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CORK Bibliography: Craving and Alcohol

132 citations. January 2005 to present

Prepared: March 2008

Addolorato G; Abenavoli L; Leggio L; Gasbarrini G; Alcoholism Treatment Study Group. How many cravings? Pharmacological aspects of craving treatment in alcohol addiction: A review. (review). Neuropsychobiology 51(2): 59-66, 2005. (83 refs.)

In the last decade, craving has increasingly been considered an important target for the treatment of patients with alcohol problems, and several drugs able to interfere with the neurotransmitters involved in craving mechanisms have been experimented. However, different subtypes of patients could have different mechanisms at the basis of alcohol craving. In this review, the main drugs currently used in the treatment of patients with alcohol problems are described. A hypothesis of pharmacological treatment of the different types of craving is also discussed.

Addolorato G; Capristo E; Leggio L; Ferrulli A; Abenavoli L; Malandrino N et al. Relationship between ghrelin levels, alcohol craving, and nutritional status in current alcoholic patients. Alcoholism: Clinical and Experimental Research 30(11): 1933-1937, 2006. (44 refs.)

Background: Ghrelin is a peptide produced mainly by the gut and hypothalamus. Ghrelin is able to stimulate food-seeking behavior. Alcohol-craving and food-seeking behavior could share common neural circuits. Ghrelin is related to nutritional status, but few data are available in alcoholic patients on the relationship between ghrelin and nutritional disorders. Methods: Plasma ghrelin was evaluated in 15 current alcoholic male patients compared with 15 healthy male volunteers. Craving was evaluated by the Obsessive-Compulsive Drinking Scale. Body composition was assessed by dual-energy X-ray absorptiometry. Energy substrate utilization was evaluated by indirect calorimetry. Results: Ghrelin was significantly reduced in alcohol-dependent patients with respect to healthy subjects (p=0.0278). A significant positive correlation was found between ghrelin and craving (r=0.55; p=0.034). A preferential utilization of lipids as an energy substrate with a reduction of the fat mass (p=0.01) and an increase of the free fat mass (p=0.0091) was found in alcoholic patients. Conclusions: Within our sample showing low ghrelin levels probably related to the impaired nutritional status; patients with higher levels of ghrelin showed higher levels of alcohol craving. These preliminary data indicate that ghrelin could be implicated in the neurobiological mechanisms of alcohol craving, other than a hormone influenced by the nutritional status.

Addolorato G; Leggio L; Agabio R; Colombo G; Gasbarrini G. Baclofen: A new drug for the treatment of alcohol dependence. (review). International Journal of Clinical Practice 60(8): 1003-1008, 2006. (49 refs.)

Recent preclinical and clinical studies have suggested that baclofen, the prototypic gamma-aminobutyric acid B (GABA(B)) receptor agonist, is a promising pharmacological compound for use in the treatment of alcohol dependence. In particular, baclofen has been found to suppress symptoms of alcohol withdrawal syndrome with an efficacy comparable with that of the 'gold standard' diazepam. Moreover, baclofen has proven effective in the prevention of relapse due to its ability to reduce alcohol intake and craving in alcoholic patients. Baclofen proved to be manageable, producing no significant side effects and displaying no addictive properties. The efficacy of the drug in the management of both alcohol withdrawal syndrome and relapse prevention should entail a vastly simplified pharmacotherapy of alcohol dependence.

Addolorato G; Leggio L; Abenavoli L; Gasbarrini G; Alcoholism Treatment Study Group. Neurobiochemical and clinical aspects of craving in alcohol addiction: A review on behalf of the Alcoholism Treatment Study Group. Addictive Behaviors 30(6): 1209-1224, 2005. (67 refs.)

Craving plays an important role in the pathogenesis of alcohol dependence and relapse. In this review we have tried to analyse how many contrasting theories have been formulated in order to clarify the concept of craving. Many complex neurobiochemical mechanisms are implicated in the etiology of craving; these mechanisms involve several neurotransmitters, such us dopamine, opioids, glutamate, and serotonin. On the other hand comportamental and/or cognitive aspects could also play a role in the etiology of craving. The coexistence of many and often contrasting theories can indicate that different subtypes of patients could have different mechanisms at the basis of alcohol craving, suggesting that it could be advisable to personalize the anti-craving therapy.

Ait-Daoud N; Wiesbeck GA; Bienkowski P; Li MD; Pfutzer RH; Singer MV et al. Comorbid alcohol and nicotine dependence: From the biomolecular basis to clinical consequences. Alcoholism: Clinical and Experimental Research 29(8): 1541-1549, 2005. (60 refs.)

This article represents the proceedings of a symposium presented at the 12th Congress of the International Society for Biomedical Research on Alcoholism held in Heidelberg/Mannheim, Germany, on October 1, 2004. The organizers and cochairs were Nassima Ait-Daoud, MD, and Gerhard A. Wiesbeck, MD. The presentations included the following: (1) The Role of Nicotinic Acetylcholine Receptors in Alcohol-Seeking Behavior, by Przemyslaw Bienkowski, MD, PhD; (2) Utilization of Linkage Analysis Combined with Microarray Technology to Identify Genes and Mechanisms Underlying Nicotine and Alcohol Use and Abuse in Humans and Rodents, by Ming D. Li, PhD; (3) Smoking and Alcoholic Chronic Pancreatitis: The Underestimated Risk?, by Roland H. Pfutzer, MD; (4) Anticraving Medication in Alcohol and Nicotine Dependence, by Otto M. Lesch, MD, PhD; and (5) Pharmacotherapy for Promotion of Abstinence from Nicotine Among Alcohol-Dependent Individuals, by Bankole A. Johnson, DSc, MD, PhD.

Ameisen O. Complete and prolonged suppression of symptoms and consequences of alcohol-dependence using high-dose baclofen: A self-case report of a physician. Alcohol and Alcoholism 40(2): 147-150, 2005. (30 refs.)

Aims: To test whether the dose-dependent motivation-suppressing effect of baclofen in animals could be transposed to humans, and suppress craving and sustain abstinence. Methods: Neurologists safely use up to 300 mg/day (10 times the dosage currently used for alcohol dependence) of high-dose oral baclofen, to control spasticity, in order to avoid invasive therapy. I am a physician with alcohol dependence and comorbid anxiety. I self-prescribed high-dose baclofen, starting at 30 mg/day, with 20 mg increments every third day and an (optional) additional 20-40 mg/day for cravings. Results: Cravings became easier to combat. After reaching the craving-suppression dose of 270 mg/day (3.6 mg/kg) after 5 weeks, I became and have remained free of alcohol dependence symptoms effortlessly for the ninth consecutive month. Anxiety is well controlled. Somnolence disappeared with a dosage reduction to 120 mg/day, now used for the eighth consecutive month. Conclusions: High-dose baclofen induced complete and prolonged suppression of symptoms and consequences of alcohol dependence, and relieved anxiety. This model, integrating cure and well-being, should be tested in randomized trials, under medical surveillance. It offers a new concept: medication-induced, dose-dependent, complete and prolonged suppression of substance-dependence symptoms with alleviation of comorbid anxiety.

Beresford HE; Deitrich R; Beresford TP. Cyclosporine-A discourages ethanol intake in C57bl/6j mice: A preliminary study. Journal of Studies on Alcohol 66(5): 658-662, 2005. (25 refs.)

OBJECTIVE: Remarkably high rates of abstinence occur among alcohol-dependent persons after a liver transplant. This was thought to be solely due to selection or other nonbiological factors. Observing sustained abstinence for many months to years after a liver transplant, however, we asked whether immunosuppressants might exert a biological effect that supported abstinence from ethanol. METHOD: We hypothesized that cyclosporine-A-treated mice would drink less ethanol given a choice between water and 10% ethyl alcohol. After a 3-day ethanol conditioning period, C57bl/6j mice (n = 20) medicated with cyclosporine-A (50 mg/kg) and a control group of unmedicated mice (n = 20) injected with saline were given free access to either water or the ethanol solution. RESULTS: The medicated mice drank significantly less ethanol throughout the 11-day choice protocol. This was significant whether measured by mean alcohol consumption per day (p = .003) or by alcohol preference as a percent of total liquid intake per day (p = .03). The two groups did not differ significantly in total daily fluid consumption. CONCLUSION: These data suggest that cyclosporine-A lowers alcohol preference in mice. Mechanism of action, similar effects by other centrally acting immunosuppressants and translation to humans all remain to be studied. If fruitful, elucidating the actions of cyclosporine and other immunosuppressants that activate central nervous system receptors may illuminate the pathophysiology of alcohol use and addiction.

Bischof G; Rumpf HJ; Meyer C; Hapke U; John U. Gender differences in temptation to drink, self-efficacy to abstain and coping behavior in treated alcohol-dependent individuals: Controlling for severity of dependence. Addiction Research & Theory 13(2): 129-136, 2005. (30 refs.)

Objectives: Studies on substance use disorders show consistent gender differences. Mainly, research has focused on etiological questions or aspects of comorbidity. Research on gender differences in variables associated with coping capabilities which may be influenced by therapeutic interventions still is scarce. Method: 230 alcohol-dependent patients at an abstinence-oriented inpatient motivational intervention programme were consecutively recruited (28.3% female). A comprehensive, standardized interview included the assessment of severity of dependence, coping-behaviour, temptation to drink and self-efficacy to resist alcohol consumption in high-risk situations. Results: Men reported higher severity of dependence on the physiological component of the dependence syndrome (p< 0.05). When controlling for severity of dependence, male alcohol-dependent individuals reported higher temptation to drink in positive situations, and female alcohol-dependent individuals reported a higher educational level, a higher temptation to drink when faced with withdrawal/urges and more coping-efforts concerning negative thinking. Gender differences in temptation to drink were affected by the severity of dependence. Conclusion: Gender differences in variables associated with alcohol dependence are not merely a result of higher levels of dependence in male subjects. Findings reveal the necessity for differentiating the results on research on addictive disorders according to gender.

Bonsch D; Greifenberg V; Bayerlein K; Biermann T; Reulbach U; Hillemacher T et al. Alpha-synuclein protein levels are increased in alcoholic patients and are linked to craving. Alcoholism: Clinical and Experimental Research 29(5): 763-765, 2005. (20 refs.)

Background: Alpha synuclein has been found to be increased in dopamine neurones of cocaine abusers and in rats whose alcohol preference is inbred. Furthermore, increased alpha-synuclein messenger RNA expression has been linked to craving in patients with alcoholism. The aim of the current study was to investigate whether protein levels of a synuclein in alcoholics are changed and possibly influence alcohol craving. Methods: The alpha-synuclein protein expression level was measured by enzyme-linked immunosorbent assay in the serum of 49 male alcoholics and 50 nondrinking healthy controls. Alcohol craving was assessed by the Obsessive-Compulsive Drinking Scale total score, including subscales for obsessive and compulsive craving. Results: alpha-Synuclein protein expression in patients with alcoholism (14.33 ng/ml; SD, 13.01 ng/ml) was significantly higher (t test, T = 3.66,p < 0.0001) when compared with that of healthy controls (5.92 ng/ml; SD, 9.72 ng/ml). Using a multivariate analysis, all craving scores (Obsessive-Compulsive Drinking Scale total score and obsessive and compulsive subscale scores) in alcoholics were significantly associated with their alpha-synuclein protein levels (multiple linear regression, p < 0.014). Conclusions: To our knowledge, this is the first study evaluating a-synuclein protein expression in alcoholics. The current study provides further evidence of altered alpha-synuclein levels in patients with alcoholism and their linkage to alcohol craving. Because a synuclein is involved in the modulation of dopaminergic neurotransmission, these results deliver further pathophysiological explanations of craving mechanisms.

Bowirrat A; Oscar-Berman M. Relationship between dopaminergic neurotransmission, alcoholism, and reward deficiency syndrome. American Journal of Medical Genetics: Part B. Neuropsychiatric Genetics 132B(1): 29-37, 2005. (0 refs.)

In this review, we described the neural substrates underlying Reward Deficiency syndrome which, in turn, is posited to underlie alcohol dependency. Alcoholism is a complex, multifactorial disorder that results from the interplay between genetic and environmental factors. The D-2 dopamine receptor (DRD2) has been associated with pleasure, and the DRD2 A1 allele has been referred to as a reward gene. Evidence suggests that there is a tripartite interaction involving dopamine receptor deficiency, a propensity to abuse alcohol, and reduced sensitivity to rewards. This interaction relies heavily on genetic characteristics of the individual, with certain ethnic groups having a greater tendency toward alcoholism than others. The DRD2 has been one of the most widely studied in neuropsychiatric disorders in general, and in alcoholism and other addictions in particular. The dopamine D-2 (DRD2) gene, and especially its allele TaqI A1 allele and its receptor, also may be involved in comorbid antisocial personality disorder symptoms, high novelty seeking, and related traits. The mesocorticolimbic dopaminergic pathway system plays an especially important role in mediating reinforcement by abused drugs, and it may be a common denominator for addictions such as alcoholism. When the mesocorticolimbic dopamine reward system dysfunctions (perhaps caused by certain genetic variants), the end result is Reward Deficiency syndrome and subsequent drug-seeking behaviors. Reward Deficiency syndrome refers to the breakdown of the reward cascade, and resultant aberrant conduct, due to genetic and environmental influences. Alcohol and other drugs of abuse, as well as most positive reinforcers, cause activation and neuronal release of brain dopamine, which can decrease negative feelings and satisfy abnormal cravings. A deficiency or absence of DRD2 receptors then predisposes individuals to a high risk for multiple addictive, impulsive, and compulsive behaviors. Although other neurotransmitters (e.g., glutamate, gamma-aminobutyric acid (GABA), and serotonin) may be important in determining the rewarding and stimulating effects of ethanol, dopamine may be critical for initiating drug use and for reinstating drug use during protracted abstinence. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http:www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html.

