnaire. Follow-up data were gathered for overall treatment success, and relapse up to 3 months after the intervention. ABM was effective in increasing the ability to disengage from alcohol-related cues. This effect generalized to untrained, new stimuli. There were no significant effects on subjective craving. For other outcome measures there were indications of clinically relevant effects. Results indicate that ABM among alcohol-dependent patients was effective and that it may affect treatment progression. Large-scale trials are warranted to further investigate this new field.

Skinner MD; Aubin HJ. Craving's place in addiction theory: Contributions of the major models. Neuroscience and Biobehavioral Reviews 34(4): 606-623, 2010. (146 refs.)

We examine in this paper the unfolding of craving concepts within 18 models that span roughly 60 years (1948-2009). The amassed evidence suggests that craving is an indispensable construct, useful as a research area because it has continued to destabilize patients seeking treatment for substances. The models fall into four categories: the conditioning-based models, the cognitive models, the psychobiological models, and the motivation models. In the conditioning models, craving is assumed to be an automatic, unconscious reaction to a stimulus. In the cognitive models, craving arises from the operation of information processing systems. In the psychobiological models, craving can be explained at least in part by biological factors with an emphasis on motivational components. Finally, in the motivation models, craving is viewed as a component of a larger decision-making framework. It is well accepted that no single model explains craving completely, suggesting that a solid understanding of the phenomenon will only occur with consideration from multiple angles. A reformulated definition of craving is proposed.

Soyka M; Helten C; Schmidt P. OCDS craving scores predict 24-month outcome in alcoholic outpatients. American Journal on Addictions 19(3): 264-269, 2010. (42 refs.)

This study was conducted to replicate previous findings on the predictive value of a German version of the Obsessive Compulsive Drinking Scale (OCDS) by investigating 24-month treatment outcome in an outpatient setting. This was a prospective, observational study with 92 alcohol-dependent patients. The OCDS was used to assess craving at the end of treatment, and at the 6-, 12-, and 24-month follow-ups. Univariate and logistic regression analyses were performed. Of the 67 patients interviewed at the 24-month follow-up, 58% were abstinent and 79% improved. OCDS scores were higher in patients with a less favorable outcome. In line with previous findings, our results showed that the intensity of craving as measured by the OCDS may predict outcome in outpatient alcoholics. (Am J Addiction 2010;19:264-269).

Thomas SE; Randall PK; Brady K; See RE; Drobes DJ. An acute psychosocial stressor does not potentiate alcohol cue reactivity in non-treatment-seeking alcoholics. Alcoholism: Clinical and Experimental Research 35(3): 464-473, 2011. (61 refs.)

Background: Relapse risk factors, such as psychological stress and alcohol cues, are often encountered together. Understanding how they interact has the potential to improve alcoholism treatments. This study was conducted to examine whether an acute psychosocial stressor enhanced alcohol cue reactivity in non-treatment-seeking alcoholics. Methods: Seventy-nine alcohol-dependent individuals (39 women) randomly received either the Trier Social Stress Test or a no-stress control condition. Stress reactivity was measured with serum adrenocorticotropic hormone and cortisol, mean arterial blood pressure, and subjective distress. Immediately following the stress manipulation, participants held and sniffed a neutral cue then their preferred alcoholic beverage. Cue reactivity was measured by 2 subjective measures of craving following each cue. Additionally, general craving was assessed with the Alcohol Urge Questionnaire at the beginning and end of the laboratory procedure. Results: The stress manipulation showed internal validity on all measures of stress reactivity. There was not a main effect of stress nor a stress x cue interaction on either cue reactivity measure. As expected, there was a main effect of cue (alcohol > neutral cue) on both measures of cue reactivity. General craving increased during the challenge, but not differently by stress group. Magnitude of stress reactivity was not associated with magnitude of cue reactivity, and all results were independent of gender. Conclusion: In this well-controlled clinical laboratory study of non-treatment-seeking alcoholics, an acute psychological stressor did not make an alcohol cue a more potent urge-inducing stimulus, and stress had no effect on general alcohol craving.

Thompson RD; Heffner JL; Strong JA; Blom TJ; Anthenelli RM. Relationship between the serotonin transporter polymorphism and obsessive-compulsive alcohol craving in alcohol-dependent adults: a pilot study. Alcohol 44(5): 401-406, 2010. (33 refs.)

A serotonin deficiency state has been implicated in alcohol-dependent individuals' experience of obsessive compulsive alcohol craving. Because the serotonin transporter (5-HTT) functions to remove serotonin from the synapse, it is thought that increased reuptake (indicated by the number of high-expressing L-A alleles present in the 5-HTT gene-linked polymorphic region [5-HTTLPR] of the SLC6A4 gene) is associated with an increase in obsessive compulsive alcohol craving. The current pilot investigation sought to explore this hypothesis by examining the extent to which obsessive compulsive alcohol craving varies by 5-HTTLPR genotype among participants enrolled in an ongoing pharmacogenetics trial. All participants were screened with a semi-structured diagnostic interview, completed self-report measures of alcohol-related behavior, and underwent peripheral venous blood draw for DNA genotyping. Cross-sectional data obtained at baseline from 176 currently drinking alcohol-dependent individuals were analyzed using multiple regression. Preliminary findings suggest that 5-HTTLPR is not predictive of Obsessive Compulsive Drinking Scale total and factor scores. Although the 5-HTTLPR polymorphism was not related to obsessive compulsive alcohol craving in this pilot study, additional research is needed to clarify the possible role of serotonergic mechanisms in alcohol craving.