Brown ES; Jeffress J; Liggin JDM; Garza M; Beard L. Switching outpatients with bipolar or schizoaffective disorders and substance abuse from their current antipsychotic to aripiprazole. Journal of Clinical Psychiatry 66(6): 756-760, 2005. (24 refs.)

Objective: Substance abuse is extremely common in patients with bipolar disorders, although minimal data are available on the treatment of this important clinical population. Aripiprazole is an atypical antipsychotic that is approved for the treatment of mania and that has a novel mechanism of action, acting as a dopamine-2 receptor partial agonist, thereby increasing dopamine release in some parts of the brain and decreasing dopamine release in other brain regions. Dopamine release is implicated in substance use, and both dopaminergic agonists and antagonists have been examined for the treatment of substance abuse. To our knowledge, dopamine receptor partial agonists have not been investigated for treatment of substance abuse in humans. Method: Twenty antipsychotic-treated patients with bipolar or schizoaffective disorder and current substance abuse were switched to open-label aripiprazole using an overlap and taper method. At baseline, diagnoses were confirmed using the Mini-International Neuropsychiatric Interview based on DSM-IV criteria. Psychiatric symptoms, side effects, and substance use and craving were assessed over 12 weeks. Psychiatric symptoms were assessed with the Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS). Substance craving was assessed with visual analogue scales, and side effects were monitored using the Abnormal Involuntary Movement Scale, Simpson-Angus Scale, Barnes Akathisia Scale, and patient report. Study enrollment was from April 2003 to February 2004. Results: Significant baseline-to-exit improvernent in HAM-D (p = .002), YMRS (p = .021), and BPRS (p = .000) scores were observed without a significant change in antipsychotic-induced side effect scales. In 17 participants with current alcohol dependence, significant reductions in dollars spent on alcohol (p = .042) and alcohol craving (p = .003) were found. In 9 participants with cocaine-related disorders, significant reductions in cocaine craving (p = .014), but not use, were found. Conclusion: A change to aripiprazole was associated with symptomatic improvement. Limitations of the study include a small sample size, high attrition, and an open-label design. Controlled trials in dual-diagnosis patients are needed to confirm these findings.

Chiang SSW; Schuetz C; Soyka M. Effects of cue exposure on the subjective perception of alcohol dependents with different types of cue reactivity. Journal of Neural Transmission 112(9): 1275-1278, 2005. (6 refs.)

Thirty male alcohol-patients were divided into 3 subgroups with increased, unchanged, or reduced craving. Despite no significant difference at baseline, after cue-exposure, the increased craving subgroup showed significantly more confusion, insecurity, and anxiety, nevertheless, stronger beliefs in the positive effects of alcohol compared to the unchanged craving subgroup.

Coffey SF; Stasiewicz PR; Hughes PM; Brimo ML. Trauma-focused imaginal exposure for individuals with comorbid posttraumatic stress disorder and alcohol dependence: Revealing mechanisms of alcohol craving in a cue reactivity paradigm. Psychology of Addictive Behaviors 20(4): 425-435, 2006. (69 refs.)

With a sample (N = 43) of participants meeting current diagnostic criteria for both alcohol dependence and posttraumatic stress disorder (PTSD), the authors tested the hypothesis that alcohol craving elicited by a trauma cue might be attenuated if trauma-elicited negative emotion were reduced following trauma-focused imaginal exposure. In a laboratory-based experiment, participants were randomly assigned to either trauma-focused imaginal exposure or imagery-based relaxation. A cue reactivity Paradigm was used to assess alcohol craving prior to. and after completion of, the 6 clinical sessions. Attrition was high but did not differ between experimental conditions. For study completers, PTSD symptoms decreased in the exposure condition but not in the relaxation condition. Alcohol craving and distress elicited by trauma images decreased in the exposure condition but did not change in the relaxation condition. Results support the hypothesis that negative emotion is a mechanism of alcohol craving.

2006, Educational Publishing Foundation

Colombo G; Serra S; Vacca G; Carai MAM; Gessa GL. Endocannabinoid system and alcohol addiction: Pharmacological studies. Pharmacology, Biochemistry and Behavior 81(2): 369-380, 2005. (81 refs.)

The present paper describes the results of recent pharmacological studies implicating the cannabinoid CB I receptor in the neural circuitry regulating alcohol consumption and motivation to consume alcohol. Cannabinoid CB, receptor agonists have been found to specifically stimulate alcohol intake and alcohol's motivational properties in rats. Conversely, the cannabinoid CB, receptor antagonist, SR 141716, has been reported to specifically suppress acquisition and maintenance of alcohol drinking behavior, relapse-like drinking and alcohol's motivational properties in rats. More recent data indicate that opioid receptor antagonists a) blocked the stimulatory effect of cannabinoids on alcohol intake, and b) synergistically potentiated the suppressing effect of SR 141716 on alcohol intake and alcohol's motivational properties. Consistently, SR 141716 blocked the stimulatory effect of morphine on alcohol intake. These results suggest a) the existence of a functional link between the cannabinoid and opioid receptor systems in the control of alcohol intake and motivation to consume alcohol, and b) that novel and potentially effective therapeutic strategies for alcoholism may come from the combination of cannabinoid and opioid receptor antagonists.

Connor JP; Feeney GFX; Young RM. A comparison of the Yale-Brown obsessive compulsive scale for "Heavy drinking" with a single item craving measure: Construct validity and clinical utility. Substance Use & Misuse 40(4): 551-561, 2005. (35 refs.)

The measurement of alcohol "craving" began with single-item scales. Multifactorial scales developed with the intention to capture more fully the phenomenon of craving. This study examines the construct validity of a multifactorial scale, the Yale-Brown Obsessive Compulsive Scale for heavy drinking (Y-BOCS-hd). The study compares its clinical utility with a single item visual-analogue craving scale. The study includes 212 alcohol dependent subjects (127 males, 75 females) undertaking an outpatient treatment program between 1999-2001. Subjects completed the Y-BOCS-hd and a single item visual-analogue scale, in addition to alcohol consumption and dependence severity measures. The Y-BOCS-hd had strong construct validity. Both the visual-analogue alcohol craving scale and Y-BOCS-hd were weakly associated with pretreatment dependence severity. There was a significant association between pretreatment alcohol consumption and the visual-analogue craving scale. Neither craving measure was able to predict total program abstinence or days abstinent. The relationship between obsessive-compulsive behavior in alcohol dependence and craving remains unclear.

Coyne CM; Jarrett ME; Burr RL; Murphy SA. Women's physical and psychological symptoms during early phase recovery from alcoholism: A longitudinal study. Journal of Addictions Nursing 17(2): 83-93, 2006. (61 refs.)

In this descriptive longitudinal pilot study, symptoms reported weekly by 18 alcohol-dependent women (AG), during their 2nd, 3rd, and 4th months of recovery, were compared with the symptoms from a comparison group (CG) of 15 healthy non-alcoholic women. The women provided weekly records of physical and psychological symptoms, craving, and use of alcohol, nicotine, psychoactive drugs, and prescription medications. During the study, two alcoholism subgroups emerged. The AG-Abstain remained abstinent while the AG-Relapse used substances intermittently. Symptom scores were compared across groups with t-test and ANOVA. An intercept, slope, and R-2 were calculated to determine the pattern of each woman's scores over time. Symptom scores diminished over time, but remained higher for the AG than the CG through the 12th study week. Significant differences in R-2 values demonstrated that the symptom scores fit a negative sloping regression line better in the AG-Abstain than the AG-Relapse subgroups. Emotional irritability reported early in the study predicted later substance use. The study findings can guide the development of therapeutic interventions specific to the persistent symptoms that impact women's health and well-being during recovery.

Cutler RB. Abatement of craving in recovering alcoholics: A descriptive analysis. Addiction Research & Theory 13(2): 111-127, 2005. (33 refs.)

Craving is an important concept in addiction but it has been somewhat mired down in controversies about definition and measurement. This article attempts to clarify the relationship between drinking and craving in recovering alcoholics. Data from two randomized clinical psychopharmacology trials were separately analyzed, a 12-week study of Nalmefene versus placebo (N = 105), and a 52-week maintenance study of Naltrexone versus placebo (N = 155). No evidence of a drug versus placebo difference in overall drinking or craving outcome was found. A simple visual analog craving score was highly correlated (p< 0.001) at multiple time points both with a multi-item craving instrument and with drinking. Alcohol dependent individuals who quit drinking had greater reduction in craving than did individuals who moderate their drinking (p <= 0.001). For abstinent alcoholics who continued in the trial, craving decreased by 50% in the first few weeks, 75% after two months, and 95% after one year. Knowledge of the potential decrease in craving may be of therapeutic benefit to alcohol dependent individuals contemplating abstinence.

Dar R; Frenk H. Nicotine may reinforce intravenous drug-taking behavior in drug users: A comment on Harvey et al. (2004) (letter). Psychopharmacology 179(2): 516-517, 2005. (7 refs.)

In a recent issue of Psychopharmacology, we reviewed the research on self-administration of nicotine, isolated from tobacco, in normal smokers (Dar and Frenk 2004). The review showed that smokers did not administer pure nicotine in any of the forms studied to date, even when abstinent and presumably nicotine-deprived. In a later issue of Psychopharmacology, Harvey et al. (2004) agree that previous studies did not demonstrate nicotine self-administration in human smokers. At the same time, they present findings which, according to the authors, "provide the first clear demonstration that IV nicotine alone - is a very effective reinforcer of drug-taking behavior in human cigarette smokers." As we could not include this study in our review, it is important to examine whether its results contradict our review and can be validly interpreted to demonstrate self-administration of pure nicotine in smokers. As Harvey et al. (2004) state, their article is a follow-up of studies conducted over 20 years ago by Henningfield et al. (1983) and Henningfield and Goldberg (1983). Similar to these original studies, which we critiqued in our review, its findings are based on a very small sample (N= 8). Moreover, the central parameters in the study, dose and FR, were not manipulated in all of the participants (see Table 1 in Harvey et al. 2004). As response rates were not significantly affected by nicotine dose in this study, its only significant finding is that "rates of responding and injections/ session were markedly and significantly higher for nicotine than for saline at FR values of 200 and above." This finding, however, is based only on four participants in whom FR was manipulated; the remaining four worked on an FR of 10 only. More importantly, as in the original studies by Henningfield et al. (1983) and Henningfield and Goldberg (1983), the participants in this study were multiple drug users. Specifically, all but one "reported occasional use of an illicit drug over the past 10 years, including cocaine or amphetamines in two of the subjects, heroin or other opiates in three of the subjects, hallucinogens in two of the subjects and marijuana in six of the subjects. Five participants reported using alcohol, marijuana, or prescribed medications in the week prior to the study" (Harvey et al. 2004). As they were expressly told that nicotine is psychoactive, there is every reason to expect such participants to seek the psychoactive effects of nicotine, especially when confined to an isolated room for 3 hours at a time. Moreover, as we note in our critique of the original studies, there is considerable evidence that injection of saline may be reinforcing in such participants (Wen and Ho 1982; Powell 1995). Self-administration of nicotine by participants with documented history of drug use, therefore, cannot be generalized to the population of smokers. This conclusion is supported by the study of Hughes et al. (2000), in which the only smokers who preferred nicotine to placebo gum were those with a past history of alcoholism. Harvey et al. (2004) do not explain why they chose drug users as participants in this study. Moreover, as shown above, they disregard this fact in interpreting their findings, claiming that they "provide the first clear demonstration that IV nicotine - is a very effective reinforcer of drug-taking behavior in human cigarette smokers." Such a Conclusion: cannot be drawn from a very small sample of smokers with a history and current use of multiple drugs. As we showed in our review (Dar and Frenk 2004), a large body of literature consistently shows the opposite, i. e., that smokers, even when deprived of smoking and nicotine for prolonged periods, do not self- administer pure nicotine in any form.

Dawes MA; Johnson BA; Ma JZ; Ait-Daoud N; Thomas SE; Cornelius JR. Reductions in and relations between "craving" and drinking in a prospective, open-label trial of ondansetron in adolescents with alcohol dependence. Addictive Behaviors 30(9): 1630-1637, 2005. (24 refs.)

Recently, we reported that ondansetron (a 5-HT3 antagonist) as an adjunct to cognitive behavioral therapy (CBT) produced significant within-group decreases (improvement) in drinking in adolescents with alcohol dependence. We previously have hypothesized that the mechanism of ondansetron treatment response in adolescents with alcohol dependence should be similar to early onset adult alcoholics, wherein blockade of serotonin-3 receptors may decrease dopamine release and subsequent alcohol consumption and craving. We now suggest that one mechanism by which ondansetron diminishes drinking in adolescents with alcohol dependence is through a reduction in "craving'' as measured by the Adolescent Obsessive-Compulsive Drinking Scale (A-OCDS). We conducted an 8-week, prospective, open-label study of ondansetron (4 mu g/kg b.i.d.) in 12 adolescents (age 14-20 years) who had alcohol dependence. Results showed that "irresistibility" and total scores as measured by the A-OCDS were correlated significantly with drinking indices (drinks/day, percent days abstinent) at the end of treatment, and that "irresistibility" and total A-OCDS scores decreased significantly by the end of treatment. These preliminary results suggest that the A-OCDS can be useful as an outcome measure in clinical studies of adolescents with alcohol dependence.

De Bruijn C; Van den Brink W; De Graaf R; Vollebergh WAM. Alcohol abuse and dependence criteria as predictors of a chronic course of alcohol use disorders in the general population. Alcohol and Alcoholism 40(5): 441-446, 2005. (49 refs.)

Aims: To investigate whether DSM-IV abuse and dependence criteria and the ICD-10 criterion for craving differentially predict a chronic course of alcohol use disorders (AUD) in the general population. Methods: Data were derived from the Netherlands Mental Health Survey and Incidence Study, a large representative sample of the general Dutch population with a baseline and a 1- and 3-year follow-up assessment. In the present study, a cohort of subjects with a DSM-IV AUD diagnosis at baseline was followed (n = 382). Diagnostic criteria of AUD according to DSM-IV and ICD-10 were assessed using the Composite International Diagnostic Interview (CIDI). Results: In our cohort of subjects with an AUD diagnosis at baseline, the presence of all dependence criteria, except tolerance, significantly increased the risk for dependence at 1 and 3 years follow-up. Abuse criteria displayed much lower and often non-significant risks for dependence at follow-up, with the exception of the criterion 'legal problems'. The ICD-10 criterion 'craving' had the highest relative risk (RR) of all criteria for dependence at 1 year (RR = 12.4, 95% CI = 5.5-27.8) and 3 years follow-up (RR = 12.9, 95% CI = 4.4-37.7). Conclusion: With the exception of tolerance, all DSM-IV dependence criteria are useful in predicting the course of AUD in the general population.

De Bruijn C; Van den Brink W; De Graaf R; Vollebergh WAM. The craving withdrawal model for alcoholism: Towards the DSM-V. Improving the discriminant validity of alcohol use disorder diagnosis. Alcohol and Alcoholism 40(4): 314-322, 2005. (39 refs.)

Aims: To compare the discriminant validity of the DSM-IV and the ICD-10 classification of alcohol use disorders (AUD) with an alternative classification, the craving withdrawal model (CWM). CWM requires craving and withdrawal for the diagnosis of alcohol dependence and raises the alcohol abuse threshold to two DSM-IV AUD criteria. Methods: Data were derived from The Netherlands Mental Health Survey and Incidence Study, a large representative sample of the general Dutch population. In the present study, only non-abstinent subjects were included (n = 6041). Three diagnostic systems (DSM-IV, ICD-10, and CWM) were compared using the following discriminant variables: alcohol intake, psychiatric comorbidity, functional status, familial alcohol problems, and treatment sought. Results: The year prevalence of CWM alcohol dependence was lower than the prevalence of ICD-10 and DSM-IV dependence (0.3% vs 1.4% and 1.4%). The year prevalence of abuse was similar for CWM and DSM-IV (4.7 and 4.9%), but lower for ICD-10 harmful use (1.7%). DSM-IV resulted in a poor distinction between normality and abuse and ICD-10 resulted in a poor distinction between harmful use and dependence. In contrast, the CWM distinctions between normality and abuse, and between abuse, and dependence were significant for most of the discriminant variables. Conclusion: This study indicates that CWM improves the discriminant validity of AUD diagnoses. The predictive validity of the CWM for alcohol and other substance use disorders remain to be studied.

de Wildt WAJM; Lehert P; Schippers GM; Nakovics H; Mann K; van den Brink W. Investigating the structure of craving using structural equation modeling in analysis of the Obsessive-Compulsive Drinking Scale: A multinational study. Alcoholism: Clinical and Experimental Research 29(4): 509-516, 2005. (27 refs.)

Background: Currently, there is no agreement among researchers on the definition of craving and its underlying theoretical model. The Obsessive-Compulsive Drinking Scale (OCDS) seems to measure certain aspects of craving, but its theoretical basis remains unclear. The aim of this study was to investigate the structure of alcohol craving, using OCDS data. Methods: OCDS data from four studies were pooled to obtain a large and heterogeneous sample of 505 participants. All participants were treatment-seeking alcoholics meeting DSM-IV criteria for alcohol dependence. The factor structures of the OCDS previously found were evaluated using confirmatory factor analyses. The goodness of fit of these solutions was compared with those of alternative causal models: an obsessive-compulsive disorder model, an inhibition model, and a cognitive-behavioral model. These alternative models were based on modern theories about craving and were tested in the OCDS data, using structural equation modeling. In this way, the current study replaced simple correlational analysis by a more sophisticated causal way of analyzing the underlying structure of the OCDS items. The best fitting model was selected by comparing the mean discrepancy between the implied and observed matrices of the models. Results: The data showed that the previously reported factor structures had to be rejected. Also, the inhibition model and obsessive-compulsive disorder model did not fit the data. The cognitive-behavioral model showed encouraging fit. Optimizing strategies were applied to further improve the fit of this model, which resulted in a model with close fit to the data. Conclusions: The causal cognitive-behavioral model proved to be superior. It showed that the OCDS contains many items that do not represent the core concept of craving but instead are indicators for the consequences of craving. From this model, it seems that craving, in a narrow sense, can be reliably assessed with only five items of the OCDS.

Dom G; Sabbe B; Hulstijn W; Van Den Brink W. Substance use disorders and the orbitofrontal cortex: Systematic review of behavioural decision-making and neuroimaging studies. (review). British Journal of Psychiatry 187: 209-220, 2005. (85 refs.)

Background: Orbitofrontal cortex dysfunctions have been frequently documented in people with substance use disorders. The exact role of this cortical region, however, remains unspecified. Aims: To assess the functionality of the orbitofrontal cortex in people with substance use disorders. Method: Reports of studies using behavioural decision-making tasks and/or neuroimaging techniques to investigate orbitofrontal cortex functioning in cases of substance misuse were reviewed. Studies focusing exclusively on tobacco-smoking and gambling were excluded. Results: Fifty-two research articles were evaluated. Most studies showed significant deficits in decision-making in people with substance use disorders. A consistent finding in the neuroimaging studies was hypoactivity of the orbitofrontal cortex after detoxification. The association between hyperactivity of this region and craving or cue reactivity was not consistent across studies. Conclusions: The orbitofrontal cortex has an important role in addictive behaviours. Further studies are needed to elucidate the underlying neuronal substrates of cue reactivity, craving and decision-making, and the implications for treatment and relapse prevention.

Ehlers CL; Wilhelmsen KC. Genomic scan for alcohol craving in Mission Indians. Psychiatric Genetics 15(1): 71-75, 2005. (32 refs.)

Alcohol dependence is a leading cause of morbidity and mortality in Native Americans, yet etiologic factors contributing to the disorder remain obscure. Complex psychiatric disorders may be influenced by a number of genes that may be difficult to detect because each has a small effect on a disorder that is broadly defined within a social context. However, such genes might be detected if they have a major effect on a more narrowly defined phenotype. Underlying alcohol dependence are appetitive drive states or instincts that lead to drug 'craving', contribute to compulsive drug usage, and influence relapse following abstinence. A whole genome scan in Mission Indian families provides evidence for genetic linkage to 'craving for alcohol' on chromosome 5. Identification of genes contributing to alcohol craving may give clues to the etiology of the disorder and also provide targets for the development of new medications to treat alcohol dependence.

Field M; Eastwood B. Experimental manipulation of attentional bias increases the motivation to drink alcohol. Psychopharmacology 183(3): 350-357, 2005. (35 refs.)

Rationale: Attentional bias for alcohol-related cues is associated with the motivation to drink alcohol, possibly because attentional bias increases craving. Objectives: We examined whether an experimentally induced attentional bias would influence subjective and behavioural indices of the motivation to drink. Methods: Heavy social drinkers (N=40) completed an attentional training procedure, in which half of the participants were trained to direct their attention towards alcohol-related cues ('attend alcohol'), and half of the participants were trained to direct their attention away from alcohol-related cues ('avoid alcohol'). After attentional training, participants rated their urge to drink alcohol, and the amount of beer consumed during a taste test was measured. Results: The attentional training procedure produced significant changes in attentional bias in the predicted direction in both experimental groups. Attentional training produced an increase in the urge to drink alcohol in the attend alcohol group, and the attend alcohol group consumed more beer than the avoid alcohol group during the taste test. Conclusions: These results suggest that a potentiated attentional bias for alcohol-related cues can increase the motivation to drink alcohol. Theoretical and clinical implications are discussed.

Field M; Mogg K; Bradley BP. Craving and cognitive biases for alcohol cues in social drinkers. Alcohol and Alcoholism 40(6): 504-510, 2005. (30 refs.)

Aims: To assess whether cognitive biases for drug-related cues are associated with subjective craving and behavioural indices of drug-seeking behaviour, as predicted by incentive models of addiction. Methods: Fifty social drinkers took part in a laboratory study in which their subjective craving and cognitive biases for alcohol cues were assessed, before they completed a progressive ratio operant task for alcohol (beer) reinforcement. Results: Social drinkers with high levels of alcohol craving at the beginning of the experiment had more pronounced attentional, approach, and evaluative biases for alcohol cues, compared with those with low craving. There were also trends for the high craving group to show greater operant responding for beer reinforcement, but the latter findings were inconclusive, and no evidence was found of associations between the operant responding and cognitive bias measures. Conclusions: The finding of a relationship between subjective craving and cognitive biases for alcohol cues is consistent with incentive models of addiction. Methodological factors may have obscured the predicted relationships between cognitive bias and operant performance, such as the use of a specific reinforcer (beer) during the operant task, while a range of alcohol-related cues were used in the cognitive bias tasks.

Foddy B; Savulescu J. Symposium - Autonomy, addiction and the drive to pleasure. Designing drugs and our biology: A reply to Neil Levy. Bioethics 20(1): 21-23, 2006. (5 refs.)

Fox HC; Talih M; Malison R; Anderson GM; Kreek MJ; Sinha R. Frequency of recent cocaine and alcohol use affects drug craving and associated responses to stress and drug-related cues. Psychoneuroendocrinology 30(9): 880-891, 2005. (71 refs.)

Rationale: Stress is known to increase drug craving, associated physiological arousal and risk of relapse in drug dependent individuals. However, it is unclear whether these responses are altered by recent frequency of drug use. The current study examined whether frequency of cocaine and alcohol abuse alters drug craving and associated arousal with laboratory exposure to stress and to drug related cues. Methods: Fifty-four recently abstinent treatment-seeking cocaine abusers who were part of a study on stress and drug craving were categorized into high- and low-frequency users on the basis of their recent cocaine use. The high use cocaine group also consumed significantly more alcohol than the low use cocaine group. Participants were exposed to a brief 5-min guided imagery procedure that involved imagining a recent personal stressful situation, a personal drug-related situation and a neutral-relaxing situation, one imagery session on separate days presented in random order. Subjective (craving and anxiety), cardiovascular (heart rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP)) and biochemical (adrenocorticotropic hormone (ACTH), cortisol, protactin) measures were assessed. Results: High-frequency abusers demonstrated a significantly greater drug craving, anxiety and associated cardiovascular and hypothatamic-pituitary-adrenal (HPA) response to both stress and drug-cue exposure as compared to tow-frequency abusers. Conclusions: Increased frequency of recent cocaine and alcohol use is associated with an enhanced stress and cue-induced drug craving and arousal response that appears to be similar to the effects of cocaine, and one that may increase the vulnerability to drug-seeking behavior and relapse in drug dependent individuals.

Garbutt JC. Emerging pharmacologic treatments for alcohol dependence. Journal of Clinical Psychiatry 67(Supplement 14): 35-40, 2006. (56 refs.)