Uva MCD; Luminet O; Cortesi M; Constant E; Derely M; De Timary P. Distinct effects of protracted withdrawal on affect, craving, selective attention and executive functions among alcohol-dependent patients. Alcohol and Alcoholism 45(3): 241-246, 2010. (33 refs.)

Aims: The present study examined the effects of protracted alcohol withdrawal on affectivity, craving, selective attention and executive functions (EFs) in alcohol-dependent patients. Methods: Selective attention (The D2 Cancerellation Test), flexibility (Trail Making Test), inhibition (Stroop Task), decision making (Iowa Gambling Task), craving (Obsessive-Compulsive Drinking Scale) and state affectivity (Positive and Negative Affectivity Schedule) were assessed in alcohol-dependent patients (DSM-IV, n = 35) matched to non-alcohol-dependent participants (n = 22) at the onset (T1: day 1 or 2) and at the end (T2: days 14-18) of protracted withdrawal during rehab. Results: Alcohol-dependent patients' abilities to focus their attention on relevant information, to switch from one pattern to another, to inhibit irrelevant information and to make advantageous choices were lower than those of control participants during both times of a withdrawal cure. No effect of time emerged from analyses for selective attention and EF deficits. Conversely, significant differences between T1 and T2 were observed for craving and affect scores indicating a weakening of alcohol craving and negative affect as well as an improvement of positive affect among patients from onset to the end of cure. Conclusion: Control functions of the Supervisory Attentional System (Norman and Shallice, 1986) were impaired and did not improve during a 3-week withdrawal cure, whereas alcohol craving and negative state affectivity significantly improved in parallel during this period. Implications for understanding the clinical processes of withdrawal are discussed.

VanBuskirk KA; Potenza MN. The treatment of obesity and its co-occurrence with substance use disorders. (review). Journal of Addiction Medicine 4(1): 1-10, 2010. (135 refs.)

Obesity and binge eating disorder are detrimental health conditions that are associated with lower qualities of life. Individuals with obesity often face societal discrimination and frequently experience related medical disorders such as diabetes, hypertension, and hyperlipidemia. Current research suggests neurobiological similarities among obesity, binge eating disorder, and substance dependence. In addition, behavioral similarities link the two conditions; obese and substance-dependent individuals often report similar features such as cravings and diminished control over consumption of food and substances, respectively. Treatment options for obesity have begun to use this information to formulate pharmacological and therapeutic interventions that may provide improved results for weight loss and decreased binge frequency. Similarly, treatment approaches to substance addictions should consider aspects of weight management. Findings from research and treatment studies are presented with the aim of reviewing the current literature of obesity within the context of an addiction framework and providing information on empirically supported approaches to the treatment of co-occurring obesity and substance addiction.

Vieten C; Astin JA; Buscemi R; Galloway GP. Development of an acceptance-based coping intervention for alcohol dependence relapse prevention. Substance Abuse 31(2): 108-116, 2010. (71 refs.)

Both psychological and neurobiological findings lend support to the long-standing clinical observation that negative affect is involved in the development and maintenance of alcohol dependence, and difficulty coping with negative affect is a common precipitant of relapse after treatment. Although many current approaches to relapse prevention emphasize change-based strategies for managing negative cognitions and affect, acceptance-based strategies for preventing relapse to alcohol use are intended to provide methods for coping with distress that are fundamentally different from, though in theory complementary to, approaches that emphasize control and change. This paper describes the development of Acceptance-Based Coping for Relapse Prevention (ABCRP), a new intervention for alcohol-dependent individuals who are within 6 months of having quit drinking. Results of preliminary testing indicate that the intervention is feasible with this population; and a small uncontrolled pilot study (N = 23) showed significant (P < .01) improvements in self-reported negative affect, emotional reactivity, perceived stress, positive affect, psychological well-being, and mindfulness level, as well as a trend (P = .06) toward reduction in craving severity between pre- and postintervention assessments. The authors conclude that this acceptance-based intervention seems feasible and holds promise for improving affect and reducing relapse in alcohol-dependent individuals, warranting further research.

Wedekind D; Herchenhein T; Kirchhainer J; Bandelow B; Falkai P; Engel K et al. Serotonergic function, substance craving, and psychopathology in detoxified alcohol-addicted males undergoing tryptophan depletion. Journal of Psychiatric Research 44(16): 1163-1169, 2010. (52 refs.)

Alcohol addiction is associated with alterations of central nervous dopaminergic and serotonergic functions. Acute tryptophan depletion has not yet been applied in detoxified alcohol-addicted patients in order to investigate its impact on psychopathology, psychoneuroendocrinology, and substance craving behaviour. 25 alcohol-addicted males randomly either received a tryptophan-free or tryptophan-containing amino acid drink and 7 days later the respective other drink. Anxiety, depression, and craving were assessed before and 5 h after the drink. Tryptophan, 5-HIAA, dopamine, norepinephrine, epinephrine, and HVA in serum were measured before and after both treatments. Nocturnal urinary cortisol measurements and genotyping for the HTTLPR polymorphism of the SLC6A4 gene were performed. Tryptophan depletion resulted in a significant reduction of total and free serum tryptophan while the tryptophan-rich drink increased serum levels. Both treatments caused a significant increase of serum serotonin levels, however, serum 5-HIAA was decreased after depletion but increased after sham depletion. Dopamine and norepinephrine were elevated after tryptophan depletion and sham. Depletion increased depression scores (MADRS), while the full amino acid drink improved state and trait anxiety ratings (STAI) and substance craving. Urinary cortisol excretion was not affected by both treatments. Patients with the II genotype of the serotonin transporter gene displayed lower baseline tryptophan levels compared to patients with the heterozygous genotype. Results suggest an impaired serotonergic function in alcohol-addicted males.