Increased understanding of the neurobiology of alcohol dependence has led to studies of pharmacologic agents that modify drinking behavior. Because alcoholism is a heterogeneous disease involving multiple neurotransmitter and receptor systems, it is likely that a variety of pharmacologic agents will be required to have the greatest impact on outcomes across individuals. Several medications have been approved for the management of alcohol dependence. In addition, several drugs currently used for other indications have been studied for use in alcohol dependence, and some of these drugs show promise. For example, selective serotonin reuptake inhibitors have been shown to reduce drinking in subgroups of alcoholic patients, including those with comorbid depression and those with later-onset alcohol dependence. Ondansetron, a selective 5-hydroxytryptamine(3) receptor antagonist, may attenuate the urge to drink and thus increase abstinence. The anticonvulsant agent topiramate also has significantly reduced drinking behavior in early clinical studies. Baclofen, a gamma-aminobutyric acid B agonist, has been shown to decrease drinking in animal models and in 1 small, placebo-controlled trial in humans. Rimonabant, a cannabinoid CB1 receptor antagonist, has been shown to help nicotine dependence in humans, and in animal studies, to reduce alcohol consumption; no clinical trials in alcoholism have been published. Dopamine antagonists, including clozapine and the newer atypical antipsychotics, may have value in the treatment of alcoholism but require further study. Corticotropin-releasing factor 1 receptor antagonists and neuropeptide Y-1 receptor antagonists have been shown to reduce drinking behavior in animals but have not undergone clinical trials.

2006, Physicians Postgraduate Press

Gau SSF; Liu CY; Lee CS; Chang JC; Chang CJ; Li CF et al. Development of a Chinese version of the Yale-Brown Obsessive Compulsive Scale for heavy drinking. Alcoholism: Clinical and Experimental Research 29(7): 1172-1179, 2005. (41 refs.)

Background: Measurement of craving is an important component in the investigation of the etiology and clinical pictures of alcoholism and dependence of other substances in different cultures. The aim of this study was to develop a Chinese version of the Yale-Brown Obsessive Compulsive Scale for heavy drinking (YBOCS-hd-C), the instrument most frequently used in assessing the severity of alcohol craving in Taiwan. Methods: Four hundred twenty Han Chinese (220 with alcohol use disorders) and 218 Bunun aborigines (150 with alcohol use disorders) in Taiwan were interviewed by mental health professionals with the YBOCS-hd-C and a Chinese version of the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry to establish the psychiatric diagnosis. Validity and reliability of the YBOCS-hd-C were examined. Results: The YBOCS-hd-C was found to have acceptable interrater reliability (intraclass correlation, 0.89-0.96), internal consistency (Cronbach's alpha = 0.99), construct validity, concurrent validity, and cross-cultural validity. The correlations between 10 items of the YBOCS-hd-C and I I items of the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry adjusted for age, gender, and ethnicity ranged from 0.39 to 1.00. The YBOCS-hd-C also discriminated effectively among individuals with alcohol dependence, alcohol abusers, and normal drinkers. Conclusions: This study demonstrated that the YBOCS-hd-C is a reliable and valid instrument for assessing the extent of craving for alcohol in Taiwanese Han and Bunun individuals.

Gordon SM; Sterling R; Siatkowski C; Raively K; Weinstein S; Hill PC. Inpatient desire to drink as a predictor of relapse to alcohol use following treatment. American Journal on Addictions 15(3): 242-245, 2006. (17 refs.)

Cravings for alcohol are identified as a trigger for relapse, though laboratory studies of cravings produce mixed results in predicting relapse. The objective of this analysis is to assess the usefulness of craving as a predictor of relapse by assessing 218 adult, alcohol-dependent patients admitted to two separate residential addiction treatment programs. Days craving reported in the week prior to discharge predicted alcohol use at three-month follow-up. Admission spirituality, alcohol-refusal self-efficacy, and depression levels differentiated cravers from non-cravers. Patients who crave alcohol in residential treatment may be at higher relapse risk and identified by intake assessments of self-efficacy, depression, and spirituality.

2006, American Academy of Psychiatrists in Alcoholism and Addictions

Grothues J; Bischof G; Reinhardt S; Hapke U; Meyer C; John U. Intention to change drinking behaviour in general practice patients with problematic drinking and comorbid depression or anxiety. Alcohol and Alcoholism 40(5): 394-400, 2005. (40 refs.)

Aims: This paper examines the interaction of intention to change drinking behaviour with comorbid depression and anxiety in pro-actively recruited individuals with a range of drinking problems. Methods: Cross-sectional data of 408 general practice (GP) patients aged 18-64 years, who meet the diagnostic criteria of alcohol dependence or abuse according to DSM-IV, criteria of at-risk drinking or binge drinking, were drawn from a brief intervention study. Of the sample, 89 participants were diagnosed with comorbid anxiety and/or depressive disorders. The Transtheoretical Model (TTM) of behaviour change constructs: stages and processes of change, self-efficacy, and decisional balance were assessed in relation to presence and absence of the respective psychiatric disorders. Results: Analysis including all categories of problematic drinking revealed comorbid anxiety and/or depression to be significantly related to later stages of change. Within subgroups, this was only true for alcohol abuse, not for dependence, at-risk or binge drinking. In addition, comorbidity was related to higher use of processes of change and more pros and cons of drinking, when compared to non-comorbid participants. Comorbid individuals showed higher temptation to drink and lower self-efficacy to abstain from drinking. Separate analyses of readiness to change drinking between the categories anxiety/no comorbidity and depression/no comorbidity both obtained significance, while for anxiety disorders, this was more profound. A multinomial logistic regression analysis revealed that adverse consequences better predicted readiness to change when compared to comorbidity. Discussion: Individuals with problematic drinking and comorbid anxiety or depression may be well accessible for pro-active intervention to reduce drinking. Strategies should focus on the enhancement of coping skills to control temptation and self-efficacy.

Grusser SM; Morsen CP; Flor H. Alcohol craving in problem and occasional alcohol drinkers. Alcohol and Alcoholism 41(4): 421-425, 2006. (43 refs.)

Aims: The impact of emotional states on alcohol craving has so far mainly been investigated in abstinent and actively consuming alcohol addicts. Alcohol craving and the variables that influence alcohol craving have not yet been examined in non-addicted, alcohol abusing drinkers and non-abusing occasional alcohol drinkers. Methods: In this study 50 problem drinkers and 50 occasional alcohol drinkers were investigated. The impact of various craving-related variables such as stress and distress, alcohol effect expectancies, and stress coping strategies on reward and relief craving was examined and compared between the groups. Results: Whereas most occasional drinkers reported little alcohol craving, problem drinkers showed a significantly higher amount of reward and relief craving accompanied by increased levels of stress-distress and a stronger tendency to use negative (inadequate) coping strategies. Stress-distress and alcohol effect expectancies were significant predictors of reward and relief craving in problem drinkers. In occasional drinkers alcohol craving was not related to any of these variables. These variables were also found to be predictive of craving in alcohol addicts. Conclusions: We hypothesized, that in non-addicted problem drinkers the expected rewarding and reinforcing alcohol effects lead to an early stage of addictive behaviour. Therefore, in this stage therapeutic interventions focusing on the awareness of the function of alcohol intake as well as alternative coping skills might be useful to prevent alcohol dependence in problem drinkers.

2006, Medical Council on Alcohol

Grusser SM; Morsen CP; Wolfling K; Flor H. The relationship of stress, coping, effect expectancies and craving. European Addiction Research 13(1): 31-38, 2007. (45 refs.)

Based on theoretical models of craving and addiction, this study investigated the association between stress-related variables and negatively and positively reinforcing dimensions of craving ( relief and reward craving) in 150 opiate addicts, 150 alcohol addicts and 150 non-addicted controls. Stress-distress was the most powerful predictor of both dimensions of craving, followed by a lack of positive coping strategies whereas expectancies of substance effects seemed to be less important. Positive coping strategies were related to reduced craving only when they were accompanied by low stress-distress. In non-addicted subjects, only positive coping strategies were negatively related to craving. This study confirms the important role of stress-distress for the occurrence of craving in addicts.

2007, Karger

Heinz A; Reimold M; Wrase J; Hermann D; Croissant B; Mundle G et al. Correlation of stable elevations in striatal mu-opioid receptor availability in detoxified alcoholic patients with alcohol craving: A positron emission tomography study using carbon 11-labeled carfentanil. Archives of General Psychiatry 62(1): 57-64, 2005. (41 refs.)

Background: The pleasant effects of food and alcohol intake are partially mediated by mu-opiate receptors in the ventral striatum, a central area of the brain reward system. Blockade of mu-opiate receptors with naltrexone reduces the relapse risk among some but not all alcoholic individuals. Objective: To test the hypothesis that alcohol craving is pronounced among alcoholic individuals with a high availability of mu-opiate receptors in the brain reward system. Design: Patients and comparison sample. The availability of central mu-opiate receptors was measured in vivo with positron emission tomography (PET) and the radioligand carbon 11-labeled carfentanil in the ventral striatum and compared with the severity of alcohol craving as assessed by the Obsessive Compulsive Drinking Scale (OCDS). Setting: Hospitalized care. Participants: Volunteer sample of 25 male alcohol-dependent inpatients assessed after detoxification of whom 12 underwent PET again 5 weeks later. Control group of 10 healthy men. Main Outcome Measures: After I to 3 weeks of abstinence, the availability of mu-opiate receptors in the ventral striatum, including the nucleus accumbens, was significantly elevated in alcoholic patients compared with healthy controls and remained elevated when 12 alcoholic patients had these levels measured 5 weeks later (P<.05 corrected for multiple testing). Higher availability of mu-opiate receptors in this brain area correlated significantly with the intensity of alcohol craving as assessed by the OCDS. Conclusions: Abstinent alcoholic patients displayed an increase in mu-opiate receptors in the ventral striatum, including the nucleus accumbens, which correlated with the severity of alcohol craving. These findings point to a neuronal correlate of alcohol urges.

Heinz A; Siessmeier T; Wrase J; Buchholz HG; Grunder G; Kumakura Y et al. Correlation of alcohol craving with striatal dopamine synthesis capacity and D-2/3 receptor availability: A combined [18F]DOPA and [18F]DMFP PET Study in detoxified alcoholic patients. American Journal of Psychiatry 162(8): 1515-1520, 2005. (38 refs.)

Objective: In abstinent alcoholic patients, a low availability of dopamine D-2/3 receptors in the ventral striatum and adjacent putamen was associated with a high level of craving for alcohol. Alcohol craving may also depend on presynaptic dysfunction of striatal dopamine production, which may contribute to the risk of relapse. In this study, positron emission tomography (PET) was used to compare dopamine synthesis capacity in the striatum in alcoholic patients and healthy comparison subjects. Method: Positron emission tomography (PET) was used to map the net blood-brain clearance of the dopa decarboxylase substrate 6-[F-18]fluoro-L-dopa, an index of dopamine synthesis capacity, in the striatum of 12 detoxified male alcoholic patients and 13 age-matched healthy men. The parametric maps were correlated with results of an earlier [F-18] desmethoxyfallypride PET study of dopamine D-2/3 receptor availability in the same 12 alcoholic patients and in 12 of the healthy volunteers. Alcohol craving was measured with the Alcohol Craving Questionnaire. Patients were followed for 6 months, and alcohol intake was recorded. Results: The magnitude of net blood-brain clearance in the striatum did not differ significantly between detoxified alcoholic patients and the comparison subjects. However, a voxel-wise correlation analysis of net blood-brain clearance in the alcoholic patients linked low levels of dopamine synthesis capacity in the bilateral putamen with high levels of alcohol craving. After normalization of net blood-brain clearance maps to the voxel-wise estimates of dopamine D-2/3 receptor availability, there was still a negative correlation with alcohol craving. Alcohol craving at the time of scanning was associated with high level of alcohol intake in the 6-month follow-up period. Conclusions: Simultaneous assay by PET of pre- and postsynaptic markers of dopamine neurotransmission indicated that a striatal dopamine deficit correlated with alcohol craving, which was associated with a high relapse risk.

Hermann D; Smolka MN; Wrase J; Klein S; Nikitopoulos J; Georgi A et al. Blockade of cue-induced brain activation of abstinent alcoholics by a single administration of amisulpride as measured with fMRI. Alcoholism: Clinical and Experimental Research 30(8): 1349-1354, 2006. (35 refs.)

Once alcohol dependence is established, alcohol-associated cues may induce dopamine release in the reward system, which is accompanied by alcohol craving and may lead to relapse. In cocaine addicts, dopamine release in the thalamus was positively correlated with cocaine craving. We tested the effects of the atypical dopamine D-2/3 blocker amisulpride on cue-induced brain activation in a functional magnetic resonance imaging (fMRI) paradigm. Alcohol-associated and neutral pictures were presented in a block design to 10 male abstinent alcoholics (1-3 weeks after detoxification) and 10 healthy men during fMRI. The fMRI scans were acquired before and 2 hours after the oral application of 400 mg amisulpride. Before and after each scan, alcohol craving was measured with visual analogue scales. Before the application of amisulpride, alcohol versus control cues elicited a higher blood oxygen level-dependent (BOLD) signal in the left frontal and orbitofrontal lobe, left cingulate gyrus, bilateral parietal lobe, and bilateral hippocampus in alcoholics compared with healthy controls. After amisulpride, alcoholics showed a reduced activation in the right thalamus compared with the first scan. Alcoholics no longer showed significant differences in their cue-elicited BOLD response after amisulpride medication compared with medication-free controls. Self-reported craving was not affected by amisulpride medication. Amisulpride medication was associated with reduced cue-induced activation of the thalamus, a brain region closely connected with frontostriatal circuits that regulate behavior and may influence relapse risk.

Hertling I; Ramskogler K; Dvorak A; Klingler A; Saletu-Zyhlarz G; Schoberberger R et al. Craving and other characteristics of the comorbidity of alcohol and nicotine dependence. European Psychiatry 20(5-6): 442-450, 2005. (45 refs.)

Purpose. - In this cross-sectional study we compared alcohol-dependent smokers and non-alcohol-dependent smokers with respect to intensity of nicotine dependence, craving conditions, sleep disturbances, comorbidity with major depression, reasons for smoking, accompanying somatic diseases and patients' prolonged abstinence from smoking during the 3 years preceding the study. Subjects and methods. - Fifty-one alcohol-dependent smokers and 327 non-alcohol-dependent smokers diagnosed as ICD-10 and DSM-IV-nicotine dependent, were investigated by means of the Fagerstrom Test for Nicotine Dependence, the Lubeck Craving-Recurrence Risk Questionnaire and the Lesch Alcohol Dependence Typology (both adapted to smoking). Results. - The intensity of nicotine dependence was more enhanced in alcohol-dependent smokers compared to non-alcohol-dependent smokers. Several variables of all factors of craving ("depressive mood", "stimulation", "relaxation", "socially triggered tension") were significantly increased in alcohol-dependent patients (P < 0.05). Alcohol-dependent smokers showed depressive symptoms and sleep disturbances, whilst non-alcohol-dependent individuals mainly smoked for stress release and weight control. Discussion. - Our study demonstrates that the intensity of nicotine dependence, several conditions of craving for nicotine, sleep disturbances and symptoms of depression appear to be enhanced in alcohol-dependent smokers compared with non-alcohol-dependent smokers. Conclusions. - It is hoped that the factors of craving and reasons for smoking identified in this study will contribute to a better understanding of smoking temptation in alcohol-dependent smokers and non-alcohol-dependent smokers in future.

Hillemacher T; Bayerlein K; Wilhelm J; Reulbach U; Frieling H; Bonsch D et al. Alteration of prolactin serum levels during alcohol withdrawal correlates with craving in female patients. Addiction Biology 10(4): 337-343, 2005. (54 refs.)

Dopaminergic transmission has been suggested to be a main mechanism mediating reinforcernent, withdrawal and craving in alcohol dependency. Dopaniine is associated with prolactin secretion, acting as a prolactin inhibitor. The aim of the present study was to investigate whether there is at? association between altered prolactin levels and craving during early and late alcohol withdrawal. Therefore, we examined 145 patients suffering from alcohol dependency after admission to the detoxification unit, assessing craving with the Obsessive Compulsive Drinking Scale (OCDS) and measuring prolactin serum levels during early withdrawal (-EW.- day 0 or day 1) and late withdrawal (-LW.- day 7- day 10). We observed a significant influence of the alteration of prolactin during withdrawal on craving in female patients (Spearman's rho, OCDS-EW.- r= -0.607, p = 0. 001; OCDS-L W.- r = - 0. 730, p < 0. 001; n = 26). The association between prolactin alteration in percentage and craving in females was confirined with general linear models (OCDS-EW.- F=15.819, p=0.001, r 2 = 0.530; OCDS-LW.- F=17.091, p<0.001, r(2) = 0.535). In male patients we did not find any significant results. Our findings support the previously described role of the hypothalamic -pituitary -adrenal (HPA) axis in the neurobiology of alcohol craving and show evidence of an association between increased prolactin serum levels and lower craving during alcohol withdrawal in female patients.

Hillemacher T; Bayerlein K; Reulbach U; Sperling W; Wilhelm J; Mugele B et al. Influence of beer, wine and spirits consumption on craving. Addiction Biology 10(2): 181-186, 2005. (31 refs.)

The importance of craving in alcoholism and the efficacy of treatment has been the subject of various studies. This study focuses on the consumption of different alcoholic beverages and their effect on craving, which has not yet been investigated. Therefore we assessed 197 inpatients using the Obsessive Compulsive Drinking Scale (OCDS) on the day of admission and after 1 week, distinguishing between the total score, the obsessive and the compulsive subscale. Socio-demographic data and the type of alcoholic beverage were recorded. Analysing data, the amount of beer consumption showed a significant influence on craving in male but not in female patients. These results were significant for the total score and both subscales of the OCDS (OCDS total score; day 0: Spearman's rho = 0.31; p = 0.001; logistic regression, dependent variable dichotomized OCDS total score day 0: OR = 1.18; 95% CI = 1.04 - 1.34; p= 0.011). On the other hand we, did not find any significant results for the amount of other beverages such as wine and spirits. Receiver operating curves analysis showed that beer consumption significantly predicts craving [area under the curve (AUC) = 0.66; p = 0.002]. We conclude that higher beer consumption is associated with higher withdrawal craving, at least in male patients. In addition, it is an important predictor for both obsessive and compulsive craving. Further studies are needed to clarify the pathophysiological basis of this finding.

Hillemacher T; Bayerlein K; Wilhelm J; Frieling H; Thurauf N; Ziegenbein M et al. Nicotine dependence is associated with compulsive alcohol craving. Addiction 101(6): 892-897, 2006. (47 refs.)

Aims: To investigate a possible association of nicotine dependence and alcohol craving. Design: A prospective cross-sectional study on patients diagnosed with alcohol dependence. Setting: Detoxification unit of a regional psychiatric hospital. Participants A total of 127 smoking male patients were included in the study at admission for detoxification from alcohol. Measurements: The Fagerstrom Test for Nicotine Dependence (FTND) was used to assess the severity of nicotine dependence while the Obsessive Compulsive Craving Scale (OCDS) was used to measure alcohol craving. The OCDS was assessed at admission and after 7 days of withdrawal treatment, distinguishing the total score, the obsessive and the compulsive subscale. Findings: Spearman's correlation revealed a significant association between the extent of alcohol craving and the FTND score (day 0, n = 127: OCDS total score r = 0.238, P = 0.007; OCDS compulsive score r = 0.280, P = 0.001; day 7; n = 94: OCDS total score r = 0.212, P = 0.040; OCDS compulsive score r = 0.225, P = 0.029). Conclusions: The severity of nicotine dependence is associated with higher craving in alcohol-dependent patients. These results point towards shared pathophysiological mechanisms in alcohol craving and nicotine addiction.

Hillemacher T; Bayerlein K; Wilhelm J; Bonsch D; Poleo D; Sperling W. Recurrent detoxifications are associated with craving in patients classified as type 1 according to Lesch's typology. Alcohol and Alcoholism 41(1): 66-69, 2006. (56 refs.)

Aims: Recurrent detoxifications have been suggested to be associated with elevated alcohol craving. The aim of this investigation was to study the influence of preceding detoxifications on craving in patients with alcoholism classified according to Lesch's typology. Methods: We examined 192 patients (154 men, 38 women) after admission for detoxification treatment. Craving was assessed using the Obsessive Compulsive Drinking Scale, and patients were classified into one of the four subgroups of Lesch's typology. The number of preceding detoxifications was assessed with a structured interview. Results: Lesch's typology type 4 patients showed significantly higher craving scores than type 1-3 patients (Mann-Whitney U-Test; P < 0.05). With respect to the influence of recurrent detoxifications, we found a significant correlation between the number of preceding detoxifications and the extent of craving for the whole population (Spearman's rho r = 0.241, P = 0.001, N = 192), particularly for patients of Lesch's type 1 (Spearman's rho r = 0.534, P = 0.001, N = 37). No significant association was found for patients of the other subgroups (Lesch's type 2-4). Conclusion: The influence of recurrent detoxifications on craving is especially important in patients with Lesch's type 1. Our results underline the importance of the kindling effect particularly in this group of patients, possibly mediated by an increase of glutamatergic neurotransmission. Furthermore, our results emphasize the need to classify patients with alcohol-dependency in addiction research.

Hillemacher T; Bayerlein K; Wilhelm J; Poleo D; Frieling H; Ziegenbein M et al. Volume intake and craving in alcohol withdrawal. Alcohol and Alcoholism 41(1): 61-65, 2006. (35 refs.)

Aims: It has been shown that beer consumption is associated with alcohol craving, in contrast to wine or spirits consumption. The present study was undertaken to evaluate whether the daily volume intake of alcoholic beverages is associated with craving in patients undergoing alcohol withdrawal. Methods: A total of 158 male patients were assessed using the obsessive compulsive drinking scale (OCDS) at admission. The daily volume intake of alcoholic beverages was calculated by adding the volume of all regularly consumed alcoholic beverages, disregarding their alcohol percentage. Lesch's typology was used to classify patients for subgroup analysis. Results: The daily volume intake of alcoholic beverages correlated significantly with the extent of the OCDS (r = 0.33; P < 0.001). With general linear models, we found a significant association of the calculated daily volume intake of all alcoholic beverages with craving (F = 6.426; P = 0.012), but not for the daily ethanol intake. Differentiating the patients according to Lesch's typology a significant association was particularly found in Lesch Type 2 (model of anxiety) patients (F = 11.31; P = 0.001). Conclusion: Our results support the hypothesis that volume intake is associated with craving and suggest a role of pathophysiological changes in volume regulating mechanisms (such as vasopressin or ANP) in the neurobiology of alcohol craving, particularly in male patients of Lesch's Type 2 undergoing alcohol withdrawal.

Hillemacher T; Wilhelm J; von Ahsen N; Bayerlein K; Frieling H; Kornhuber J et al. Obsessive-compulsive alcohol craving is not associated with Apolipoprotein E genotype. Psychiatric Genetics 16(6): 231-232, 2006. (4 refs.)

This study examined a possible association with obsessive and compulsive alcohol craving in 192 alcohol-dependent patients undergoing detoxification treatment. Statistical analysis revealed no significant association between Apolipoprotein E polymorphism and obsessive-compulsive alcohol craving (analysis of variance: F = 1.11, P = 0.358).

2006, Lippincott, Williams & Wilkins

Hobbs M; Remington B; Glautier S. Dissociation of wanting and liking for alcohol in humans: A test of the incentive-sensitisation theory. Psychopharmacology 178(4): 493-499, 2005. (25 refs.)

Rationale: Incentive sensitisation theory (IST) claims that the mechanism of reward is comprised of separate neurobiological systems of wanting and liking, that dependent drug use occurs as a result of sensitisation of the system controlling wanting, and that the two systems can be dissociated. Objective: To test the IST prediction that wanting and liking for alcohol can be dissociated in humans. Methods: Measures of wanting and liking for alcohol were obtained in three experiments. Experiment 1 examined whether liking for alcohol was associated with levels of wanting, as indexed by self-reported weekly alcohol intake. Experiments 2 and 3 also assessed the association between liking and wanting but in these experiments wanting was also indexed by alcohol consumption in the laboratory. Experiment 2 increased wanting for alcohol using an alcohol priming dose to determine whether liking would be similarly affected. Experiment 3 reduced liking for alcohol by adulterating drinks with Tween to see whether wanting would also be reduced. Results: Little evidence for an association between liking and wanting for alcohol was found in Experiments 1-3 but, collapsing across all experiments, a weak positive correlation between liking and wanting was found. However, in Experiment 2. wanting was increased by the alcohol priming dose whereas liking was not and in Experiment 3 liking was reduced without a concurrent reduction in wanting. Conclusions: Although correlations between wanting and liking can be observed these results support the contention of the IST that wanting and liking for alcohol can be dissociated in human participants.

Hunter K; Ochoa R. Acamprosate (campral) for treatment of alcoholism. American Family Physician 74(4): 645-646, 2006. (10 refs.)

Acamprosate has been used in Europe for the treatment of alcohol dependency since 1989. In 2004 it became the third drug to receive approval from the U.S. Food and Drug Administration for this indication, following disulfiram (Antabuse) and naltrexone (ReVia). Acamprosate is a structural analogue of gamma-aminobutyric acid (GABA). It is thought to decrease alcohol intake by affecting calcium channels and modifying transmission along GABA and glutamine pathways in the brain, which may result in decreased positive reinforcement of alcohol intake and decreased withdrawal cravings. However, the exact mechanism of action of acamprosate is unknown.

Hutchison KE; Ray L; Sandman E; Rutter MC; Peters A; Davidson D et al. The effect of olanzapine on craving and alcohol consumption. Neuropsychopharmacology 31(6): 1310-1317, 2006. (33 refs.)

Previous studies have indicated that olanzapine decreases craving after a priming dose of alcohol, that craving after a priming dose of alcohol is greater among individuals with the seven-repeat allele of the DRD4 variable number of tandem repeats (VNTR) polymorphism, and that the effect of olanzapine (a D2/D4 antagonist) is more pronounced among individuals with this allele. The present study tested the hypothesis that olanzapine may be differentially effective at reducing cue-elicited craving and differentially effective as a treatment for alcohol dependence over the course of a 12-week, randomized, placebo-controlled trial among individuals with and without the seven-repeat allele. Participants who met DSM IV criteria for alcohol dependence were randomly assigned to receive olanzapine (5 mg) or a placebo over the course of the trial. After 2 weeks of treatment, participants completed a cue reactivity assessment. The results suggested that participants who were homozygous or heterozygous for the seven (or longer)-repeat allele of the DRD4 VNTR responded to olanzapine with reductions in cue-elicited craving as well as reductions in alcohol consumption over the course of the 12-week trial, whereas individuals with the shorter alleles did not respond favorably to olanzapine.

Ilhan IO; Demirbas H; Dogan YB. Validation study of the Turkish version of the Yale-Brown Obsessive Compulsive Scale for heavy drinking in a group of male patients. Drug and Alcohol Review 25(4): 357-360, 2006. (21 refs.)

Psychometric properties of Turkish version of the Yale Brown Obsessive Compulsive Scale for heavy drinking (YBOCS-hd) were examined in alcohol-dependent male patients. Factor structure, internal consistency and discriminant validity of the YBOCS-hd were analysed in a sample of 117 male patients diagnosed with alcohol dependence. To study its convergent validity, the YBOCS-hd was correlated with the Addiction Severity Index in 34 of the patients. A test -retest reliability study was performed on the data from 34 patients. Correlation between the YBOCS-hd total score and the ASI Alcohol Use score was moderate (r = 0.51). One factor explained 50.2% of the variance. The YBOCS-hd was able to discriminate the groups abstinent for less than 1 month and a second group with at least 1 month of abstinence. Test -retest correlation was high (r = 0.81, ICC = 0.81). The Turkish version of the YBOCS-hd proved to be a reliable and valid instrument measuring craving in alcohol-dependent male individuals.

Johnson BA; Koob GF; Schuckit MA; Mason BJ; Ait-Daoud N. Understanding and treating alcohol dependence. (review). Alcoholism: Clinical and Experimental Research 30(9): 567-584, 2006. (167 refs.)

This article represents the proceedings of a symposium presented at the 158th Annual Meeting of the American Psychiatric Association held in Atlanta, Georgia, on May 24, 2005. The organizer/chairman was Bankole A. Johnson, DSc, MD, PhD. The presentations included the following: (1) Neuropharmacological Basis of Alcohol Dependence, by George F. Koob, PhD; (2) Recent Developments in the Genetics of Alcohol Dependence, by Marc A. Schuckit, MD; (3) New Pharmacological Strategies for Treating Alcohol Dependence, by Barbara J. Mason, PhD; (4) New Medications: The Use of Anticonvulsants, Both Alone and in Combination, with Various Forms of Psychotherapy, by Bankole A. Johnson, DSc, MD, PhD; and (5) Differential Effects of Pharmacological Agents on Craving, by Nassima Ait-Daoud, MD.

Johnson BA; Swift RM; Addolorato G; Ciraulo DA; Myrick H. Safety and efficacy of GABAergic medications for treating alcoholism. Alcoholism: Clinical and Experimental Research 29(2): 248-254, 2005. (51 refs.)

This article highlights the proceedings of a symposium presented at the 27th Annual Scientific Meeting of the Research Society on Alcoholism in Vancouver, British Columbia, Canada, June 29, 2004. The organizers and co-chairs were Bankole A. Johnson, MD, PhD, and Robert M. Swift, MD, PhD. The presentations included (1) Introduction, by Bankole A. Johnson; (2) Safety, Tolerability, and Efficacy of gamma-Hydroxybutyric Acid and Baclofen in the Treatment of Alcohol Addiction, by Giovanni Addolorato; (3) Safety of Gabapentin in Treating Alcoholism, by Hugh Myrick; (4) New Data on the Safety and Effectiveness of Topiramate in the Treatment of Alcohol Dependence, by Bankole A. Johnson; (5) Evaluating the Risk of Benzodiazepine Prescription to Alcohol-Dependent Individuals, by Domenic A. Ciraulo; and (6) Safety and Efficacy of GABAergic Agents in Treating Alcoholics: Discussion, by Robert M. Swift.

Jung YC; Namkoong K. Pharmacotherapy for alcohol dependence: Anticraving medications for relapse prevention. (review). Yonsei Medical Journal 47(2): 167-178, 2006. (77 refs.)

Alcohol dependence is a chronic disorder that results from a variety of genetic, psychosocial, and environmental factors. Relapse prevention for alcohol dependence has traditionally involved psychosocial and psychotherapeutic interventions. Pharmacotherapy, however, in conjunction with behavioral therapy, is generating interest as another modality to prevent relapse and enhance abstinence. Naltrexone and acamprosate are at the forefront of the currently available pharmacological options. Naltrexone is an opioid receptor antagonist and is thought to reduce the rewarding effect of alcohol. Acamprosate normalizes the dysregulation of N-methyl-Daspartate (NMDA)-mediated glutamatergic excitation that occurs in alcohol withdrawal and early abstinence.These different mechanisms of action and different target neurotransmitter systems may endow the two drugs with efficacy for different aspects of alcohol use behavior. Since not all patients seem to benefit from naltrexone and acamprosate, there are ongoing efforts to improve the treatment outcomes by examining the advantages of combined pharmacotherapy and exploring the variables that might predict the response of the medications. In addition, novel medications are being investigated to assess their efficacy in preventing relapse and increasing abstinence.

Junghanns K; Backhaus J; Tietz U; Lange W; Rink L; Wetterling T et al. The consumption of cigarettes, coffee and sweets in detoxified alcoholics and its association with relapse and a family history of alcoholism. European Psychiatry 20(5-6): 451-455, 2005. (28 refs.)

Thirty male alcohol dependent inpatients without concurrent depressive disorder, 13 of them with a positive family history of alcohol dependence in a first degree relative (PFH), were questioned about their desire and consumption habits with respect to cigarettes, coffee, and sweets while on a three-week inpatient treatment after detoxification from alcohol. Six weeks after discharge from hospital, the patients were reassessed for relapse. Eleven patients (36.6%) had relapsed at follow-up. Relapsers were younger than abstainers. The days until relapse correlated negatively with intensity of desire to drink alcohol, desire to smoke cigarettes, and with a higher consumption of cigarettes. PFH patients did not relapse earlier but they had a stronger desire to drink coffee and eat sweets and had a higher coffee consumption.

King AC; Epstein AM. Alcohol dose-dependent increases in smoking urge in light smokers. Alcoholism: Clinical and Experimental Research 29(4): 547-552, 2005. (32 refs.)

Background: The current study assessed dose-dependent effects of alcohol compared with placebo on ratings of urge to smoke in light smokers. Methods: Sixteen nonalcoholic social drinker-smokers were tested individually in three separate early evening sessions where they received a placebo (with 1% ethanol as a taste mask), a low-dose (0.4 g/kg) alcoholic beverage, or high-dose (0.8 g/kg) alcoholic beverage administered in random order. Participants refrained from smoking 2 hr before and throughout the entire early evening experimental sessions. Two subfactors of the Brief Questionnaire of Smoking Urges, BQSU; (factor 1, urge to smoke for stimulation; factor 2, urge to smoke to relieve negative mood and withdrawal) were assessed at baseline and again at rising and declining portions of the blood alcohol curve. Results: Both the high and low doses of alcohol significantly increased BQSU factor 1 scores during the rising and declining blood alcohol concentration (BAC) limbs (p < 0.05). Comparisons across doses during both limbs revealed that the high dose significantly increased factor 1 smoking urge compared with the low dose and placebo beverage (p < 0.05, high > low = placebo). Alcohol tended to increase factor 2 scores throughout the BAC curve, but levels were not as increased as factor 1 scores. Finally, there was no significant association between participants' smoking levels and smoking urge ratings during the high- and low-dose sessions. Conclusions: The results support a dose-dependent alcohol-induced increase in smoking urge in cigarette-deprived light smokers. These smoking urge increases were apparent during the rising limb of the BAC and maintained throughout the declining limb. Smoking urge increases were greater for positive reinforcing effects than for negative reinforcing effects.

Krahn DD; Bohn MJ; Henk HJ; Grossman JL; Gosnell B. Patterns of urges during early abstinence in alcohol-dependent subjects. American Journal on Addictions 14(3): 248-255, 2005. (20 refs.)

Urges for alcohol can lead to relapse, but some alcoholics report few urges. We hypothesized that ecological momentary assessment techniques would reveal multiple urge patterns in newly-abstinent alcoholics. Forty-eight alcohol-dependent subjects used PDAs to assess urges to drink in abstinence. Mean and standard deviation of urges were used in cluster analysis, and cluster characteristics were compared. Four clusters were defined, the largest cluster including 29 subjects with low mean urge and low variability. Clusters differed in negative affect and anger but not in abstinence rates. Four distinct urge patterns during abstinence were identified, and 60% of abstinent, alcohol-dependent subjects reported low, stable urge levels.

Krahn D; Grossman J; Henk H; Mussey M; Crosby R; Gosnell B. Sweet intake, sweet-liking, urges to eat, and weight change: Relationship to alcohol dependence and abstinence. Addictive Behaviors 31(4): 622-631, 2006. (30 refs.)

Introduction: Linkages between alcohol dependence (AD) and abstinence and aspects of food ingestion and preference have been described in animals and humans, including (1) eating sweets decreases urges to drink alcohol; (2) preferences for highly sweet tastants is associated with alcohol dependence; and (3) food deprivation leads to increased alcohol intake. Methods: We randomly assigned AD subjects in early abstinence to 3 different sets of dietary instructions (eat sweets for alcohol urges; eat a balanced diet; avoid sweets). We compared the groups on urges for alcohol, alcohol consumption, weight, and sweet preference at baseline, one, and six months. We also compared these AD subjects with light-drinking C's and compared AD subjects who remained abstinent for 6 month follow-up with nonabstinent AD subjects. Results: Recruited AS subjects, 38 of 68, completed 6 month follow-up; 27 of 36 C's completed the follow-up. 21 AD's were abstinent while 17 were non-abstinent. There was no effect of dietary recommendations on urges to drink or alcohol consumption. AD's were more likely than C's to prefer highly sweet tastants. The proportion of AD's preferring the sweetest tastant decreased over time. AD's gained more weight than C's over the 6-month follow-up. Discussion: While the use of sweets did not affect urges to drink or drinking, important relationships between sweet preference, weight gain, and alcohol dependence or abstinence were identified.

Kraus T; Schanze A; Groschl M; Bayerlein K; Hillemacher T; Reulbach U et al. Ghrelin levels are increased in alcoholism. Alcoholism: Clinical and Experimental Research 29(12): 2154-2157, 2005. (27 refs.)

BACKGROUND: The neuropeptides leptin and ghrelin are involved in the appetite regulating network consisting of distinct orexigenic (ghrelin) and anorexigenic (leptin) circuitries. Recently, it has been shown that elevated leptin levels are associated with alcohol craving in patients suffering from alcoholism. Therefore, the aim of the present pilot study was to determine whether the gut-derived peptide ghrelin which increases hunger and food intake is altered and associated with alcohol craving in alcoholic patients. METHODS: Two types of alcoholic inpatients, group A (active drinker, acutely intoxicated, n = 97) and group B (early abstainer, who had stopped drinking 24-72 hrs before, n = 21) were consecutively included in a prospective study from the first day of hospitalization. Ghrelin plasma levels and craving data were assessed on days 0, 1, 2 and 7(-10) and compared to those of 24 healthy controls RESULTS: At each time-point ghrelin plasma levels of alcoholic patients were significantly increased compared to healthy subjects. Furthermore, early abstainers showed significantly higher ghrelin levels than active drinkers. In the group of active drinkers ghrelin plasma levels were significantly increased at each time point compared to baseline. No correlations were found between ghrelin levels and craving data measured by the visual analogue scale or the Obsessive Compulsive Drinking Scale. CONCLUSIONS: Ghrelin levels are elevated in alcoholism and seem to further increase during alcohol withdrawal. However, ghrelin levels do not seem to be associated with alcohol craving.

Lallemand F; De Witte P. SR147778, a CB1 cannabinoid receptor antagonist, suppresses ethanol preference in chronically alcoholized Wistar rats. Alcohol 40(1): 125-134, 2007. (61 refs.)

This study investigated the effect of the new CBI cannabinoid receptor antagonist, SR147778, on ethanol preference in chronically alcoholized Wistar rats. In study 1, SR147778, at doses of 0.3, 1, or 10 mg/kg/day (mg/kg/d) intraperitonealy (ip), was administered during chronic pulmonary ethanol intoxication for 30 days. The rats were then exposed to a two-bottle choice (ethanol 10% v/v vs. water) for at least 30 days. Neither 0.3 nor 1 mg/kg/d had any effect on ethanol preference. In contrast, the high dose induced a significant transient increase in ethanol intake between days 6 and 10. In study 2, SR147778, at doses of 0.3, 1, or 10 mg/kg/d ip, was administered during the free-choice period after chronic alcoholization. Both ethanol preference and intake were significantly reduced only for 1 and 10 mg/kg/d. These results reinforce the hypothesis that the cannabinoid CBI receptor is part of the neural substrate mediating alcohol intake and the motivational properties of alcohol. When these results are compared with those obtained with SR141716 (Rimonabant) on ethanol preference, we observed that (1) coadministration of 10 mg/kg/d SR147778 during chronic alcoholization induced a shorter transient increase of ethanol intake than Rimonabant and (2) SR147778 treatment during the free-choice period at doses of 1 and 10 mg/kg/d decreased ethanol intake more dramatically than SR141716 which, furthermore, continued for the duration of the free choice.

2007, Elsevier Science

Levy N. Addiction, autonomy and ego-depletion: A response to Bennett Foddy and Julian Savulescu. Bioethics 20(1): 16-20, 2006. (18 refs.)

The dominant view is that addicts are incapable of excercising any significant degree of controlover drug-taking, indeed that lack of choice defines addiction. Foddy and Savulescu argue this is false, as addictive desires can be construed as an appetite, simply more compelling. The author sees this goes too far, and endeavors to show how addiction impairs autonomy without overwhelming agency. The author proceeds to discuss the phenomenon of "ego depletion", i.e., a limited resource which needs to restored with rest. Key to this hypothesis is that addictive desires can be resisted when efforts are undertaken to break the phenomenon of craving and desire, which involves removing themselves from cues to use.

Lukas SE; Penetar D; Berko J; Vicens L; Palmer C; Mallya G et al. An extract of the Chinese herbal root kudzu reduces alcohol drinking by heavy drinkers in a naturalistic setting. Alcoholism: Clinical and Experimental Research 29(5): 756-762, 2005. (39 refs.)

Background: Of the available medications for treating alcohol-related problems, none are universally effective, and all have side effects that may limit their use. Extracts of kudzu containing a variety of isoflavones have been shown to reduce alcohol drinking in rats and hamsters. Methods: The present study was designed to test the efficacy of a kudzu extract in a clinical population. Mate and female "heavy" alcohol drinkers were treated with either placebo or a kudzu extract for 7 days and then given an opportunity to drink their preferred brand of beer while in a naturalistic laboratory setting. Participants served as their own controls, and order of treatment exposure was counterbalanced. Drinking behavior was monitored by a digital scale that was located in the top of an end table. Results: Kudzu treatment resulted in significant reduction in the number of beers consumed that was paralleled by an increase in the number of sips and the time to consume each beer and a decrease in the volume of each sip. These changes occurred in the absence of a significant effect on the urge to drink alcohol. There were no reported side effects of kudzu treatment. Conclusion: These data suggest that an extract of this leguminous plant may be a useful adjunct in reducing alcohol intake in a naturalistic setting.

Lukasiewicz M; Benyamina A; Reynaud M; Falissard B. An in vivo study of the relationship between craving and reaction time during alcohol detoxification using the Ecological Momentary Assessment. Alcoholism: Clinical and Experimental Research 29(12): 2135-2143, 2005. (69 refs.)

BACKGROUND: To study cognitive interference associated with craving for alcohol, the Ecological Momentary Assessment (EMA) method was used to measure the relationship between craving and reaction time. A secondary aim was the study of the predictive factors for craving during alcohol detoxification. The EMA enables both repeated measures of craving in a natural setting and the recording of reaction time without the patient being aware of this. METHODS: Craving for alcohol, reaction time, sadness and anxiety were recorded 8 to 12 times a day, over three weeks of detoxification in 14 alcoholics (n = 1767 measures), on an electronic diary issuing random prompts. Mixed models were used for statistical analysis (alpha = 5%, 1-beta = 88%). RESULTS: Reaction time was significantly increased in univariate analysis when a craving episode occurred but this difference did not persist after multivariate analysis. Craving episodes were more frequent and intense than previously reported. Predictive factors of craving during detoxification were: age, gender, sadness, anxiety and the number of previous detoxifications. Antidepressants, anticraving medications but not benzodiazepines were negatively associated to craving.

MacKillop J. Factor structure of the Alcohol Urge Questionnaire under neutral conditions and during a cue-elicited urge state. Alcoholism: Clinical and Experimental Research 30(8): 1315-1321, 2006. (59 refs.)

The Alcohol Urge Questionnaire (AUQ) is a promising multi-item measure of self-reported urges to drink in human laboratory studies; however, its factor structure has not been examined during an acute urge state. This study sought to validate the AUQ's factor structure under neutral conditions and during a cue-elicited urge state in heavy drinkers. Participants (248 heavy drinkers; 70% male) completed the AUQ, the Alcohol Dependence Scale (ADS), and the Positive and Negative Affect Scale (PANAS) under neutral conditions. A randomly selected subsample (n=61; 74% male) then underwent a multimodal alcohol cue exposure and completed the AUQ and PANAS a second time. Under neutral conditions, confirmatory factor analysis (CFA) replicated the previously reported single-factor structure, on which all items significantly loaded (p < 0.001). Alcohol urges, as measured by the AUQ, exhibited significant positive associations with drinks per week and severity of dependence. Following the alcohol cue exposure, participants exhibited a significant increase in urge on the AUQ. Confirmatory factor analysis of the AUQ during the cue-elicited urge state also supported the single factor structure, on which all items significantly loaded (p < 0.001). Positive and negative affect were positively associated with urges across the experimental protocol, but at greater magnitudes during an acutely elevated urge state. These results further validate the use of the AUQ for real-time measurement of alcohol craving in human laboratory research.

MacKillop J; Lisman SA; Weinstein A. Psychometric validation of the Temptation and Restraint Inventory in two samples of college drinkers. Journal of Psychopathology and Behavioral Assessment 28(3): 157-163, 2006. (33 refs.)

Drinking restraint, commonly measured by the Temptation and Restraint Inventory (TRI; Collins & Lapp, 1992), refers to a cycle of temptation to drink alcohol and attempts to control alcohol use that results in excessive consumption. Recent research has examined college drinkers using the TRI, however, it has been validated only in adult samples. This study validated the TRI in two samples of college drinkers, designated as "hazardous" (n = 480) and "harmful" (n = 231) drinkers. Using confirmatory factor analysis, the previously reported higher order two-factor structure was identified in both samples. In addition, multiple regression analyses using derived component scores demonstrated that TRI performance was associated with degree of alcohol dependence in both samples. These data support the use of the TRI in college samples.

McGeary JE; Monti PM; Rohsenow DJ; Tidey J; Swift R; Miranda R. Genetic moderators of naltrexone's effects on alcohol cue reactivity. Alcoholism: Clinical and Experimental Research 30(8): 1288-1296, 2006. (63 refs.)

Naltrexone (NTX) reduces drinking and craving in alcoholic individuals in treatment and also in heavy drinkers. Polymorphisms in the D4 dopamine receptor (DRD4) gene and mu-opiate receptor gene (OPRM1) may moderate NTX's effects on craving. This study examined these candidate genes as moderators of the effects of NTX on cue-elicited urge to drink in non-treatment-seeking heavy drinkers. Data from the subset of 93 participants who consented for genetic testing in a larger study of medication effects were used to examine pharmacogenetic hypotheses. The non-treatment-seeking male and female heavy drinkers (62% alcohol dependent) were genotyped for the variable number of tandem repeats polymorphism in the DRD4 gene [L=7 or more (n=34), S=less than 7 (n=56)] and Asn40Asp single-nucleotide polymorphism in the OPRM1 gene [29 aspartate (Asp) carriers and 59 asparagine (Asn) homozygotes]. Ten days after randomization to NTX (50 mg) or placebo, participants completed an alcohol cue reactivity assessment. Any medication effects were all accounted for by interaction with genotype. Naltrexone increased urge for alcohol in Asp carriers across alcohol and neutral beverage cue trials and had no effect on homozygous Asn carriers. Asp40 carriers on either medication had greater decreases (from resting baseline) in mean arterial blood pressure across all beverage cue trials compared with Asn carriers. For DRD4, no differential medication effects by DRD4 polymorphism were found. Alcohol dependence diagnosis did not moderate the effects of gene and medication on cue-elicited measures. The differential responses to NTX due to variation in the OPRM1 gene may help explain conflicting results in clinical trials and suggest directions for patient-treatment matching.

Muraven M; Shmueli D. The self-control costs of fighting the temptation to drink. Psychology of Addictive Behaviors 20(2): 154-160, 2006. (42 refs.)

Being exposed to the sight and smell of an alcoholic beverage and not drinking it should require self-control. On the basis of the self-control strength model (M. Muraven & R. F. Baumeister, 2000), exerting self-control should lead to poorer performance on subsequent self-control tasks. Using a cue exposure paradigm, the authors had 160 social drinkers alternately sniff water and alcohol. After each trial, the drinkers engaged in 2 self-control tasks: squeezing a handgrip and a self-stopping task. Performance on these tasks was worse after sniffing alcohol than after sniffing water. Mood and arousal did not mediate the effects; urge to drink was negatively related to outcomes. The effects were stronger for individuals high in trait temptation to drink. Resisting the temptation of drinking appears to undermine self-control capacity.

Nava F; Premi S; Manzato E; Lucchini A. Comparing treatments of alcoholism on craving and biochemical measures of alcohol consumptions. Journal of Psychoactive Drugs 38(3): 211-217, 2006. (39 refs.)

An open randomized study was conducted to compare different treatments of alcoholism on ethanol intake, craving, and on biochemical measures of alcohol consumptions. Eighty-six alcoholics were abstinent for a mean of two weeks prior to random assignment to g-hydroxybutyrate (GHB, 50 mg/kg of body weight t.i.d), naltrexone (NTX, 50 mg/day) or disulfiram (DSF, 200 mg/day) treatment for 12 months. All treatments were equally effective in reducing alcohol intake and in maintaining abstinence. In all patients, the treatments were able to reduce both craving and the altered biological markers of alcohol abuse. The maximum effects were observed in GHB-treated patients. The results of the present study suggest that GHB might act both as anticraving and cellular protector agent.

2006, Haight-Ashbury Publishing

Noel X; Colmant M; Van der Linden M; Bechara A; Bullens Q; Hanak C et al. Time course of attention for alcohol cues in abstinent alcoholic patients: The role of initial orienting. Alcoholism: Clinical and Experimental Research 30(11): 1871-1877, 2006. (33 refs.)

Objective: Addicted people are characterized by enhanced attention for drug cues leading to drug use. However, there is little research on the component processes of attention in individuals with alcoholism. Here, we examine 2 distinct components of attention in abstinent alcohol-dependent individuals and social drinkers of alcohol, that is to say, the initial orienting to alcohol-related cues, and the maintenance of attention to them. Method: The present study used an "alcohol" version of the visual probe detection task with alcohol-related or neutral pictures being presented briefly (i.e., 50 ms), to assess initial orienting, or longer (i.e., 500 and 1,250 ms), to assess the maintenance of attention. Results: Only alcoholic patients were faster in detecting a probe displayed immediately after pictures related to alcohol presented for 50 ms than in detecting the same probe replacing non-alcohol-related pictures. However, when pictures were presented for 500 ms, only social alcohol drinkers were faster in detecting the probe replacing alcohol scenes. At a stimulus of 1,250 ms duration, no group showed attentional bias toward alcohol cues. In addition, the severity of alcoholism measured by the total number of prior detoxification treatments was positively correlated with the attentional bias (or "attraction") for alcohol pictures presented for 50 ms. Conclusions: These results show that, subsequent to initial visual orienting to alcohol-related cues, abstinent patients' attention was disengaged from these stimuli, thus suggesting a visual approach-disengagement attentional pattern. The influence of these findings on relapse was discussed.

O'Brien CP. Anticraving medications for relapse prevention: A possible new class of psychoactive medications. American Journal of Psychiatry 162(8): 1423-1431, 2005. (71 refs.)

Psychiatrists have gradually developed a list of medications that are effective in the treatment of addictive disorders. Although alcoholism has received the most attention, nicotine, heroin, and cocaine have all been shown to be influenced by heredity. Of course, the immediate goal is the reduction of drug craving and the prevention of relapse to compulsive drug taking. A medication that can aid in the maintenance of the opiate-free state is naltrexone, a specific opiate antagonist. Naltrexone is also a good example of an anticraving medication used in the treatment of alcoholism. Clinicians currently have two types of medication to aid in the treatment of tobacco use disorder, arguably the most important addiction. Bupropion propion and nicotine replacement can be given in a coordinated fashion to provide the best available results. At present, no medication is approved by the Food and Drug Administration for the indication of cocaine addiction. Recently, however, five different medications, already approved for other purposes, have been found to be effective among cocaine addicts. Despite clinical trials that show benefit, anti-craving medications are not well known and are underused by clinicians. Addiction is a heterogeneous condition, with variability in reactivity to the drug of abuse and to the medications available to treat it. Recent developments in pharmacogenetics may result in improved selection of medications based on genotype.

Olbrich HM; Valerius G; Paris C; Hagenbuch F; Ebert D; Juengling FD. Brain activation during craving for alcohol measured by positron emission tomography. Australian and New Zealand Journal of Psychiatry 40(2): 171-178, 2006. (50 refs.)

Objective: Craving for alcohol is probably involved in acquisition and maintenance of alcohol dependence to a substantial degree. However, the brain substrates and mechanisms that underlie alcohol craving await more detailed elucidation. Method: Positron emission tomography was used to map regional cerebral blood flow (CBF) in 21 detoxified patients with alcohol dependence during exposure to alcoholic and non-alcoholic beverages. Results: During the alcohol condition compared with the control condition, significantly increased CBF was found in the ventral putamen. Additionally, activated areas included insula, dorsolateral prefrontal cortex and cerebellum. Cerebral blood flow increase in these regions was related to self-reports of craving assessed in the alcoholic patients. Conclusions: In this investigation, cue-induced alcohol craving was associated with activation of brain regions particularly involved in brain reward mechanisms, memory and attentional processes. These results are consistent with studies on craving for other addictive substances and may offer strategies for more elaborate studies on the neurobiology of addiction.

Ooteman W; Koeter MWJ; Vserheul R; Schippers GM; van den Brink W. Measuring craving: An attempt to connect subjective craving with cue reactivity. Alcoholism: Clinical and Experimental Research 30(1): 57-69, 2006. (56 refs.)

Background: Better insight into craving may contribute to the development of more efficient relapse prevention strategies. Inconsistent findings on the relation between craving and relapse may be due to difficulties in the measurement of craving. These difficulties are accounted for by 3 interrelated problems: lack of consensus regarding the definition of craving, the use of different time frames (craving now vs craving in the past), and lack of concordance between self-reported craving and psychophysiological measures of cue reactivity. The aim of this study is to develop and validate a new self-report questionnaire for the assessment of the core aspects of craving, taking into account different time frames and emphasizing the psychophysiological aspects of craving. It is hypothesized that this questionnaire will show higher concordance with measures of cue reactivity than existing self-report craving questionnaires. Methods: Based on a semantic mapping sentence, a 24-item self-report questionnaire was developed: the Jellinek Alcohol Craving Questionnaire (JACQ). The questionnaire was tested in 2 samples of treatment-seeking alcohol-dependent patients (sample A, n = 25 1; sample B, n = 48). Psychometric properties were examined in sample A and cross-validated in sample B. The associations with psychophysiological and neuroendocrine measures of cue reactivity were studied in sample B. Results: The JACQ consists of 1 dimension with the following 4 aspects: (1) emotional urge, (2) physical sensations, (3) temptation to drink, and (4) uncontrolled thoughts. All (sub)scales had a good internal consistency (alpha = 0.77-0.95) and were highly intercorrelated (r = 0.57-0.86). Craving-past correlated low with craving-now (r = 0.32). Craving-now (sub)scales showed a moderate association with heart rate (0.46-0.49), but not with respiration rate, skin conductance, or cortisol production in saliva following cue exposure. In contrast, craving-past (sub)scales showed a moderate association with cortisol production in saliva (0.15-0.42) following cue exposure. Remarkably, the physical symptoms scale did not show stronger association with psychophysiological and neuroendocrine measures than the other subscales. Conclusions: The JACQ reliably measures 1 dimension including 4 aspects of craving for distinct time frames. Despite the presence of a special subscale for physical sensations, only moderate relationships were found between self-reported craving and biological indicators of cue reactivity. These findings suggest individual differences between alcoholics in the detection and/or reporting of cue-related psychophysiological signs as indicators of cue reactivity. Further research should focus on the nature of these individual differences. In addition, more research is needed on the relative predictive validity of subjective phenotypic indicators of craving (such as self-reported craving) versus objective endophenotypic indicators of craving (such as physiological measures of cue reactivity) for example in the prediction of relapse.

Oslin DW; Berrettini WH; O'Brien CP. Targeting treatments for alcohol dependence: The pharmacogenetics of naltrexone. (review). Addiction Biology 11(3/4): 397-403, 2006. (65 refs.)

Alcohol dependence is one of the leading causes of morbidity worldwide, yet only a minority of those afflicted engages in treatment. While increasing access to treatment is an important public health approach, increasing the success of treatment is also likely to lead to greater engagement. However, alcohol dependence is a complex disorder likely to consist of several biological subtypes. Recent evidence from a number of different studies has suggested that genetic variation in the mu-opioid receptor has a significant influence on clinical presentation of alcohol problems and response to treatment with an opioid antagonist. Most notably, the A118G polymorphism of the mu-receptor gene has been demonstrated to predict clinical response to naltrexone in alcohol-dependent individuals. This article reviews the biological correlates and outlines a scientific agenda for better understanding the role of opioid neurotransmission in the etiology, maintenance and treatment of alcohol dependence.

Petrakis IL; Poling J; Levinson C; Nich C; Carroll K; Rounsaville B; VA New England VISN I MIRECC Study G. Naltrexone and disulfiram in patients with alcohol dependence and comorbid psychiatric disorders. Biological Psychiatry 57(10): 1128-1137, 2005. (36 refs.)

Background: Disulfiram and naltrexone are approved by the Food and Drug Administration (FDA)for the treatment of alcoholism, but these agents have not been rigorously evaluated in dually diagnosed individuals. Method: Two-hundred and fifty-four patients with an Axis 1 psychiatric disorder and comorbid alcohol dependence were treated for 12 weeks in an outpatient medication study conducted at three Veterans Administration outpatient clinics. Randomization included assignment to one of four groups: 1) naltrexone alone; 2) placebo alone; 3) (open-label) disulfiram and (blinded) naltrexone; or 4) (open-label) disulfiram and (blinded) placebo. Medication compliance was evaluated using the Microelectric Events Monitoring System. Primary outcomes were measures of alcohol use. Secondary outcomes included psychiatric symptoms, alcohol craving, g-GGT levels and adverse events. Results: There was a high rate of abstinence across groups. Subjects treated with an active medication had significantly more consecutive weeks of abstinence and less craving than those treated with placebo, but there were no significant group differences in other measures of alcohol consumption. There was no advantage of the combination of both medications. Conclusions. These data suggest a modest advantage for the use of disulfiram and naltrexone for this group of dually diagnosed alcohol-dependent individuals but did not suggest an advantage in the combination.

Raabe A; Grusser SM; Wessa M; Podschus J; Flor H. The assessment of craving: Psychometric properties, factor structure and a revised version of the Alcohol Craving Questionnaire (ACQ). Addiction 100(2): 227-234, 2005. (32 refs.)

Aims; The goal of the present study was to examine the psychometric properties and factor structure of the Alcohol Craving Questionnaire (ACQ). Design and participants: The German version of the ACQ was administered to a sample of 243 alcohol-dependent or alcohol-abusing subjects. A subgroup of the sample (n = 46) completed the German translation of the Obsessive Compulsive Drinking Scale (OCDS) and the ACQ a second time. Measurements: To validate the factor models, confirmatory factor analyses (CFA) were carried out. Examination of the psychometric properties of the ACQ included the analysis of the item characteristics to exclude non-sensitive items, an exploratory factor analysis of the remaining items and calculation of internal consistency, test-retest reliability and convergent validity. Findings: Neither of the two models showed a satisfactory correspondence. An exploratory factor analysis of a revised version of the ACQ (ACQ-R), based on the psychometric properties of the items, revealed two stable factors ('urge and intention to drink alcohol' and 'reinforcement') with high internal consistency, test-retest reliability and convergent validity. The model fit was also excellent in the CFA. Conclusions: The ACQ-R is a reliable and valid instrument to assess alcohol craving. However, the ACQ-R lacks items related to loss of control. Therefore a multi-dimensional assessment, e.g. the combination of the ACQ-R and the OCDS, is recommended.

Ray LA; Hutchison KE; Bryan A. Psychosocial predictors of treatment outcome, dropout, and change processes in a pharmacological clinical trial for alcohol dependence. Addictive Disorders and their Treatment 5(4): 179-190, 2006. (38 refs.)

OBJECTIVES: The purpose of this study was to examine psychosocial variables associated with treatment outcome, dropout, and the change process in a clinical trial that combines pharmacotherapy with a psychosocial intervention. METHODS: Participants (N=72) were men and women who enrolled in a 12-week clinical trial of olanzapine for alcohol dependence. All participants received 2 individual sessions of a motivation-based intervention. RESULTS: Analysis revealed that higher motivation for change and higher problem severity were individually associated with lower rates of treatment dropout. The effects of problem severity on treatment dropout were found to be mediated by motivation for change. Regarding treatment outcome, baseline measures of craving for alcohol significantly predicted drinking outcomes during follow-up. Furthermore, changes in craving for alcohol before and after treatment were found to predict drinking outcomes at follow-up. CONCLUSIONS: Results are discussed in terms of their implications for the treatment of alcohol dependence, particularly regarding clinical trials that combine pharmacotherapy with a psychosocial intervention.

2006, Lippincott Williams & Wilkins

Reynolds M; Valmana A; Kouimtsidis C; Donaldson C; Ghodse H. An investigation of descriptive and experimental aspects of intrusive thoughts in a sample of substance-dependent inpatients. Addiction Research & Theory 13(4): 347-357, 2005. (24 refs.)

Aims: Thought processes have been hypothesised to play a role in addiction and relapse (Salkovskis and Reynolds (1994)). Thought suppression and smoking cessation showed that suppression was associated with an increase in smoking-related intrusive thoughts, whilst a distracting task (relaxation) reduced intrusion frequency. This is a report of a similar study with a substance-dependent sample undergoing detoxification. Design: Subjects were randomly allocated to one of three groups (mention control, relaxation and suppress) and respectively were asked to monitor, suppress and do relaxation exercises, and suppress substance-related intrusive thoughts in period 1. In period 2 they were told that they could think about anything. Subjects recorded all substance-related intrusions in both periods. Participants and Setting: Inpatient opiate or multisubstance-dependent sample undergoing detoxification. Findings: Deliberate suppression of substance- related intrusive thoughts did not result in an increase in the frequency of the same for the suppression group compared to the mention control group. Relaxation facilitated thought suppression in the first period, but this effect was not carried over to the second period. Conclusions: In the absence of the task which acted as an effective structured distracter, feeling relaxed may act as a trigger for drug-related thoughts. This may have some implications for the use of relaxation as a form of distraction in the treatment for substance misusers.

Rose AK; Duka T. Effects of dose and time on the ability of alcohol to prime social drinkers. Behavioural Pharmacology 17(1): 61-70, 2006. (29 refs.)

Interoceptive drug cues, through associations with the drug's reinforcing properties, may act as conditioned stimuli and elicit conditioned responses. For instance, a dose of alcohol, given to alcohol-experienced people, can lead to an enhancement of alcohol drinking, a phenomenon known as the priming effect. The present study aimed to investigate the alcohol priming effect in non-dependent social drinkers with respect to the dose of alcohol preload and the time of testing after preload. Fifteen social drinkers participated in five daily consecutive sessions. On days 1 and 2 (training sessions), participants consumed a 500 ml beverage of either 0.6 g/kg of alcohol or placebo (50 ml aliquots) presented in 10 colour-coded cups. During days 3, 4 and 5 (testing sessions), a preload of placebo, 0.3 or 0.6 g/kg of alcohol was given (in randomized sequence) in 10 opaque colourless cups. Thirty, 60 and 90 min following the preload, participants responded to an imagery script referring to the drinks sampled at training including a question on the number of aliquots participants would consume from each of the drinks if given the opportunity (hypothetical choice). Participants completed questionnaires evaluating mood and alcohol desires at baseline (before the beverages were given) and after the hypothetical choice. The hypothetical choice showed significant interactions between dose and time: the greatest number of alcohol aliquots were wanted 30 min following the 0.6 g/kg dose of alcohol preload. Ratings from the Desires for Alcohol Questionnaire also showed that alcohol desires peaked 30 min following the 0.6 g/kg of alcohol preload. These data support previous evidence that priming with alcohol can occur and indicate that dose of, and time after preload might affect the strength of, the priming effect for alcohol-related behaviours.

Sayette MA; Martin CS; Wertz JM; Perrott MA; Peters AR. The effects of alcohol on cigarette craving in heavy smokers and tobacco chippers. Psychology of Addictive Behaviors 19(3): 263-270, 2005. (41 refs.)

The authors examined the effects of alcohol consumption on cigarette craving in heavy smokers and tobacco chippers (n = 138) who were instructed not to smoke for 12 hr. Participants were exposed to both smoking cues (a lit cigarette) and control cues. Half received a moderate dose of alcohol, adjusted for gender, and half received a placebo. Results indicated that alcohol consumption produced an increase in urge-to-smoke ratings before smoking cue exposure. Moreover, during cue exposure, alcohol consumption produced a sharper increase in urge ratings than did the placebo. In addition, during smoking cue exposure, alcohol increased the likelihood of displaying facial expressions associated with positive affect. These findings suggest that alcohol consumption influences both the magnitude and the emotional valence of cigarette cravings.

Schumacher JA; Coffey SF; Stasiewicz PR. Symptom severity, alcohol craving, and age of trauma onset in childhood and adolescent trauma survivors with comorbid alcohol dependence and posttraumatic stress disorder. American Journal on Addictions 15(6): 422-425, 2006. (25 refs.)

Posttraumatic stress disorder (PTSD) and alcohol dependence ( AD) are frequently comorbid disorders. Given evidence that childhood traumas may be associated with broader, more severe psychological sequelae than later traumas, the present study examined whether the association between alcohol and trauma symptomatology is more pronounced among individuals with earlier trauma onsets in a sample of 42 childhood and adolescent trauma survivors diagnosed with comorbid AD-PTSD. As predicted, individuals reporting childhood traumas reported greater